FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Taborsky, GJ Mei, Q Hackney, DJ Mundinger, TO AF Taborsky, G. J., Jr. Mei, Q. Hackney, D. J. Mundinger, T. O. TI The search for the mechanism of early sympathetic islet neuropathy in autoimmune diabetes SO DIABETES OBESITY & METABOLISM LA English DT Review DE glucagon; hypoglycaemia; neuropathy; P75 neurotrophin receptor; sympathetic; type 1 diabetes ID INSULIN-INDUCED HYPOGLYCEMIA; AUTONOMIC NERVOUS-SYSTEM; INCREASED GLUCAGON-SECRETION; P75 NEUROTROPHIN RECEPTOR; GROWTH-FACTOR; B-CELLS; NERVES; RESPONSES; PANCREAS; RELEASE AB This review outlines our search for the mechanism causing the early loss of islet sympathetic nerves in autoimmune diabetes. Since our previous work has documented the importance of autonomic stimulation of glucagon secretion during hypoglycaemia, the loss of these nerves may contribute to the known impairment of this specific glucagon response early in human type 1 diabetes. We therefore briefly review the contribution that autonomic activation, and sympathetic neural activation in particular, makes to the subsequent glucagon response to hypoglycaemia. We also detail evidence that animal models of autoimmune diabetes mimic both the early loss of islet sympathetic nerves and the impaired glucagon response seen in human type 1 diabetes. Using data from these animal models, we examine mechanisms by which this loss of islet nerves could occur. We provide evidence that it is not due to diabetic hyperglycaemia, but is related to the lymphocytic infiltration of the islet. Ablating the p75 neurotrophin receptor, which is present on sympathetic axons, prevents early sympathetic islet neuropathy (eSIN), but, interestingly, not diabetes. Thus, we appear to have separated the immune-related loss of islet sympathetic nerves from the immune-mediated destruction of islet -cells. Finally, we speculate on a way to restore the sympathetic innervation of the islet. C1 [Taborsky, G. J., Jr.] Vet Affairs Puget Sound Hlth Care Syst, Div Endocrinol Metab, Seattle, WA USA. [Taborsky, G. J., Jr.; Mei, Q.; Mundinger, T. O.] Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. [Hackney, D. J.] Seattle Inst Biomed & Clin Res, Seattle, WA USA. RP Taborsky, GJ (reprint author), VA Puget Sound Hlth Care Syst, Res 151,1660 S Columbian Way, Seattle, WA 98108 USA. EM taborsky@u.washington.edu FU Medical Research Service of the Department of Veterans Affairs; National Institutes of Health [R01-DK-50154, P30-DK-017047] FX This work was supported by the Medical Research Service of the Department of Veterans Affairs and National Institutes of Health grants R01-DK-50154 and P30-DK-017047. The authors wish to thank Trish Banik for technical assistance and Pam Henderson for administrative assistance (both of the VA Puget Sound Health Care System). NR 48 TC 2 Z9 2 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1462-8902 EI 1463-1326 J9 DIABETES OBES METAB JI Diabetes Obes. Metab. PD SEP PY 2014 VL 16 SU 1 BP 96 EP 101 DI 10.1111/dom.12341 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AP2EY UT WOS:000341886600014 PM 25200302 ER PT J AU Burge, SK Becho, J Ferrer, RL Wood, RC Talamantes, M Katerndahl, DA AF Burge, Sandra K. Becho, Johanna Ferrer, Robert L. Wood, Robert C. Talamantes, Melissa Katerndahl, David A. TI Safely Examining Complex Dynamics of Intimate Partner Violence SO FAMILIES SYSTEMS & HEALTH LA English DT Article DE spouse abuse; battered women; domestic violence; nonlinear dynamics; longitudinal studies ID DOMESTIC VIOLENCE; PRIMARY-CARE; HEALTH; RELIABILITY; WOMEN; DISORDERS; VALIDITY; STRESS; ADULT; ABUSE AB The overall goal of this study is to use complexity science to gain a deeper understanding of the nonlinear day-to-day dynamics of intimate partner violence, with implications for clinical interventions. This report describes research methods for gathering information about partner violence in real time and assesses recruitment and retention, adherence to study protocol, data validity, and participant safety. Research assistants enrolled 200 women in moderately violent intimate relationships and asked them to report about their relationships every day for 12 weeks. Daily, participants telephoned an Interactive Voice Response (IVR) system and responded to 34 survey questions. They also completed baseline and end-of-study surveys and maintained telephone contact with the study team weekly. Forty-two participants completed qualitative end-of-study interviews to describe their relationships and the impact of the study on their lives. Of 200 enrollees, 145 women provided enough data for nonlinear analyses, averaging 63.5 daily reports of 84 possible. Participants submitted 9,201 daily reports, documenting partner's verbal or physical aggression on 39.4% of days, and their own aggression on 23.1%. Two women were withdrawn from the study for safety reasons; the remainder reported that study participation posed no additional threat. Eighty women sought assistance from community resources. Violence severity did not appear to change over the 12 weeks. The research team successfully and safely recruited and retained 145 women who provided valuable data for a study of complex dynamics of intimate partner violence. C1 [Burge, Sandra K.; Becho, Johanna; Ferrer, Robert L.; Wood, Robert C.; Katerndahl, David A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Family & Community Med, San Antonio, TX 78229 USA. [Talamantes, Melissa] South Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Burge, SK (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Family & Community Med, 7703 Floyd Curl Dr,Mail Code 7795, San Antonio, TX 78229 USA. EM burge@uthscsa.edu FU "Dynamics of Human Behavior" program, National Science Foundation [0525026] FX This study was funded with a grant from the "Dynamics of Human Behavior" program, National Science Foundation, Award 0525026. Automated data collection was provided by the University of Colorado, Department of Family Medicine Information Services group. We thank Stephanie Mitchell, Kelli Giacomini, and Wilson Pace for their invaluable assistance with IVR. We also express appreciation to Norma Cantu and Diandrea Garza for their commitment to screening and enrolling women for this study. NR 36 TC 9 Z9 9 U1 2 U2 13 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1091-7527 EI 1939-0602 J9 FAM SYST HEALTH JI Fam. Syst. Health PD SEP PY 2014 VL 32 IS 3 BP 259 EP 270 DI 10.1037/fsh0000013 PG 12 WC Health Care Sciences & Services; Family Studies; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Family Studies; Public, Environmental & Occupational Health GA AP1QF UT WOS:000341845300002 PM 24911769 ER PT J AU Martin, WJ Shim, M Paulus, HE Chaudhari, S Feng, JY Elashoff, D Hahn, TJ Ranganath, VK AF Martin, William J. Shim, Man Paulus, Harold E. Chaudhari, Sandeep Feng, JingYuan Elashoff, David Hahn, Theodore J. Ranganath, Veena K. CA RADIUS Investigators TI Older Age at Rheumatoid Arthritis Onset and Comorbidities Correlate With Less Health Assessment Questionnaire-Disability Index and Clinical Disease Activity Index Response to Etanercept in the RADIUS 2 Registry SO JCR-JOURNAL OF CLINICAL RHEUMATOLOGY LA English DT Article DE rheumatoid arthritis; age; outcomes; disease activity; functional status; etanercept ID ANTIRHEUMATIC DRUG INTERVENTION; ELDERLY-PATIENTS; SERIOUS INFECTIONS; YOUNGER; THERAPY; POPULATION; BIOLOGICS; REMISSION; CRITERIA; OUTCOMES AB Background: Controversy exists in understanding the effects of age at onset and comorbidities in predicting rheumatoid arthritis (RA) response to biologic therapy. Objective: The objective of this study was to investigate the influence of age at onset and number of comorbidities on Health Assessment Questionnaire-Disability Index (HAQ-DI) and Clinical Disease Activity Index (CDAI) responses in active RA patients after 6 months of treatment with etanercept. Methods: One thousand eight hundred ninety-nine RA patients were assessed after 6 months of etanercept therapy. Patients met the following inclusion criteria: initiated etanercept, continued therapy for at least 6 months, and were not in CDAI low disease activity (LDA) at baseline (CDAI <= 10.0). Changes in HAQ-DI and CDAI scores over 6 months were analyzed across age of onset quintiles. Multivariate regression models evaluated the independent association between both age at onset and number of comorbidities with change in HAQ-DI/CDAI scores or achieving LDA, while accounting for other covariates. Results: Significant improvements in HAQ-DI and CDAI scores were observed in all age-onset groups, although HAQ-DI improvements were less in older-onset patients. Results of multiple linear regression demonstrated that younger age at onset, higher baseline HAQ-DI/CDAI score, rheumatoid factor positivity, shorter disease duration, and fewer comorbidities at baseline were independently associated with improvement in both HAQ-DI and CDAI scores. Similarly, achieving CDAI LDA after 6 or more months of etanercept was associated with younger age at onset, higher baseline CDAI, shorter disease duration, and fewer comorbidities. Conclusions: These patients with older-onset RA and more comorbidities clinically improved with etanercept, but had lower odds of achieving CDAI LDA. Age of onset and number of comorbidities may be important in determining RA tumor necrosis factor inhibitor response. C1 [Martin, William J.; Shim, Man; Paulus, Harold E.; Elashoff, David; Hahn, Theodore J.; Ranganath, Veena K.] Univ Calif Los Angeles, Los Angeles, CA 90095 USA. [Chaudhari, Sandeep] PharmaNet i3 Strateg Resourcing, Tampa, FL USA. [Feng, JingYuan] Amgen Inc, Thousand Oaks, CA 91320 USA. [Hahn, Theodore J.] VA Greater Los Angeles Geriatr Res Educ & Clin Ct, Los Angeles, CA USA. RP Ranganath, VK (reprint author), Univ Calif Los Angeles, 1000 Vet Ave,Rehab Bldg 32-59, Los Angeles, CA 90095 USA. EM vranganath@mednet.ucla.edu FU Immunex, a wholly owned subsidiary of Amgen Inc; Wyeth; ACR/REF/ASP; UCLA Older Americans Independence Center, NIA [AG028748] FX This study was sponsored by Immunex, a wholly owned subsidiary of Amgen Inc, and by Wyeth, which was acquired by Pfizer in October 2009.; V.K.R. received the ACR/REF/ASP Junior Career Development Award in Geriatric Medicine and UCLA Older Americans Independence Center, NIA AG028748. The remaining authors declare no conflict of interest. NR 42 TC 3 Z9 3 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1076-1608 EI 1536-7355 J9 JCR-J CLIN RHEUMATOL JI JCR-J. Clin. Rheumatol. PD SEP PY 2014 VL 20 IS 6 BP 301 EP 305 DI 10.1097/RHU.0000000000000152 PG 5 WC Rheumatology SC Rheumatology GA AO7WJ UT WOS:000341563000006 PM 25160011 ER PT J AU Boehme, AK Rawal, PV Lyerly, MJ Albright, KC Shahripour, RB Palazzo, P Kapoor, N Alvi, M Houston, JT Harrigan, MR Cava, L Sisson, A Alexandrov, AW Alexandrov, AV AF Boehme, Amelia K. Rawal, Pawan V. Lyerly, Michael J. Albright, Karen C. Shahripour, Reza Bavarsad Palazzo, Paola Kapoor, Niren Alvi, Mohammad Houston, J. Thomas Harrigan, Mark R. Cava, Luis Sisson, April Alexandrov, Anne W. Alexandrov, Andrei V. TI Investigating the Utility of Previously Developed Prediction Scores in Acute Ischemic Stroke Patients in the Stroke Belt SO JOURNAL OF STROKE & CEREBROVASCULAR DISEASES LA English DT Article DE Stroke; epidemiology; stroke recovery; outcome ID TISSUE-PLASMINOGEN ACTIVATOR; TOTALED HEALTH-RISKS; EVENTS THRIVE SCORE; INTRAARTERIAL THERAPY; UNITED-STATES; THROMBOLYSIS; VALIDATION; EXPERIENCE; OUTCOMES AB Background: To assess the utility of previously developed scoring systems, we compared SEDAN, named after the components of the score (baseline blood Sugar, Early infarct signs and (hyper) Dense cerebral artery sign on admission computed tomography scan, Age, and National Institutes of Health Stroke Scale on admission), Totaled Health Risks in Vascular Events (THRIVE), Houston Intra-arterial Therapy (HIAT), and HIAT-2 scoring systems among patients receiving systemic (intravenous [IV] tissue plasminogen activator [tPA]) and endovascular (intra-arterial [IA]) treatments. Methods: We retrospectively reviewed all IV tPA and IA patients presenting to our center from 2008-2011. The scores were assessed in patients who were treated with IV tPA only, IA only, and a combination of IV tPA and IA (IV-IA). We tested the ability of THRIVE to predict discharge modified Rankin scale (mRS) 3-6, HIAT and HIAT-2 discharge mRS 4-6, and SEDAN symptomatic intracerebral hemorrhage (sICH). Results: Of the 366 patients who were included in this study, 243 had IV tPA only, 89 had IA only, and 34 had IV-IA. THRIVE was predictive of mRS 3-6 in the IV-IA (odds ratio [OR], 1.95; 95% confidence interval [CI], 1.30-2.91) and the IV group (OR, 1.71; 95% CI, 1.43-2.04), but not in the IA group. HIAT was predictive of mRS 4-6 in the IA (OR, 3.55; 95% CI, 1.65-7.25), IV (OR, 3.47; 95% CI, 2.26-5.33), and IV-IA group (OR, 6.48; 95% CI, 1.41-29.71). HIAT-2 was predictive of mRS 4-6 in the IA (OR, 1.39; 95% CI, 1.03-1.87) and IV group (OR, 1.36; 95% CI, 1.18-1.57), but not in the IV-IA group. SEDAN was not predictive of sICH in the IA or the IV-IA group, but was predictive in the IV group (OR, 1.54; 95% CI, 1.01-2.36). Conclusions: Our study demonstrated that although highly predictive of outcome in the original study design treatment groups, prediction scores may not generalize to all patient samples, highlighting the importance of validating prediction scores in diverse samples. C1 [Boehme, Amelia K.; Rawal, Pawan V.; Lyerly, Michael J.; Shahripour, Reza Bavarsad; Palazzo, Paola; Kapoor, Niren; Alvi, Mohammad; Houston, J. Thomas; Sisson, April; Alexandrov, Andrei V.] Univ Alabama Birmingham, Dept Neurol, Stroke Ctr, Birmingham, AL 35294 USA. [Boehme, Amelia K.; Albright, Karen C.] Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA. [Lyerly, Michael J.] Birmingham Vet Affairs Med Ctr, Stroke Ctr, Birmingham, AL USA. [Harrigan, Mark R.] Univ Alabama Birmingham, Sch Med, Dept Neurosurg, Birmingham, AL USA. [Cava, Luis] Univ Colorado, Dept Neurosurg, Denver, CO 80202 USA. [Alexandrov, Anne W.] Univ Alabama Birmingham, Sch Nursing, Birmingham, AL USA. RP Boehme, AK (reprint author), 1240 Jefferson Tower,619 19th St South, Birmingham, AL 35294 USA. EM akboehme@gmail.com OI Alexandrov, Andrei V/0000-0001-8871-1023; Lyerly, Michael/0000-0003-4236-1018 FU Agency for Healthcare Research and Quality (AHRQ) [5 T32 HS013852-10]; National Institute on Minority Health and Health Disparities (NIMHD), National Institutes of Health (NIH) [3 P60 MD000502-08S1]; American Heart Association (AHA) [13PRE13830003] FX The project described was supported by award numbers 5 T32 HS013852-10 from The Agency for Healthcare Research and Quality (AHRQ), 3 P60 MD000502-08S1 from The National Institute on Minority Health and Health Disparities (NIMHD), National Institutes of Health (NIH) and 13PRE13830003 from the American Heart Association (AHA). The content is solely the responsibility of the authors and does not necessarily represent the official views of the AHA, AHRQ, or the NIH. NR 22 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1052-3057 EI 1532-8511 J9 J STROKE CEREBROVASC JI J. Stroke Cerebrovasc. Dis. PD SEP PY 2014 VL 23 IS 8 BP 2001 EP 2006 DI 10.1016/j.jstrokecerebrovasdis.2014.02.003 PG 6 WC Neurosciences; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA AO6TQ UT WOS:000341484900011 PM 25113079 ER PT J AU Jacobus, J Squeglia, LM Sorg, SF Nguyen-Louie, TT Tapert, SF AF Jacobus, Joanna Squeglia, Lindsay M. Sorg, Scott F. Nguyen-Louie, Tam T. Tapert, Susan F. TI Cortical Thickness and Neurocognition in Adolescent Marijuana and Alcohol Users Following 28 Days of Monitored Abstinence SO JOURNAL OF STUDIES ON ALCOHOL AND DRUGS LA English DT Article ID SPATIAL WORKING-MEMORY; HUMAN CEREBRAL-CORTEX; SURFACE-BASED ANALYSIS; ADULT CANNABIS USERS; WHITE-MATTER; NEUROPSYCHOLOGICAL PERFORMANCE; SUBSTANCE-ABUSE; BINGE DRINKING; COMPLEX FIGURE; FMRI RESPONSE AB Objective: Adolescent marijuana use continues to increase in prevalence as harm perception declines. Better understanding of marijuana's impact on neurodevelopment is crucial. This prospective study aimed to investigate cortical thickness and neurocognitive performance before and after 28 days of monitored abstinence in adolescent marijuana and alcohol users. Method: Subjects (N = 54; >70% male) were adolescent marijuana users (ages 15-18 years) with regular alcohol use (MJ + ALC; n = 24) and non-using controls (CON; n = 30) who were compared before and after 4 weeks of sequential urine toxicology to confirm abstinence. Participants underwent magnetic resonance imaging, neuropsychological assessment, and substance use assessment at both time points. Repeated-measures analysis of covariance was used to look at the main effects of group, time, and Group x Time interactions on cortical thickness and neurocognitive functioning. Bivariate correlations estimated associations between cortical thickness, substance use severity, and cognitive performance. Results: Marijuana users showed thicker cortices than controls in the left entorhinal cortex (ps < .03) before and after monitored abstinence, after adjusting for lifetime alcohol use. More lifetime marijuana use was linked to thinner cortices in temporal and frontal regions, whereas more lifetime alcohol use and heavy episodic drinking episodes was linked to thicker cortices in all four lobes (ps < .05). Age of onset of regular marijuana use was positively related to cortical thickness (ps < .03). Conclusions: Adolescent alcohol and marijuana use may be linked to altered longer-term neurodevelopmental trajectories and compromised neural health. Cortical thickness alterations and dose-dependent associations with thickness estimates were observed both before and after monitored abstinence and suggest neural differences continue to persist 28 days after cessation of marijuana use. Neural recovery may be identified with longer follow-up periods; however, observed changes related to use severity could have implications for future psychosocial outcomes. C1 [Jacobus, Joanna; Tapert, Susan F.] VA San Diego Healthcare Syst, San Diego, CA 92161 USA. [Jacobus, Joanna; Squeglia, Lindsay M.; Nguyen-Louie, Tam T.; Tapert, Susan F.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Sorg, Scott F.] Vet Affairs Puget Sound Healthcare Syst, Seattle, WA USA. [Nguyen-Louie, Tam T.] Univ Calif San Diego, San Diego State Univ, Joint Doctoral Program Clin Psychol, San Diego, CA 92103 USA. RP Tapert, SF (reprint author), VA San Diego Healthcare Syst, Psychol Serv 116B, 3350 La Jolla Village Dr, San Diego, CA 92161 USA. EM stapert@ucsd.edu FU National Institute on Drug Abuse; National Institute on Alcohol Abuse and Alcoholism [P20 DA024194, R01 DA021182, F32 DA032188, R01 AA013419, T32 AA013525, U01 AA021692] FX This study was supported by National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism Grants P20 DA024194, R01 DA021182, F32 DA032188, R01 AA013419, T32 AA013525, and U01 AA021692. NR 96 TC 14 Z9 14 U1 4 U2 21 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA C/O DEIRDRE ENGLISH, 607 ALLISON RD, PISCATAWAY, NJ 08854-8001 USA SN 1937-1888 EI 1938-4114 J9 J STUD ALCOHOL DRUGS JI J. Stud. Alcohol Drugs PD SEP PY 2014 VL 75 IS 5 BP 729 EP 743 PG 15 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA AO8PA UT WOS:000341615500001 PM 25208190 ER PT J AU Narayana, S Wong, CJ AF Narayana, Sirisha Wong, Christopher J. TI Office-Based Screening of Common Psychiatric Conditions SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article DE Screening; Depression; Anxiety; Cost-effectiveness; Outcomes ID PATIENT HEALTH QUESTIONNAIRE; PRIMARY-CARE PATIENTS; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; COMORBIDITY SURVEY REPLICATION; GENERALIZED ANXIETY DISORDER; CASE-FINDING INSTRUMENTS; UTAH RATING-SCALE; DSM-IV DISORDERS; MAJOR DEPRESSION AB Depression and anxiety disorders are common conditions with significant morbidity. Many screening tools of varying length have been well validated for these conditions in the office-based setting. Novel instruments, including Internet-based and computerized adaptive testing, may be promising tools in the future. The best evidence for cost-effectiveness currently is for screening of major depression linked with the collaborative care model for treatment. Data are not conclusive regarding comparative cost-effectiveness of screening for multiple conditions at once or for other conditions. This article reviews screening tools for depression and anxiety disorders in the ambulatory setting. C1 [Narayana, Sirisha] Univ Washington, VA Puget Sound Hlth Care Syst, Dept Med, Div Gen Internal Med, Seattle, WA 98108 USA. [Wong, Christopher J.] Univ Washington, Dept Med, Div Gen Internal Med, Seattle, WA 98105 USA. RP Wong, CJ (reprint author), Univ Washington, Dept Med, Div Gen Internal Med, 4245 Roosevelt Way Northeast,Box 354760, Seattle, WA 98105 USA. EM cjwong@uw.edu NR 77 TC 4 Z9 4 U1 2 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0025-7125 EI 1557-9859 J9 MED CLIN N AM JI Med. Clin. N. Am. PD SEP PY 2014 VL 98 IS 5 BP 959 EP + DI 10.1016/j.mcna.2014.06.002 PG 23 WC Medicine, General & Internal SC General & Internal Medicine GA AO8OO UT WOS:000341614300005 PM 25134868 ER PT J AU Lin, Y Luo, J Zhu, WE Srivastava, M Schaue, D Elashoff, DA Dubinett, SM Sharma, S Wu, B St John, MA AF Lin, Yuan Luo, Jie Zhu, Weichao Eric Srivastava, Minu Schaue, Dorthe Elashoff, David A. Dubinett, Steven M. Sharma, Sherven Wu, Benjamin St John, Maie A. TI A Cytokine-Delivering Polymer Is Effective in Reducing Tumor Burden in a Head and Neck Squamous Cell Carcinoma Murine Model SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article DE head and neck cancer; squamous cell carcinoma; polymer; novel therapeutics ID LYMPHOID-TISSUE CHEMOKINE; CC-CHEMOKINE; RECEPTOR CCR7; GENE-THERAPY; MOUSE MODEL; CANCER; RADIOTHERAPY; CCL21; ACTIVATION; MECHANISMS AB Objective This study aimed to evaluate the therapeutic efficacy of a novel polymer platform delivering cisplatin and cytokines in the treatment of head and neck squamous cell carcinoma (HNSCC). Study Design In vivo study. Setting Academic research laboratory. Subjects and Methods Mice were randomized to receive implantation of (1) no polymer, (2) plain polymer, (3) plain polymer with local cisplatin injection, or (4) cisplatin polymer. The 2 groups of mice implanted with cisplatin polymer or no polymer were further randomized to receive (1) 4 Grays external beam radiation for 4 days or (2) no radiation. For cytokine studies, mice were grouped into (1) no polymer, (2) plain polymer, (3) plain polymer with intratumoral injection of recombinant CCL21 twice a week, (4) polymer containing parental dendritic cells, or (5) polymer containing dendritic cells secreting CCL21 (DC-CCL21). Results The cisplatin-secreting polymer effectively reduced tumors in the mice by more than 16-fold (P < .01). We also observed a statistically significant lower tumor weight among mice treated with cisplatin polymer and concomitant radiation compared to control groups. The DC-CCL21 polymer reduced SCCVII/SF tumors in the C3H/HeJ mice by more than 41% (P < .01). Conclusion Herein, we demonstrate the efficacy of a novel polymer platform in delivering cisplatin and cytokines. We also demonstrate that we can effectively grow dendritic cells in the polymer that can actively secrete CCL21 for a minimum of 5 days. This polymer may represent a new therapeutic modality for patients with HNSCC. Once this polymer platform is optimized, we will plan to pursue prospective trials in patients with HNSCC. C1 [Lin, Yuan; Luo, Jie; St John, Maie A.] Univ Calif Los Angeles, Dept Head & Neck Surg, Los Angeles, CA 90095 USA. [Lin, Yuan; Luo, Jie; St John, Maie A.] Univ Calif Los Angeles, UCLA Head & Neck Canc Program, Los Angeles, CA 90095 USA. [Lin, Yuan; Luo, Jie; Srivastava, Minu; Dubinett, Steven M.; Sharma, Sherven] Univ Calif Los Angeles, Dept Med, Div Pulm & Crit Care Med, Los Angeles, CA 90095 USA. [Zhu, Weichao Eric; Wu, Benjamin] Univ Calif Los Angeles, Dept Bioengn, Los Angeles, CA 90095 USA. [Srivastava, Minu; Dubinett, Steven M.; Sharma, Sherven] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Schaue, Dorthe] Univ Calif Los Angeles, Dept Radiat Oncol, Los Angeles, CA 90095 USA. [Elashoff, David A.; Dubinett, Steven M.; St John, Maie A.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. [Elashoff, David A.] Univ Calif Los Angeles, Dept Biostat, Los Angeles, CA 90095 USA. [Wu, Benjamin] Univ Calif Los Angeles, Div Adv Prosthodont Biomat & Hosp Dent, Los Angeles, CA 90095 USA. [Wu, Benjamin] Univ Calif Los Angeles, Dept Mat Sci & Engn, Los Angeles, CA 90095 USA. [Wu, Benjamin] Univ Calif Los Angeles, David Geffen Sch Med, Dept Orthoped Surg, Los Angeles, CA 90095 USA. RP St John, MA (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, 37-131 CHS,10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM mstjohn@mednet.ucla.edu FU American Academy of Otolaryngology-American Head & Neck Society Surgeon Scientist Career Development Award; Tobacco-Related Disease Research Program of the University of California; STOP Cancer Foundation; Jonsson Cancer Center; NIDCR K23 FX Funding source: This study was supported by the American Academy of Otolaryngology-American Head & Neck Society Surgeon Scientist Career Development Award (M.A.S.J.), the Tobacco-Related Disease Research Program of the University of California (M.A.S.J.), the STOP Cancer Foundation (M.A.S.J.), The Jonsson Cancer Center, and NIDCR K23 (M.A.S.J.). NR 35 TC 2 Z9 2 U1 1 U2 6 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0194-5998 EI 1097-6817 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD SEP PY 2014 VL 151 IS 3 BP 447 EP 453 DI 10.1177/0194599814533775 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA AP0MU UT WOS:000341757000014 PM 24825873 ER PT J AU Bibas, L Levi, M Bendayan, M Mullie, L Forman, DE Afilalo, J AF Bibas, Lior Levi, Michael Bendayan, Melissa Mullie, Louis Forman, Daniel E. Afilalo, Jonathan TI Therapeutic Interventions for Frail Elderly Patients: Part I. Published Randomized Trials SO PROGRESS IN CARDIOVASCULAR DISEASES LA English DT Review DE Frailty; Sarcopenia; Randomized clinical trials ID PHYSICAL-ACTIVITY INTERVENTION; JAPANESE SARCOPENIC WOMEN; PLACEBO-CONTROLLED TRIAL; DWELLING OLDER-ADULTS; FUNCTIONAL DECLINE; BODY-COMPOSITION; CLINICAL-TRIAL; DOUBLE-BLIND; MUSCLE MASS; HEART-FAILURE AB The body of literature for frailty as a prognostic marker continues to grow, yet the evidence for frailty as a therapeutic target is less well defined. In the setting of cardiovascular disease, the prevalence of frailty is elevated and its impact on mortality and major morbidity is substantial. Therapeutic interventions aimed at improving frailty may impart gains in functional status and survival. Randomized clinical trials that tested one or more therapeutic interventions in a population of frail older adults were reviewed. The interventions studied were exercise training in 13 trials, nutritional supplementation in 4 trials, combined exercise plus nutritional supplementation in 7 trials, pharmaceutical agents in 8 trials, multi-dimensional programs in 5 trials, and home-based services in 1 trial. The main findings of these trials are explored along with a discussion of their relative merits and limitations. (c) 2014 Elsevier Inc. All rights reserved. C1 [Bibas, Lior; Levi, Michael; Mullie, Louis] McGill Univ, Dept Med, Montreal, PQ H3T 1E2, Canada. [Bibas, Lior; Levi, Michael; Afilalo, Jonathan] McGill Univ, Div Cardiol, Montreal, PQ H3T 1E2, Canada. [Bendayan, Melissa; Afilalo, Jonathan] McGill Univ, Dept Physiol, Montreal, PQ H3T 1E2, Canada. [Forman, Daniel E.] Univ Pittsburgh, Med Ctr, Sect Geriatr Cardiol, Pittsburgh, PA USA. [Forman, Daniel E.] VA Pittsburgh Healthcare Syst, Geratr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Afilalo, Jonathan] McGill Univ, Jewish Gen Hosp, Div Cardiol, Montreal, PQ H3T 1E2, Canada. [Afilalo, Jonathan] McGill Univ, Jewish Gen Hosp, Div Clin Epidemiol, Montreal, PQ H3T 1E2, Canada. RP Afilalo, J (reprint author), McGill Univ, Jewish Gen Hosp, Div Cardiol, 3755 Cote Ste Catherine Rd,E-222, Montreal, PQ H3T 1E2, Canada. EM jonathan.afilalo@mcgill.ca NR 48 TC 33 Z9 33 U1 4 U2 29 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0033-0620 EI 1873-1740 J9 PROG CARDIOVASC DIS JI Prog. Cardiovasc. Dis. PD SEP-OCT PY 2014 VL 57 IS 2 BP 134 EP 143 DI 10.1016/j.pcad.2014.07.004 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AP1AN UT WOS:000341798900003 PM 25216612 ER PT J AU Bendayan, M Bibas, L Levi, M Mullie, L Forman, DE Afilalo, J AF Bendayan, Melissa Bibas, Lior Levi, Michael Mullie, Louie Forman, Daniel E. Afilalo, Jonathan TI Therapeutic Interventions for Frail Elderly Patients: Part II. Ongoing and Unpublished Randomized Trials SO PROGRESS IN CARDIOVASCULAR DISEASES LA English DT Review DE Frailty; Sarcopenia; Randomized clinical trials ID MUSCLE STRENGTH; OLDER-ADULTS; SARCOPENIA; MEN; SUPPLEMENTATION; METAANALYSIS; EXERCISE; HEALTH; PEOPLE AB There is increasing momentum to measure frailty in clinical practice given its proven value as a predictor of outcomes, particularly in elderly patients with cardiovascular disease. The number of randomized clinical trials targeting frail older adults has been modest to date. Therefore, we systematically searched the ClinicalTrials.gov registry in order to review the frailty intervention trials that had been actively initiated or completed but not yet published. The interventions studied were exercise training in 2 trials, nutritional supplementation in 3 trials, combined exercise plus nutritional supplementation in 5 trials, pharmaceutical agents in 5 trials, multidimensional programs in 2 trials, and home-based services in 3 trials. Their respective study designs, populations, interventions, and planned outcomes are presented in this article. (c) 2014 Elsevier Inc. All rights reserved. C1 [Bendayan, Melissa] McGill Univ, Dept Physiol, Montreal, PQ H3T 1E2, Canada. [Bibas, Lior; Levi, Michael; Mullie, Louie; Afilalo, Jonathan] McGill Univ, Dept Med, Montreal, PQ H3T 1E2, Canada. [Bibas, Lior; Levi, Michael; Afilalo, Jonathan] McGill Univ, Div Cardiol, Montreal, PQ H3T 1E2, Canada. [Forman, Daniel E.] Univ Pittsburgh, Med Ctr, Sect Geriatr Cardiol, Pittsburgh, PA USA. [Forman, Daniel E.] VA Pittsburgh Healthcare Syst, Geratr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Afilalo, Jonathan] McGill Univ, Jewish Gen Hosp, Div Cardiol, Montreal, PQ H3T 1E2, Canada. [Afilalo, Jonathan] McGill Univ, Jewish Gen Hosp, Div Clin Epidemiol, Montreal, PQ H3T 1E2, Canada. RP Afilalo, J (reprint author), McGill Univ, Jewish Gen Hosp, Div Cardiol, 3755 Cote Ste Catherine Rd,E-222, Montreal, PQ H3T 1E2, Canada. EM jonathan.afilalo@mcgill.ca NR 16 TC 14 Z9 14 U1 1 U2 13 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0033-0620 EI 1873-1740 J9 PROG CARDIOVASC DIS JI Prog. Cardiovasc. Dis. PD SEP-OCT PY 2014 VL 57 IS 2 BP 144 EP 151 DI 10.1016/j.pcad.2014.07.005 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AP1AN UT WOS:000341798900004 PM 25216613 ER PT J AU Bradley, SM Stanislawski, MA Bekelman, DB Monteith, LL Cohen, BE Schilling, JH Hunt, SC Milek, D Maddox, TM Ho, PM Shore, S Varosy, PD Matthieu, MM Rumsfeld, JS AF Bradley, Steven M. Stanislawski, Maggie A. Bekelman, David B. Monteith, Lindsey L. Cohen, Beth E. Schilling, John H. Hunt, Stephen C. Milek, Debra Maddox, Thomas M. Ho, P. Michael Shore, Supriya Varosy, Paul D. Matthieu, Monica M. Rumsfeld, John S. TI Invasive coronary procedure use and outcomes among veterans with posttraumatic stress disorder: Insights from the Veterans Affairs Clinical Assessment, Reporting, and Tracking Program SO AMERICAN HEART JOURNAL LA English DT Article ID GENERALIZED ANXIETY DISORDER; MAJOR DEPRESSIVE DISORDER; HEART-DISEASE; CART PROGRAM; MYOCARDIAL-INFARCTION; PSYCHIATRIC-DISORDERS; CARDIOVASCULAR EVENTS; HEALTH BEHAVIORS; ARTERY-DISEASE; RISK-FACTOR AB Background Posttraumatic stress disorder (PTSD) is prevalent in the general population and US veterans in particular and is associated with an increased risk of developing coronary artery disease (CAD). We compared the patient characteristics and postprocedural outcomes of veterans with and without PTSD undergoing coronary angiography. Methods This is a multicenter observational study of patients who underwent coronary angiography in Veterans Affairs hospitals nationally from October 2007 to September 2011. We described patient characteristics at angiography, angiographic results, and after coronary angiography, we compared risk-adjusted 1-year rates of all-cause mortality, myocardial infarction (MI), and revascularization by the presence or absence of PTSD. Results Overall, of 116,488 patients undergoing angiography, 14,918 (12.8%) had PTSD. Compared with those without PTSD, patients with PTSD were younger (median age 61.9 vs 63.7; P < .001), had higher rates of cardiovascular risk factors, and were more likely to have had a prior MI (26.4% vs 24.7%; P < .001). Patients with PTSD were more likely to present for stable angina (22.4% vs 17.0%) or atypical chest pain (58.5% vs 48.6%) and less likely to have obstructive CAD identified at angiography (55.9% vs 62.2%; P < .001). After coronary angiography, PTSD was associated with lower unadjusted 1-year rates of MI (hazard ratio (HR), 0.86; 95% CI [0.75-1.00]; P = 0.04), revascularization (HR, 0.88; 95% CI [0.83-0.93]; P < .001), and all-cause mortality (HR, 0.66; 95% CI [0.60-0.71]; P < .001). After adjustment for cardiovascular risk, PTSD was no longer associated with 1-year rates of MI or revascularization but remained associated with lower 1-year all-cause mortality (HR, 0.91; 95% CI [0.84-0.99]; P = .03). Findings were similar after further adjustment for depression, anxiety, alcohol or substance use disorders, and frequency of outpatient follow-up. Conclusions Among veterans undergoing coronary angiography in the Veterans Affairs, those with PTSD were more likely to present with elective indications and less likely to have obstructive CAD. After coronary angiography, PTSD was not associated with adverse 1-year outcomes of MI, revascularization, or all-cause mortality. C1 [Bradley, Steven M.; Stanislawski, Maggie A.; Bekelman, David B.; Monteith, Lindsey L.; Maddox, Thomas M.; Ho, P. Michael; Shore, Supriya; Varosy, Paul D.; Rumsfeld, John S.] VA Eastern Colorado Hlth Care Syst, Denver, CO 80220 USA. [Bradley, Steven M.; Bekelman, David B.; Schilling, John H.; Maddox, Thomas M.; Ho, P. Michael; Shore, Supriya; Varosy, Paul D.; Rumsfeld, John S.] Univ Colorado, Sch Med, Aurora, CO USA. [Bradley, Steven M.; Stanislawski, Maggie A.; Bekelman, David B.; Maddox, Thomas M.; Ho, P. Michael; Shore, Supriya; Varosy, Paul D.; Rumsfeld, John S.] Colorado Cardiovasc Outcomes Res Consortium, Denver, CO USA. [Cohen, Beth E.] San Francisco VA Med Ctr, San Francisco, CA USA. [Hunt, Stephen C.] VA Puget Sound Healthcare Syst, Seattle, WA USA. [Hunt, Stephen C.; Milek, Debra] Univ Washington, Seattle, WA 98195 USA. [Matthieu, Monica M.] St Louis VA Med Ctr, St Louis, MO USA. [Matthieu, Monica M.] St Louis Univ, St Louis, MO 63103 USA. RP Bradley, SM (reprint author), VA Eastern Colorado Hlth Care Syst, Dept Vet Affairs, 1055 Clermont St,111B, Denver, CO 80220 USA. EM Steven.Bradley@va.gov FU VA Health Services Research Development [HSRD-CDA2 10-199] FX Dr Bradley is supported by a Career Development Award (HSR&D-CDA2 10-199) from VA Health Services Research & Development. The authors report no relevant relationships with industry or other disclosures. NR 47 TC 1 Z9 1 U1 2 U2 6 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 EI 1097-5330 J9 AM HEART J JI Am. Heart J. PD SEP PY 2014 VL 168 IS 3 BP 381 EP U200 DI 10.1016/j.ahj.2014.05.015 PG 16 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AO4QY UT WOS:000341327200020 PM 25173551 ER PT J AU Koyner, JL Cerda, J Goldstein, SL Jaber, BL Liu, KD Shea, JA Faubel, S AF Koyner, Jay L. Cerda, Jorge Goldstein, Stuart L. Jaber, Bertrand L. Liu, Kathleen D. Shea, Judy A. Faubel, Sarah CA Amer Soc Nephrology TI The Daily Burden of Acute Kidney Injury: A Survey of US Nephrologists on World Kidney Day SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Acute kidney injury (AKI); survey; nephrology; dialysis; dialysis dosing; World Kidney Day; epidemiology; workload; public health ID ACUTE-RENAL-FAILURE; CRITICALLY-ILL PATIENTS; REPLACEMENT THERAPY; AKI; DISEASE; OUTCOMES; DIALYSIS; RISK; CKD; HEMODIALYSIS AB Background: World Kidney Day 2013 focused on raising awareness of the impact and consequences of acute kidney injury (AKI). Although many studies have examined rates of AKI in hospitalized patients, we were interested in the impact of AKI on the workload of nephrologists. Study Design: Cross-sectional forced-choice internet-based survey. Setting & Participants: 598 survey respondents who were US-based nephrologist members of the American Society of Nephrology. Outcomes: Numbers of inpatients and outpatients seen on World Kidney Day 2013 for the management of AKI or other conditions (and specifically in-hospital renal replacement therapies [RRTs]), based on self-report of number/percentage of patients seen on World Kidney Day and in the prior year. Results: Of 598 physician respondents (response rate, 12%), 310 saw patients in the hospital on World Kidney Day. Of 3,285 patients seen by respondents, 1,500 were seen for AKI (46%); 1,233, for end-stage renal disease (37%); and 552, for non-AKI/end-stage renal disease-related problems (17%). Of patients with AKI, 688 (46%) were in the intensive care unit and 415 (28%) received RRT. Intermittent hemodialysis was performed in 315 patients (76%) who received RRT. Delivered dialysis dose was quantified in only 48 (15%) of those receiving intermittent hemodialysis. 260 respondents saw 2,380 patients in the ambulatory setting, of whom 207 (9%) were seen for follow-up of AKI. Limitations: There was a low response rate to the survey. Numbers of patients were self-reported. Conclusions: This is the first physician survey examining the care of patients and impact of AKI on current in-hospital and ambulatory nephrology practices. In our sample, AKI was the most common reason for in-hospital nephrology consultation. Furthermore, our findings point to significant areas in which improvement is needed, including inadequate quantification of dialysis delivered dose. Finally, our survey highlights that AKI is a major public health issue. (C) 2014 by the National Kidney Foundation, Inc. C1 [Koyner, Jay L.] Univ Chicago, Nephrol Sect, Chicago, IL 60637 USA. [Cerda, Jorge] Albany Med Coll, Albany, NY 12208 USA. [Goldstein, Stuart L.] Cincinnati Childrens Hosp Med Ctr, Ctr Acute Care Nephrol, Cincinnati, OH 45229 USA. [Jaber, Bertrand L.] Tufts Univ, Sch Med, St Elizabeths Med Ctr, Dept Med,Div Nephrol, Boston, MA 02111 USA. [Liu, Kathleen D.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Shea, Judy A.] Univ Penn, Div Gen Internal Med, Philadelphia, PA 19104 USA. [Faubel, Sarah] Univ Colorado, Denver Vet Affairs Med Ctr, Div Nephrol, Aurora, CO 80045 USA. RP Faubel, S (reprint author), Univ Colorado, Denver Vet Affairs Med Ctr, Div Nephrol, 12700 19th Ave,Box C281, Aurora, CO 80045 USA. EM sarah.faubel@ucdenver.edu FU ASN FX Support: The study was supported by the ASN, which had no role in the development of the survey, analysis and interpretation of data, writing the report, or the decision to submit the report for publication. NR 38 TC 10 Z9 10 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD SEP PY 2014 VL 64 IS 3 BP 394 EP 401 DI 10.1053/j.ajkd.2014.03.018 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA AO5BV UT WOS:000341357100016 PM 24815216 ER PT J AU Backus, LI Belperio, PS Loomis, TP Mole, LA AF Backus, Lisa I. Belperio, Pamela S. Loomis, Timothy P. Mole, Larry A. TI Impact of Race/Ethnicity and Gender on HCV Screening and Prevalence Among US Veterans in Department of Veterans Affairs Care SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID HEPATITIS-C VIRUS; UNITED-STATES; AFRICAN-AMERICANS; INFECTION; EPIDEMIOLOGY; MORTALITY AB Objectives. We assessed HCV screening and prevalence among veterans and estimated the potential impact of complete birth cohort screening, accounting for the disparate HCV disease burden by race/ethnicity and gender. Methods. We used the Department of Veterans Affairs (VA) Corporate Data Warehouse to identify birth dates, gender, race/ethnicity, and laboratory tests for veterans with at least 1 VA outpatient visit in 2012. We calculated HCV screening rates, prevalence, and HCV infection incident diagnosis. Results. Among 5 499 743 veterans, 54.7% had HCV screening through the VA. In more than 2.9 million veterans screened, HCV prevalence was 6.1% overall and highest among Blacks (11.8%), particularly Black men born in 1945 to 1965 (17.7%). HCV infection incident diagnosis in 2012 was 5.9% for men and 2.3% for women. An estimated additional 48 928 male veterans, including 12 291 Black men, and 1484 female veterans would potentially be identified as HCV infected with full birth cohort screening. Conclusions. HCV prevalence was markedly elevated among veterans born in 1945 to 1965, with substantial variation by race/ethnicity and gender. Full adoption of birth cohort screening may reveal substantial numbers of veterans with previously unknown HCV infection. C1 [Backus, Lisa I.; Belperio, Pamela S.; Loomis, Timothy P.; Mole, Larry A.] Off Publ Health Populat Hlth, Dept Vet Affairs, Washington, DC USA. [Backus, Lisa I.] VA Palo Alto Hlth Care Syst, Dept Med, Palo Alto, CA USA. [Belperio, Pamela S.] VA Greater Los Angeles Hlth Care Syst, Dept Pharm, Los Angeles, CA USA. RP Backus, LI (reprint author), 3801 Miranda Ave,Mail Code 132, Palo Alto, CA 94304 USA. EM Lisa.Backus@va.gov NR 22 TC 13 Z9 13 U1 0 U2 3 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD SEP PY 2014 VL 104 SU 4 BP S555 EP S561 DI 10.2105/AJPH.2014.302090 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AO5DR UT WOS:000341363000014 PM 25100421 ER PT J AU Blosnich, JR Mays, VM Cochran, SD AF Blosnich, John R. Mays, Vickie M. Cochran, Susan D. TI Suicidality Among Veterans: Implications of Sexual Minority Status SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID OF-LIFE SURVEY; HEALTH; INDIVIDUALS; GAY; ORIENTATION; MILITARY; DISORDER; IDEATION; RISK AB Using the California Quality of Life surveys, we examined suicidal ideation and attempts in 129 lesbian, gay, and bisexual (LGB) veterans and in 315 heterosexual veterans in 2008-2009 and 2012-2013. Although there were no significant differences in the past 12-month suicidal ideation and lifetime attempts, LGB veterans had higher odds of lifetime suicidal ideation than heterosexual veterans (adjusted odds ratio = 3.00; 95% confidence interval = 1.38, 6.53). Suicide assessment and prevention efforts in LGB veterans could benefit from a life-course perspective regarding suicide risk. C1 [Blosnich, John R.] Ctr Hlth Equ Res & Promot, Dept Vet Affairs, Pittsburgh, PA USA. [Blosnich, John R.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Behav & Community Hlth Sci, Pittsburgh, PA 15260 USA. [Mays, Vickie M.] Univ Calif Los Angeles, Dept Hlth Policy & Management, Fielding Sch Publ Hlth, Los Angeles, CA USA. [Mays, Vickie M.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. [Cochran, Susan D.] Univ Calif Los Angeles, Dept Epidemiol, Fielding Sch Publ Hlth, Los Angeles, CA USA. [Cochran, Susan D.] Univ Calif Los Angeles, Dept Stat, Los Angeles, CA USA. RP Blosnich, JR (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Univ Dr C 151C-U,Bldg 30, Pittsburgh, PA 15240 USA. EM John.blosnich@va.gov FU Office of Academic Affiliations in the Department of Veterans Affairs; Center for Health Equity Research and Promotion in the VA Pittsburgh Healthcare System; National Center for Minority Health and Health Disparities [MD006923]; National Institute on Drug Abuse [DA20826] FX This work was supported by a postdoctoral fellowship to J. R. B. from the Office of Academic Affiliations in the Department of Veterans Affairs and the Center for Health Equity Research and Promotion in the VA Pittsburgh Healthcare System. This work was supported by a grant from the National Center for Minority Health and Health Disparities (MD006923) to V. M. M. and a grant from the National Institute on Drug Abuse (DA20826) to S. D. C. NR 19 TC 5 Z9 5 U1 0 U2 5 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD SEP PY 2014 VL 104 SU 4 BP S535 EP S537 DI 10.2105/AJPH.2014.302100 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AO5DR UT WOS:000341363000011 PM 25100418 ER PT J AU Blosnich, JR Gordon, AJ Bossarte, RM AF Blosnich, John R. Gordon, Adam J. Bossarte, Robert M. TI Suicidal Ideation and Mental Distress Among Adults With Military Service History: Results From 5 US States, 2010 SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; VIETNAM VETERANS; OEF/OIF VETERANS; HEALTH SYSTEM; WAR VETERANS; RISK-FACTORS; FOLLOW-UP; MORTALITY; SAMPLE; BEHAVIOR AB Objectives. We examined the association of military service history with past-year suicidal ideation and past-30-days mental distress in a probability-based sample of adults. Methods. We gathered 2010 Behavioral Risk Factor Surveillance System data from 5 states that asked about past-year suicidal ideation. Military service was defined as current or former active-duty service or National Guard or Reserves service. We stratified analyses into 18 to 39 years, 40 to 64 years, and 65 years and older age groups and used multiple logistic regression analyses, adjusted for demographic confounders, to discern the association of military service history with past-year suicidal ideation and past-30-days mental distress. Results. Among the 26 736 respondents, 13.1% indicated military service history. After adjusting for several confounders, we found military history status among those aged 40 to 64 years was associated with both past-year suicidal ideation and past-30-days mental distress. We found no significant associations among the younger or older age groups. Conclusions. Differences in suicidal ideation between military and nonmilitary individuals may occur in midlife. Future research should examine the possibility of cohort effects, service era effects, or both. C1 [Blosnich, John R.; Gordon, Adam J.] US Dept Vet Affairs, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Blosnich, John R.; Bossarte, Robert M.] Univ Rochester, Dept Psychiat, Rochester, NY 14627 USA. [Gordon, Adam J.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. [Bossarte, Robert M.] VISN 2 Ctr Excellence Suicide Prevent, Canandaigua, NY USA. RP Blosnich, JR (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Univ Dr C,151C-U,Bldg 30, Pittsburgh, PA 15240 USA. EM John.blosnich@va.gov FU VISN 2 Center of Excellence for Suicide Prevention; US Department of Veterans Affairs Office of Academic Affiliations; Center for Health Equity Research and Promotion, VA Pittsburgh Healthcare System FX This work was partially supported by the VISN 2 Center of Excellence for Suicide Prevention and a postdoctoral fellowship to J. R. Blosnich through the US Department of Veterans Affairs Office of Academic Affiliations and the Center for Health Equity Research and Promotion, VA Pittsburgh Healthcare System. NR 56 TC 5 Z9 5 U1 5 U2 11 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD SEP PY 2014 VL 104 SU 4 BP S595 EP S602 DI 10.2105/AJPH.2014.302064 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AO5DR UT WOS:000341363000019 PM 25100426 ER PT J AU Copeland, LA McIntyre, RT Stock, EM Zeber, JE MacCarthy, DJ Pugh, MJ AF Copeland, Laurel A. McIntyre, Raphael T. Stock, Eileen M. Zeber, John E. MacCarthy, Daniel J. Pugh, Mary Jo TI Prevalence of Suicidality Among Hispanic and African American Veterans Following Surgery SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID QUALITY-OF-LIFE; OLDER-ADULTS; PAIN; MECHANISMS; ETHNICITY; IMPACT; RISK AB Objectives. We evaluated factors associated with suicidal behavior and ideation (SBI) during 3 years of follow-up among 89 995 Veterans Health Administration (VHA) patients who underwent major surgery from October 2005 to September 2006. Methods. We analyzed administrative data using Cox proportional hazards models. SBI was ascertained by International Classification of Disease, 9th Revision codes. Results. African Americans (18% of sample; 16 252) were at an increased risk for SBI (hazard ratio [HR] = 1.21; 95% confidence interval [CI] = 1.10, 1.32), whereas Hispanics were not (HR = 1.10; 95% CI = 0.95, 1.28). Other risk factors included schizophrenia, bipolar disorder, depression, posttraumatic stress disorder, pain disorders, postoperative new-onset depression, and postoperative complications; female gender and married status were protective against SBI. Conclusions. The postoperative period might be a time of heightened risk for SBI among minority patients in the VHA. Tailored monitoring and postoperative management by minority status might be required to achieve care equity. C1 [Copeland, Laurel A.; McIntyre, Raphael T.; Stock, Eileen M.; Zeber, John E.] Cent Texas Vet Hlth Care Syst Scott & White Healt, Ctr Appl Hlth Res, Temple, TX USA. [MacCarthy, Daniel J.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Pugh, Mary Jo] South Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Copeland, LA (reprint author), Ctr Appl Hlth Res, 2102 Birdcreek Dr, Temple, TX 76502 USA. EM LaurelACopeland@gmail.com OI Pugh, Mary Jo/0000-0003-4196-7763; Copeland, Laurel/0000-0002-9478-0209 FU Veterans Health Administration, Health Services Research Development [IIR-09-335]; Center for Applied Health Research - Central Texas Veterans Health Care System; Center for Applied Health Research - Scott & White Healthcare, in Temple, Texas, Scott & White Minority Health Research Predoctoral Fellowship FX This work was supported by a research award from Veterans Health Administration, Health Services Research & Development #IIR-09-335 to Central Texas Veterans Health Care System to partially support the salaries of L. A. Copeland, J. E. Zeber, M. J. Pugh, and D. J. MacCarthy. Additional support was provided by the Center for Applied Health Research, a center jointly sponsored by Central Texas Veterans Health Care System and Scott & White Healthcare, in Temple, Texas, including the Scott & White Minority Health Research Predoctoral Fellowship awarded to R. T. McIntyre. NR 39 TC 2 Z9 2 U1 2 U2 5 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD SEP PY 2014 VL 104 SU 4 BP S603 EP S608 DI 10.2105/AJPH.2014.301938 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AO5DR UT WOS:000341363000020 PM 25100427 ER PT J AU Ibrahim, SA Egede, LE Uchendu, US Fine, MJ AF Ibrahim, Said A. Egede, Leonard E. Uchendu, Uchenna S. Fine, Michael J. TI The Struggle for Health Equity: The Sustained Effort by the VA Healthcare System SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material ID QUALITY-OF-CARE C1 [Ibrahim, Said A.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Ibrahim, Said A.] Ctr Hlth Equ Res & Promot, Dept Vet Affairs VA, Philadelphia, PA USA. [Egede, Leonard E.] Med Univ S Carolina, Charleston, SC USA. [Egede, Leonard E.] Charleston Hlth Equ & Rural Outreach Innovat Ctr, Charleston, SC USA. [Uchendu, Uchenna S.] VA Cent Off, Vet Hlth Adm Off Hlth Equ, Washington, DC USA. [Fine, Michael J.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Fine, Michael J.] Ctr Hlth Equ Res & Promot, VA, Pittsburgh, PA USA. RP Ibrahim, SA (reprint author), Philadelphia VA Med Ctr ANNEX, Ctr Hlth Equ Res & Promot, 3900 Woodland Ave, Philadelphia, PA 19104 USA. EM said.ibrahim2@va.gov FU NIAMS NIH HHS [K24 AR055259]; NIDDK NIH HHS [K24 DK093699] NR 16 TC 0 Z9 0 U1 2 U2 7 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD SEP PY 2014 VL 104 SU 4 BP S514 EP S516 DI 10.2105/AJPH.2014.302199 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AO5DR UT WOS:000341363000003 PM 25100410 ER PT J AU Lynch, J Whatley, A Uchendu, US Ibrahim, SA AF Lynch, Julie Whatley, Angela Uchendu, Uchenna S. Ibrahim, Said A. TI Race and Genomics in the Veterans Health Administration SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material ID GROWTH-FACTOR RECEPTOR; WIDE ASSOCIATION; PROSTATE-CANCER; UNITED-STATES; ANCESTRY; MEN C1 [Lynch, Julie] CHOIR, Vet Hlth Adm, Bedford, MA 01730 USA. [Lynch, Julie] Res Triangle Inst, Res Triangle Pk, NC 27709 USA. [Whatley, Angela] Vet Hlth Adm, Washington, DC USA. [Uchendu, Uchenna S.] Off Hlth Equ, Dept Vet Affairs, Washington, DC USA. [Ibrahim, Said A.] Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Ibrahim, Said A.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Lynch, J (reprint author), CHOIR, Vet Hlth Adm, 200 Springs Ave, Bedford, MA 01730 USA. EM julie.lynch@va.gov FU NIAMS NIH HHS [K24 AR055259] NR 10 TC 3 Z9 3 U1 1 U2 2 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD SEP PY 2014 VL 104 SU 4 BP S522 EP S524 DI 10.2105/AJPH.2014.302202 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AO5DR UT WOS:000341363000006 PM 25100413 ER PT J AU Feemster, LC Au, DH AF Feemster, Laura C. Au, David H. TI Chronic Obstructive Pulmonary Disease Readmissions and Medicare Reimbursement Reply SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Letter C1 [Feemster, Laura C.] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Seattle, WA 98195 USA. RP Feemster, LC (reprint author), VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. FU NHLBI NIH HHS [K23 HL111116, K23HL111116] NR 2 TC 1 Z9 1 U1 0 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD SEP 1 PY 2014 VL 190 IS 5 BP 591 EP 592 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA AO7TB UT WOS:000341554400018 PM 25171313 ER PT J AU Busch, RA Heneghan, AF Pierre, JF Wang, XY Kudsk, KA AF Busch, Rebecca A. Heneghan, Aaron F. Pierre, Joseph F. Wang, Xinying Kudsk, Kenneth A. TI The Enteric Nervous System Neuropeptide, Bombesin, Reverses Innate Immune Impairments During Parenteral Nutrition SO ANNALS OF SURGERY LA English DT Article DE antimicrobial peptides; bombesin; enteric nervous system; parenteral nutrition; Paneth cells ID RESPIRATORY-TRACT IMMUNITY; POLYMERIC IMMUNOGLOBULIN RECEPTOR; INTESTINAL PANETH CELLS; MAJOR ABDOMINAL-TRAUMA; LECTIN REGIII-GAMMA; MUCOSAL IMMUNITY; LYMPHOID-TISSUE; PHOSPHOLIPASE A(2); BARRIER FUNCTION; FED MICE AB Background: Lack of enteral stimulation during parenteral nutrition (PN) impairs mucosal immunity. Bombesin (BBS), a gastrin-releasing peptide analogue, reverses PN-induced defects in acquired immunity. Paneth cells produce antimicrobial peptides (AMPs) of innate immunity for release after cholinergic stimulation. Objective: Determine if BBS restores AMPs and bactericidal function during PN. Methods: Intravenously cannulated male ICR mice were randomized to Chow, PN, or PN+BBS (15 mu g 3 times daily, n = 7 per group) for 5 days. Ileum was analyzed for AMPs (Protein: sPLA2 by fluorescence, lysozyme and RegIII-gamma by western andcryptdin-4 by ELISA; mRNA: all by RT-PCR). Cholinergic stimulated (100 mu M bethanechol) ileal specimens assessed Pseudomonas bactericidal activity. Ileum (Chow: n = 7; PN: n = 9; PN+BBS: n = 8) was assessed for Escherichia coli invasion in ex-vivo culture. Results: PN significantly decreased most AMPs versus Chow while BBS maintained Chow levels (sPLA(2):Chow: 107 + 14*, PN: 44.6 + 7.2, PN+BBS: 78.7 + 13.4* Fl/min/mu L/total protein; Lysozyme: Chow: 63.9 + 11.9*, PN: 26.8 + 6.2; PN+BBS: 64.9 + 13.8* lysozyme/total protein; RegIII-gamma: Chow: 51.5 + 10.0*, PN: 20.4 + 4.3, PN+BBS: 31.0 + 8.4 RegIII-gamma/total protein; Cryptdin-4: Chow: 18.4 + 1.5*, PN: 12.7 + 1.6, PN+BBS: 26.1 + 2.4*dagger pg/mg [all *P < 0.05 vs PN and dagger P < 0.05 vs Chow]). Functionally, BBS prevented PN loss of bactericidal activity after cholinergic stimulation (Chow: 25.3 + 3.6*, PN: 13.0 + 3.2; PN+BBS: 27.0 + 4.7* percent bacterial killing, *P < 0.05 vs PN). BBS reduced bacterial invasion in unstimulated tissue barely missing significance (P = 0.06). Conclusions: The enteric nervous system (ENS) controls AMP levels in Paneth cells during PN but mucosal protection by innate immunity requires both ENS and parasympathetic stimulation. C1 [Busch, Rebecca A.; Heneghan, Aaron F.; Pierre, Joseph F.; Wang, Xinying; Kudsk, Kenneth A.] Univ Wisconsin, Dept Surg, Sch Med & Publ Hlth, Madison, WI 53792 USA. [Wang, Xinying] Nanjing Univ, Dept Surg, Jinling Hosp, Sch Med, Nanjing, Peoples R China. [Kudsk, Kenneth A.] William S Middleton Mem Vet Adm Med Ctr, Vet Adm Surg Serv, Madison, WI USA. RP Kudsk, KA (reprint author), Univ Wisconsin, Dept Surg, Sch Med & Publ Hlth, 600 Highland Ave,H4-736 CSC, Madison, WI 53792 USA. EM kudsk@surgery.wisc.edu FU Biomedical Laboratory Research & Development Service of the VA Office of Research and Development [I01BX001672]; National Institute of Health [T32 CA090217-13] FX Supported by award No. I01BX001672 from the Biomedical Laboratory Research & Development Service of the VA Office of Research and Development. Also based upon work supported in part by National Institute of Health grant T32 CA090217-13. The contents of this article do not represent the views of the Department of Veterans Affairs or the US government. The authors have no conflicts of interest to declare. NR 100 TC 8 Z9 8 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD SEP PY 2014 VL 260 IS 3 BP 432 EP 444 DI 10.1097/SLA.0000000000000871 PG 13 WC Surgery SC Surgery GA AO2SJ UT WOS:000341175600004 PM 25115419 ER PT J AU Ju, MH Chung, JW Kinnier, CV Bentrem, DJ Mahvi, DM Ko, CY Bilimoria, KY AF Ju, Mila H. Chung, Jeanette W. Kinnier, Christine V. Bentrem, David J. Mahvi, David M. Ko, Clifford Y. Bilimoria, Karl Y. TI Association Between Hospital Imaging Use and Venous Thromboembolism Events Rates Based on Clinical Data SO ANNALS OF SURGERY LA English DT Article DE ACS NSQIP; clinical registry data; hospital quality performance; surveillance bias; venous thromboembolism (VTE) ID DEEP-VEIN THROMBOSIS; QUALITY IMPROVEMENT PROGRAM; TRAUMA DATA-BANK; PATIENT SAFETY INDICATORS; FACTORS-AN ANALYSIS; REPORTED DVT RATES; SURVEILLANCE BIAS; SURGICAL QUALITY; OF-CARE; TEACHING STATUS AB Objective: The objective was to assess the presence and extent of venous thromboembolic (VTE) surveillance bias using high-quality clinical data. Background: Hospital VTE rates are publicly reported and used in pay-for-performance programs. Prior work suggested surveillance bias: hospitals that look more for VTE with imaging studies find more VTE, thereby incorrectly seem to have worse performance. However, these results have been questioned as the risk adjustment and VTE measurement relied on administrative data. Methods: Data (2009-2010) from 208 hospitals were available for analysis. Hospitals were divided into quartiles according to VTE imaging use rates (Medicare claims). Observed and risk-adjusted postoperative VTE event rates (regression models using American College of Surgeons National Surgical Quality Improvement Project data) were examined across VTE imaging use rate quartiles. Multivariable linear regression models were developed to assess the impact of hospital characteristics (American Hospital Association) and hospital imaging use rates on VTE event rates. Results: The mean risk-adjusted VTE event rates at 30 days after surgery increased across VTE imaging use rate quartiles: 1.13% in the lowest quartile to 1.92% in the highest quartile (P < 0.001). This statistically significant trend remained when examining only the inpatient period. Hospital VTE imaging use rate was the dominant driver of hospital VTE event rates (P < 0.001), as no other hospital characteristics had significant associations. Conclusions: Even when examined with clinically ascertained outcomes and detailed risk adjustment, VTE rates reflect hospital imaging use and perhaps signify vigilant, high-quality care. The VTE outcome measure may not be an accurate quality indicator and should likely not be used in public reporting or pay-for-performance programs. C1 [Ju, Mila H.; Ko, Clifford Y.; Bilimoria, Karl Y.] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL 60611 USA. [Ju, Mila H.; Chung, Jeanette W.; Kinnier, Christine V.; Bentrem, David J.; Mahvi, David M.; Bilimoria, Karl Y.] Northwestern Univ, Dept Surg, Surg Outcomes & Qual Improvement Ctr, Chicago, IL 60611 USA. [Ko, Clifford Y.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. [Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Bilimoria, KY (reprint author), Amer Coll Surg, Div Res & Optimal Patient Care, 633 N St Clair St,22nd Floor, Chicago, IL 60611 USA. EM kbilimoria@facs.org FU AHRQ [R21HS021857]; National Institutes of Health [5T32HL094293]; American College of Surgeons Clinical Scholar in Residence program FX Dr Bilimoria is partially supported by AHRQ R21HS021857. Dr Ju is supported by National Institutes of Health #5T32HL094293 and American College of Surgeons Clinical Scholar in Residence program. No conflict of interest related to this work. NR 40 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD SEP PY 2014 VL 260 IS 3 BP 558 EP 566 DI 10.1097/SLA.0000000000000897 PG 9 WC Surgery SC Surgery GA AO2SJ UT WOS:000341175600017 PM 25115432 ER PT J AU Li, J Echevarria, KL Hughes, DW Cadena, JA Bowling, JE Lewis, JS AF Li, Julius Echevarria, Kelly L. Hughes, Darrel W. Cadena, Jose A. Bowling, Jason E. Lewis, James S., II TI Comparison of Cefazolin versus Oxacillin for Treatment of Complicated Bacteremia Caused by Methicillin-Susceptible Staphylococcus aureus SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ANTIMICROBIAL THERAPY; RISK-FACTORS; ENDOCARDITIS; NAFCILLIN; OUTCOMES AB Contrary to prior case reports that described occasional clinical failures with cefazolin for methicillin-susceptible Staphylococcus aureus (MSSA) infections, recent studies have demonstrated no difference in outcomes between cefazolin and antistaphylococcal penicillins for the treatment of MSSA bacteremia. While promising, these studies described low frequencies of high-inoculum infections, such as endocarditis. This retrospective study compares clinical outcomes of cefazolin versus oxacillin for complicated MSSA bacteremia at two tertiary care hospitals between January 2008 and June 2012. Fifty-nine patients treated with cefazolin and 34 patients treated with oxacillin were included. Osteoarticular (41%) and endovascular (20%) sources were the predominant sites of infection. The rates of clinical cure at the end of therapy were similar between cefazolin and oxacillin (95% versus 88%; P = 0.25), but overall failure at 90 days was higher in the oxacillin arm (47% versus 24%; P = 0.04). Failures were more likely to have received surgical interventions (63% versus 40%; P = 0.05) and to have an osteoarticular source (57% versus 33%; P = 0.04). Failures also had a longer duration of bacteremia (7 versus 3 days; P = 0.0002), which was the only predictor of failure. Antibiotic selection was not predictive of failure. Rates of adverse drug events were higher in the oxacillin arm (30% versus 3%; P = 0.0006), and oxacillin was more frequently discontinued due to adverse drug events (21% versus 3%; P = 0.01). Cefazolin appears similar to oxacillin for the treatment of complicated MSSA bacteremia but with significantly improved safety. The higher rates of failure with oxacillin may have been confounded by other patient factors and warrant further investigation. C1 [Li, Julius; Echevarria, Kelly L.; Cadena, Jose A.] South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Li, Julius; Echevarria, Kelly L.; Hughes, Darrel W.; Lewis, James S., II] Univ Texas Austin, Coll Pharm, Austin, TX 78712 USA. [Li, Julius; Echevarria, Kelly L.; Hughes, Darrel W.; Lewis, James S., II] Univ Texas Hlth Sci Ctr San Antonio, Pharmacotherapy Educ & Res Ctr, San Antonio, TX 78229 USA. [Echevarria, Kelly L.; Cadena, Jose A.; Bowling, Jason E.; Lewis, James S., II] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Infect Dis, San Antonio, TX 78229 USA. [Hughes, Darrel W.; Lewis, James S., II] Univ Hlth Syst, Dept Pharm, San Antonio, TX USA. RP Li, J (reprint author), South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. EM juli@ochsner.org NR 30 TC 16 Z9 16 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 EI 1098-6596 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD SEP PY 2014 VL 58 IS 9 BP 5117 EP 5124 DI 10.1128/AAC.02800-14 PG 8 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA AO3UV UT WOS:000341262700015 PM 24936596 ER PT J AU Pape, TLB Mallinson, T Guernon, A AF Pape, Theresa Louise-Bender Mallinson, Trudy Guernon, Ann TI Psychometric Properties of the Disorders of Consciousness Scale SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Brain injuries; Consciousness disorders; Outcome measures; Rehabilitation ID PERSISTENT VEGETATIVE STATE; COMA; PRECISION; ATTENTION; VALIDITY; INJURY AB Objective: To provide evidence for psychometric properties of the Disorders of Consciousness Scale (DOCS). Design: Prospective observational cohort. Settings: Seven rehabilitation facilities. Participants: Patients (N=174) with severe brain injury. Interventions: Not applicable. Main Outcome Measure: DOCS. Results: Initial analyses suggested eliminating 6 items to maximize psychometrics, resulting in the DOCS-25. The 25 items form a unidimensional hierarchy, rating scale categories are ordered, there are no misfitting items, and differential item functioning was not found according to sex, type of brain injury, veteran status, and days from onset. Person separation reliability (.91) indicates that the DOCS-25 is appropriate for individual patient measurement. Items are well targeted to the sample, with the difference between mean person and item calibrations less than 1 logit. DOCS-25 Rasch measures result in a 62% gain in relative precision over total raw scores. Internal consistency is very good (Cronbach alpha=.86); interrater agreement is excellent (intracIass correlation coefficient =.90) for both the DOCS-25 and the sensory subscales. The DOCS-25 total measure, but not subscale measures, correlates with the Glasgow Coma Scale and the Coma/Near-Coma Scales and distinguishes significantly between vegetative and minimally conscious states, indicating concurrent validity. Conclusions: The DOCS-25 is psychometrically strong. It has excellent measurement precision and captures a broad range of patient function, which is critical for capturing recovery of consciousness. The sensory subscales are clinically informative but should not be reported as separate measures. The Keyform synthesizes clinical observations to visualize response patterns with potential for informing clinical decision-making Future studies should determine sensitivity to change, examine issues of rater severity, and explore the usefulness of the Keyform in clinical practice. (c) 2014 by the American Congress of Rehabilitation Medicine C1 [Pape, Theresa Louise-Bender] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Ctr Innovat Complex Chron Healthcare, Hines, IL 60141 USA. [Pape, Theresa Louise-Bender] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Res Serv, Dept Vet Affairs, Hines, IL 60141 USA. [Pape, Theresa Louise-Bender] Northwestern Univ, Feinberg Sch Med, Dept Phys Med & Rehabil, Chicago, IL 60611 USA. [Mallinson, Trudy] George Washington Univ, Sch Med & Hlth Sci, Washington, DC 20052 USA. [Guernon, Ann] Marianjoy Rehabil Hosp, Wheaton, IL USA. RP Pape, TLB (reprint author), Edward Hines Jr Vet Hosp, Res & Dev Serv, POB 5000,MC 151H, Hines, IL 60141 USA. EM Theresa.Pape@va.gov OI Pape, Theresa/0000-0001-7738-5963; Mallinson, Trudy/0000-0002-4888-5579 FU United States Department of Veterans Affairs, Office of Research and Development, Health Services Research and Development [CCN 07-133-1]; Rehabilitation Research and Development Career Development Transition Award [B4949N] FX Supported by the United States Department of Veterans Affairs, Office of Research and Development, Health Services Research and Development (merit grant no. CCN 07-133-1) and Rehabilitation Research and Development Career Development Transition Award (no. B4949N). The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the United States Department of Veterans Affairs or the United States Government. NR 55 TC 2 Z9 2 U1 0 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 EI 1532-821X J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD SEP PY 2014 VL 95 IS 9 BP 1672 EP 1684 DI 10.1016/j.apmr.2014.04.015 PG 13 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA AO4TU UT WOS:000341335100010 PM 24814459 ER PT J AU Bartels, CM Johnson, H Voelker, K Thorpe, C McBride, P Jacobs, EA Pandhi, N Smith, M AF Bartels, Christie M. Johnson, Heather Voelker, Katya Thorpe, Carolyn McBride, Patrick Jacobs, Elizabeth A. Pandhi, Nancy Smith, Maureen TI Impact of Rheumatoid Arthritis on Receiving a Diagnosis of Hypertension Among Patients With Regular Primary Care SO ARTHRITIS CARE & RESEARCH LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; CARDIOVASCULAR RISK-FACTORS; QUALITY-OF-CARE; EULAR RECOMMENDATIONS; ADMINISTRATIVE DATA; DISEASE; MEDICARE; COMORBIDITIES; POPULATION; MORTALITY AB Objective. Despite numerous studies reporting increased cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA), the impact of RA on managing modifiable CVD risk factors remains understudied. We tested the hypothesis that RA is a risk factor for not receiving a hypertension diagnosis. Methods. Using a cohort design, we studied adult patients with and without RA/inflammatory arthritis from a large academic multispecialty practice. All were seen regularly in primary care and met clinical guideline hypertension criteria, but lacked prior hypertension diagnosis/treatment. The primary outcome was time to International Classification of Diseases, Ninth Revision code for hypertension or elevated blood pressure, or antihypertensive medication prescription. Kaplan-Meier survival curve analysis and Cox proportional hazards modeling were used to examine the impact of RA on diagnosis of hypertension. Results. Among 14,974 patients with undiagnosed hypertension, 201 patients had RA codes. RA patients had equivalent primary care visits and more total visits compared to patients without RA. At the end of the study, the likelihood of hypertension diagnosis was 36% in RA patients compared to 51% in patients without RA. In adjusted Cox models, RA patients had a 29% lower hypertension diagnosis hazard (hazard ratio 0.71, 95% confidence interval 0.55-0.93), reflecting more undiagnosed hypertension than with other comorbidities. Conclusion. Among patients meeting guideline-based hypertension criteria, RA patients were less likely to be diagnosed despite more visits than those without RA. Given heightened CVD risks in RA and the importance of hypertension diagnosis as a first step toward controlling risk, rheumatologists should collaborate to improve rates of diagnosis for this modifiable CVD risk factor. C1 [Bartels, Christie M.; Johnson, Heather; Voelker, Katya; McBride, Patrick; Jacobs, Elizabeth A.; Pandhi, Nancy; Smith, Maureen] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Voelker, Katya] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Thorpe, Carolyn] Univ Pittsburgh, Pittsburgh, PA USA. RP Bartels, CM (reprint author), 1685 Highland Ave,Room 4132, Madison, WI 53705 USA. EM cb4@medicine.wisc.edu FU National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH [K23-AR062381]; NIH/National Heart, Lung, and Blood Institute [1-K23-HL112907]; National Center for Advancing Translational Sciences, NIH [9U54TR000021]; Health Innovation Program/Community-Academic Partnerships core of the University of Wisconsin Institute for Clinical and Translational Research/Clinical and Translational Science Award; Shapiro Student Research Program FX Dr. Bartels's work was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH (award K23-AR062381). Dr. Johnson's work was supported by the NIH/National Heart, Lung, and Blood Institute (grant 1-K23-HL112907). Additional project support was provided through the National Center for Advancing Translational Sciences, NIH (grant 9U54TR000021) and the Health Innovation Program/Community-Academic Partnerships core of the University of Wisconsin Institute for Clinical and Translational Research/Clinical and Translational Science Award and the Shapiro Student Research Program. NR 48 TC 10 Z9 10 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2151-464X EI 2151-4658 J9 ARTHRIT CARE RES JI Arthritis Care Res. PD SEP PY 2014 VL 66 IS 9 BP 1281 EP 1288 DI 10.1002/acr.22302 PG 8 WC Rheumatology SC Rheumatology GA AO3OK UT WOS:000341241200002 PM 24585741 ER PT J AU Li, J Hsu, HC Ding, YN Li, H Wu, Q Yang, PA Luo, B Rowse, AL Spalding, DM Bridges, SL Mountz, JD AF Li, Jun Hsu, Hui-Chen Ding, Yana Li, Hao Wu, Qi Yang, PingAr Luo, Bao Rowse, Amber L. Spalding, David M. Bridges, S. Louis, Jr. Mountz, John D. TI Inhibition of Fucosylation Reshapes Inflammatory Macrophages and Suppresses Type II Collagen-Induced Arthritis SO ARTHRITIS & RHEUMATOLOGY LA English DT Article ID RHEUMATOID-ARTHRITIS; T-CELLS; SYNOVIAL FIBROBLASTS; ANTIGEN PRESENTATION; LYMPH-NODES; E-SELECTIN; FUCT-VII; ACTIVATION; FUCOSE; IL-10 AB Objective. Fucosylation catalyzed by fucosyltransferases (FUTs) is an important posttranslational modification involved in a variety of biologic processes. This study was undertaken to determine the roles of fucosylation in rheumatoid arthritis (RA) and to assess the efficacy of reestablishing immune homeostasis with the use of 2-deoxy-D-galactose (2-D-gal), a fucosylation inhibitor. Methods. Quantitative polymerase chain reaction was performed to determine the expression of FUT genes in synovial tissue from RA and osteoarthritis (OA) patients and in fluorescence-activated cell-sorted cells from RA synovial fluid. The in vivo inhibitory effect of 2-D-gal was evaluated in a murine collagen-induced arthritis (CIA) model. The in vitro effects of 2-D-gal on differentiation of inflammatory macrophages, production of cytokines, and antigen uptake, processing, and presentation functions were analyzed. Results. FUTs that are involved in terminal or subterminal fucosylation, but not those involved in core fucosylation or O-fucosylation, were up-regulated in RA compared to OA synovial tissue. The expression of terminal FUTs was highly positively correlated with the expression of TNF (encoding for tumor necrosis factor alpha). Terminal FUTs were predominantly expressed in M1 macrophages. In vivo, 2-D-gal treatment of mice precluded the development of CIA by reducing inflammatory macrophages and Th17 cells in the draining lymph nodes and decreasing the levels of TNF alpha, interleukin-6 (IL-6), and antibodies to type II collagen in the serum. In vitro, treatment with 2-D-gal skewed the differentiation of M1 macrophages to IL-10-producing M2 macrophages. Furthermore, 2-D-gal significantly inhibited the antigen-presenting function of M1 macrophages. Conclusion. Terminal fucosylation is a novel hallmark of inflammatory macrophages. Inhibition of terminal FUTs reshapes the differentiation and functions of M1 macrophages, leading to resolution of inflammation in arthritis. C1 [Hsu, Hui-Chen; Wu, Qi; Yang, PingAr; Mountz, John D.] Univ Alabama Birmingham, Birmingham, AL 35294 USA. [Hsu, Hui-Chen; Wu, Qi; Yang, PingAr; Mountz, John D.] Birmingham VA Med Ctr, Birmingham, AL USA. RP Mountz, JD (reprint author), Univ Alabama Birmingham, Div Clin Immunol & Rheumatol, Dept Med, SHEL Bldg,Suite 307,1825 Univ Blvd, Birmingham, AL 35294 USA. EM jdmountz@uab.edu RI Li, Hao/N-7406-2015 OI Li, Hao/0000-0002-2171-8826 FU Arthritis Foundation; Lupus Research Institute; Daiichi Sankyo Co., Ltd; NIH [1R01-AI-083705, 1R01-AI-071110, P30-AR-048311, P30-AI-027767, P30-AR-46031]; Rheumatology Research Foundation; Department of Veterans Affairs [1I01BX000600] FX Supported by the Arthritis Foundation (grant to Dr. J. Li), the Lupus Research Institute (grant to Dr. Hsu), and Daiichi Sankyo Co., Ltd (grant to Dr. Mountz), the NIH (grants 1R01-AI-083705 to Dr. Hsu and 1R01-AI-071110 and P30-AR-048311 to Dr. Mountz), a Rheumatology Research Foundation grant to Dr. Mountz, and the Department of Veterans Affairs (Merit Review grant 1I01BX000600 to Dr. Mountz). Portions of the study were performed at the University of Alabama at Birmingham Rheumatic Diseases Core Center (Analytical Genomics and Transgenics Core, Comprehensive Flow Cytometry Core, and Analytic Imaging and Immunoreagents Core), supported by NIH grant P30-AR-048311, the Center for AIDS Research flow cytometry facility, supported by NIH grant P30-AI-027767, and the Center for Metabolic Bone Disease-Histomorphometry and Molecular Analysis Core Laboratory, supported by NIH grant P30-AR-46031. NR 46 TC 6 Z9 6 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD SEP PY 2014 VL 66 IS 9 BP 2368 EP 2379 DI 10.1002/art.38711 PG 12 WC Rheumatology SC Rheumatology GA AO3RD UT WOS:000341251100009 PM 24838610 ER PT J AU Ding, YN Li, J Yang, PA Luo, B Wu, Q Zajac, AJ Wildner, O Hsu, HC Mountz, JD AF Ding, Yanna Li, Jun Yang, PingAr Luo, Bao Wu, Qi Zajac, Allan J. Wildner, Oliver Hsu, Hui-Chen Mountz, John D. TI Interleukin-21 Promotes Germinal Center Reaction by Skewing the Follicular Regulatory T Cell to Follicular Helper T Cell Balance in Autoimmune BXD2 Mice SO ARTHRITIS & RHEUMATOLOGY LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; FOXP3 EXPRESSION; B-CELLS; GENERATION; IL-21; DIFFERENTIATION; RECEPTOR; SUBSET; MTOR; TH17 AB Objective. Follicular regulatory T (Tfr) cells act as the regulatory counterpart of follicular helper T (Tfh) cells to suppress germinal center (GC) B cell differentiation. We recently showed that interleukin-21 (IL-21) promoted Tfh cell differentiation in autoimmune BXD2 mice that develop spontaneous GCs. This study was undertaken to determine the modulatory effects of IL-21 on Tfr cells and the Tfr cell to Tfh cell balance in BXD2 mice. Methods. The percentage and phenotype of Tfr cells were determined in BXD2 and BXD2-IL21(-/-) mice. The effects of IL-21 on Tfr cells and the Tfr cell:Tfh cell ratio were evaluated. Sorted Tfr cells from BXD2-IL21(-/-) mice were cocultured with Tfh cells and B cells, or transferred into BXD2 mice to determine their function. Results. The percentages and numbers of GC B cells and Tfh cells were significantly reduced, but the percentage of Tfr cells was 2-fold higher in BXD2-IL21(-/-) mice than in wild-type BXD2 mice. Administration of AdIL-21 to BXD2-IL21(-/-) mice decreased the percentages and numbers of Tfr cells and the Tfr cell:Tfh cell ratio but increased the number of GC B cells in the spleen. Recombinant murine IL-21 suppressed FoxP3 and significantly reduced Tgfb1, Il2, and Gitr but enhanced Il21, Il6, Pd1, Cxcr5, and Icos expression in Tfr cells. IL-21 also counteracted Tfr cell-mediated inhibition of antibody secretion in the Tfh cell-B cell coculture system. Transfer of Tfr cells into young BXD2 mice reduced GC size and decreased the numbers of autoantibody-producing B cells. Conclusion. Our findings indicate that high levels of IL-21 selectively enhance Tfh cell differentiation but inhibit Tfr cell commitment and the suppressive function of Tfr cells on Tfh cells and B cells, suggesting that IL-21 skews the balance from Tfr cells to Tfh cells to promote autoreactive GC reactions in BXD2 mice. C1 [Ding, Yanna; Li, Jun; Yang, PingAr; Luo, Bao; Wu, Qi; Zajac, Allan J.; Hsu, Hui-Chen; Mountz, John D.] Univ Alabama Birmingham, Birmingham, AL 35294 USA. [Wildner, Oliver] Swissmedic, Swiss Agcy Therapeut Prod, Bern, Switzerland. [Mountz, John D.] Birmingham VA Med Ctr, Birmingham, AL USA. RP Hsu, HC (reprint author), Univ Alabama Birmingham, Dept Med, 1825 Univ Blvd, Birmingham, AL 35294 USA. EM rheu078@uab.edu; jdmountz@uab.edu FU Arthritis Foundation; NIH (National Institute of Allergy and Infectious Diseases) [U01-AI-082966, 1R01-AI-0837051, R01-AI-071110]; Lupus Research Institute; Rheumatology Research Foundation; Department of Veterans Affairs [1I01BX000600]; NIH [P30-AR-048311, P30-A-I027767] FX Supported by the Arthritis Foundation (grant to Dr. Li), the NIH (National Institute of Allergy and Infectious Diseases grants U01-AI-082966 to Dr. Zajac, 1R01-AI-083705 to Dr. Hsu, and 1R01-AI-071110 to Dr. Mountz), the Lupus Research Institute (grant to Dr. Hsu), a Disease Targeted Research Grant from the Rheumatology Research Foundation (to Dr. Mountz), and the Department of Veterans Affairs (Merit Review grant 1I01BX000600 to Dr. Mountz). Flow cytometry and confocal imaging data acquisition were performed at the University of Alabama at Birmingham Comprehensive Flow Cytometry Core (supported by NIH grants P30-AR-048311 and P30-A-I027767) and Analytic Imaging and Immunoreagents Core (supported by NIH grant P30-AR-048311). NR 40 TC 22 Z9 25 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD SEP PY 2014 VL 66 IS 9 BP 2601 EP 2612 DI 10.1002/art.38735 PG 12 WC Rheumatology SC Rheumatology GA AO3RD UT WOS:000341251100031 PM 24909430 ER PT J AU Swenson, ER AF Swenson, Erik R. TI New Insights into Carbonic Anhydrase Inhibition, Vasodilation, and Treatment of Hypertensive-Related Diseases SO CURRENT HYPERTENSION REPORTS LA English DT Article DE Sulfonamide; Acetazolamide; Hypoxic pulmonary vasoconstriction; Arterial hypertension; Thiazide; Loop diuretic ID INTRACELLULAR PH REGULATION; CHRONIC KIDNEY-DISEASE; CEREBRAL-BLOOD-FLOW; THIAZIDE DIURETICS; SMOOTH-MUSCLE; NITRIC-OXIDE; IN-VITRO; IMMUNOHISTOCHEMICAL LOCALIZATION; CARDIOMYOCYTE HYPERTROPHY; PULMONARY VASODILATION AB Carbonic anhydrase (CA) and its inhibitors are relevant to many physiological processes and diseases. The enzyme is differentially expressed throughout the body, in concentration and subcellular location, and as 13 catalytically active isoforms. Blood vessels contain small amounts of CA, but the enzyme's role in vascular physiology and blood pressure regulation is uncertain. However, considerable recent evidence points to vasodilation by CA inhibitors. CA inhibition in vascular smooth muscle, endothelium, heart, blood cells, and nervous system could all contribute. It is equally plausible that other targets besides CA for all known CA inhibitors may account for their vascular effects. I will review this knowledge and important remaining gaps relating to treatment of hypertensive-related diseases with potent sulfonamide inhibitors, such as acetazolamide; but also the possibility that CA inhibition by thiazides and loop diuretics, although generally weaker, may have antihypertensive effects beyond their inhibition of renal sodium transporters. C1 Univ Washington, Dept Vet Affairs Pulm & Crit Care Med, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. RP Swenson, ER (reprint author), Univ Washington, Dept Vet Affairs Pulm & Crit Care Med, VA Puget Sound Hlth Care Syst, 1660 S Columbian Way, Seattle, WA 98195 USA. EM eswenson@u.washington.edu NR 108 TC 9 Z9 9 U1 1 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1522-6417 EI 1534-3111 J9 CURR HYPERTENS REP JI Curr. Hypertens. Rep. PD SEP PY 2014 VL 16 IS 9 AR 467 DI 10.1007/s11906-014-0467-3 PG 11 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AO6AE UT WOS:000341428700002 PM 25079851 ER PT J AU Beam, CA Gitelman, SE Palmer, JP AF Beam, Craig A. Gitelman, Stephen E. Palmer, Jerry P. CA Type 1 Diabet TrialNet Study Grp TI Recommendations for the Definition of Clinical Responder in Insulin Preservation Studies SO DIABETES LA English DT Article ID BETA-CELL FUNCTION; C-PEPTIDE; COMPLICATIONS TRIAL; MEASUREMENT ERROR; DIABETES CONTROL; TEPLIZUMAB; MISCLASSIFICATION; IMPACT AB Clinical responder studies should contribute to the translation of effective treatments and interventions to the clinic. Since ultimately this translation will involve regulatory approval, we recommend that clinical trials prespecify a responder definition that can be assessed against the requirements and suggestions of regulatory agencies. In this article, we propose a clinical responder definition to specifically assist researchers and regulatory agencies in interpreting the clinical importance of statistically significant findings for studies of interventions intended to preserve -cell function in newly diagnosed type 1 diabetes. We focus on studies of 6-month -cell preservation in type 1 diabetes as measured by 2-h-stimulated C-peptide. We introduce criteria (bias, reliability, and external validity) for the assessment of responder definitions to ensure they meet U.S. Food and Drug Administration and European Medicines Agency guidelines. Using data from several published TrialNet studies, we evaluate our definition (no decrease in C-peptide) against published alternatives and determine that our definition has minimum bias with external validity. We observe that reliability could be improved by using changes in C-peptide later than 6 months beyond baseline. In sum, to support efficacy claims of -cell preservation therapies in type 1 diabetes submitted to U.S. and European regulatory agencies, we recommend use of our definition. C1 [Beam, Craig A.] Univ S Florida, Dept Pediat, Div Epidemiol & Biostat, Tampa, FL 33620 USA. [Gitelman, Stephen E.] Univ Calif San Francisco, Dept Pediat, San Francisco, CA USA. [Palmer, Jerry P.] VA Puget Sound Hlth Care Syst, Dept Med, Seattle, WA USA. [Palmer, Jerry P.] Univ Washington, Seattle, WA 98195 USA. RP Beam, CA (reprint author), Western Michigan Univ, Homer Stryker MD Sch Med, Dept Biomed Sci, Div Epidemiol & Biostat, Kalamazoo, MI 49008 USA. EM craig.beam@med.wmich.edu FU National Institutes of Health through the National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Allergy and Infectious Diseases; Eunice Kennedy Shriver National Institute of Child Health and Human Development [U01-DK-061010, U01-DK-061016, U01-DK-061034, U01-DK-061036, U01-DK-061040, U01-DK-061041, U01-DK-061042, U01-DK-061055, U01-DK-061058, U01-DK-084565, U01-DK-085453, U01-DK-085461, U01-DK-085463, U01-DK-085466, U01-DK-085499, U01-DK-085505, U01-DK-085509, HHSN267200800019C]; National Center for Research Resources [UL1-RR-024131, UL1-RR-024139, UL1-RR-024153, UL1-RR-024975, UL1-RR-024982, UL1-RR-025744, UL1-RR-025761, UL1-RR-025780, UL1-RR-029890, UL1-RR-031986, M01-RR-00400]; Juvenile Diabetes Research Foundation International; American Diabetes Association FX Type 1 Diabetes TrialNet Study Group is a clinical trials network funded by the National Institutes of Health through the National Institute of Diabetes and Digestive and Kidney Diseases; the National Institute of Allergy and Infectious Diseases; and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, through the cooperative agreements U01-DK-061010, U01-DK-061016, U01-DK-061034, U01-DK-061036, U01-DK-061040, U01-DK-061041, U01-DK-061042, U01-DK-061055, U01-DK-061058, U01-DK-084565, U01-DK-085453, U01-DK-085461, U01-DK-085463, U01-DK-085466, U01-DK-085499, U01-DK-085505, and U01-DK-085509 and contract HHSN267200800019C; the National Center for Research Resources, through Clinical and Translational Science Awards UL1-RR-024131, UL1-RR-024139, UL1-RR-024153, UL1-RR-024975, UL1-RR-024982, UL1-RR-025744, UL1-RR-025761, UL1-RR-025780, UL1-RR-029890, and UL1-RR-031986 and General Clinical Research Center Award M01-RR-00400; the Juvenile Diabetes Research Foundation International; and the American Diabetes Association. NR 25 TC 5 Z9 5 U1 0 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD SEP PY 2014 VL 63 IS 9 BP 3120 EP 3127 DI 10.2337/db14-0095 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AO7AV UT WOS:000341505300029 PM 24722251 ER PT J AU Grossbard, JR Malte, CA Saxon, AJ Hawkins, EJ AF Grossbard, Joel R. Malte, Carol A. Saxon, Andrew J. Hawkins, Eric J. TI Clinical monitoring and high-risk conditions among patients with SUD newly prescribed opioids and benzodiazepines SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Opioid therapy; Substance use disorders; Clinical monitoring; Veterans; Benzodiazepines ID SUBSTANCE USE DISORDER; CHRONIC NONCANCER PAIN; PRESCRIPTION OPIOIDS; ELDERLY PERSONS; UNITED-STATES; VETERANS; THERAPY; CARE; PREVALENCE; ALCOHOL AB Background: Opioid therapy alone or in combination with benzodiazepines poses safety concerns among patients with substance use disorders (SUD). Guidelines for opioid therapy recommend SUD treatment and enhanced monitoring, especially in patients with additional risk factors, but information on monitoring practices is sparse. This study estimated high-risk conditions - psychiatric comorbidity, suicide risk, and age <35 and >= 65 - and described clinical monitoring among patients with SUD who were newly prescribed opioids alone and concurrent with benzodiazepines long-term. Methods: This study included VA Northwest Veterans Network patients with SUD who started opioids only (n = 980) or benzodiazepines and opioids concurrently (n = 353) long-term (>= 90 days) in 2009-2010. Clinical characteristics, outpatient visits and urine drug screens (UDS) documented within 7-months after starting medications were extracted from VA data. Results: Approximately 67% (95% CI: 64-70) of opioids only and 94% (92-97) of concurrent medications groups had >= 1 psychiatric diagnoses. Prevalences of suicide risk and age <35 and >= 65 were 7% (5-8), 6% (5-8) and 18% (15-20) among the opioids only group, and 20% (16-24), 8% (5-11) and 13% (9-16) among the concurrent medications group. Among patients prescribed opioids only and medications concurrently, 87% and 91% attended primary care, whereas 28% and 26% attended SUD specialty-care. Overall, 30% and 48% of opioids only and concurrent medications groups engaged in mental health or SUD care, and 35% and 39% completed UDS. Conclusions: Improvements in clinical monitoring are needed as many VA patients with SUD and comorbid risks who initiate opioid therapy do not receive sufficient mental health/SUD care or UDS monitoring. Published by Elsevier Ireland Ltd. C1 [Grossbard, Joel R.; Malte, Carol A.; Hawkins, Eric J.] VA Hlth Serv Res & Dev, Seattle, WA 98101 USA. [Malte, Carol A.; Saxon, Andrew J.; Hawkins, Eric J.] VA Puget Sound Hlth Care Syst, Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA 98108 USA. [Saxon, Andrew J.; Hawkins, Eric J.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Grossbard, JR (reprint author), VA Hlth Serv Res & Dev, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM joel.grossbard@va.gov FU VA Puget Sound Health Services Research and Development Service (PhD Postdoctoral Fellowship Program) [TPP 61-025]; Department of Veterans Affairs, Veterans Health Administration, Center of Excellence in Substance Abuse Treatment Education FX The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or University of Washington. The research reported here was supported by the Department of Veterans Affairs, Veterans Health Administration, Center of Excellence in Substance Abuse Treatment & Education, and VA Puget Sound Health Services Research and Development Service (PhD Postdoctoral Fellowship Program, TPP 61-025) and these organizations had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. We certify that we have no affiliation with or financial involvement in any organization or entity with a direct financial interest in the subject matter or materials discussed in the manuscript (e.g., employment, consultancies, stock, ownership, honoraria). NR 40 TC 2 Z9 2 U1 0 U2 8 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 EI 1879-0046 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD SEP 1 PY 2014 VL 142 BP 24 EP 32 DI 10.1016/j.drugalcdep.2014.03.020 PG 9 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA AO4YQ UT WOS:000341347700003 PM 24969956 ER PT J AU Lapham, GT Rubinsky, AD Williams, EC Hawkins, EJ Grossbard, J Chavez, LJ Kivlahan, DR Bradley, KA AF Lapham, Gwen T. Rubinsky, Anna D. Williams, Emily C. Hawkins, Eric J. Grossbard, Joel Chavez, Laura J. Kivlahan, Daniel R. Bradley, Katharine A. TI Decreasing sensitivity of clinical alcohol screening with the AUDIT-C after repeated negative screens in VA clinics SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Unhealthy alcohol use; Alcohol screening; Validation; AUDIT-C ID DISORDERS IDENTIFICATION TEST; US GENERAL-POPULATION; PRIMARY-CARE PATIENTS; RISK DRINKING; VETERANS-AFFAIRS; COUNSELING INTERVENTIONS; CONSUMPTION QUESTIONS; DIAGNOSTIC-TESTS; MISUSE; PROBABILITY AB Background: Routine screening for unhealthy alcohol use is widely recommended in primary care settings. However, the validity of repeat screening among patients who have previously screened negative remains unknown. This study aims to evaluate the performance of a clinical alcohol screen compared to a confidential comparison alcohol screen among patients with previous negative alcohol screens. Methods: This study included four nested samples of Veteran Health Administration (VA) outpatients with at least one (N=18,493) and up to four (N=714) prior negative annual clinical AUDIT-C screens who completed the AUDIT-C the following year, both in a VA clinic (clinical screen) and on a confidential mailed survey (comparison screen). AUDIT-C screens were categorized as either negative (0-3 points men; 0-2 women) or positive (>= 4 men; >= 3 women). For each sample, the performance of the clinical screen was compared to the comparison screen, the reference measure for unhealthy alcohol use. Results: The sensitivity of clinical screens decreased as the number of prior negative screens in a sample increased (40.0-17.4%) for patients with 1-4 negative screens. The positive predictive value also decreased as the number of prior negative screens in a sample increased (67.7-33.3%) while specificity was consistently high for all samples (>= 97.8%). Conclusions: Repeat clinical alcohol screens became progressively less sensitive for identifying unhealthy alcohol use among patients who repeatedly screened negative over several years. Alternative approaches for assessing unhealthy alcohol use may be needed for these patients. Published by Elsevier Ireland Ltd. C1 [Lapham, Gwen T.; Rubinsky, Anna D.; Williams, Emily C.; Hawkins, Eric J.; Grossbard, Joel; Chavez, Laura J.; Kivlahan, Daniel R.; Bradley, Katharine A.] Denver Seattle Ctr Innovat Vet Ctr & Value Driven, Vet Hlth Adm VA, Seattle, WA 98101 USA. [Lapham, Gwen T.; Rubinsky, Anna D.; Williams, Emily C.; Hawkins, Eric J.; Grossbard, Joel; Chavez, Laura J.; Kivlahan, Daniel R.; Bradley, Katharine A.] VA Puget Sound Hlth Serv Res & Dev, Seattle, WA 98101 USA. [Rubinsky, Anna D.; Hawkins, Eric J.; Grossbard, Joel; Kivlahan, Daniel R.; Bradley, Katharine A.] VA Puget Sound Hlth Care Syst, Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA 98108 USA. [Bradley, Katharine A.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Williams, Emily C.; Chavez, Laura J.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Hawkins, Eric J.; Kivlahan, Daniel R.; Bradley, Katharine A.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Lapham, Gwen T.; Bradley, Katharine A.] Grp Hlth Res Inst, Seattle, WA 98101 USA. [Rubinsky, Anna D.] VA Palo Alto Hlth Care Syst, HSR&D Ctr Innovat Implementat Ci2i, Menlo Pk, CA 94304 USA. RP Lapham, GT (reprint author), Grp Hlth Res Inst, 1730 Minor Ave,Suite 1600, Seattle, WA 98101 USA. EM lapham.g@ghc.org FU US Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development (HSRD) [RRP 11-021]; National Institute of Mental Health [R25 MH080916-01A2]; Department of Veterans Affairs, HSRD QUERI; Agency for Healthcare Research and Quality (AHRQ) [NIH 1R36HS022800-01] FX The research reported here was funded by the US Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development (HSR&D) Substance Use Disorders Quality Enhancement Research Initiative (QUERI) RRP 11-021. A preliminary version of this work was presented at both the 36th Annual Research Society for Alcoholism Scientific Meeting in Orlando, FL, June 25, 2013 and the Addiction Health Services Conference in Portland, OR, October 24, 2013. Dr. Williams is supported by a Career Development Award from the VA Health Services Research & Development (CDA 12-276) and a fellowship from the Implementation Research Institute (IRI) at the George Warren Brown School of Social Work at Washington University. IRI is supported through an award from the National Institute of Mental Health (R25 MH080916-01A2) and the Department of Veterans Affairs, HSR&D QUERI. Ms. Chavez is supported by an Agency for Healthcare Research and Quality (AHRQ) dissertation grant (NIH 1R36HS022800-01). These funding sources had no influence on the study's design, data collection, analyses or interpretation and reporting of results. NR 53 TC 2 Z9 2 U1 3 U2 11 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 EI 1879-0046 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD SEP 1 PY 2014 VL 142 BP 209 EP 215 DI 10.1016/j.drugalcdep.2014.06.017 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA AO4YQ UT WOS:000341347700029 PM 25034900 ER PT J AU Baumeister, SE Gelberg, L Leake, BD Yacenda-Murphy, J Vahidi, M Andersen, RM AF Baumeister, Sebastian E. Gelberg, Lillian Leake, Barbara D. Yacenda-Murphy, Julia Vahidi, Mani Andersen, Ronald M. TI Effect of a primary care based brief intervention trial among risky drug users on health-related quality of life SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Primary care clinics; Illicit drug use; Screening; Brief intervention; Quality of life ID OPIATE-DEPENDENT INDIVIDUALS; SCREENING-TEST ASSIST; CLINICALLY IMPORTANT DIFFERENCE; STARTING METHADONE TREATMENT; RANDOMIZED CONTROLLED-TRIAL; SUBSTANCE-ABUSE TREATMENT; ALCOHOL; SETTINGS; OUTCOMES; SMOKING AB Background: Improvement in quality of life (QOL) is a long term goal of drug treatment. Although some brief interventions have been found to reduce illicit drug use, no trial among adult risky (moderate non-dependent) drug users has tested effects on health-related quality of life. Methods: A single-blind randomized controlled trial of patients enrolled from February 2011 to November 2012 was conducted in waiting rooms of five federally qualified health centers. 413 adult primary care patients were identified as risky drug users using the WHO-ASSIST and 334 (81% response; 171 intervention, 163 control) consented to participate in the trial. Three-month follow-ups were completed by 261 patients (78%). Intervention patients received the QUIT intervention of brief clinician advice and up to two drug-use health telephone sessions. The control group received usual care and information on cancer screening. Outcomes were three-month changes in the Short Form Health Survey (SF-12) mental health component summary score (MCS) and physical health component summary score (PCS). Results: The average treatment effect (ATE) was non-significant for MCS (0.2 points, p-value = 0.87) and marginally significant for PCS (1.7 points, p-value = 0.08). The average treatment effect on the treated (ATT) was 0.1 (p-value = 0.93) for MCS and 1.9 (p-value = 0.056) for PCS. The effect on PCS was stronger at higher (above median) baseline number of drug use days: ATE = 2.7, p-value = 0.04; ATT = 3.21, p-value = 0.02. Conclusions: The trial found a marginally significant effect on improvement in PCS, and significant and stronger effect on the SF-12 physical component among patients with greater frequency of initial drug use. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Baumeister, Sebastian E.] Univ Med Greifswald, Inst Community Med, D-17489 Greifswald, Germany. [Gelberg, Lillian; Leake, Barbara D.; Yacenda-Murphy, Julia; Vahidi, Mani] Univ Calif Los Angeles, David Geffen Sch Med, Dept Family Med, Los Angeles, CA 90095 USA. [Gelberg, Lillian; Andersen, Ronald M.] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA 90095 USA. [Gelberg, Lillian] VA Greater Angeles Healthcare Syst, Off Healthcare Transformat & Innovat, Los Angeles, CA 90073 USA. RP Baumeister, SE (reprint author), Univ Med Greifswald, Inst Community Med, Walther Rathenau Str 48, D-17489 Greifswald, Germany. EM sebastian.baumeister@uni-greifswald.de FU NIDA ("Preventing Drug Use in Low Income Clinic Populations") [R01 DA022445-01]; UCLA/DREW Project EXPORT, National Center on Minority Health and Health Disparities [P20MD000148/P20MD000182] FX This research was funded primarily by a grant from NIDA ("Preventing Drug Use in Low Income Clinic Populations." R01 DA022445-01). Ronald Andersen received additional support from the UCLA/DREW Project EXPORT, National Center on Minority Health and Health Disparities, P20MD000148/P20MD000182. Sebastian E. Baumeister received travel expenses for short stays at UCLA from the International Office at the University of Greifswald. NR 56 TC 6 Z9 6 U1 1 U2 13 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 EI 1879-0046 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD SEP 1 PY 2014 VL 142 BP 254 EP 261 DI 10.1016/j.drugalcdep.2014.06.034 PG 8 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA AO4YQ UT WOS:000341347700035 PM 25042213 ER PT J AU Durazzo, TC Mattsson, N Weiner, MW Korecka, M Trojanowski, JQ Shaw, LM AF Durazzo, Timothy C. Mattsson, Niklas Weiner, Michael W. Korecka, Magdalena Trojanowski, John Q. Shaw, Leslie M. CA Alzheimer's Dis Neuroimaging Initi TI History of cigarette smoking in cognitively-normal elders is associated with elevated cerebrospinal fluid biomarkers of oxidative stress SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Cigarette smoking; Oxidative stress; Isoprostanes; Hippocampus; Cerebrospinal fluid; Elder adults ID SURFACE-BASED ANALYSIS; HUMAN CEREBRAL-CORTEX; ALZHEIMERS-DISEASE; TOBACCO-SMOKE; CARDIOVASCULAR-DISEASE; LIPID-PEROXIDATION; UNITED-STATES; HUMAN URINE; RISK-FACTOR; BACOSIDE-A AB Background: Cigarette smoking in adults is associated with abnormalities in brain neurobiology. Smoking-induced central nervous system oxidative stress (OxS) is a potential mechanism associated with these abnormalities. The goal of this study was to compare cognitively-normal elders on cerebrospinal fluid (CSF) levels of F-2-isoprostane biomarkers of OxS. Methods: Elders with a lifetime history of smoking (smokers; n = 50; 75 +/- 5 years of age; 34 +/- 28 pack-years; approximately 12% were actively smoking at the time of study) were compared to never-smokers (n = 61; 76 +/- 6 years of age) on CSF iPF(2 alpha)-III and 8,12, iso-iPF(2 alpha)-VI F-2-isoprostanes levels. F-2-isoprostanes levels were quantitated with HPLC-atmospheric pressure chemical ionization-tandem mass spectrometry. Associations between F-2-isoprostanes levels, hippocampal volumes, and cigarette exposure measures were also evaluated. Results: Smokers showed higher iPF(2 alpha)-III level than never-smokers. An age x smoking status interaction was observed for 8,12, iso-iPF(2 alpha)-VI, where smokers demonstrate a significantly greater concentration with increasing age than never-smokers. In smokers only, higher 8,12, iso-iPF(2 alpha)-VI concentration was associated with smaller hippocampal volume, and greater iPF(2 alpha)-III level was related to greater pack years. Conclusions: This is the first study to demonstrate that a history of cigarette smoking in cognitively-normal elders was associated with significantly elevated CSF F-2-isoprostane levels and greater age-related increases in F-2-isoprostanes, and that higher F-2-isoprostane levels in smokers were related to smaller hippocampal volume. These findings provide additional novel evidence that a history of chronic smoking during adulthood is associated with adverse effects on the human brain that are potentially enduring even with extended smoking cessation. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Durazzo, Timothy C.; Mattsson, Niklas; Weiner, Michael W.] San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis CIND, San Francisco, CA 94121 USA. [Durazzo, Timothy C.; Mattsson, Niklas; Weiner, Michael W.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Mattsson, Niklas] Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Clin Neurochem Lab, Molndal, Sweden. [Weiner, Michael W.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Weiner, Michael W.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Weiner, Michael W.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Korecka, Magdalena; Trojanowski, John Q.; Shaw, Leslie M.] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Korecka, Magdalena; Trojanowski, John Q.; Shaw, Leslie M.] Univ Penn, Ctr Neurodegenerat Dis Res, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Durazzo, TC (reprint author), San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis 114M, 4150 Clement St, San Francisco, CA 94121 USA. EM timothy.durazzo@ucsf.edu RI Kowall, Neil/G-6364-2012 OI Kowall, Neil/0000-0002-6624-0213; Preda, Adrian /0000-0003-3373-2438 FU National Institutes of Health [NIH DA24136]; ADNI; National Institute on Aging [U01 AG024904]; National Institute of Biomedical Imaging and Bioengineering; Abbott; AstraZeneca AB; Bayer Schering Pharma AG; Bristol-Myers Squibb; Eisai Global Clinical Development; Elan Corporation; Genentech; GE Healthcare; GlaxoSmithKline; Innogenetics; Johnson and Johnson; Eli Lilly and Co.; Medpace, Inc.; Merck and Co.,Inc.; Novartis AG; Pfizer Inc; F. Hoffman-La Roche; Schering-Plough; Synarc, Inc.; Wyeth; Alzheimer's Association; Alzheimer's Drug Discovery Foundation; U.S. Food and Drug Administration; Northern California Institute for Research and Education; NIH [P30 AG010129, K01 AG030514, R01 AG010897, R01 AG012435]; Dana Foundation FX This work was supported by the National Institutes of Health (NIH DA24136 to TCD) and by the use of resources and facilities at the San Francisco Veterans Administration Medical Center. All data collection and sharing for this project was supported by ADNI. ADNI is funded by the National Institute on Aging (U01 AG024904; PI MWW), the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Abbott, AstraZeneca AB, Bayer Schering Pharma AG, Bristol-Myers Squibb, Eisai Global Clinical Development, Elan Corporation, Genentech, GE Healthcare, GlaxoSmithKline, Innogenetics, Johnson and Johnson, Eli Lilly and Co., Medpace, Inc., Merck and Co.,Inc., Novartis AG, Pfizer Inc, F. Hoffman-La Roche, Schering-Plough, Synarc, Inc., and Wyeth, as well as non-profit partners the Alzheimer's Association and Alzheimer's Drug Discovery Foundation, with participation from the U.S. Food and Drug Administration. Private sector contributions to ADNI are facilitated by the Foundation for the National Institutes of Health (www.fnih.org; http://www.fnih.org; http://www.fnih.org; http://www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University Southern California. This research was also supported by NIH grants P30 AG010129, K01 AG030514, R01 AG010897, R01 AG012435, and The Dana Foundation and by resources. The above funding agencies had no role in the design and conduct of the study, collection, management, analysis, and interpretation of the data, preparation, review, or approval of the manuscript. Original data used in preparation of this article were obtained from the ADNI database (www.loni.usc.edu/ADNI). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNLAuthorship_ List.pdf. NR 83 TC 5 Z9 5 U1 0 U2 7 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 EI 1879-0046 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD SEP 1 PY 2014 VL 142 BP 262 EP 268 DI 10.1016/j.drugalcdep.2014.06.030 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA AO4YQ UT WOS:000341347700036 PM 25037769 ER PT J AU McCauley, JL Mercer, MA Barth, KS Brady, KT Back, SE AF McCauley, Jenna L. Mercer, Mary Ashley Barth, Kelly S. Brady, Kathleen T. Back, Sudie E. TI Pain management perceptions among prescription opioid dependent individuals SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Prescription opioid; Pain management; Addictive behaviors; Substance abuse ID MOTIVES; ABUSE AB Background: Nearly two-thirds of prescription opioid dependent individuals report chronic pain conditions as both an initial and current motivation for prescription opioid use. However, to date, limited information exists regarding perceptions of the adequacy of pain management and pain management behaviors among prescription opioid dependent individuals with a history of treatment for chronic pain. Methods: The current study examined perceptions of the medical management of chronic pain among community-recruited individuals (N = 39) who met DSM-IV-TR criteria for current prescription opioid dependence and reported a history of treatment for chronic pain. Prescription opioid dependence, symptoms of depression, and pain management perceptions were assessed using the Structured Clinical Interview for DSM disorders, Beck Depression Inventory, and the Pain Management Questionnaire, respectively. Results: Reports of insufficient pain management were common (46.2%), as was utilization of emergency room services for pain management (56.4%). Nearly half reported a physician as their initial source (46.2%) and pain management as their primary initial reason for prescription opioid use (53.8%), whereas 35.9% reported pain relief as their primary reason for current prescription opioid use. Symptoms of depression were common (51.3%), as was comorbid abuse of other substances and history of treatment for substance abuse. Conclusions: Results highlight the complicated clinical presentation and prevalent perception of the under-treatment of pain among this population. Findings underscore the importance of interdisciplinary approaches to managing the complex presentation of chronic pain patients with comorbid prescription opioid dependence. Implications for future research are discussed. Published by Elsevier Ireland Ltd. C1 [McCauley, Jenna L.; Mercer, Mary Ashley; Barth, Kelly S.; Brady, Kathleen T.; Back, Sudie E.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Brady, Kathleen T.; Back, Sudie E.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP McCauley, JL (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, 67 President St MSC 861, Charleston, SC 29425 USA. EM mccaule@musc.edu OI Mercer, Mary/0000-0001-9538-5019 FU NIDA [K23 DA021228, K12 DA031794]; MUSC Clinical & Translational Research Center (CTRC) NIH/NCRR [UL1 RR029880] FX Funding for this study was provided by NIDA grant K23 DA021228 (PI: Back), NIDA grant K12 DA031794 (PI: Brady; Sub-Award PI: McCauley), and the MUSC Clinical & Translational Research Center (CTRC) NIH/NCRR Grant number UL1 RR029880 (PI: Brady). The NIH had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. NR 28 TC 1 Z9 1 U1 2 U2 10 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 EI 1879-0046 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD SEP 1 PY 2014 VL 142 BP 354 EP 358 DI 10.1016/j.drugalcdep.2014.06.024 PG 5 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA AO4YQ UT WOS:000341347700050 PM 25034899 ER PT J AU McMillan, GP AF McMillan, Garnett P. TI On Reliability SO EAR AND HEARING LA English DT Editorial Material ID SPEECH; THRESHOLD; CHILDREN; NOISE C1 Natl Ctr Rehabil Auditory Res, Portland VA Med Ctr, Portland, OR 97239 USA. RP McMillan, GP (reprint author), Natl Ctr Rehabil Auditory Res, Portland VA Med Ctr, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. NR 12 TC 2 Z9 2 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0196-0202 EI 1538-4667 J9 EAR HEARING JI Ear Hear. PD SEP-OCT PY 2014 VL 35 IS 5 BP 589 EP 590 PG 2 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA AO7BI UT WOS:000341506600018 PM 24722511 ER PT J AU Cai, CC Huang, H Whelan, S Liu, L Kautza, B Luciano, J Wang, GL Chen, GQ Stratimirovic, S Tsung, A Billiar, TR Zuckerbraun, BS AF Cai, Changchun Huang, Hai Whelan, Sean Liu, Li Kautza, Benjamin Luciano, Jason Wang, Guoliang Chen, Guoqiang Stratimirovic, Sladjana Tsung, Allan Billiar, Timothy R. Zuckerbraun, Brian S. TI Benzyl Alcohol Attenuates Acetaminophen-Induced Acute Liver Injury in a Toll-Like Receptor-4-Dependent Pattern in Mice SO HEPATOLOGY LA English DT Article ID GROUP BOX-1 PROTEIN; INDUCED HEPATOTOXICITY; CELL-DEATH; MITOCHONDRIAL DYSFUNCTION; ISCHEMIA-REPERFUSION; STERILE INFLAMMATION; HEPATIC-INJURY; UNITED-STATES; RECEPTOR 4; HMGB1 AB Acetaminophen (APAP) toxicity is the most common cause of acute liver failure in industrialized countries. Understanding the mechanisms of APAP-induced liver injury as well as other forms of sterile liver injury is critical to improve the care of patients. Recent studies demonstrate that danger signaling and inflammasome activation play a role in APAP-induced injury. The aim of these investigations was to test the hypothesis that benzyl alcohol (BA) is a therapeutic agent that protects against APAP-induced liver injury by modulation of danger signaling. APAP-induced liver injury was dependent, in part, on Toll-like receptor (TLR) 9 and receptor for advanced glycation endproducts (RAGE) signaling. BA limited liver injury over a dose range of 135-540 mu g/g body weight or when delivered as a pre-, concurrent, or post-APAP therapeutic. Furthermore, BA abrogated APAP-induced cytokines and chemokines as well as high-mobility group box 1 release. Moreover, BA prevented APAP-induced inflammasome signaling as determined by interleukin (IL)-1 beta, IL-18, and caspase-1 cleavage in liver tissues. Interestingly, the protective effects of BA on limiting liver injury and inflammasome activation were dependent on TLR4 signaling, but not TLR2 or CD14. Cell-type-specific knockouts of TLR4 were utilized to further determine the protective mechanisms of BA. These studies found that TLR4 expression specifically in myeloid cells (LyzCre-tlr4(-/-)) were necessary for the protective effects of BA. Conclusion: BA protects against APAP-induced acute liver injury and reduced inflammasome activation in a TLR4-dependent manner. BA may prove to be a useful adjunct in the treatment of APAP and other forms of sterile liver injury. C1 [Cai, Changchun; Chen, Guoqiang] Cent Hosp Wuhan, Wuhan, Peoples R China. [Cai, Changchun; Huang, Hai; Whelan, Sean; Liu, Li; Kautza, Benjamin; Luciano, Jason; Wang, Guoliang; Chen, Guoqiang; Stratimirovic, Sladjana; Tsung, Allan; Billiar, Timothy R.; Zuckerbraun, Brian S.] Univ Pittsburgh, Dept Surg, Pittsburgh, PA 15213 USA. [Stratimirovic, Sladjana; Zuckerbraun, Brian S.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Zuckerbraun, BS (reprint author), Univ Pittsburgh, Dept Surg, F1271 PUH,200 Lothrop St, Pittsburgh, PA 15213 USA. EM zuckerbraunbs@upmc.edu RI Huang, Hai/F-4286-2012 OI Huang, Hai/0000-0001-7430-0119 FU NIGMS NIH HHS [R01 GM082830] NR 39 TC 11 Z9 11 U1 0 U2 22 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD SEP PY 2014 VL 60 IS 3 BP 990 EP 1002 DI 10.1002/hep.27201 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AO3NV UT WOS:000341239200025 PM 24798499 ER PT J AU Ju, MH Cohen, ME Bilimoria, KY Latus, MS Scholl, LM Schwab, BJ Byrd, CM Ko, CY Dellinger, EP Hall, BL AF Ju, Mila H. Cohen, Mark E. Bilimoria, Karl Y. Latus, Melissa S. Scholl, Lisa M. Schwab, Bradley J. Byrd, Claudia M. Ko, Clifford Y. Dellinger, E. Patchen Hall, Bruce L. TI Effect of Wound Classification on Risk Adjustment in American College of Surgeons NSQIP SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID SURGICAL QUALITY; ACS-NSQIP; INFECTIONS AB BACKGROUND: Surgical wound classification has been used in risk-adjustment models. However, it can be subjective and could potentially improperly bias hospital quality comparisons. The objective is to examine the effect of wound classification on hospital performance risk-adjustment models. STUDY DESIGN: Retrospective review of the 2011 American College of Surgeons NSQIP database was conducted for the following wound classification categories: clean, clean-contaminated, contaminated, and dirty-infected. To assess the influence of wound classification on risk adjustment, 2 models were developed for all outcomes: 1 including and 1 excluding wound classification. For each model, hospital postoperative complications were estimated using hierarchical multivariable regression methods. Absolute changes in hospital rank, correlations of odds ratios, and outlier status agreement between models were examined. RESULTS: Of the 442,149 cases performed in 315 hospitals: 53.6% were classified as clean; 34.2% as clean-contaminated; 6.7% as contaminated; and 5.5% as dirty-infected. The surgical site infection rate was highest in dirty-infected (8.5%) and lowest in clean (1.8%) cases. For overall surgical site infection, the absolute change in risk-adjusted hospital performance rank between models, including vs excluding wound classification, was minimal (mean 4.5 of 315 positions). The correlations between odds ratios of the 2 performance models were nearly perfect (R 0.9976, p < 0.0001), and outlier status agreement was excellent (kappa = 0.95ss08, p < 0.0001). Similar findings were observed in models of subgroups of surgical site infections and other postoperative outcomes. CONCLUSIONS: In circumstances where alternate information is available for risk adjustment, there appear to be minimal differences in performance models that include vs exclude wound classification. Therefore, the American College of Surgeons NSQIP is critically evaluating the continued use of wound classification in hospital performance risk-adjustment models. (C) 2014 by the American College of Surgeons C1 [Ju, Mila H.; Cohen, Mark E.; Bilimoria, Karl Y.; Latus, Melissa S.; Scholl, Lisa M.; Schwab, Bradley J.; Byrd, Claudia M.; Ko, Clifford Y.; Hall, Bruce L.] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL 60611 USA. [Ju, Mila H.; Bilimoria, Karl Y.] Northwestern Univ, Feinberg Sch Med, Dept Surg, Surg Outcomes & Qual Improvement Ctr, Chicago, IL 60611 USA. [Ju, Mila H.; Bilimoria, Karl Y.] NW Mem Hosp, Chicago, IL 60611 USA. [Ko, Clifford Y.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. [Ko, Clifford Y.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Dellinger, E. Patchen] Univ Washington, Sch Med, Dept Surg, Seattle, WA 98195 USA. [Hall, Bruce L.] Washington Univ, Dept Surg, St Louis, MO USA. [Hall, Bruce L.] Washington Univ, Olin Business Sch, St Louis, MO USA. [Hall, Bruce L.] Washington Univ, Ctr Hlth Policy, St Louis, MO USA. [Hall, Bruce L.] BJC Healthcare, St Louis VA Med Ctr, St Louis, MO USA. RP Ju, MH (reprint author), Amer Coll Surg, 633 North St Clair St,22nd Fl, Chicago, IL 60611 USA. EM mju@facs.org FU NIH [5T32HL094293]; AHRQ; NCCN; ACS; ACoS; BCBS-IL; Tetraphrase; Applied Medical; Health and Human Services; Michigan Hospital Association; Louisiana Woman's Hospital FX Dr Ju is supported by NIH Grant #5T32HL094293, and is a Scholar in Residence at the ACS. Dr Bilimoria receives grants from NIH, AHRQ, NCCN, ACS, ACoS, and BCBS-IL; and lecture payments from hospitals and professional societies for grand rounds. Dr Dellinger is a paid consultant to Merck, Targanta, Astellas, Care Fusion, Durata, Pfizer, Rib-X, Affinium, and 3M; receives grants from Tetraphrase and lecture payments from Applied Medical; and other expenses paid by Health and Human Services, Michigan Hospital Association, and Louisiana Woman's Hospital. Dr Hall is a paid consultant to the ACS. This study received no outside funding. NR 20 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 EI 1879-1190 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2014 VL 219 IS 3 BP 371 EP + DI 10.1016/j.jamcollsurg.2014.04.009 PG 16 WC Surgery SC Surgery GA AO5VW UT WOS:000341415100008 PM 25053222 ER PT J AU Dawes, AJ Sacks, GD Russell, MM Lin, AY Maggard-Gibbons, M Winograd, D Chung, HR Tillou, A Hiatt, JR Ko, C AF Dawes, Aaron J. Sacks, Greg D. Russell, Marcia M. Lin, Anne Y. Maggard-Gibbons, Melinda Winograd, Deborah Chung, Hallie R. Tillou, Areti Hiatt, Jonathan R. Ko, Clifford TI Preventable Readmissions to Surgical Services: Lessons Learned and Targets for Improvement SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; HOSPITAL READMISSION; RISK-FACTORS; MEDICARE BENEFICIARIES; UNPLANNED READMISSION; PATIENT READMISSION; 30-DAY READMISSIONS; COLORECTAL SURGERY; ILEOSTOMY CREATION; DEHYDRATION AB BACKGROUND: Hospital readmissions are under intense scrutiny as a measure of health care quality. The Center for Medicare and Medicaid Services (CMS) has proposed using readmission rates as a benchmark for improving care, including targeting them as nonreimbursable events. Our study aim was to describe potentially preventable readmissions after surgery and to identify targets for improvement. STUDY DESIGN: Patients discharged from a general surgery service over 8 consecutive quarters (Q4 2009 to Q3 2011) were selected. A working group of attending surgeons defined terms and created classification schemes. Thirty-day readmissions were identified and reviewed by a 2-physician team. Readmissions were categorized as preventable or unpreventable, and by target for future quality improvement intervention. RESULTS: Overall readmission rate was 8.3% (315 of 3,789). The most common indication for initial admission was elective general surgery. Among readmitted patients in our sample, 28% did not undergo an operation during their index admission. Only 21% (55 of 258) of readmissions were likely preventable based on medical record review. Of the preventable readmissions, 38% of patients were discharged within 24 hours and 60% within 48 hours. Dehydration occurred more frequently among preventable readmissions (p < 0.001). Infection accounted for more than one-third of all readmissions. Among preventable readmissions, targets for improvement included closer follow-up after discharge (49%), management in the outpatient setting (42%), and avoidance of premature discharge (9%). CONCLUSIONS: A minority of readmissions may potentially be preventable. Targets for reducing readmissions include addressing the clinical issues of infection and dehydration as well as improving discharge planning to limit both early and short readmissions. Policies aimed at penalizing reimbursements based on readmission rates should use clinical data to focus on inappropriate hospitalization in order to promote high quality patient care. (C) 2014 by the American College of Surgeons C1 [Dawes, Aaron J.; Sacks, Greg D.; Russell, Marcia M.; Lin, Anne Y.; Maggard-Gibbons, Melinda; Winograd, Deborah; Chung, Hallie R.; Tillou, Areti; Hiatt, Jonathan R.; Ko, Clifford] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. [Dawes, Aaron J.; Sacks, Greg D.] Univ Calif Los Angeles, Robert Wood Johnson Clin Scholars Program, Los Angeles, CA 90095 USA. [Dawes, Aaron J.; Russell, Marcia M.; Maggard-Gibbons, Melinda; Ko, Clifford] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Dawes, AJ (reprint author), Univ Calif Los Angeles, Ronald Reagan UCLA Med Ctr, David Geffen Sch Med, Dept Surg, 757 Westwood Plaza B7-11, Los Angeles, CA 90095 USA. EM adawes@mednet.ucla.edu OI Dawes, Aaron/0000-0003-4574-6765 FU VA Office of Academic Affiliations through the VA/Robert Wood Johnson Clinical Scholars Program FX Dr Dawes was supported by the VA Office of Academic Affiliations through the VA/Robert Wood Johnson Clinical Scholars Program. NR 33 TC 21 Z9 21 U1 3 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 EI 1879-1190 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2014 VL 219 IS 3 BP 382 EP 389 DI 10.1016/j.jamcollsurg.2014.03.046 PG 8 WC Surgery SC Surgery GA AO5VW UT WOS:000341415100009 PM 24891209 ER PT J AU Friedlander, AH Bertolami, CN AF Friedlander, Arthur H. Bertolami, Charles N. TI The ethics of managing incidental findings Implications and challenges for the profession SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Editorial Material C1 [Friedlander, Arthur H.] Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90024 USA. [Friedlander, Arthur H.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Bertolami, Charles N.] NYU, Coll Dent, New York, NY USA. RP Friedlander, AH (reprint author), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM arthur.friedlander@med.va.gov NR 4 TC 2 Z9 2 U1 0 U2 2 PU AMER DENTAL ASSOC PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 EI 1943-4723 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD SEP PY 2014 VL 145 IS 9 BP 910 EP 911 PG 2 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA AO5IV UT WOS:000341378700001 PM 25169990 ER PT J AU Clapp, JD Grubaugh, AL Allen, JG Oldham, JM Fowler, JC Hardesty, S Frueh, BC AF Clapp, Joshua D. Grubaugh, Anouk L. Allen, Jon G. Oldham, John M. Fowler, J. Christopher Hardesty, Susan Frueh, B. Christopher TI Interpersonal Change Following Intensive Inpatient Treatment SO PSYCHIATRY-INTERPERSONAL AND BIOLOGICAL PROCESSES LA English DT Article ID THERAPEUTIC ALLIANCE; PSYCHOMETRIC PROPERTIES; PSYCHODYNAMIC THERAPY; PERSONALITY-DISORDERS; SYMPTOM IMPROVEMENT; TREATMENT RESPONSE; PSYCHOTHERAPY; BEHAVIOR; OUTCOMES; INVENTORY AB Objective: Persons admitted for inpatient psychiatric care often present with interpersonal difficulties that disrupt adaptive social relations and complicate the provision of treatment. Whereas domains of psychosocial functioning in this population demonstrate clear growth in response to intervention, the impact of treatment on more complex patterns of interpersonal behavior has been largely overlooked within the existing literature. Interpersonal profiles characteristic of psychiatric inpatients were identified in the current study to determine rates of transition to adaptive functioning following hospitalization. Methods: Personality disturbance was assessed in 513 psychiatric inpatients using the Inventory of Interpersonal Problems. Scores were analyzed within a series of latent profile models to isolate unique interpersonal profiles at admission and at discharge. Longitudinal modeling was then employed to determine rates of transition from dysfunctional to adaptive profiles. Relationships with background characteristics, clinical presentation, and treatment response were explored. Results: Normative, Submissive, and Hostile/Withdrawn profiles emerged at both admission and discharge. Patients in the Normative profile demonstrated relatively moderate symptoms. Submissive and Hostile/Withdrawn profiles were related to known risk factors and elevated psychopathology. Approximately half of the patients who had been identified as Submissive or Hostile/Withdrawn transitioned to the Normative profile by discharge. Transition status evidenced modest associations with background characteristics and clinical presentation. Treatment engagement and reduction of clinical symptoms were strongly associated with adaptive transition. Conclusion: Maladaptive interpersonal profiles characteristic of psychiatric inpatients demonstrated categorical change following inpatient hospitalization. Enhanced therapeutic engagement and overall reductions in psychiatric symptoms appear to increase potential for interpersonal change. C1 [Clapp, Joshua D.] Univ Wyoming, Dept Psychol, Laramie, WY 82071 USA. [Grubaugh, Anouk L.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC USA. [Grubaugh, Anouk L.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Allen, Jon G.; Oldham, John M.; Fowler, J. Christopher; Hardesty, Susan; Frueh, B. Christopher] Menninger Clin, Houston, TX USA. [Allen, Jon G.; Oldham, John M.; Fowler, J. Christopher; Hardesty, Susan] Baylor Coll Med, Houston, TX 77030 USA. [Frueh, B. Christopher] Univ Hawaii, Dept Psychol, Hilo, HI 96720 USA. RP Clapp, JD (reprint author), Univ Wyoming, Dept Psychol, 1000 E Univ Ave, Laramie, WY 82071 USA. EM jclapp@uwyo.edu FU Menninger Foundation; McNair Medical Institute; National Institute of Mental Health; NIMH [T32-MH18869] FX Research was supported in part by funding from the Menninger Foundation, the McNair Medical Institute, and the National Institute of Mental Health. Dr. Clapp was an NIMH-sponsored psychology intern at the Medical University of South Carolina (T32-MH18869) during the development of this project. Dr. Frueh is a McNair Scholar. We are grateful for the assistance of Steve Herrera, MA, and all the research assistants at the Menninger Clinic. NR 44 TC 1 Z9 1 U1 0 U2 3 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0033-2747 J9 PSYCHIATRY JI Psychiatry-Interpers. Biol. Process. PD FAL PY 2014 VL 77 IS 3 BP 247 EP 262 PG 16 WC Psychiatry SC Psychiatry GA AO4WF UT WOS:000341341400007 PM 25162133 ER PT J AU Szafranski, DD Gros, DF Menefee, DS Wanner, JL Norton, PJ AF Szafranski, Derek D. Gros, Daniel F. Menefee, Deleene S. Wanner, Jill L. Norton, Peter J. TI Predictors of Length of Stay Among OEF/OIF/OND Veteran Inpatient PTSD Treatment Noncompleters SO PSYCHIATRY-INTERPERSONAL AND BIOLOGICAL PROCESSES LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; PSYCHOMETRIC PROPERTIES; BEHAVIORAL ACTIVATION; PROLONGED EXPOSURE; AFGHANISTAN; DEPRESSION; THERAPY; DROPOUT; SAMPLE; IRAQ AB High rates of attrition occur in outpatient and inpatient evidence-based treatments (EBTs) targeting newly returning veterans from Operation Enduring Freedom (OEF), Operation Iraqi Freedom (OIF) and Operation New Dawn (OND) with posttraumatic stress disorder (PTSD). Traditionally, research has examined attrition as a dichotomous variable (i.e., noncompleters vs. completers) and focused almost exclusively on outpatient EBTs for PTSD. These studies have provided little information to inpatient psychiatric providers about timing-related predictors of treatment discontinuation. The present study attempted to mend these gaps by examining attrition as a continuous variable and investigated predictors of length of stay (LOS) among 282 OEF/OIF/OND male veterans, 69 of which did not complete the full 25-day intensive, multimodal inpatient PTSD EBT program. At admission, participants completed a series of clinician-rated, biological, and self-report assessments. Linear regression analyses were used to identify predictors of shorter LOS. The results demonstrated that less improvement in symptom reduction, overall functioning, and greater number of drugs used at admission were significant and unique predictors of shorter LOS. Overall, these findings reveal clinically relevant, timing-related predictors of attrition and provide generalizable clinical information to inpatient psychiatric providers. C1 [Szafranski, Derek D.; Norton, Peter J.] Univ Houston, Dept Psychol, Houston, TX 77204 USA. [Szafranski, Derek D.; Menefee, Deleene S.; Wanner, Jill L.] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Gros, Daniel F.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Gros, Daniel F.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC USA. [Menefee, Deleene S.; Wanner, Jill L.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. RP Szafranski, DD (reprint author), Univ Houston, Dept Psychol, 126 Heyne Bldg, Houston, TX 77204 USA. EM ddszafranski@gmail.com NR 38 TC 3 Z9 3 U1 0 U2 6 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 370 SEVENTH AVE, SUITE 1200, NEW YORK, NY 10001-1020 USA SN 0033-2747 J9 PSYCHIATRY JI Psychiatry-Interpers. Biol. Process. PD FAL PY 2014 VL 77 IS 3 BP 263 EP 274 PG 12 WC Psychiatry SC Psychiatry GA AO4WF UT WOS:000341341400008 PM 25162134 ER PT J AU Cicero, DC Martin, EA Becker, TM Docherty, AR Kerns, JG AF Cicero, David C. Martin, Elizabeth A. Becker, Theresa M. Docherty, Anna R. Kerns, John G. TI Correspondence Between Psychometric and Clinical High Risk for Psychosis in an Undergraduate Population SO PSYCHOLOGICAL ASSESSMENT LA English DT Article DE schizotypy; psychometric high risk; clinical high risk; psychotic-like experiences; prodrome ID WISCONSIN SCHIZOTYPY SCALES; PERSISTENT NEGATIVE SYMPTOMS; AGE-OF-ONSET; UNTREATED PSYCHOSIS; PRODROMAL SYNDROMES; SOCIAL ANHEDONIA; SELF-REPORT; AT-RISK; 1ST-EPISODE SCHIZOPHRENIA; INTERRATER RELIABILITY AB Despite the common use of either psychometric or clinical methods for identifying individuals at risk for psychosis, previous research has not examined the correspondence and extent of convergence of these 2 approaches. Undergraduates (n = 160), selected from a larger pool, completed 3 self-report schizotypy scales: the Magical Ideation Scale, the Perceptual Aberration Scale, and the Revised Social Anhedonia Scale. They were administered the Structured Interview for Prodromal Syndromes. First, high correlations were observed for self-report and interview-rated psychotic-like experiences (rs between .48 and .61, p < .001). Second, 77% of individuals who identified as having a risk for psychosis with the self-report measures reported at least 1 clinically meaningful psychotic-like experience on the Structured Interview for Prodromal Syndromes. Third, receiver operating characteristic curve analyses showed that the self-report scales can be used to identify which participants report clinically meaningful positive symptoms. These results suggest that mostly White undergraduate participants who identify as at risk with the psychometric schizotypy approach report clinically meaningful psychotic-like experiences in an interview format and that the schizotypy scales are moderately to strongly correlated with interview-rated psychotic-like experiences. The results of the current research provide a baseline for comparing research between these 2 approaches. C1 [Cicero, David C.] Univ Hawaii Manoa, Dept Psychol, Honolulu, HI 96822 USA. [Martin, Elizabeth A.] VA Pittsburgh Healthcare Syst, Mental Illness Res Educ & Clin Ctr, Pittsburgh, PA USA. [Becker, Theresa M.] Univ Washington, Inst Learning & Brain Sci, Seattle, WA 98195 USA. [Docherty, Anna R.] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Dept Stat Genet, Richmond, VA 23284 USA. [Kerns, John G.] Univ Missouri, Dept Psychol Sci, Columbia, MO 65211 USA. RP Cicero, DC (reprint author), Univ Hawaii Manoa, Dept Psychol, Sakamaki Hall,C400,2530 Dole St, Honolulu, HI 96822 USA. EM dcicero@hawaii.edu RI Cicero, David/E-2046-2016 OI Cicero, David/0000-0002-5666-9139; Docherty, Anna/0000-0001-7139-7007 FU NIMH NIH HHS [F31 MH086190, MH086190, T32 MH020030] NR 85 TC 14 Z9 14 U1 2 U2 9 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1040-3590 EI 1939-134X J9 PSYCHOL ASSESSMENT JI Psychol. Assess. PD SEP PY 2014 VL 26 IS 3 BP 901 EP 915 DI 10.1037/a0036432 PG 15 WC Psychology, Clinical SC Psychology GA AO6WA UT WOS:000341491800020 PM 24708081 ER PT J AU Schacht, JP Anton, RF Randall, P Li, XB Henderson, S Myrick, H AF Schacht, Joseph P. Anton, Raymond F. Randall, PatrickK. Li, Xingbao Henderson, Scott Myrick, Hugh TI Varenicline effects on drinking, craving and neural reward processing among non-treatment-seeking alcohol-dependent individuals SO PSYCHOPHARMACOLOGY LA English DT Article DE Varenicline; Alcohol; fMRI; Neuroimaging; Craving ID PARTIAL AGONIST VARENICLINE; RECEPTOR PARTIAL AGONIST; NICOTINIC ACETYLCHOLINE-RECEPTORS; INDUCED BRAIN ACTIVATION; ETHANOL-CONSUMPTION; DOPAMINE RELEASE; CUE REACTIVITY; DOUBLE-BLIND; NALTREXONE; RESPONSES AB The alpha 4 beta 2 nicotinic acetylcholine receptor partial agonist varenicline has been reported to reduce drinking among both heavy-drinking smokers and primary alcoholics, and this effect may be related to varenicline-mediated reduction of alcohol craving. Among smokers, varenicline has been reported to modulate cigarette cue-elicited brain activation in several reward-related areas. This pilot study tested varenicline's effects on drinking, alcohol craving, and alcohol cue-elicited activation of reward-related brain areas among non-treatment-seeking alcohol-dependent individuals. Thirty-five such individuals (mean age = 30, 57 % male, 76 % heavy drinking days in the past month, 15 smokers) were randomized to either varenicline (titrated to 2 mg) or placebo for 14 days, and were administered an alcohol cue reactivity fMRI task on day 14. A priori regions of interest (ROIs) were bilateral and medial orbitofrontal cortex (OFC), right ventral striatum (VS), and medial prefrontal cortex (mPFC). Despite good medication adherence, varenicline did not reduce heavy drinking days or other drinking parameters. It did, however, increase self-reported control over alcohol-related thoughts and reduced cue-elicited activation bilaterally in the OFC, but not in other brain areas. These data indicate that varenicline reduces alcohol craving and some of the neural substrates of alcohol cue reactivity. However, varenicline effects on drinking mediated by cue-elicited brain activation and craving might be best observed among treatment-seekers motivated to reduce their alcohol consumption. C1 [Schacht, Joseph P.; Anton, Raymond F.; Randall, PatrickK.; Li, Xingbao; Henderson, Scott; Myrick, Hugh] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Myrick, Hugh] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Schacht, JP (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, 171 Ashley Ave, Charleston, SC 29425 USA. EM schacht@musc.edu FU National Institute on Alcohol Abuse and Alcoholism (NIAAA); Charleston Alcohol Research Center [P50 AA010761]; [K99 AA021419]; [K05 AA017435] FX Portions of this work were presented at the 34th Annual Meeting of the Research Society on Alcoholism (June 2011, Atlanta) and the 52nd Annual Meeting of the American College on Neuropsychopharmacology (December 2013, Hollywood, FL). This research was supported by grants from the National Institute on Alcohol Abuse and Alcoholism (NIAAA), including the Charleston Alcohol Research Center (P50 AA010761). NIAAA had no involvement in the study design, in the collection, analysis, and interpretation of data, in the writing of the paper, or in the decision to submit for publication. Drs. Schacht and Anton are supported by K99 AA021419 and K05 AA017435, respectively. NR 45 TC 14 Z9 14 U1 7 U2 14 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 EI 1432-2072 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD SEP PY 2014 VL 231 IS 18 BP 3799 EP 3807 DI 10.1007/s00213-014-3518-1 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AO5GG UT WOS:000341371300013 PM 24647921 ER PT J AU Williams, EC Rubinsky, AD Chavez, LJ Lapham, GT Rittmueller, SE Achtmeyer, CE Bradley, KA AF Williams, Emily C. Rubinsky, Anna D. Chavez, Laura J. Lapham, Gwen T. Rittmueller, Stacey E. Achtmeyer, Carol E. Bradley, Katharine A. TI An early evaluation of implementation of brief intervention for unhealthy alcohol use in the US Veterans Health Administration SO ADDICTION LA English DT Article DE Alcohol; brief intervention; implementation; unhealthy alcohol use; veterans ID RANDOMIZED CONTROLLED-TRIAL; ELECTRONIC CLINICAL REMINDER; PRIMARY-CARE PHYSICIANS; SERVICES-TASK-FORCE; RE-AIM FRAMEWORK; AT-RISK DRINKING; PREVENTIVE-SERVICES; USE DISORDERS; AUDIT-C; COUNSELING INTERVENTIONS AB Aims The US Veterans Health Administration [Veterans Affairs (VA)] used performance measures and electronic clinical reminders to implement brief intervention for unhealthy alcohol use. We evaluated whether documented brief intervention was associated with subsequent changes in drinking during early implementation. Design Observational, retrospective cohort study using secondary clinical and administrative data. Setting Thirty VA facilities. Participants Outpatients who screened positive for unhealthy alcohol use [Alcohol Use Disorders Identification Test Consumption (AUDIT-C >= 5)] in the 6 months after the brief intervention performance measure (n = 22 214) and had follow-up screening 9-15 months later (n = 6210; 28%). Measurements Multi-level logistic regression estimated the adjusted prevalence of resolution of unhealthy alcohol use (follow-up AUDIT-C < 5 with <= 2 point reduction) for patients with and without documented brief intervention (documented advice to reduce or abstain from drinking). Findings Among 6210 patients with follow-up alcohol screening, 1751 (28%) had brief intervention and 2922 (47%) resolved unhealthy alcohol use at follow-up. Patients with documented brief intervention were older and more likely to have other substance use disorders, mental health conditions, poor health and more severe unhealthy alcohol use than those without (P-values < 0.05). Adjusted prevalences of resolution were 47% [95% confidence interval (CI) = 42-52%] and 48% (95% CI = 42-54%) for patients with and without documented brief intervention, respectively (P = 0.50). Conclusions During early implementation of brief intervention in the US Veterans Health Administration, documented brief intervention was not associated with subsequent changes in drinking among outpatients with unhealthy alcohol use and repeat alcohol screening. C1 [Williams, Emily C.; Rubinsky, Anna D.; Chavez, Laura J.; Lapham, Gwen T.; Rittmueller, Stacey E.; Achtmeyer, Carol E.; Bradley, Katharine A.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev HSR&D, Seattle, WA 98101 USA. [Williams, Emily C.; Chavez, Laura J.; Bradley, Katharine A.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Lapham, Gwen T.; Bradley, Katharine A.] Grp Hlth Res Inst, Seattle, WA USA. [Achtmeyer, Carol E.] VA Puget Sound Hlth Care Syst, Primary & Specialty Med Care Serv, Seattle, WA 98101 USA. [Bradley, Katharine A.] Univ Washington, Dept Med, Seattle, WA USA. RP Williams, EC (reprint author), VA Puget Sound Hlth Care Syst, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM emily.williams3@va.gov FU US Department of Veterans Affairs (VA) Quality Enhancement Research Initiative [RRP 11-268]; VA Health Services Research and Development [IIR 08-314, CDA 12-276]; National Institute of Mental Health [R25 MH080916-01A2]; Department of Veterans Affairs, Health Services Research and Development Service, Quality Enhancement Research Initiative (QUERI); VA Center of Excellence for Substance Abuse Treatment and Education (CESATE) FX This study was supported by funding from the US Department of Veterans Affairs (VA) Quality Enhancement Research Initiative (RRP 11-268; Principle Investigator E.C.W.) and VA Health Services Research and Development (IIR 08-314; Principle Investigator K.A.B.). E.C.W. is supported by El Career Development Award from VA Health Services Research and Development (CDA 12-276) and is an investigator with the Implementation Research Institute (IRI) at the George Warren Brown School of Social Work at Washington University in St Louis. IRI is supported through an award from the National Institute of Mental Health (R25 MH080916-01A2) and the Department of Veterans Affairs, Health Services Research and Development Service, Quality Enhancement Research Initiative (QUERI). K.A.B. and A.D.R. were supported by the VA Center of Excellence for Substance Abuse Treatment and Education (CESATE) for their work on this project. The views expressed in this paper are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs, the University of Washington or Group Health Research Institute. NR 91 TC 13 Z9 13 U1 4 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0965-2140 EI 1360-0443 J9 ADDICTION JI Addiction PD SEP PY 2014 VL 109 IS 9 BP 1472 EP 1481 DI 10.1111/add.12600 PG 10 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA AN4OE UT WOS:000340566600015 PM 24773590 ER PT J AU Khan, NH Almukhtar, RM AF Khan, N. H. Almukhtar, R. M. TI Editorial: early corticosteroids in ulcerative colitis - authors' reply SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material ID REMISSION; DISEASE C1 [Khan, N. H.; Almukhtar, R. M.] Southeast Louisiana Vet Hlth Care Syst, Gastroenterol Sect, Dept Internal Med, New Orleans, LA 70112 USA. [Khan, N. H.] Univ Penn, Gastroenterol Sect, Perelman Sch Med, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. [Almukhtar, R. M.] Tulane Univ, Hlth Sci Ctr, Dept Internal Med, Sect Gastroenterol & Hepatol, New Orleans, LA 70118 USA. [Almukhtar, R. M.] Louisiana State Univ, Hlth Sci Ctr, Dept Epidemiol, New Orleans, LA USA. RP Khan, NH (reprint author), Southeast Louisiana Vet Hlth Care Syst, Gastroenterol Sect, Dept Internal Med, New Orleans, LA 70112 USA. EM nabeel.khan@va.gov NR 7 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0269-2813 EI 1365-2036 J9 ALIMENT PHARM THER JI Aliment. Pharmacol. Ther. PD SEP PY 2014 VL 40 IS 6 BP 728 EP 728 DI 10.1111/apt.12898 PG 1 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA AN4LS UT WOS:000340559900015 PM 25123385 ER PT J AU Liu, YN Yuan, JZ Tan, TY Jia, WZ Lugea, A Mareninova, O Waldron, RT Pandol, SJ AF Liu, Yannan Yuan, Jingzhen Tan, Tanya Jia, Wenzhuo Lugea, Aurelia Mareninova, Olga Waldron, Richard T. Pandol, Stephen J. TI Genetic inhibition of protein kinase C epsilon attenuates necrosis in experimental pancreatitis SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE apoptosis; necrosis; inhibitors of apoptotic proteins (IAPs); Bcl-2 family proteins; receptor-interacting protein kinase (RIP) ID NF-KAPPA-B; RECEPTOR-INTERACTING PROTEIN; MITOCHONDRIAL-MEMBRANE PERMEABILIZATION; CELL-DEATH; ACINAR-CELLS; PROGRAMMED NECROSIS; ZYMOGEN ACTIVATION; INDUCED APOPTOSIS; TNF-ALPHA; BCL-2 AB Understanding the regulation of death pathways, necrosis and apoptosis, in pancreatitis is important for developing therapies directed to the molecular pathogenesis of the disease. Protein kinase C epsilon (PKC epsilon) has been previously shown to regulate inflammatory responses and zymogen activation in pancreatitis. Furthermore, we demonstrated that ethanol specifically activated PKCe in pancreatic acinar cells and that PKCe mediated the sensitizing effects of ethanol on inflammatory response in pancreatitis. Here we investigated the role of PKCe in the regulation of death pathways in pancreatitis. We found that genetic deletion of PKCe resulted in decreased necrosis and severity in the in vivo cerulein-induced pancreatitis and that inhibition of PKCe protected the acinar cells from CCK-8 hyperstimulation-induced necrosis and ATP reduction. These findings were associated with upregulation of mitochondrial Bak and Bcl-2/Bcl-xL, proapoptotic and prosurvival members in the Bcl-2 family, respectively, as well as increased mitochondrial cytochrome c release, caspase activation, and apoptosis in pancreatitis in PKCe knockout mice. We further confirmed that cerulein pancreatitis induced a dramatic mitochondrial translocation of PKCe, suggesting that PKCe regulated necrosis in pancreatitis via mechanisms involving mitochondria. Finally, we showed that PKCe deletion downregulated inhibitors of apoptosis proteins, c-IAP2, survivin, and c-FLIPs while promoting cleavage/inactivation of receptor-interacting protein kinase (RIP). Taken together, our findings provide evidence that PKCe activation during pancreatitis promotes necrosis through mechanisms involving mitochondrial proapoptotic and prosurvival Bcl-2 family proteins and upregulation of nonmitochondrial pathways that inhibit caspase activation and RIP cleavage/inactivation. Thus PKCe is a potential target for prevention and/or treatment of acute pancreatitis. C1 [Liu, Yannan; Yuan, Jingzhen; Tan, Tanya; Jia, Wenzhuo; Lugea, Aurelia; Mareninova, Olga; Waldron, Richard T.; Pandol, Stephen J.] Univ Calif Los Angeles, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Liu, Yannan; Yuan, Jingzhen; Tan, Tanya; Jia, Wenzhuo; Lugea, Aurelia; Mareninova, Olga; Waldron, Richard T.; Pandol, Stephen J.] South Calif Res Ctr Alcohol Liver & Pancreat Dis, Los Angeles, CA USA. [Liu, Yannan; Jia, Wenzhuo] Beijing Hosp, Beijing, Peoples R China. [Tan, Tanya] St Georges Univ, Sch Med, St Georges, Grenada. [Lugea, Aurelia; Waldron, Richard T.; Pandol, Stephen J.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. RP Yuan, JZ (reprint author), UCLA VA Greater Los Angeles Healthcare Syst, West Los Angeles VA Healthcare Ctr, South Calif Res Ctr Alcohol Liver & Pancreat Dis, 11301 Wilshire Blvd,Bldg 258,Rm 340, Los Angeles, CA 90073 USA. EM jzyuan@ucla.edu FU Southern California Research Center for Alcoholic Liver and Pancreatic Diseases (NIH) [P50-A11999]; UCLA Center of Excellence in Pancreatic Diseases (NIH) [1P01AT0003960-01]; Department of Veterans Affairs Merits Grant; Southern California Research Center for Liver and Pancreatic Diseases FX This study was supported by the Southern California Research Center for Alcoholic Liver and Pancreatic Diseases (NIH Grant P50-A11999); UCLA Center of Excellence in Pancreatic Diseases (NIH Grant 1P01AT0003960-01); the Department of Veterans Affairs Merits Grant; and Lee Summer Student Research Award from Southern California Research Center for Liver and Pancreatic Diseases (to T. Tan). NR 57 TC 5 Z9 5 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 EI 1522-1547 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD SEP 1 PY 2014 VL 307 IS 5 BP G550 EP G563 DI 10.1152/ajpgi.00432.2013 PG 14 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA AO1SP UT WOS:000341094700006 PM 25035113 ER PT J AU Yarbrough, WM Baicu, C Mukherjee, R Van Laer, A Rivers, WT McKinney, RA Prescott, CB Stroud, RE Freels, PD Zellars, KN Zile, MR Spinale, FG AF Yarbrough, William M. Baicu, Catalin Mukherjee, Rupak Van Laer, An Rivers, William T. McKinney, Richard A. Prescott, Corey B. Stroud, Robert E. Freels, Parker D. Zellars, Kia N. Zile, Michael R. Spinale, Francis G. TI Cardiac-restricted overexpression or deletion of tissue inhibitor of matrix metalloproteinase-4: differential effects on left ventricular structure and function following pressure overload-induced hypertrophy SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE remodeling; tissue inhibitors of metalloproteinase; pressure-overload hypertrophy ID AORTIC-VALVE REPLACEMENT; MYOCARDIAL FIBROSIS; HEART-FAILURE; MICE; DISEASE; REGRESSION; INDUCTION; DYSFUNCTION; INFARCTION; EXPRESSION AB Historically, the tissue inhibitors of matrix metalloproteinases (TIMPs) were considered monochromatic in function. However, differential TIMP profiles more recently observed with left ventricular (LV) dysfunction and matrix remodeling suggest more diverse biological roles for individual TIMPs. This study tested the hypothesis that cardiac-specific overexpression (TIMP-4OE) or deletion (knockout; TIMP-4KO) would differentially affect LV function and structure following pressure overload (LVPO). LVPO (transverse aortic constriction) was induced in mice (3.5 +/- 0.1 mo of age, equal sex distribution) with TIMP-4OE (n = 38), TIMP4-KO (n = 24), as well as age/strain-matched wild type (WT, n = 25), whereby indexes of LV remodeling and function such as LV mass and ejection fraction (LVEF) were determined at 28 days following LVPO. Following LVPO, both early (7 days) and late (28 days) survival was similar to 25% lower in the TIMP-4KO group (P < 0.05). While LVPO increased LV mass in all groups, the relative hypertrophic response was attenuated with TIMP-4OE. With LVPO, LVEF was similar between WT and TIMP-4KO (48 +/- 2% and 45 +/- 3%, respectively) but was higher with TIMP-4OE (57 +/- 2%, P < 0.05). With LVPO, LV myocardial collagen expression (type I, III) increased by threefold in all groups (P < 0.05), but surprisingly this response was most robust in the TIMP-4KO group. These unique findings suggest that increased myocardial TIMP-4 in the context of a LVPO stimulus may actually provide protective effects with respect to survival, LV function, and extracellular matrix (ECM) remodeling. These findings challenge the canonical belief that increased levels of specific myocardial TIMPs, such as TIMP-4 in and of themselves, contribute to adverse ECM accumulation following a pathological stimulus, such as LVPO. C1 [Freels, Parker D.; Zellars, Kia N.; Spinale, Francis G.] Univ S Carolina, Sch Med, WJB Dorn Vet Affairs Med Ctr, Columbia, SC USA. [Baicu, Catalin; Mukherjee, Rupak; Van Laer, An; Rivers, William T.; McKinney, Richard A.; Prescott, Corey B.; Stroud, Robert E.; Zile, Michael R.] Med Univ S Carolina, Div Cardiothorac Surg & Adult Cardiol, Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. [Yarbrough, William M.] Sisters Char Providence Hosp, Columbia, SC USA. RP Spinale, FG (reprint author), Univ S Carolina, Sch Med, Cardiovasc Translat Res Ctr, CBA, 6439 Garners Ferry Rd, Columbia, SC 29208 USA. EM cvctrc@uscmed.sc.edu FU National Institutes of Health [HL-11090, HL-089944]; Veterans Affairs Health Administration; Research Service of the Department of Veterans Affairs FX This work was supported by National Institutes of Health Grants HL-11090 and HL-089944 and a Merit Award from the Veterans Affairs Health Administration. F. G. Spinale and M. R. Zile are supported by the Research Service of the Department of Veterans Affairs. NR 37 TC 3 Z9 3 U1 0 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 EI 1522-1539 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD SEP 1 PY 2014 VL 307 IS 5 BP H752 EP H761 DI 10.1152/ajpheart.00063.2014 PG 10 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA AO1NZ UT WOS:000341081200013 PM 24993046 ER PT J AU Gooz, MB Maldonado, EN Dang, YJ Amria, MY Higashiyama, S Abboud, HE Lemasters, JJ Bell, PD AF Gooz, Monika Beck Maldonado, Eduardo N. Dang, Yujing Amria, May Y. Higashiyama, Shigeki Abboud, Hanna E. Lemasters, John J. Bell, P. Darwin TI ADAM17 promotes proliferation of collecting duct kidney epithelial cells through ERK activation and increased glycolysis in polycystic kidney disease SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE ADAM17; glycolysis; ERK; cell proliferation; polycystic kidney disease (PKD) ID CONVERTING-ENZYME TACE; GROWTH; ALPHA; EGFR; RECEPTORS; POLARIS; CANCER; CILIA; MICE AB Polycystic kidney disease (PKD) is a common genetic disorder leading to cyst formation in the kidneys and other organs that ultimately results in kidney failure and death. Currently, there is no therapy for slowing down or stopping the progression of PKD. In this study, we identified the disintegrin metalloenzyme 17 (ADAM17) as a key regulator of cell proliferation in kidney tissues of conditional knockout Ift88(-/-) mice and collecting duct epithelial cells from Ift88(orpk) mice, animal models of autosomal recessive polycystic kidney disease (ARPKD). Using Western blotting, an enzyme activity assay, and a growth factor-shedding assay in the presence or absence of the specific ADAM17 inhibitor TMI-005, we show that increased expression and activation of ADAM17 in the cystic kidney and in collecting duct epithelial cells originating from the Ift88(orpk) mice (designated as PKD cells) lead to constitutive shedding of several growth factors, including heparin-binding EGF-like growth factor (HB-EGF), amphiregulin, and transforming growth factor-alpha (TGF-alpha). Increased growth factor shedding induces activation of the EGFR/MAPK/ERK pathway and maintains higher cell proliferation rate in PKD cells compared with control cells. PKD cells also displayed increased lactate formation and extracellular acidification indicative of aerobic glycolysis (Warburg effect), which was blocked by ADAM17 inhibition. We propose that ADAM17 is a key promoter of cellular proliferation in PKD cells by activating the EGFR/ERK axis and a proproliferative glycolytic phenotype. C1 [Gooz, Monika Beck; Dang, Yujing; Amria, May Y.; Bell, P. Darwin] Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA. [Maldonado, Eduardo N.; Lemasters, John J.] Med Univ S Carolina, Dept Drug Discovery & Pharmaceut Sci, Charleston, SC 29425 USA. [Higashiyama, Shigeki] Ehime Univ, Dept Biochem & Mol Genet, Matsuyama, Ehime 790, Japan. [Abboud, Hanna E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Nephrol, San Antonio, TX 78229 USA. [Lemasters, John J.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Bell, P. Darwin] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Gooz, MB (reprint author), Med Univ S Carolina, Dept Med, Div Nephrol, 96 Jonathan Lucas St,CSB829,MS 629, Charleston, SC 29425 USA. EM beckm@musc.edu FU National Institutes of Health (NIH) [NIDDK P30 DK074038, R01 DK32032]; Veterans Administration (Ralph H. Johnson VA Medical Center); Dialysis Clinic, Inc. FX This work was supported by grants from the National Institutes of Health (NIH NIDDK P30 DK074038 and R01 DK32032), a Merit Grant from the Veterans Administration (Ralph H. Johnson VA Medical Center), and grants from the Dialysis Clinic, Inc. NR 26 TC 7 Z9 7 U1 0 U2 8 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X EI 1522-1466 J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD SEP 1 PY 2014 VL 307 IS 5 BP F551 EP F559 DI 10.1152/ajprenal.00218.2014 PG 9 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA AO1QA UT WOS:000341086900007 ER PT J AU Siroky, BJ Yin, H Dixon, BP Reichert, RJ Hellmann, AR Ramkumar, T Tsuchihashi, Z Bunni, M Dillon, J Bell, PD Sampson, JR Bissler, JJ AF Siroky, Brian J. Yin, Hong Dixon, Bradley P. Reichert, Ryan J. Hellmann, Anna R. Ramkumar, Thiruvamoor Tsuchihashi, Zenta Bunni, Marlene Dillon, Joshua Bell, P. Darwin Sampson, Julian R. Bissler, John J. TI Evidence for pericyte origin of TSC-associated renal angiomyolipomas and implications for angiotensin receptor inhibition therapy SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE tuberous sclerosis complex; angiomyolipoma; angiotensin II type 1 receptor; pericyte; perivascular epithelioid cell tumor; mammalian target of rapamycin ID TUBEROUS SCLEROSIS COMPLEX; GROWTH-FACTOR; ER STRESS; CELLS; LYMPHANGIOLEIOMYOMATOSIS; EXPRESSION; NEOPLASMS; PROTEIN; KIDNEY; MICE AB Nearly all patients with tuberous sclerosis complex (TSC) develop renal angiomyolipomas, although the tumor cell of origin is unknown. We observed decreased renal angiomyolipoma development in patients with TSC2- polycystic kidney disease 1 deletion syndrome and hypertension that were treated from an early age with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers compared with patients who did not receive this therapy. TSC-associated renal angiomyolipomas expressed ANG II type 1 receptors, platelet-derived growth factor receptor-beta, desmin, alpha-smooth muscle actin, and VEGF receptor 2 but did not express the adipocyte marker S100 or the endothelial marker CD31. Sera of TSC patients exhibited increased vascular mural cell-secreted peptides, such as VEGF-A, VEGF-D, soluble VEGF receptor 2, and collagen type IV. These findings suggest that angiomyolipomas may arise from renal pericytes. ANG II treatment of angiomyolipoma cells in vitro resulted in an exaggerated intracellular Ca2+ response and increased proliferation, which were blocked by the ANG II type 2 receptor antagonist valsartan. Blockade of ANG II signaling may have preventative therapeutic potential for angiomyolipomas. C1 [Siroky, Brian J.; Dixon, Bradley P.; Reichert, Ryan J.; Hellmann, Anna R.] Cincinnati Childrens Hosp Med Ctr, Div Nephrol & Hypertens, Cincinnati, OH 45229 USA. [Yin, Hong] Cincinnati Childrens Hosp Med Ctr, Div Pathol, Cincinnati, OH 45229 USA. [Ramkumar, Thiruvamoor] Novartis Inst Biomed Res, Cambridge, MA USA. [Tsuchihashi, Zenta] Daiichi Sankyo, Parsippany, NJ USA. [Bunni, Marlene; Dillon, Joshua; Bell, P. Darwin] Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA. [Tsuchihashi, Zenta] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Hellmann, Anna R.; Sampson, Julian R.] Cardiff Univ, Sch Med, Inst Med Genet, Cardiff CF10 3AX, S Glam, Wales. [Bissler, John J.] Univ Tennessee, Le Bonheur Childrens Hosp, Coll Med, Tuberous Sclerosis Complex Ctr Excellence, Memphis, TN USA. RP Bissler, JJ (reprint author), Le Bonheur Childrens Hosp, Div Pediat, 848 Adams Ave, Memphis, TN 38138 USA. EM jbissler@uthsc.edu FU Rothberg Courage Award from Tuberous Sclerosis Alliance; Tuberous Sclerosis Alliance; Wales Gene Park FX This work was supported by a Rothberg Courage Award from the Tuberous Sclerosis Alliance (to J. J. Bissler), a Fellowship Award from the Tuberous Sclerosis Alliance (to B. J. Siroky), and the Wales Gene Park (to J. R. Sampson). NR 56 TC 9 Z9 9 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X EI 1522-1466 J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD SEP 1 PY 2014 VL 307 IS 5 BP F560 EP F570 DI 10.1152/ajprenal.00569.2013 PG 11 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA AO1QA UT WOS:000341086900008 PM 24920756 ER PT J AU Tregellas, JR AF Tregellas, Jason R. TI Right Versus Left Hippocampal Activity as a Biomarker in Schizophrenia Response SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Letter C1 [Tregellas, Jason R.] Univ Colorado, Sch Med, Denver VA Med Ctr, Res Serv, Aurora, CO 80204 USA. [Tregellas, Jason R.] Univ Colorado, Sch Med, Dept Psychiat, Aurora, CO USA. RP Tregellas, JR (reprint author), Univ Colorado, Sch Med, Denver VA Med Ctr, Res Serv, Aurora, CO 80204 USA. RI Tregellas, Jason/J-3637-2015 NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X EI 1535-7228 J9 AM J PSYCHIAT JI Am. J. Psychiat. PD SEP PY 2014 VL 171 IS 9 BP 1001 EP 1001 DI 10.1176/appi.ajp.2014.14050687r PG 1 WC Psychiatry SC Psychiatry GA AO1MU UT WOS:000341077000020 PM 25178756 ER PT J AU Weisbord, SD Mor, MK Sevick, MA Shields, AM Roffman, BL Palevsky, PM Arnold, RM Green, JA Fine, MJ AF Weisbord, Steven D. Mor, Maria K. Sevick, Mary Ann Shields, Anne Marie Roffman, Bruce L. Palevsky, Paul M. Arnold, Robert M. Green, Jamie A. Fine, Michael J. TI Associations of Depressive Symptoms and Pain with Dialysis Adherence, Health Resource Utilization, and Mortality in Patients Receiving Chronic Hemodialysis SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID STAGE RENAL-DISEASE; QUALITY-OF-LIFE; MANAGEMENT STRATEGIES; HOSPITALIZATION; PREVALENCE; SEVERITY; TERM; METAANALYSIS; VALIDATION; FLUOXETINE AB Background and objectives Depressive symptoms and pain are common in patients receiving chronic hemodialysis, yet their effect on dialysis adherence, health resource utilization, and mortality is not fully understood. This study sought to characterize the longitudinal associations of these symptoms with dialysis adherence, emergency department (ED) visits, hospitalizations, and mortality. Design, setting, participants, & measurements As part of a trial comparing symptom management strategies in patients receiving chronic hemodialysis, this study prospectively assessed depressive symptoms using the Patient Health Questionnaire 9, and pain using the Short-Form McGill Pain Questionnaire, monthly between 2009 and 2011. This study used negative binomial, Poisson, and proportional hazards regression to analyze the longitudinal associations of depressive symptoms and pain, scaled based on 5-point increments in symptom scores, with missed and abbreviated hemodialysis treatments, ED visits, hospitalizations, and mortality, respectively. Results Among 286 patients, moderate-to-severe depressive symptoms were identified on 788 of 4452 (18%) assessments and pain was reported on 3537 of 4459 (79%) assessments. Depressive symptoms were independently associated with missed (incident rate ratio [IRR], 1.21; 95% confidence interval [95% CI], 1.10 to 1.33) and abbreviated (IRR, 1.08; 95% CI, 1.03 to 1.14) hemodialysis treatments, ED visits (IRR, 1.24; 95% CI, 1.12 to 1.37), hospitalizations (IRR, 1.19; 95% CI, 1.10 to 1.30), and mortality (IRR, 1.40; 95% CI, 1.11 to 1.77). Pain was independently associated with abbreviated hemodialysis treatments (IRR, 1.03; 95% CI, 1.01 to 1.06) and hospitalizations (IRR, 1.05; 95% CI, 1.00 to 1.10). Severe pain was independently associated with abbreviated hemodialysis treatments (IRR, 1.16; 95% CI, 1.06 to 1.28), ED visits (IRR, 1.58; 95% CI, 1.28 to 1.94), and hospitalizations (IRR, 1.22; 95% CI, 1.03 to 1.45), but not mortality (hazard ratio, 1.71; 95% CI, 0.81 to 2.96). Conclusions Depressive symptoms and pain are independently associated with dialysis nonadherence and health services utilization. Depressive symptoms are also associated with mortality. Interventions to alleviate these symptoms have the potential to reduce costs and improve patient-centered outcomes. C1 [Weisbord, Steven D.; Palevsky, Paul M.] Vet Affairs Pittsburgh Healthcare Syst, Renal Sect, Med Serv Line, Pittsburgh, PA 15240 USA. [Weisbord, Steven D.; Mor, Maria K.; Shields, Anne Marie; Fine, Michael J.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. [Weisbord, Steven D.; Palevsky, Paul M.] Univ Pittsburgh, Sch Med, Dept Med, Renal Electrolyte Div, Pittsburgh, PA 15213 USA. [Arnold, Robert M.; Fine, Michael J.] Univ Pittsburgh, Sch Med, Div Gen Internal Med, Pittsburgh, PA USA. [Arnold, Robert M.] Univ Pittsburgh, Sch Med, Div Palliat Care, Pittsburgh, PA USA. [Mor, Maria K.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. [Sevick, Mary Ann; Roffman, Bruce L.] NYU, Sch Med, Dept Populat Hlth, New York, NY USA. [Green, Jamie A.] Geisinger Med Ctr, Dept Nephrol, Danville, PA 17822 USA. RP Weisbord, SD (reprint author), Vet Affairs Pittsburgh Healthcare Syst, Renal Sect, Med Serv Line, 7E Room 120,111F-U, Pittsburgh, PA 15240 USA. EM weisbordsd@upmc.edu OI Palevsky, Paul/0000-0002-7334-5400 FU US Department of Veterans Affairs Health Services Research and Development Merit Review award [IIR 07-190] FX This work was supported by a US Department of Veterans Affairs Health Services Research and Development Merit Review award (IIR 07-190). The opinions expressed in this article are those of the authors and do not represent the views of the US Department of Veterans Affairs or the US Government. NR 43 TC 13 Z9 14 U1 2 U2 10 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 EI 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD SEP PY 2014 VL 9 IS 9 BP 1594 EP 1602 DI 10.2215/CJN.00220114 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA AO3ZE UT WOS:000341275200015 PM 25081360 ER PT J AU Berns, JS Ellison, DH Linas, SL Rosner, MH AF Berns, Jeffrey S. Ellison, David H. Linas, Stuart L. Rosner, Mitchell H. TI Training the Next Generation's Nephrology Workforce SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID LUPUS NEPHRITIS; NEXT-GENERATION; KIDNEY-DISEASE; RHEUMATOLOGISTS; COMPETENCE; FELLOWS; REQUIREMENTS; ULTRASOUND; PROGRAMS AB The subspecialty of nephrology faces several critical challenges, including declining interest among medical students and internal medicine residents and worrisome declines in the number of applicants for nephrology fellowships. There is an urgent need to more clearly define the subspecialty and its scope of practice, reinvigorate meaningful research training and activities among trainees, and ensure that fellows who complete training and enter the practice of nephrology are experts in the broad scope of nephrology. This need requires a critical look at fellowship training programs and training requirements. A new workforce analysis is also needed that is not focused on primarily meeting estimated future clinical needs but rather, ensuring that there is alignment of supply and demand for nephrology trainees, which will ensure that those entering nephrology fellowships are highly qualified and capable of becoming outstanding nephrologists and that there are desirable employment opportunities for them when they complete their training. C1 [Berns, Jeffrey S.] Univ Penn, Hosp Univ Penn, Renal Electrolyte & Hypertens Div, Perelman Sch Med, Philadelphia, PA 19104 USA. [Ellison, David H.] Oregon Hlth & Sci Univ, Div Nephrol, Portland, OR 97201 USA. [Ellison, David H.] Portland VA Med Ctr, Portland, OR USA. [Linas, Stuart L.] Univ Colorado, Div Nephrol, Denver Hlth Med Ctr, Denver, CO 80202 USA. [Rosner, Mitchell H.] Univ Virginia, Sch Med, Div Nephrol, Charlottesville, VA 22908 USA. RP Berns, JS (reprint author), Hosp Univ Penn, 3400 Spruce St,1 Founders Pavil, Philadelphia, PA 19104 USA. EM bernsj@uphs.upenn.edu NR 35 TC 6 Z9 6 U1 1 U2 2 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 EI 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD SEP PY 2014 VL 9 IS 9 BP 1639 EP 1644 DI 10.2215/CJN.00560114 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA AO3ZE UT WOS:000341275200020 PM 24970877 ER PT J AU Tafti, BA Mandelkern, M Berenji, GR AF Tafti, Bashir Akhavan Mandelkern, Mark Berenji, Gholam Reza TI Subclinical Seizures as a Pitfall in F-18-FDG PET Imaging of Temporal Lobe Epilepsy SO CLINICAL NUCLEAR MEDICINE LA English DT Editorial Material DE PET; epilepsy; subclinical seizure; MRI; electroencephalography ID POSITRON-EMISSION-TOMOGRAPHY; STATUS EPILEPTICUS C1 [Tafti, Bashir Akhavan; Mandelkern, Mark; Berenji, Gholam Reza] Vet Adm Greater Los Angeles Hlth Care Syst, Dept Nucl Med, Los Angeles, CA 90073 USA. RP Berenji, GR (reprint author), Vet Adm Greater Los Angeles Hlth Care Syst, Dept Nucl Med, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM gholam.berenji@va.gov NR 8 TC 3 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-9762 EI 1536-0229 J9 CLIN NUCL MED JI Clin. Nucl. Med. PD SEP PY 2014 VL 39 IS 9 BP 819 EP 821 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AN6SU UT WOS:000340728300023 PM 24873791 ER PT J AU Arney, J Street, RL Naik, AD AF Arney, Jennifer Street, Richard L., Jr. Naik, Aanand D. TI Factors Shaping Physicians' Willingness to Accommodate Medication Requests SO EVALUATION & THE HEALTH PROFESSIONS LA English DT Article DE patient-provider relationships; physician behavior; prescribing patterns/practices; patient-centered care; primary care ID GENERAL-PRACTITIONERS; DECISION-MAKING; COMMUNICATION; PRESCRIBE AB Medical decisions, including physicians' prescribing behaviors, are shaped by a complex interplay of clinical and nonclinical factors. We aim to determine how physician, patient, and relationship characteristics influence physicians' decisions to accommodate brand-name prescription drug requests. We applied multivariate logistic regression to data from the Attitudinal and Behavioral Effects of Direct-to-Consumer Promotion of Prescription Drugs physician survey. We used a national probability sample of 500 primary care and specialty physicians reporting on a clinical encounter that involved a prescription drug request. Independent variables include physician's assessment of the patient's understanding of risks and benefits of a requested medication, whether the patient had the condition the drug treats, duration of the clinical relationship, and physician's age, area of practice, years of experience, and gender. These variables were used to predict whether the physician prescribed the requested drug. Physicians were more willing to accommodate requests when they believed that patients had a clear understanding of the drug's risks and when patients had the condition the drug treats. Primary care practitioners, compared to specialists, had higher odds of prescribing a requested drug. We conclude that clinical and communicative factors shape physicians' decisions to prescribe requested brand-name drugs. Findings offer insight into the influence that direct-to-consumer advertising can have in medical encounters, and may guide efforts to enhance physician-patient communication and shared decision making. C1 [Arney, Jennifer] Univ Houston Clear Lake, Dept Sociol, Houston, TX 77058 USA. [Arney, Jennifer; Street, Richard L., Jr.; Naik, Aanand D.] Michael E DeBakey Dept Vet Affairs Med Ctr, Hlth Serv Res & Dev Ctr Excellence, Houston, TX USA. [Arney, Jennifer; Street, Richard L., Jr.; Naik, Aanand D.] Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA. [Street, Richard L., Jr.] Texas A&M Univ, Dept Commun, College Stn, TX USA. RP Arney, J (reprint author), Univ Houston Clear Lake, Dept Sociol, 2700 Bay Area Blvd, Houston, TX 77058 USA. EM Arney@bcm.edu FU Division of Graduate Studies at Arizona State University; National Science Foundation's Division of Social, Behavioral, and Economic Sciences [0828582]; Houston VA HSR&D Center of Excellence [HFP90-020]; National Institute on Aging [K23AG027144] FX The author(s) disclosed receipt of the following financial support for the research, authorship and/or publication of this article: This work was supported by the Division of Graduate Studies at Arizona State University and by the National Science Foundation's Division of Social, Behavioral, and Economic Sciences (Award ID 0828582). Additional support was provided by the Houston VA HSR&D Center of Excellence (HFP90-020), and the National Institute on Aging (K23AG027144). NR 24 TC 2 Z9 2 U1 0 U2 8 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0163-2787 EI 1552-3918 J9 EVAL HEALTH PROF JI Eval. Health Prof. PD SEP PY 2014 VL 37 IS 3 BP 349 EP 365 DI 10.1177/0163278712468756 PG 17 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA AN6PE UT WOS:000340716700004 PM 23232050 ER PT J AU Copeland, LA Sako, EY Zeber, JE Pugh, MJ Wang, CP MacCarthy, AA Restrepo, MI Mortensen, EM Lawrence, VA AF Copeland, Laurel A. Sako, Edward Y. Zeber, John E. Pugh, Mary Jo Wang, Chen-Pin MacCarthy, Andrea A. Restrepo, Marcos I. Mortensen, Eric M. Lawrence, Valerie A. TI Mortality after cardiac or vascular operations by preexisting serious mental illness status in the Veterans Health Administration SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE Cardiovascular surgical procedures; Comorbidity; Mental disorders; Mortality; Veterans ID POSTTRAUMATIC-STRESS-DISORDER; CARDIOVASCULAR-DISEASE; SCHIZOPHRENIC-PATIENTS; MAJOR DEPRESSION; BIPOLAR DISORDER; NATIONAL SAMPLE; CARE; AFFAIRS; PREVALENCE; ANESTHESIA AB Objective: To estimate 1-year mortality risk associated with preoperative serious mental illness (SMI) as defined by the Veterans Health Administration (schizophrenia, bipolar disorder, posttraumatic stress disorder [PTSD], major depression) following nonambulatory cardiac or vascular surgical procedures compared to patients without SMI. Cardiac/vascular operations were selected because patients with SMI are known to be at elevated risk of cardiovascular disease. Method: Retrospective analysis of system-wide data from electronic medical records of patients undergoing nonambulatory surgery (inpatient or day-of-surgery admission) October 2005-September 2009 with 1-year follow-up (N=55,864; 99% male; <30 days of postoperative hospitalization). Death was hypothesized to be more common among patients with preoperative SMI. Results: One in nine patients had SMI, mostly PTSD (6%). One-year mortality varied by procedure type and SMI status. Patients had vascular operations (64%; 23% died), coronary artery bypass graft (26%; 10% died) or other cardiac operations (11%; 15%-18% died). Fourteen percent of patients with PTSD died, 20% without SMI and 24% with schizophrenia, with other groups intermediate. In multivariable stratified models, SMI was associated with increased mortality only for patients with bipolar disorder following cardiac operations. Bipolar disorder and PTSD were negatively associated with death following vascular operations. Conclusions: SMI is not consistently associated with postoperative mortality in covariate-adjusted analyses. Published by Elsevier Inc. C1 [Copeland, Laurel A.; Zeber, John E.] Baylor Scott & White Hlth, Ctr Appl Hlth Res, Cent Texas Vet Hlth Care Syst, Temple, TX USA. [Copeland, Laurel A.; Zeber, John E.] Texas A&M Hlth Sci Ctr, Dept Med, Bryan Coll Stn, TX USA. [Copeland, Laurel A.; Zeber, John E.] Sch Rural Publ Hlth, Bryan Coll Stn, TX USA. [Sako, Edward Y.; Pugh, Mary Jo; Wang, Chen-Pin; MacCarthy, Andrea A.; Restrepo, Marcos I.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Sako, Edward Y.; Pugh, Mary Jo; Wang, Chen-Pin; Restrepo, Marcos I.; Lawrence, Valerie A.] UT Hlth Sci Ctr San Antonio, San Antonio, TX USA. [Mortensen, Eric M.] VA North Texas Hlth Care Syst, Dallas, TX USA. [Mortensen, Eric M.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. RP Copeland, LA (reprint author), Scott & White Healthcare, Ctr Appl Hlth Res, Cent Texas Vet Hlth Care Syst, 2102 Birdcreek Dr, Temple, TX 76502 USA. EM LaurelACopeland@gmail.com OI Pugh, Mary Jo/0000-0003-4196-7763; Mortensen, Eric/0000-0002-3880-5563; Copeland, Laurel/0000-0002-9478-0209 FU VHA, Health Services Research Development [IIR-09-335]; Center for Applied Health Research - Central Texas Veterans Health Care System, Temple, TX; VERDICT Research Center at South Texas Veterans Health Care System, San Antonio, TX; VA North Texas Health Care System, Dallas, TX FX This research was supported by the VHA, Health Services Research & Development, Grant No. IIR-09-335 (L.A. Copeland, principal investigator), with additional support from Center for Applied Health Research jointly sponsored by Central Texas Veterans Health Care System, Temple, TX, and Scott & White Healthcare System, Temple, TX; VERDICT Research Center at South Texas Veterans Health Care System, San Antonio, TX; and VA North Texas Health Care System, Dallas, TX. Views are those of the authors and do not necessarily reflect the views of the Department of Veterans Affairs. NR 53 TC 9 Z9 9 U1 5 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 EI 1873-7714 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD SEP PY 2014 VL 36 IS 5 BP 502 EP 508 DI 10.1016/j.genhosppsych.2014.04.003 PG 7 WC Psychiatry SC Psychiatry GA AN8RT UT WOS:000340872400014 PM 24957928 ER PT J AU Buchanan, R Beckett, RD AF Buchanan, Rachel Beckett, Robert D. TI Assessment of vaccination-related information for consumers available on Facebook (R) SO HEALTH INFORMATION AND LIBRARIES JOURNAL LA English DT Article DE consumer health information; health information needs; information seeking behaviour; social media; social networking ID PERTUSSIS; VACCINES; RUBELLA; AUTISM AB Objectives: To assess the magnitude, interest, purpose and validity of vaccination-related information on Facebook and to determine whether information varies by site viewpoint. Methods: The 10 largest vaccination-focused Facebook (R) pages, groups and places in each category were identified and classified by viewpoint (i.e. anti-, pro-, neutral) and purpose. Number of members, posts per week, likes, comments and shares per post were recorded. Posts were assessed for concordance with CDC and FDA recommendations. Results: Of 30 sites, 43% (n = 13) were anti-vaccination, 7% (n = 2) neutral and 50% (n = 15) pro-vaccination. Most sites were most popular with American users. Median members were similar between anti-vaccination (2703 members, range 337-33 631 members) and pro-vaccination sites (2142 members, range 456-61 565 members, P = 0.262); however, anti-vaccination sites accumulated more posts per week by authors (median 15 vs. 3, P = 0.031) and members (median 33 vs. 1, P < 0.001). Pro-vaccination sites more commonly had commercial purpose (53% [n = 8] vs. 8% [n = 1], P = 0.02). Anti-vaccination sites more commonly gave medical advice (54% [n = 7] vs. 0%, P = 0.004). Overall, 48% (n = 22) of author posts were concordant with regulatory recommendations; concordance was more common on pro-vaccination sites (78% [n = 21] vs. 5% [n = 1], P = 0.0002). Conclusion: Vaccination-related information is prevalent on Facebook regardless of viewpoint; however, anti-vaccination information generates more interest. Anti-vaccination sites were likely to provide medical advice and disagree with regulatory bodies. C1 [Buchanan, Rachel] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Beckett, Robert D.] Univ Manchester, Coll Pharm, Ft Wayne, IN 46845 USA. RP Beckett, RD (reprint author), Univ Manchester, Coll Pharm, 10627 Diebold Rd, Ft Wayne, IN 46845 USA. EM rdbeckett@manchester.edu NR 15 TC 4 Z9 4 U1 8 U2 28 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1471-1834 EI 1471-1842 J9 HEALTH INFO LIBR J JI Heatlth Info. Libr. J. PD SEP PY 2014 VL 31 IS 3 BP 227 EP 234 DI 10.1111/hir.12073 PG 8 WC Information Science & Library Science SC Information Science & Library Science GA AO2KV UT WOS:000341151500006 PM 25041499 ER PT J AU Peralta, CA Katz, R Newman, AB Psaty, BM Odden, MC AF Peralta, Carmen A. Katz, Ronit Newman, Anne B. Psaty, Bruce M. Odden, Michelle C. TI Systolic and Diastolic Blood Pressure, Incident Cardiovascular Events, and Death in Elderly Persons The Role of Functional Limitation in the Cardiovascular Health Study SO HYPERTENSION LA English DT Article DE activities of daily living; aged; hypertension ID OLDER-ADULTS; HYPERTENSION; MORTALITY; ASSOCIATION; SURVIVAL; STROKE; DISEASE; FRAILTY; SPEED; RISK AB Whether limitation in the ability to perform activities of daily living (ADL) or gait speed can identify elders in whom the association of systolic and diastolic blood pressure (DBP) with cardiovascular events (CVDs) and death differs is unclear. We evaluated whether limitation in ADL or gait speed modifies the association of systolic blood pressure or DBP with incident CVD (n=2358) and death (n=3547) in the Cardiovascular Health Study. Mean age was 78 +/- 5 and 21% reported limitation in >= 1 ADL. There were 778 CVD and 1289 deaths over 9 years. Among persons without and those with ADL limitation, systolic blood pressure was associated with incident CVD: hazard ratio [HR] (per 10-mm Hg increase) 1.08 (95% confidence interval, 1.03, 1.13) and 1.06 (0.97, 1.17), respectively. ADL modified the association of DBP with incident CVD. Among those without ADL limitation, DBP was weakly associated with incident CVD, HR 1.04 (0.79, 1.37) for DBP >80, compared with <65 mm Hg. Among those with ADL limitation, DBP was inversely associated with CVD: HR 0.65 (0.44, 0.96) for DBP 66 to 80 mm Hg and HR 0.49 (0.25, 0.94) for DBP >80, compared with DBP <= 65. Among people with ADL limitation, a DBP of 66 to 80 had the lowest risk of death, HR 0.72 (0.57, 0.91), compared with a DBP of <= 65. Associations did not vary by 15-feet walking speed. ADL can identify elders in whom diastolic hypotension is associated with higher cardiovascular risk and death. Functional status, rather than chronologic age alone, should inform design of hypertension trials in elders. C1 [Peralta, Carmen A.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Peralta, Carmen A.] San Francisco VA Med Ctr, Div Nephrol, San Francisco, CA USA. [Katz, Ronit] Univ Washington, Kidney Res Inst, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15260 USA. [Odden, Michelle C.] Oregon State Univ, Coll Publ Hlth & Human Sci, Corvallis, OR 97331 USA. RP Peralta, CA (reprint author), San Francisco VA Med Ctr, Box 111A1,4150 Clement St, San Francisco, CA 94121 USA. EM carmenalicia.peralta@ucsf.edu RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU National Heart, Lung, and Blood Institute (NHLBI) [HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, HL080295]; National Institute on Aging [AG023629, K01AG039387]; National Institutes of Diabetes and Digestive and Kidney Diseases [K23SK082793]; Robert Wood Johnson Harold Amos Award; American Heart Association Western States Affiliate [CRP7210088] FX This research was supported by contracts HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, and grant HL080295 from the National Heart, Lung, and Blood Institute (NHLBI), with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided by the National Institute on Aging (AG023629). A full list of principal Cardiovascular Health Study (CHS) investigators and institutions can be found at https://CHS-NHLBI.org. C.A. Peralta is supported by the National Institutes of Diabetes and Digestive and Kidney Diseases (K23SK082793) and a Robert Wood Johnson Harold Amos Award. M. C. Odden is supported by the American Heart Association Western States Affiliate (CRP7210088) and the National Institute on Aging (K01AG039387). The content is solely our responsibility and does not necessarily represent the official views of the National Institutes of Health. NR 28 TC 11 Z9 13 U1 2 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X EI 1524-4563 J9 HYPERTENSION JI Hypertension PD SEP PY 2014 VL 64 IS 3 BP 472 EP 480 DI 10.1161/HYPERTENSIONAHA.114.03831 PG 9 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AN9MB UT WOS:000340929900009 PM 24935945 ER PT J AU Dubberke, ER Carling, P Carrico, R Donskey, CJ Loo, VG McDonald, LC Maragakis, LL Sandora, TJ Weber, DJ Yokoe, DS Gerding, DN AF Dubberke, Erik R. Carling, Philip Carrico, Ruth Donskey, Curtis J. Loo, Vivian G. McDonald, L. Clifford Maragakis, Lisa L. Sandora, Thomas J. Weber, David J. Yokoe, Deborah S. Gerding, Dale N. TI Strategies to Prevent Clostridium difficile Infections in Acute Care Hospitals: 2014 Update SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID RESISTANT STAPHYLOCOCCUS-AUREUS; HIGH-RISK ANTIBIOTICS; ENVIRONMENTAL CONTAMINATION; HYPOCHLORITE SOLUTION; COLONIZED PATIENTS; CONTACT ISOLATION; TOXIN PRODUCTION; ISOLATION ROOMS; UNITED-STATES; NORTH-AMERICA C1 [Dubberke, Erik R.] Washington Univ, Sch Med, St Louis, MO 63110 USA. [Carling, Philip] Boston Univ, Sch Med, Boston, MA 02118 USA. [Carrico, Ruth] Univ Louisville, Sch Med, Div Infect Dis, Louisville, KY 40292 USA. [Donskey, Curtis J.] Case Western Reserve Univ, Louis Stokes Cleveland Vet Affairs Med Ctr, Cleveland, OH 44106 USA. [Loo, Vivian G.] McGill Univ, Ctr Hlth, Montreal, PQ, Canada. [McDonald, L. Clifford] Ctr Dis Control & Prevent, Div Healthcare Qual Promot, Atlanta, GA USA. [Maragakis, Lisa L.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Sandora, Thomas J.] Harvard Univ, Sch Med, Boston Childrens Hosp, Boston, MA USA. [Weber, David J.] Univ N Carolina, Sch Med, Chapel Hill, NC USA. [Yokoe, Deborah S.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Yokoe, Deborah S.] Harvard Univ, Sch Med, Boston, MA USA. [Gerding, Dale N.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. [Gerding, Dale N.] Loyola Univ, Stritch Sch Med, Chicago, IL 60611 USA. RP Dubberke, ER (reprint author), Washington Univ, Sch Med, 660 South Euclid Ave,Box 8051, St Louis, MO 63110 USA. EM edubberk@dom.wustl.edu FU Sanofi Pasteur; ViroPharma; Optimer; Merck; Rebiotix; Steris; Pfizer; GOJO Industries FX E.R.D. reports serving as an advisor/consultant for Sanofi Pasteur, Merck, and Pfizer and receiving research grants/contracts from Sanofi Pasteur, ViroPharma, Optimer, Merck, and Rebiotix. P.C. reports serving as an advisor/consultant for Steris and holding a patent/copyright/license with Ecolab. R.C. reports serving on the speakers' bureau for Sanofi Pasteur, MedImmune, Abbott Diabetes Care, and 3M; performing technical writing for Ketchum; and receiving research grants/contracts from Sanofi Pasteur. C.J.D. reports serving as an advisor/consultant for Steris, GOJO Industries, and 3M; receiving honoraria from Ecolab; and receiving research grants/contracts from Merck, ViroPharma, Steris, and Pfizer. V.G.L. reports serving as an advisor/consultant for Optimer Pharmaceuticals. D.J.W. reports serving as an advisor/consultant for Johnson & Johnson and Clorox. D.N.G. reports serving as an advisor/consultant for Merck, Cubist, Novartis, Cangene, Actelion, ViroPharma, Rebiotix, and Sanofi Pasteur; receiving honoraria from Robert Michael; holding a patent/license (no royalties) with ViroPharma; and receiving research grant/contracts from GOJO Industries. L.C.M., L.L.M., T.J.S., and D.S.Y. report no conflicts of interest. NR 120 TC 0 Z9 0 U1 0 U2 6 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0899-823X EI 1559-6834 J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD SEP PY 2014 VL 35 SU 2 BP 628 EP 645 DI 10.1086/676023 PG 18 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA AO0QB UT WOS:000341014500008 ER PT J AU Yin, J Reisinger, HS Vander Weg, M Schweizer, ML Jesson, A Morgan, DJ Forrest, G Graham, M Pineles, L Perencevich, EN AF Yin, Jun Reisinger, Heather Schacht Vander Weg, Mark Schweizer, Marin L. Jesson, Andrew Morgan, Daniel J. Forrest, Graeme Graham, Margaret Pineles, Lisa Perencevich, Eli N. TI Establishing Evidence-Based Criteria for Directly Observed Hand Hygiene Compliance Monitoring Programs: A Prospective, Multicenter Cohort Study SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID HEALTH-CARE SETTINGS; HAWTHORNE; INFECTIONS; RECOMMENDATIONS; PRECAUTIONS; GUIDELINE; HOSPITALS; FEEDBACK; TIME AB OBJECTIVE. Hand hygiene surveillance programs that rely on direct observations of healthcare worker activity may be limited by the Hawthorne effect. In addition, comparing compliance rates from period to period requires adequately sized samples of observations. We aimed to statistically determine whether the Hawthorne effect is stable over an observation period and statistically derive sample sizes of observations necessary to compare compliance rates. DESIGN. Prospective multicenter cohort study. SETTING. Five intensive care units and 6 medical/surgical wards in 3 geographically distinct acute care hospitals. METHODS. Trained observers monitored hand hygiene compliance during routine care in fixed 1-hour periods, using a standardized collection tool. We estimated the impact of the Hawthorne effect using empirical fluctuation processes and F tests for structural change. Standard sample-size calculation methods were used to estimate how many hand hygiene opportunities are required to accurately measure hand hygiene across various levels of baseline and target compliance. RESULTS. Exit hand hygiene compliance increased after 14 minutes of observation (from 56.2% to 60.5%; P<.001) and increased further after 50 minutes (from 60.5% to 66.0%; P<.001). Entry compliance increased after 38 minutes (from 40.4% to 43.4%; P=.005). Between 79 and 723 opportunities are required during each period, depending on baseline compliance rates (range, 35%-90%) and targeted improvement (5% or 10%). CONCLUSIONS. Limiting direct observation periods to approximately 15 minutes to minimize the Hawthorne effect and determining required number of hand hygiene opportunities observed per period on the basis of statistical power calculations would be expected to improve the validity of hand hygiene surveillance programs. C1 [Yin, Jun] Univ Iowa, Coll Publ Hlth, Dept Biostat, Iowa City, IA USA. [Reisinger, Heather Schacht; Vander Weg, Mark; Schweizer, Marin L.; Jesson, Andrew; Perencevich, Eli N.] Univ Iowa, Dept Internal Med, Carver Coll Med, Iowa City, IA 52242 USA. [Reisinger, Heather Schacht; Schweizer, Marin L.; Graham, Margaret; Perencevich, Eli N.] Iowa City Vet Affairs Hlth Care Syst, Ctr Comprehens Access & Delivery Res & Evaluat, Iowa City, IA 52246 USA. [Vander Weg, Mark] Univ Iowa, Dept Psychol, Iowa City, IA 52242 USA. [Morgan, Daniel J.; Pineles, Lisa] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Morgan, Daniel J.] Vet Affairs Maryland Hlth Care Syst, Baltimore, MD USA. [Forrest, Graeme] Portland VA Med Ctr, Portland, OR USA. RP Perencevich, EN (reprint author), Iowa City Vet Affairs Hlth Care Syst, Ctr Comprehens Access & Delivery Res & Evaluat, Iowa City, IA 52246 USA. EM eli-perencevich@uiowa.edu FU Veterans Affairs Health Services Research and Development [09-099] FX Veterans Affairs Health Services Research and Development Investigator Initiated research grant 09-099 (to E.N.P.). NR 22 TC 5 Z9 7 U1 3 U2 8 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X EI 1559-6834 J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD SEP PY 2014 VL 35 IS 9 BP 1163 EP 1168 DI 10.1086/677629 PG 6 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA AN6TI UT WOS:000340729900011 PM 25111925 ER PT J AU Yanke, E Carayon, P Safdar, N AF Yanke, Eric Carayon, Pascale Safdar, Nasia TI Translating Evidence into Practice Using a Systems Engineering Framework for Infection Prevention SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Editorial Material ID CLOSTRIDIUM-DIFFICILE INFECTION; CARE-ASSOCIATED INFECTIONS; PATIENT SAFETY; ICU; ACQUISITION; MANAGEMENT; COMMUNITY; QUALITY; UNIT C1 [Yanke, Eric] William S Middleton Mem Vet Adm Med Ctr, Dept Med, Madison, WI USA. [Carayon, Pascale] Univ Wisconsin, Ctr Qual & Prod Improvement, Dept Ind & Syst Engn, Madison, WI USA. [Safdar, Nasia] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Safdar, Nasia] Univ Wisconsin, Sch Med, Dept Med, Div Infect Dis, Madison, WI USA. RP Safdar, N (reprint author), UWMF Centennial Bldg,1685 Highland Ave, Madison, WI 53705 USA. EM ns2@medicine.wisc.edu FU NCATS NIH HHS [9U54TR000021, UL1 TR000427]; NCRR NIH HHS [1UL1RR025011] NR 40 TC 3 Z9 3 U1 4 U2 6 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X EI 1559-6834 J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD SEP PY 2014 VL 35 IS 9 BP 1176 EP 1182 DI 10.1086/677638 PG 7 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA AN6TI UT WOS:000340729900013 PM 25111927 ER PT J AU Sonnenberg, A AF Sonnenberg, Amnon TI Time Trends of US Hospitalization for Esophageal Disease SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Article DE achalasia; dyskinesia; epidemiology of digestive disease; gastroesophageal reflux disease; Mallory-Weiss syndrome ID GASTROESOPHAGEAL-REFLUX DISEASE; PEPTIC-ULCER; ADENOCARCINOMA; METAANALYSIS; OBESITY AB Background and Aims: The occurrence of reflux disease seems to be rising in the United States. The aim of the present study was to follow the time trends of hospitalization for gastroesophageal reflux disease (GERD) and other esophageal disease during the past 4 decades. Methods: US hospital utilization data were available for individual years from 1970 to 2010 through the National Hospital Discharge Survey. Esophageal diagnoses were stratified by their ninth revision of the International Classification of Diseases codes. Annual hospitalizations were expressed as rates per 100,000 living US population. Results: GERD was by far the most common esophageal disorder resulting in hospitalization. However, in only 5% of instances did GERD-related diagnoses constitute the primary cause of hospitalization. Between 1970 and 2010 the rates of GERD-related hospitalizations increased in an exponential manner almost 10-fold. This rise affected both sex and all age groups alike. A 3-fold rise was noted in hospitalizations for esophageal adenocarcinoma. Other esophageal diagnoses, such as achalasia, dyskinesia, or stricture were characterized by falling or stable trends. Conclusions: US hospitalization data show a continued exponential rise in the occurrence of GERD without any signs of leveling off. These trends are likely to represent ongoing changes in the underlying incidence and prevalence of the disease. C1 [Sonnenberg, Amnon] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Div Gastroenterol, Portland, OR 97239 USA. RP Sonnenberg, A (reprint author), Oregon Hlth & Sci Univ, Portland VA Med Ctr GI P3, Div Gastroenterol, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu NR 20 TC 3 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0192-0790 EI 1539-2031 J9 J CLIN GASTROENTEROL JI J. Clin. Gastroenterol. PD SEP PY 2014 VL 48 IS 8 BP E71 EP E75 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AN6TC UT WOS:000340729100002 PM 24440940 ER PT J AU Langevin, JP Srikandarajah, N Krahl, SE Gorgulho, A Behnke, E Malkasian, D DeSalles, AAF AF Langevin, Jean-Philippe Srikandarajah, Nisaharan Krahl, Scott E. Gorgulho, Alessandra Behnke, Eric Malkasian, Dennis DeSalles, Antonio A. F. TI Eyelid apraxia associated with deep brain stimulation of the periaqueductal gray area SO JOURNAL OF CLINICAL NEUROSCIENCE LA English DT Article DE Deep brain stimulation; Eyelid apraxia; Periaqueductal gray area AB We report a patient with eyelid apraxia following deep brain stimulation of the periaqueductal gray area. Based on the position of our electrode, we argue that the phenomenon is linked to inhibition of the nearby central caudal nucleus of the oculomotor nucleus by high frequency stimulation. Published by Elsevier Ltd. C1 [Langevin, Jean-Philippe; Krahl, Scott E.; Gorgulho, Alessandra; Behnke, Eric; Malkasian, Dennis; DeSalles, Antonio A. F.] Univ Calif Los Angeles, Dept Neurosurg, Los Angeles, CA 90095 USA. [Langevin, Jean-Philippe] Greater Los Angeles VA Healthcare Syst, Neurosurg Serv, Los Angeles, CA 90073 USA. [Srikandarajah, Nisaharan] Walton Ctr, Liverpool, Merseyside, England. RP Langevin, JP (reprint author), Univ Calif Los Angeles, Dept Neurosurg, Los Angeles, CA 90095 USA. EM jlangevin@mednet.ucla.edu NR 6 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0967-5868 EI 1532-2653 J9 J CLIN NEUROSCI JI J. Clin. Neurosci. PD SEP PY 2014 VL 21 IS 9 BP 1652 EP 1653 DI 10.1016/j.jocn.2014.03.002 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AN7XZ UT WOS:000340815600038 PM 24726237 ER PT J AU Frank, JW Linder, JA Becker, WC Fiellin, DA Wang, EA AF Frank, Joseph W. Linder, Jeffrey A. Becker, William C. Fiellin, David A. Wang, Emily A. TI Increased Hospital and Emergency Department Utilization by Individuals with Recent Criminal Justice Involvement: Results of a National Survey SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE vulnerable populations; emergency medicine; hospital medicine; health care costs ID HEALTH-CARE; CORRECTIONAL FACILITIES; NICOTINE DEPENDENCE; FORMER INMATES; PUBLIC-HEALTH; HIGH-RISK; PRISON; RELEASE; PREVALENCE; SERVICES AB Individuals involved with the criminal justice system have increased health needs and poor access to primary care. To examine hospital and emergency department (ED) utilization and related costs by individuals with recent criminal justice involvement. Cross-sectional survey. Non-institutionalized, civilian U.S. adult participants (n = 154,356) of the National Survey on Drug Use and Health (2008-2011). Estimated proportion of adults who reported past year 1) hospitalization or 2) ED utilization according to past year criminal justice involvement, defined as 1) parole or probation, 2) arrest without subsequent correctional supervision, or 3) no criminal justice involvement; estimated annual expenditures using unlinked data from the Medical Expenditure Panel Survey. An estimated 5.7 million adults reported parole or probation and an additional 3.9 million adults reported an arrest in the past year. Adults with recent parole or probation and those with a recent arrest, compared with the general population, had higher rates of hospitalization (12.3 %, 14.3 %, 10.5 %; P < 0.001) and higher rates of ED utilization (39.3 %, 47.2 %, 26.9 %; P < 0.001). Recent parole or probation was an independent predictor of hospitalization (adjusted odds ratio [AOR], 1.21; 95 % confidence interval [CI], 1.02-1.44) and ED utilization (AOR, 1.35; 95 % CI, 1.12-1.63); Recent arrest was an independent predictor of hospitalization (AOR, 1.26; 95 % CI, 1.08-1.47) and ED utilization (AOR, 1.81; 95 % CI, 1.53-2.15). Individuals with recent criminal justice involvement make up 4.2 % of the U.S. adult population, yet account for an estimated 7.2 % of hospital expenditures and 8.5 % of ED expenditures. Recent criminal justice involvement is associated with increased hospital and ED utilization and costs. The criminal justice system may offer an important point of contact for efforts to improve the healthcare utilization patterns of a large and vulnerable population. C1 [Frank, Joseph W.] Univ Colorado, Sch Med, Div Gen Internal Med, Aurora, CO 80045 USA. [Frank, Joseph W.] Denver VA Med Ctr, Denver, CO USA. [Linder, Jeffrey A.] Brigham & Womens Hosp, Div Gen Med & Primary Care, Boston, MA 02115 USA. [Linder, Jeffrey A.] Harvard Univ, Sch Med, Boston, MA USA. [Becker, William C.] VA Connecticut Healthcare Syst, West Haven, CT USA. [Becker, William C.; Fiellin, David A.; Wang, Emily A.] Yale Univ, Sch Med, Gen Internal Med Sect, New Haven, CT USA. RP Frank, JW (reprint author), Univ Colorado, Sch Med, Div Gen Internal Med, 8th Floor,Acad Off 1,12631 E 17th Ave, Aurora, CO 80045 USA. EM joseph.frank@ucdenver.edu OI Fiellin, David/0000-0002-4006-010X FU Health Resources and Services Administration [T32 HP10251]; Veterans Health Administration Health Services Research & Development Career Development Award [08-276]; National Heart, Lung and Blood Institute [K23 HL103720] FX Dr. Frank was supported by the Health Resources and Services Administration through an institutional National Research Service Award (T32 HP10251). Dr. Becker is supported by a Veterans Health Administration Health Services Research & Development Career Development Award (08-276). Dr. Wang is supported by the National Heart, Lung and Blood Institute (K23 HL103720). NR 38 TC 11 Z9 11 U1 1 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD SEP PY 2014 VL 29 IS 9 BP 1226 EP 1233 DI 10.1007/s11606-014-2877-y PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AN9OO UT WOS:000340936600007 PM 24817280 ER PT J AU Dattalo, M Nothelle, S Tackett, S Larochelle, M Porto-Carreiro, F Yu, E Hanyok, LA AF Dattalo, Melissa Nothelle, Stephanie Tackett, Sean Larochelle, Marc Porto-Carreiro, Fernanda Yu, Eunice Hanyok, Laura A. TI Frontline Account: Targeting Hot Spotters in an Internal Medicine Residency Clinic SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material DE medical education graduate; primary care redesign; patient-centered care ID SATISFACTION C1 [Dattalo, Melissa; Nothelle, Stephanie; Tackett, Sean; Porto-Carreiro, Fernanda; Yu, Eunice; Hanyok, Laura A.] Johns Hopkins Bayview Med Ctr, Dept Internal Med, Baltimore, MD USA. [Dattalo, Melissa] Univ Wisconsin, Sch Med & Publ Hlth, Div Geriatr & Gerontol, Madison, WI USA. [Dattalo, Melissa] Univ Wisconsin Hosp & Clin, William S Middleton Mem Vet Adm Hosp, Geriatr Res Educ & Clin Ctr, Madison, WI 53792 USA. [Larochelle, Marc] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA USA. [Larochelle, Marc] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. RP Dattalo, M (reprint author), Univ Wisconsin Hosp & Clin, William S Middleton Mem Vet Adm Hosp, Geriatr Res Educ & Clin Ctr, Madison, WI 53792 USA. EM mdattalo@uwhealth.org OI Tackett, Sean/0000-0001-5369-7225 FU NCATS NIH HHS [UL1 TR000427] NR 4 TC 4 Z9 4 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD SEP PY 2014 VL 29 IS 9 BP 1305 EP 1307 DI 10.1007/s11606-014-2861-6 PG 3 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AN9OO UT WOS:000340936600021 PM 24830738 ER PT J AU Bischoff, K Shah, SM Dhaliwal, G Hollander, H AF Bischoff, Kara Shah, Shilpa M. Dhaliwal, Gurpreet Hollander, Harry TI A Heart-Breaking Case of Fever and Rash SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material DE clinical problem solving; rash; fever ID KAWASAKI-DISEASE; MEDICINE C1 [Bischoff, Kara; Shah, Shilpa M.; Dhaliwal, Gurpreet; Hollander, Harry] Univ Calif San Francisco, Dept Med, San Francisco, CA 94121 USA. [Dhaliwal, Gurpreet] San Francisco VA Med Ctr, Med Serv, San Francisco, CA USA. RP Shah, SM (reprint author), Univ Calif San Francisco, Dept Med, 1545 Divisadero St, San Francisco, CA 94121 USA. EM shilpa.shah@ucsf.edu NR 13 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD SEP PY 2014 VL 29 IS 9 BP 1310 EP 1314 DI 10.1007/s11606-014-2775-3 PG 5 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AN9OO UT WOS:000340936600024 PM 24687288 ER PT J AU Deyo, RA Dworkin, SF Amtmann, D Andersson, G Borenstein, D Carragee, E Carrino, J Chou, R Cook, K DeLitto, A Goertz, C Khalsa, P Loeser, J Mackey, S Panagis, J Rainville, J Tosteson, T Turk, D Von Korff, M Weiner, DK AF Deyo, Richard A. Dworkin, Samuel F. Amtmann, Dagmar Andersson, Gunnar Borenstein, David Carragee, Eugene Carrino, John Chou, Roger Cook, Karon DeLitto, Anthony Goertz, Christine Khalsa, Partap Loeser, John Mackey, Sean Panagis, James Rainville, James Tosteson, Tor Turk, Dennis Von Korff, Michael Weiner, Debra K. TI REPORT OF THE NATIONAL INSTITUTES OF HEALTH TASK FORCE ON RESEARCH STANDARDS FOR CHRONIC LOW BACK PAIN SO JOURNAL OF MANIPULATIVE AND PHYSIOLOGICAL THERAPEUTICS LA English DT Article DE Low Back Pain; Chronic Pain; Patient Outcome Assessment; Research Design ID CLINICAL-PRACTICE GUIDELINE; DEFINING CHRONIC PAIN; INFORMATION-SYSTEM PROMIS; FUNCTION ITEM BANK; PRIMARY-CARE; PROGNOSTIC APPROACH; SCREENING TOOL; START BACK; OUTCOME MEASURES; INTERVENTIONAL THERAPIES AB Objectives: Despite rapidly increasing intervention, functional disability due to chronic low back pain (cLBP) has increased in recent decades. We often cannot identify mechanisms to explain the major negative impact cLBP has on patients' lives. Such cLBP is often termed nonspecific and may be due to multiple biologic and behavioral etiologies. Researchers use varied inclusion criteria, definitions, baseline assessments, and outcome measures, which impede comparisons and consensus. The purpose of this article is to disseminate the report of the National Institutes of Health (NIH) task force on research standards for cLBP. Methods: The NIH Pain Consortium charged a research task force (RTF) to draft standards for research on cLBP. The resulting multidisciplinary panel developed a 3-stage process, each with a 2-day meeting. Results: The panel recommended using 2 questions to define cLBP; classifying cLBP by its impact (defined by pain intensity, pain interference, and physical function); use of a minimal data set to describe research subjects (drawing heavily on the Patient Reported Outcomes Measurement Information System methodology); reporting "responder analyses" in addition to mean outcome scores; and suggestions for future research and dissemination. The Pain Consortium has approved these recommendations, which investigators should incorporate into NIH grant proposals. Conclusions: The RTF believes that these recommendations will advance the field, help to resolve controversies, and facilitate future research addressing the genomic, neurologic, and other mechanistic substrates of cLBP. Greater consistency in reporting should facilitate comparisons among studies and the development of phenotypes. We expect the RTF recommendations will become a dynamic document and undergo continual improvement. C1 [Deyo, Richard A.] OHSU, Dept Family Med, Portland, OR 97239 USA. [Deyo, Richard A.; Chou, Roger] OHSU, Dept Med, Portland, OR 97239 USA. [Deyo, Richard A.] OHSU, Dept Publ Hlth & Community Med, Portland, OR 97239 USA. [Dworkin, Samuel F.] Univ Washington, Dept Psychiat & Behav Sci, Dept Oral Med, Seattle, WA 98195 USA. [Amtmann, Dagmar] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Andersson, Gunnar] Rush Univ, Dept Orthopaed Surg, Med Ctr, Chicago, IL 60612 USA. [Borenstein, David] George Washington Univ, Med Ctr, Dept Med, Washington, DC 20037 USA. [Carragee, Eugene] Stanford Univ, Dept Orthopaed Surg, Sch Med, Stanford, CA 94305 USA. [Carrino, John] Johns Hopkins Univ, Dept Radiol, Baltimore, MD USA. [Chou, Roger] OHSU, Dept Med Informat & Clin Epidemiol, Portland, OR 97239 USA. [Cook, Karon] Northwestern Univ, Dept Med Social Sci, Feinberg Sch Med, Chicago, IL 60611 USA. [DeLitto, Anthony] Univ Pittsburgh, Dept Phys Therapy, Pittsburgh, PA USA. [Goertz, Christine] Palmer Coll Chiropract, Palmer Ctr Chiropract Res, Davenport, IA USA. [Khalsa, Partap] NIH, Div Extramural Res, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. [Loeser, John] Univ Washington, Dept Neurol Surg, Seattle, WA 98195 USA. [Loeser, John; Turk, Dennis] Univ Washington, Dept Anesthesiol & Pain Med, Seattle, WA 98195 USA. [Mackey, Sean] Stanford Univ, Dept Anesthesia & Pain Management, Stanford, CA 94305 USA. [Panagis, James] NIAMSD, NIH, Orthopaed Res Program, Bethesda, MD 20892 USA. [Rainville, James] New England Baptist Hosp, Dept Phys Med & Rehabil, Roxbury Crossing, MA USA. [Tosteson, Tor] Geisel Sch Med Dartmouth, Dept Community & Family Med, Hanover, NH USA. [Tosteson, Tor] Geisel Sch Med Dartmouth, Dartmouth Inst, Hanover, NH USA. [Von Korff, Michael] Grp Hlth Res Inst, Seattle, WA USA. [Weiner, Debra K.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Weiner, Debra K.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Weiner, Debra K.] Univ Pittsburgh, Dept Anesthesiol, Pittsburgh, PA USA. [Weiner, Debra K.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. RP Deyo, RA (reprint author), OHSU, Mail Code FM,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM deyor@ohsu.edu FU NCCAM; National Institute for Arthritis, Musculoskeletal, and Skin Diseases, NIH FX This study was supported by the NCCAM and the National Institute for Arthritis, Musculoskeletal, and Skin Diseases, NIH. No conflicts of interest were reported for this study. NR 125 TC 4 Z9 4 U1 8 U2 15 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-4754 J9 J MANIP PHYSIOL THER JI J. Manip. Physiol. Ther. PD SEP PY 2014 VL 37 IS 7 BP 449 EP 467 DI 10.1016/j.jmpt.2014.07.006 PG 19 WC Health Care Sciences & Services; Integrative & Complementary Medicine; Rehabilitation SC Health Care Sciences & Services; Integrative & Complementary Medicine; Rehabilitation GA AO2XD UT WOS:000341189600001 PM 25127996 ER PT J AU Pantilat, S Bragg, A O'Riordan, D Ferrell, B Lindenauer, P Lorenz, K Stoneberg, J AF Pantilat, Steven Bragg, Ashley O'Riordan, David Ferrell, Betty Lindenauer, Peter Lorenz, Karl Stoneberg, Jeffrey TI Palliative Care Quality Network: Toward Quality Improvement in Palliative Care SO JOURNAL OF PALLIATIVE CARE LA English DT Meeting Abstract C1 [Pantilat, Steven; Bragg, Ashley; O'Riordan, David] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Ferrell, Betty] City Hope Natl Med Ctr, Los Angeles, CA USA. [Lindenauer, Peter] Bay State Med Ctr, Springfield, MA USA. [Lorenz, Karl] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Stoneberg, Jeffrey] Alta Bates Summit Med Ctr, Oakland, CA USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU CENTRE RECHERCHE INSTITUT UNIV GERIATRIE MONTREAL PI MONTREAL PA 4565 CHEMIN QUEEN MARY, MONTREAL, QUEBEC H3W 1W5, CANADA SN 0825-8597 J9 J PALLIAT CARE JI J. Palliative Care PD FAL PY 2014 VL 30 IS 3 MA B08-D BP 204 EP 205 PG 2 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AO3IQ UT WOS:000341223300045 ER PT J AU Onur, T Dang, A AF Onur, Tarik Dang, Alexis TI Reduction of Environmental Temperature Mitigates Local Anesthetic Cytotoxicity in Bovine Articular Chondrocytes SO JOURNAL OF SPORTS SCIENCE AND MEDICINE LA English DT Article DE Clinical hypothermia; local anesthetics; articular cartilage; osteoarthritis; chondrolysis ID IN-VITRO; BUPIVACAINE; CARTILAGE; CHONDROTOXICITY; HYPOTHERMIA; CHONDROLYSIS; ROPIVACAINE; CRYOTHERAPY; EPINEPHRINE; EXPOSURE AB The purpose of this study was to assess whether reducing environmental temperature will lead to increased chondrocyte viability following injury from a single-dose of local anesthetic treatment. Bovine articular chondrocytes from weight bearing portion s of femoral condyles were harvested and cultured. 96-well plates were seeded with 15,000 chondrocytes per well. Chondrocytes were treated with one of the following conditions: ITS Media, 1x PBS, 2% lidocaine, 0.5% bupivacaine, or 0.5% ropivacaine. Each plate was then incubated at 37 degrees C, 23 degrees C, or 4 degrees C for one hour and then returned to media at 37 degrees C. Chondrocyte viability was assessed 24 hours after treatment. Chondrocyte viability is presented as a ratio of the fluorescence of the treatment group over the average of the media group at that temperature (ratio +/- SEM). At 37 degrees C, lidocaine (0.35 +/- 0.04) and bupivacaine (0.30 +/- 0.05) treated chondrocytes show low cell viability when compared to the media (1.00 +/- 0.03) control group (p < 0.001). Lidocaine treated chondrocytes were significantly more viable at 23 degrees C (0.84 +/- 0.08) and 4 degrees C (0.86 +/- 0.085) than at 37 degrees C (p < 0.001). Bupivacaine treated chondrocytes were significantly more viable at 4 degrees C (0.660 +/- 0.073) than at 37 degrees C or 23 degrees C (0.330 +/- 0.069) (p < 0.001 and p = 0.002 respectively). Reducing the temperature from 37 degrees C to 23 degrees C during treatment with lidocaine increases chondrocyte viability following injury. Chondrocytes treated with bupivacaine can be rescued by reducing the temperature to 4 degrees C. C1 [Onur, Tarik; Dang, Alexis] San Francisco VA Med Ctr, Dept Orthopaed Surg, San Francisco, CA 91458 USA. RP Onur, T (reprint author), San Francisco VA Med Ctr, Dept Orthopaed Surg, 1700 Owens St,366, San Francisco, CA 91458 USA. EM t.s.onur17@gmail.com; alexis.dang@gmail.com NR 25 TC 1 Z9 1 U1 0 U2 0 PU JOURNAL SPORTS SCIENCE & MEDICINE PI BURSA PA MEDICAL FACULTY ULUDAG UNIV, DEPT SPORTS MEDICINE, BURSA, 16059, TURKEY SN 1303-2968 J9 J SPORT SCI MED JI J. Sport. Sci. Med. PD SEP PY 2014 VL 13 IS 3 BP 516 EP 521 PG 6 WC Sport Sciences SC Sport Sciences GA AN7BL UT WOS:000340753400008 PM 25177176 ER PT J AU Semkova, K Lott, JP Lazova, R AF Semkova, Kristina Lott, Jason P. Lazova, Rossitza TI Clinicopathologic features and survival in Spitzoid malignant melanoma and conventional malignant melanoma SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE conventional melanoma; melanoma; metastasis; prognosis; sentinel lymph node; sentinel lymph node biopsy; Spitzoid malignant melanoma; survival ID MELANOCYTIC TUMORS; BRAF; NRAS; DIAGNOSIS; MUTATION; NEVUS AB Background: Although recent advances in genetics have revealed distinct mutational profiles and molecular signaling pathways associated with Spitzoid malignant melanoma (SMM), less is known about the clinicopathologic characteristics and behavior of SMM compared with conventional melanoma. Objective: We sought to determine the clinicopathologic characteristics and mortality risk associated with SMM and conventional malignant melanoma. Methods: We conducted a retrospective study of 30 patients with SMM and 30 patients with conventional melanoma. The two groups were matched by age, gender, and depth of tumor invasion. Additional patient- and tumor-level characteristics were compared between groups and regression modeling was used to assess relative mortality risk. Results: Unadjusted analyses of SMM and conventional malignant melanoma revealed no significant differences in clinical impression, anatomic location, mitotic rate, and presence of ulceration. Sentinel lymph node biopsy, completion lymphadenectomy, and visceral metastases did not differ between groups. Cox proportional hazards regression showed no differences in mortality between Spitzoid and conventional melanoma. Limitations: Small sample size, short follow-up duration, and residual confounding may limit the accuracy and generalizability of our results. Conclusions: SMM and conventional malignant melanoma differ in some clinicopathologic features. We did not find a statistically significant difference in mortality between the two. C1 [Semkova, Kristina] Med Univ Sofia, Dept Dermatol & Venereol, Sofia, Bulgaria. [Lott, Jason P.; Lazova, Rossitza] Yale Univ, Sch Med, Dept Dermatol, New Haven, CT 06510 USA. [Lott, Jason P.] Yale Univ, Robert Wood Johnson Fdn Clin Scholars Program, New Haven, CT USA. [Lott, Jason P.] US Dept Vet Affairs, West Haven, CT USA. [Lazova, Rossitza] Yale Canc Ctr, New Haven, CT USA. RP Lazova, R (reprint author), Dermatopathol Lab, 15 York St,POB 208059, New Haven, CT 06520 USA. EM rossitza.lazova@yale.edu OI Lott, Jason/0000-0002-4097-7225 NR 14 TC 1 Z9 1 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD SEP PY 2014 VL 71 IS 3 BP 516 EP 520 DI 10.1016/j.jaad.2014.04.012 PG 5 WC Dermatology SC Dermatology GA AO2JH UT WOS:000341146700042 PM 24836544 ER PT J AU Li, XZ Dai, Y Chuang, PY He, JC AF Li, Xuezhu Dai, Yan Chuang, Peter Y. He, John Cijiang TI Induction of Retinol Dehydrogenase 9 Expression in Podocytes Attenuates Kidney Injury SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID FOCAL SEGMENTAL GLOMERULOSCLEROSIS; VITAMIN-A; TRANSGENIC MICE; KEY REGULATOR; ACID; DIFFERENTIATION; NEPHROPATHY; RECEPTOR; PROTEIN; NEF AB The intracellular concentration of retinoic acid is determined by two sequential oxidation reactions that convert retinol to retinoic acid. We recently demonstrated that retinoic acid synthesis is significantly impaired in glomeruli of HIV-1 transgenic mice (Tg26), a murine model of HIV-associated nephropathy. This impaired retinoic acid synthesis correlates with reduced renal expression of retinol dehydrogenase 9, which catalyzes the rate-limiting step of retinoic acid synthesis by converting retinol to retinal. Because retinoic acid has renal protective effects and can induce podocyte differentiation, we hypothesized that restoration of retinoic acid synthesis could slow the progression of renal disease. Herein, we demonstrate that overexpression of retinol dehydrogenase 9 in cultured podocytes induces the expression of podocyte differentiation markers. Furthermore, we confirm that podocyte-specific overexpression of retinol dehydrogenase 9 in mice with established kidney disease due to either HIV-associated nephropathy or adriamycin-induced nephropathy decreases proteinuria, attenuates kidney injury, and restores podocyte differentiation markers. Our data suggest that restoration of retinoic acid synthesis could be a new approach to treat kidney disease. C1 [Li, Xuezhu; Dai, Yan; Chuang, Peter Y.; He, John Cijiang] Icahn Sch Med Mt Sinai, Dept Med, Div Nephrol, New York, NY 10029 USA. [Li, Xuezhu] Tongji Univ, Sch Med, Shanghai East Hosp, Dept Nephrol, Shanghai 200092, Peoples R China. [Dai, Yan; He, John Cijiang] James J Peters Vet Affairs Med Ctr, Renal Sect, Bronx, NY USA. RP He, JC (reprint author), Icahn Sch Med Mt Sinai, Dept Med, Div Nephrol, One Gustave L Levy Pl,Box 1243, New York, NY 10029 USA. EM cijiang.he@mssm.edu FU National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [1R01-DK078897, 1R01-DK088541, P01-DK56492, 5K08-DK082760]; Chinese 973 fund [2012CB517601] FX J.C.H. and P.Y.C. are supported by grants from the National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases (1R01-DK078897, 1R01-DK088541, and P01-DK56492 to J.C.H.; 5K08-DK082760 to P.Y.C.). J.C.H. is also supported by the Chinese 973 fund (2012CB517601). NR 39 TC 1 Z9 1 U1 1 U2 4 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 EI 1533-3450 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2014 VL 25 IS 9 BP 1933 EP 1941 DI 10.1681/ASN.2013111150 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA AO1FY UT WOS:000341059200010 PM 24652806 ER PT J AU Leonardis, RL Duvvuri, U Mehta, D AF Leonardis, Rachel L. Duvvuri, Umamaheswar Mehta, Deepak TI Transoral Robotic-Assisted Laryngeal Cleft Repair in the Pediatric Patient SO LARYNGOSCOPE LA English DT Article DE Robotic; pediatric robotics; transoral robotics; laryngeal cleft repair ID SURGERY; SAFETY AB Objectives/Hypothesis: To assess the feasibility of performing robotic-assisted laryngeal cleft repair in the pediatric population. Study Design: Retrospective chart review at a tertiary academic children's hospital. Methods: All patients underwent transoral robotic-assisted laryngeal cleft repair from March 2011 to June 2013. Demographics, robotic docking time, operative time, and postoperative course and swallowing function were collected and analyzed. Results: Five children, three male and two female, underwent successful transoral robotic-assisted laryngeal cleft repair for closure of a type I laryngeal cleft. Mean age at time of surgery was 21.6 months (standard deviation 6.1 months; range, 15-29 months). From case 1 to case 5, robotic docking time (18-10 minutes), robotic operative time (102-36 minutes), and total operating room time (173-105 minutes) decreased. There were no complications with time until extubation (range, 2-3 days), length of intensive care unit stay (range, 3-4 days), and total hospital stay (range, 3-5 days) within acceptable range following laryngeal cleft repair. Modified barium swallow (two patients) or fiberoptic endoscopic evaluation of swallowing (three patients) was performed postoperatively, with all patients showing complete resolution of penetration and aspiration. In addition, all patients experienced subjective resolution of dysphagia and/or choking with feeds postoperatively. Conclusions: Transoral robotic-assisted laryngeal cleft repair may offer specific advantages over a traditional endoscopic approach. In our experience, the procedure was well tolerated and associated with definitive surgical cure in all patients. The scope of robotic technology continually expands and should be considered a feasible tool at an institution-based level. C1 [Leonardis, Rachel L.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Duvvuri, Umamaheswar] Univ Pittsburgh, Med Ctr, Vet Affairs Pittsburgh Hlth Syst, Pittsburgh, PA USA. [Duvvuri, Umamaheswar] Univ Pittsburgh, Dept Otolaryngol, Med Ctr, Pittsburgh, PA 15260 USA. [Mehta, Deepak] Univ Pittsburgh, Childrens Hosp Pittsburgh, Med Ctr, Dept Otolaryngol, Pittsburgh, PA 15213 USA. RP Duvvuri, U (reprint author), Univ Pittsburgh, Inst Eye & Ear, Suite 300,203 Lothrop St, Pittsburgh, PA 15213 USA. EM duvvuriu@upmc.edu FU Department of Veterans Affairs; PNC foundation FX This work was funded in part by the Department of Veterans Affairs, and the PNC foundation (U.D.). NR 9 TC 6 Z9 6 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X EI 1531-4995 J9 LARYNGOSCOPE JI Laryngoscope PD SEP PY 2014 VL 124 IS 9 BP 2167 EP 2169 DI 10.1002/lary.24680 PG 3 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA AO1UM UT WOS:000341100500047 PM 24648210 ER PT J AU Korn, LL Thomas, HL Hubbeling, HG Spencer, SP Sinha, R Simkins, HMA Salzman, NH Bushman, FD Laufer, TM AF Korn, L. L. Thomas, H. L. Hubbeling, H. G. Spencer, S. P. Sinha, R. Simkins, H. M. A. Salzman, N. H. Bushman, F. D. Laufer, T. M. TI Conventional CD4+ T cells regulate IL-22-producing intestinal innate lymphoid cells SO MUCOSAL IMMUNOLOGY LA English DT Article ID COMMENSAL BACTERIA; MICROBIAL COMMUNITIES; NKP46(+) CELLS; DEFICIENT MICE; HOMEOSTASIS; IMMUNITY; INFLAMMATION; HOST; MICROFLORA; INFECTION AB The innate and adaptive immune systems in the intestine cooperate to maintain the integrity of the intestinal barrier and to regulate the composition of the resident microbiota. However, little is known about the crosstalk between the innate and adaptive immune systems that contribute to this homeostasis. We find that CD4 + Tcells regulate the number and function of barrier-protective innate lymphoid cells (ILCs), as well as production of antimicrobial peptides (AMPs), Reg3 gamma and Reg3 beta. RAG1 - / - mice lacking T and B cells had elevated ILC numbers, interleukin-22 (IL-22) production, and AMP expression, which were corrected by replacement of CD4 + Tcells. Major histocompatibility class II - / - (MHCII - / -) mice lacking CD4 + T cells also had increased ILCs, IL- 22, and AMPs, suggesting that negative regulation by CD4 + T cells occurs at steady state. We utilized transfers and genetically modified mice to show that reduction of IL- 22 is mediated by conventional CD4 + Tcells and is T- cell receptor dependent. The IL-22-AMP axis responds to commensal bacteria; however, neither the bacterial repertoire nor the gross localization of commensal bacteria differed between MHCII + / - and MHCII - / - littermates. These data define a novel ability of CD4 + T cells to regulate intestinal IL-22-producing ILCs and AMPs. C1 [Korn, L. L.; Thomas, H. L.; Hubbeling, H. G.; Spencer, S. P.; Simkins, H. M. A.; Laufer, T. M.] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Hubbeling, H. G.; Laufer, T. M.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Sinha, R.; Bushman, F. D.] Univ Penn, Perelman Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA. [Salzman, N. H.] Med Coll Wisconsin, Dept Pediat, Milwaukee, WI 53226 USA. RP Laufer, TM (reprint author), Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA. EM tlaufer@mail.med.upenn.edu OI Salzman, Nita/0000-0003-0939-6139; Bushman, Frederic/0000-0003-4740-4056 FU Penn-CHOP Joint Center for Digestive, Liver and Pancreatic Medicine [P30-DK050306]; Penn Genome Frontiers Institute; University of Pennsylvania Center for AIDS Research (CFAR) [P30 AI 045008, R01-AI57757]; Training Program in Rheumatic Disease [5T32AR007442-25] FX This work was supported by a pilot grant from the Penn-CHOP Joint Center for Digestive, Liver and Pancreatic Medicine P30-DK050306, the Penn Genome Frontiers Institute, and the University of Pennsylvania Center for AIDS Research (CFAR) P30 AI 045008, and R01-AI57757 (NHS). LLK was supported by the Training Program in Rheumatic Disease 5T32AR007442-25. NR 45 TC 19 Z9 19 U1 2 U2 13 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1933-0219 EI 1935-3456 J9 MUCOSAL IMMUNOL JI Mucosal Immunol. PD SEP PY 2014 VL 7 IS 5 BP 1045 EP 1057 DI 10.1038/mi.2013.121 PG 13 WC Immunology SC Immunology GA AO3FW UT WOS:000341215600003 PM 24448096 ER PT J AU Bethoux, F Rogers, HL Nolan, KJ Abrams, GM Annaswamy, TM Brandstater, M Browne, B Burnfield, JM Feng, WW Freed, MJ Geis, C Greenberg, J Gudesblatt, M Ikramuddin, F Jayaraman, A Kautz, SA Lutsep, HL Madhavan, S Meilahn, J Pease, WS Rao, N Seetharama, S Sethi, P Turk, MA Wallis, RA Kufta, C AF Bethoux, Francois Rogers, Helen L. Nolan, Karen J. Abrams, Gary M. Annaswamy, Thiru M. Brandstater, Murray Browne, Barbara Burnfield, Judith M. Feng, Wuwei Freed, Mitchell J. Geis, Carolyn Greenberg, Jason Gudesblatt, Mark Ikramuddin, Farha Jayaraman, Arun Kautz, Steven A. Lutsep, Helmi L. Madhavan, Sangeetha Meilahn, Jill Pease, William S. Rao, Noel Seetharama, Subramani Sethi, Pramod Turk, Margaret A. Wallis, Roi Ann Kufta, Conrad TI The Effects of Peroneal Nerve Functional Electrical Stimulation Versus Ankle-Foot Orthosis in Patients With Chronic Stroke: A Randomized Controlled Trial SO NEUROREHABILITATION AND NEURAL REPAIR LA English DT Article DE functional electrical stimulation; stroke rehabilitation; foot drop; gait speed; quality of life; ankle-foot orthosis ID AMERICAN-HEART-ASSOCIATION; PERFORMANCE-MEASURES; WALKING PERFORMANCE; CHRONIC HEMIPARESIS; DROP STIMULATOR; GAIT; RELIABILITY; NEUROPROSTHESIS; SCALE; REHABILITATION AB Background. Evidence supports peroneal nerve functional electrical stimulation (FES) as an effective alternative to ankle-foot orthoses (AFO) for treatment of foot drop poststroke, but few randomized controlled comparisons exist. Objective. To compare changes in gait and quality of life (QoL) between FES and an AFO in individuals with foot drop poststroke. Methods. In a multicenter randomized controlled trial (ClinicalTrials.gov#NCT01087957) with unblinded outcome assessments, 495 Medicare-eligible individuals at least 6 months poststroke wore FES or an AFO for 6 months. Primary endpoints: 10-Meter Walk Test (10MWT), a composite of the Mobility, Activities of Daily Living/Instrumental Activities of Daily Living, and Social Participation subscores on the Stroke Impact Scale (SIS), and device-related serious adverse event rate. Secondary endpoints: 6-Minute Walk Test, GaitRite Functional Ambulation Profile (FAP), Modified Emory Functional Ambulation Profile (mEFAP), Berg Balance Scale (BBS), Timed Up and Go, individual SIS domains, and Stroke-Specific Quality of Life measures. Multiply imputed intention-to-treat analyses were used with primary endpoints tested for noninferiority and secondary endpoints tested for superiority. Results. A total of 399 subjects completed the study. FES proved noninferior to the AFO for all primary endpoints. Both the FES and AFO groups improved significantly on the 10MWT. Within the FES group, significant improvements were found for SIS composite score, total mFEAP score, individual Floor and Obstacle course time scores of the mEFAP, FAP, and BBS, but again, no between-group differences were found. Conclusions. Use of FES is equivalent to the AFO. Further studies should examine whether FES enables better performance in tasks involving functional mobility, activities of daily living, and balance. C1 [Bethoux, Francois] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Rogers, Helen L.; Kufta, Conrad] Innovat Neurotron, Austin, TX USA. [Nolan, Karen J.] Kessler Fdn, Res Ctr, W Orange, NJ USA. [Nolan, Karen J.] Rutgers New Jersey Med Sch, Newark, NJ USA. [Abrams, Gary M.] San Francisco VA Med Ctr, San Francisco, CA USA. [Annaswamy, Thiru M.] VA North Texas Hlth Care Syst, Dallas, TX USA. [Annaswamy, Thiru M.] UT Southwestern Med Ctr, Dallas, TX USA. [Brandstater, Murray] Loma Linda Univ, Med Ctr, Loma Linda, CA USA. [Browne, Barbara] Magee Mem Rehabilitat Ctr, Philadelphia, PA USA. [Burnfield, Judith M.] Madonna Rehabil Hosp, Lincoln, NE USA. [Feng, Wuwei] Med Univ S Carolina, Charleston, SC 29425 USA. [Freed, Mitchell J.] Florida Hosp, Neurosci & Orthoped Res Inst, Orlando, FL USA. [Geis, Carolyn] Halifax Hlth Ctr Neurosci, Daytona Beach, FL USA. [Greenberg, Jason] Helen Hayes Hosp, New York, NY USA. [Gudesblatt, Mark] South Shore Neurol Associates, Patchogue, NY USA. [Ikramuddin, Farha] Univ Minnesota Fairview, Minneapolis, MN USA. [Jayaraman, Arun] Rehabil Inst Chicago, Chicago, IL 60611 USA. [Kautz, Steven A.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Lutsep, Helmi L.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Madhavan, Sangeetha] Univ Illinois, Chicago, IL USA. [Meilahn, Jill] Marshfield Clin Res Fdn, Marshfield, WI 54449 USA. [Pease, William S.] Ohio State Univ, Wexner Med Ctr, Columbus, OH 43210 USA. [Rao, Noel] Marianjoy Rehabil Hosp, Wheaton, IL USA. [Seetharama, Subramani] Hartford Hosp, Hartford, CT 06115 USA. [Sethi, Pramod] Guilford Neurol Associates, Greensboro, NC USA. [Turk, Margaret A.] SUNY Upstate Med Univ, Syracuse, NY 13210 USA. [Wallis, Roi Ann] West Los Angeles VA Med Ctr, Los Angeles, CA USA. RP Bethoux, F (reprint author), Cleveland Clin Fdn, Desk U10,9500 Euclid Ave, Cleveland, OH 44195 USA. EM bethouf@ccf.org OI Nolan, PhD, Karen J/0000-0002-4667-0873 FU Innovative Neurotronics FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was sponsored by Innovative Neurotronics. NR 38 TC 16 Z9 19 U1 6 U2 19 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1545-9683 EI 1552-6844 J9 NEUROREHAB NEURAL RE JI Neurorehabil. Neural Repair PD SEP PY 2014 VL 28 IS 7 BP 688 EP 697 DI 10.1177/1545968314521007 PG 10 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA AN6ST UT WOS:000340728100008 PM 24526708 ER PT J AU Bramlett, HM Dietrich, WD Marcillo, A Mawhinney, LJ Furones-Alonso, O Bregy, A Peng, Y Wu, Y Pan, J Wang, J Guo, XE Bauman, WA Cardozo, C Qin, W AF Bramlett, H. M. Dietrich, W. D. Marcillo, A. Mawhinney, L. J. Furones-Alonso, O. Bregy, A. Peng, Y. Wu, Y. Pan, J. Wang, J. Guo, X. E. Bauman, W. A. Cardozo, C. Qin, W. TI Effects of low intensity vibration on bone and muscle in rats with spinal cord injury SO OSTEOPOROSIS INTERNATIONAL LA English DT Article DE Bone loss; Bone marrow cells; Low intensity vibration; Spinal cord injury ID WHOLE-BODY VIBRATION; LEVEL MECHANICAL VIBRATIONS; MINERAL DENSITY; LOW-MAGNITUDE; SKELETAL-MUSCLE; HIGH-FREQUENCY; GROWING RATS; RISK-FACTORS; SOST GENE; STIMULATION AB Spinal cord injury (SCI) causes rapid and marked bone loss. The present study demonstrates that low-intensity vibration (LIV) improves selected biomarkers of bone turnover and gene expression and reduces osteoclastogenesis, suggesting that LIV may be expected to benefit to bone mass, resorption, and formation after SCI. Sublesional bone is rapidly and extensively lost following spinal cord injury (SCI). Low-intensity vibration (LIV) has been suggested to reduce loss of bone in children with disabilities and osteoporotic women, but its efficacy in SCI-related bone loss has not been tested. The purpose of this study was to characterize effects of LIV on bone and bone cells in an animal model of SCI. The effects of LIV initiated 28 days after SCI and provided for 15 min twice daily 5 days each week for 35 days were examined in female rats with moderate severity contusion injury of the mid-thoracic spinal cord. Bone mineral density (BMD) of the distal femur and proximal tibia declined by 5 % and was not altered by LIV. Serum osteocalcin was reduced after SCI by 20 % and was increased by LIV to a level similar to that of control animals. The osteoclastogenic potential of bone marrow precursors was increased after SCI by twofold and associated with 30 % elevation in serum CTX. LIV reduced the osteoclastogenic potential of marrow precursors by 70 % but did not alter serum CTX. LIV completely reversed the twofold elevation in messenger RNA (mRNA) levels for SOST and the 40 % reduction in Runx2 mRNA in bone marrow stromal cells resulting from SCI. The findings demonstrate an ability of LIV to improve selected biomarkers of bone turnover and gene expression and to reduce osteoclastogenesis. The study indicates a possibility that LIV initiated earlier after SCI and/or continued for a longer duration would increase bone mass. C1 [Bramlett, H. M.; Dietrich, W. D.; Marcillo, A.; Mawhinney, L. J.; Furones-Alonso, O.; Bregy, A.] Univ Miami, Miller Sch Med, Miami Project Cure Paralysis, Dept Neurol Surg, Miami, FL 33136 USA. [Bramlett, H. M.] Bruce W Carter Miami VA Med Ctr, Miami, FL USA. [Peng, Y.; Wu, Y.; Pan, J.; Bauman, W. A.; Cardozo, C.; Qin, W.] James J Peters VA Med Ctr, Natl Ctr Excellence Med Consequences Spinal Cord, Bronx, NY 10468 USA. [Wang, J.; Guo, X. E.] Columbia Univ, Dept Biomed Engn, New York, NY USA. [Bauman, W. A.; Cardozo, C.; Qin, W.] Mt Sinai Sch Med, New York, NY USA. RP Qin, W (reprint author), James J Peters VA Med Ctr, Natl Ctr Excellence Med Consequences Spinal Cord, 130 West Kingsbridge Rd, Bronx, NY 10468 USA. EM Weiping.Qin@mssm.edu FU Veterans Health Administration; Biomedical Laboratory Research and Development Service [BX000521]; Department of Defense [SC090504]; Miami Project to Cure Paralysis; Rehabilitation Research and Development Service [B9212-C, B0687-R] FX This work was supported by the Veterans Health Administration, Rehabilitation Research and Development Service (B9212-C and B0687-R), Biomedical Laboratory Research and Development Service (BX000521), the Department of Defense (#SC090504), and The Miami Project to Cure Paralysis. We wish to thank Drs. Edelle Field-Fote and Mark Nash for critical reading of the manuscript. NR 59 TC 5 Z9 6 U1 1 U2 8 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0937-941X EI 1433-2965 J9 OSTEOPOROSIS INT JI Osteoporosis Int. PD SEP PY 2014 VL 25 IS 9 BP 2209 EP 2219 DI 10.1007/s00198-014-2748-8 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AN6AK UT WOS:000340675200006 PM 24861907 ER PT J AU Inslicht, SS Richards, A Madden, E Rao, MN O'Donovan, A Talbot, LS Rucker, E Metzler, TJ Hauger, RL Neylan, TC AF Inslicht, Sabra S. Richards, Anne Madden, Erin Rao, Madhu N. O'Donovan, Aoife Talbot, Lisa S. Rucker, Evelyn Metzler, Thomas J. Hauger, Richard L. Neylan, Thomas C. TI Sex differences in neurosteroid and hormonal responses to metyrapone in posttraumatic stress disorder SO PSYCHOPHARMACOLOGY LA English DT Article DE Sex differences; Posttraumatic stress disorder; Progesterone; Allopregnanolone; ACTH; Metyrapone ID CORTICOTROPIN-RELEASING HORMONE; PITUITARY-ADRENAL AXIS; GABA(A) RECEPTOR FUNCTION; DEXAMETHASONE-SUPPRESSION; PARAVENTRICULAR NUCLEUS; GLUCOCORTICOID-RECEPTOR; GENDER-DIFFERENCES; RAT HYPOTHALAMUS; COMBAT VETERANS; MESSENGER-RNA AB Mechanisms contributing to sex differences in the regulation of acute stress responsivity and their effect on the increased incidence of posttraumatic stress disorder (PTSD) in women are poorly understood. The reproductive hormone, progesterone, through conversion to allopregnanolone (ALLO), suppresses the hypothalamic pituitary adrenal (HPA) axis and has potent anxiolytic effects. The potential that progesterone and allopregnanolone reactivity modulate HPA axis responses and account for sex differences in PTSD has not been previously examined. The present study examined the effects of sex and PTSD on adrenocorticotropic hormone (ACTH), progesterone, and allopregnanolone responses to metyrapone and whether progesterone and allopregnanolone reactivity could affect the ACTH response in PTSD. Healthy medication-free male and premenopausal follicular phase female participants with chronic PTSD (n = 43; 49 % female) and controls (n = 42; 50 % female) completed an overnight metyrapone challenge and ACTH, progesterone, and allopregnanolone were obtained by repeated blood sampling. The increase in ACTH response to metyrapone was higher in PTSD subjects compared to controls and in women compared to men. Contrary to our initial prediction of an inverse relationship, progesterone and allopregnanolone were positively associated with ACTH. Progesterone and allopregnanolone partially mediated the relationship between PTSD and ACTH. Our findings of increased ACTH to metyrapone in PTSD and in women may reflect heightened hypothalamic CRF hypersecretion. Progesterone and allopregnanolone partially mediated the ACTH response in PTSD. Further characterizing sex differences in these processes will advance our understanding of the pathophysiology of PTSD, and may ultimately lead to better-targeted, more effective treatment. C1 [Inslicht, Sabra S.; Richards, Anne; Madden, Erin; Rao, Madhu N.; O'Donovan, Aoife; Talbot, Lisa S.; Rucker, Evelyn; Metzler, Thomas J.; Neylan, Thomas C.] San Francisco VA Med Ctr, Stress & Hlth Res Program, San Francisco, CA 94121 USA. [Inslicht, Sabra S.; Richards, Anne; Madden, Erin; O'Donovan, Aoife; Talbot, Lisa S.; Rucker, Evelyn; Metzler, Thomas J.; Neylan, Thomas C.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Inslicht, Sabra S.; Richards, Anne; Madden, Erin; Rao, Madhu N.; O'Donovan, Aoife; Talbot, Lisa S.; Rucker, Evelyn; Metzler, Thomas J.; Neylan, Thomas C.] Vet Hlth Res Inst, NCIRE, San Francisco, CA 94121 USA. [Rao, Madhu N.] Univ Calif San Francisco, Dept Med, Div Endocrinol, San Francisco, CA 94143 USA. [Hauger, Richard L.] San Diego VA Healthcare Syst, Ctr Excellence Stress & Mental Hlth, San Diego, CA 92161 USA. [Hauger, Richard L.] Univ Calif San Diego, Sch Med, Dept Psychiat, La Jolla, CA 92093 USA. RP Inslicht, SS (reprint author), San Francisco VA Med Ctr, Stress & Hlth Res Program, 4150 Clement St 116P, San Francisco, CA 94121 USA. EM sabra.inslicht@ucsf.edu FU National Institute for Mental Health [5R01MH073978-04, 5R34MH077667-03]; Veterans Health Research Institute; Mental Illness Research and Education Clinical Center of the US Veterans Health Administration; Clinical Research Center of the National Center for Advancing Translational Sciences, National Institutes of Health, through UCSF-CTSI [UL1 RR024131]; BLR&D Merit Review grant from the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development; VA Center of Excellence for Stress and Mental Health (CESAMH); NIH/NIMH [MH074697] FX This research and development project was conducted by the Stress and Health Research Program at the San Francisco VA Medical Center and is made possible by a research grant that was awarded and administered by the US Army Medical Research and Materiel Command (USAMRMC) and the Telemedicine & Advanced Technology Research Center (TATRC), at Fort Detrick, MD (SI: W81XWH-05-2-0094). This study was also supported by the National Institute for Mental Health (TCN: 5R01MH073978-04, 5R34MH077667-03), the Veterans Health Research Institute, the Mental Illness Research and Education Clinical Center of the US Veterans Health Administration, and the Clinical Research Center of the National Center for Advancing Translational Sciences, National Institutes of Health, through UCSF-CTSI Grant Number UL1 RR024131. RLH was supported by a BLR&D Merit Review grant from the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, the VA Center of Excellence for Stress and Mental Health (CESAMH), and a NIH/NIMH (MH074697) RO1 grant. NR 106 TC 3 Z9 3 U1 0 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 EI 1432-2072 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD SEP PY 2014 VL 231 IS 17 BP 3581 EP 3595 DI 10.1007/s00213-014-3621-3 PG 15 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AN6DN UT WOS:000340684300030 PM 24952092 ER PT J AU Montgomery, AE Fargo, JD Kane, V Culhane, DP AF Montgomery, Ann Elizabeth Fargo, Jamison D. Kane, Vincent Culhane, Dennis P. TI Development and Validation of an Instrument to Assess Imminent Risk of Homelessness Among Veterans SO PUBLIC HEALTH REPORTS LA English DT Article ID PREVENTION; ASSISTANCE AB Objectives. Veterans are overrepresented within the homeless population compared with their non-veteran counterparts, particularly when controlling for poverty. The U.S. Department of Veterans Affairs (VA) aims to prevent new episodes of homelessness by targeting households at greatest risk; however, there are no instruments that systematically assess veterans' risk of homelessness. We developed and tested a brief screening instrument to identify imminent risk of homelessness among veterans accessing VA health care. Methods. The study team developed initial assessment items, conducted cognitive interviews with veterans experiencing homelessness, refined pilot items based on veterans' and experts' feedback and results of psychometric analyses, and assigned weights to items in the final instrument to indicate a measure of homelessness risk. Results. One-third of veterans who responded to the field instrument reported imminent risk of homelessness (i.e., housing instability in the previous 90 days or expected in the next 90 days). The reliability coefficient for the instrument was 0.85, indicating good internal consistency. Veterans who had a recent change in income, had unpaid housing expenses, were living temporarily with family and friends, needed help to get or keep housing, and had poor rental and credit histories were more likely to report a risk of homelessness than those who did not: Conclusion. This study provides the field with an instrument to identify individuals and households at risk of or experiencing homelessness, which is necessary to prevent and end homelessness. In addition, it supports VA's investment in homelessness prevention and rapid rehousing services for veterans who are experiencing or are at risk for homelessness. C1 [Montgomery, Ann Elizabeth; Fargo, Jamison D.; Kane, Vincent; Culhane, Dennis P.] US Dept Vet Affairs, Natl Ctr Homelessness Vet, Philadelphia, PA 19104 USA. [Fargo, Jamison D.] Utah State Univ, Dept Psychol, Logan, UT 84322 USA. [Culhane, Dennis P.] Univ Penn, Sch Social Policy & Practice, Philadelphia, PA 19104 USA. RP Montgomery, AE (reprint author), US Dept Vet Affairs, Natl Ctr Homelessness Vet, 4100 Chester Ave,Ste 201, Philadelphia, PA 19104 USA. EM ann.montgomery2@va.gov NR 16 TC 2 Z9 2 U1 0 U2 9 PU ASSOC SCHOOLS PUBLIC HEALTH PI WASHINGTON PA 1900 M ST NW, STE 710, WASHINGTON, DC 20036 USA SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD SEP-OCT PY 2014 VL 129 IS 5 BP 428 EP 436 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AO2DC UT WOS:000341124700005 PM 25177054 ER PT J AU Sprangers, MAG Thong, MSY Bartels, M Barsevick, A Ordonana, J Shi, QL Wang, XS Klepstad, P Wierenga, EA Singh, JA Sloan, JA AF Sprangers, Mirjam A. G. Thong, Melissa S. Y. Bartels, Meike Barsevick, Andrea Ordonana, Juan Shi, Qiuling Wang, Xin Shelley Klepstad, Pal Wierenga, Eddy A. Singh, Jasvinder A. Sloan, Jeff A. TI Biological pathways, candidate genes, and molecular markers associated with quality-of-life domains: an update SO QUALITY OF LIFE RESEARCH LA English DT Review DE Biological pathways; Genes; Molecular markers; Quality of life; Patient-reported outcomes (PROs) ID GENOME-WIDE ASSOCIATION; BREAST-CANCER SURVIVORS; METHYLTRANSFERASE GENOTYPE VAL158MET; SINGLE NUCLEOTIDE POLYMORPHISMS; MAJOR DEPRESSIVE DISORDER; FUNCTIONAL POLYMORPHISM; PERSONALITY DIMENSIONS; SLEEP DISTURBANCE; SYMPTOM CLUSTER; MENTAL-HEALTH AB There is compelling evidence of a genetic foundation of patient-reported quality of life (QOL). Given the rapid development of substantial scientific advances in this area of research, the current paper updates and extends reviews published in 2010. The objective was to provide an updated overview of the biological pathways, candidate genes, and molecular markers involved in fatigue, pain, negative (depressed mood) and positive (well-being/happiness) emotional functioning, social functioning, and overall QOL. We followed a purposeful search algorithm of existing literature to capture empirical papers investigating the relationship between biological pathways and molecular markers and the identified QOL domains. Multiple major pathways are involved in each QOL domain. The inflammatory pathway has the strongest evidence as a controlling mechanism underlying fatigue. Inflammation and neurotransmission are key processes involved in pain perception, and the catechol-O-methyltransferase (COMT) gene is associated with multiple sorts of pain. The neurotransmitter and neuroplasticity theories have the strongest evidence for their relationship with depression. Oxytocin-related genes and genes involved in the serotonergic and dopaminergic pathways play a role in social functioning. Inflammatory pathways, via cytokines, also play an important role in overall QOL. Whereas the current findings need future experiments and replication efforts, they will provide researchers supportive background information when embarking on studies relating candidate genes and/or molecular markers to QOL domains. The ultimate goal of this area of research is to enhance patients' QOL. C1 [Sprangers, Mirjam A. G.; Thong, Melissa S. Y.] Univ Amsterdam, Acad Med Ctr, Dept Med Psychol J3 211, NL-1105 AZ Amsterdam, Netherlands. [Thong, Melissa S. Y.] Tilburg Univ, Ctr Res Psychol Somat Dis CoRPS, NL-5000 LE Tilburg, Netherlands. [Bartels, Meike] Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands. [Barsevick, Andrea] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. [Ordonana, Juan] Univ Murcia, Dept Human Anat & Psychobiol, Murcia, Spain. [Shi, Qiuling; Wang, Xin Shelley] Univ Texas MD Anderson Canc Ctr, Dept Symptom Res, Houston, TX 77030 USA. [Klepstad, Pal] St Olavs Univ Hosp, Chair Dept Intens Care Med, Trondheim, Norway. [Wierenga, Eddy A.] Univ Amsterdam, Acad Med Ctr, Dept Cell Biol & Histol, NL-1105 AZ Amsterdam, Netherlands. [Singh, Jasvinder A.] Univ Alabama Birmingham, Birmingham VA Med Ctr, Birmingham, AL USA. [Singh, Jasvinder A.] Mayo Clin, Coll Med, Rochester, MN USA. [Sloan, Jeff A.] Mayo Clin, Sect Canc Ctr Stat, Dept Hlth Sci, Div Biomed Stat & Informat, Rochester, MN USA. RP Sprangers, MAG (reprint author), Univ Amsterdam, Acad Med Ctr, Dept Med Psychol J3 211, Meibergdreef 15, NL-1105 AZ Amsterdam, Netherlands. EM m.a.sprangers@amc.uva.nl RI Ordonana, Juan/M-1196-2014; Bartels, Meike/D-4492-2014 OI Ordonana, Juan/0000-0001-7779-6017; Bartels, Meike/0000-0002-9667-7555; Barsevick, Andrea/0000-0003-1829-6826 FU Social Psychology Fellowship from the Dutch Cancer Society [UVT2011-4960] FX The present research is supported in part by a Social Psychology Fellowship from the Dutch Cancer Society to Melissa Thong (#UVT2011-4960). NR 66 TC 15 Z9 15 U1 1 U2 21 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0962-9343 EI 1573-2649 J9 QUAL LIFE RES JI Qual. Life Res. PD SEP PY 2014 VL 23 IS 7 BP 1997 EP 2013 DI 10.1007/s11136-014-0656-1 PG 17 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AN4ZF UT WOS:000340597900009 PM 24604075 ER PT J AU Gonzalez, S Camarillo, C Rodriguez, M Ramirez, M Zavala, J Armas, R Contreras, SA Contreras, J Dassori, A Almasy, L Flores, D Jerez, A Raventos, H Ontiveros, A Nicolini, H Escamilla, M AF Gonzalez, Suzanne Camarillo, Cynthia Rodriguez, Marco Ramirez, Mercedes Zavala, Juan Armas, Regina Contreras, Salvador A. Contreras, Javier Dassori, Albana Almasy, Laura Flores, Deborah Jerez, Alvaro Raventos, Henriette Ontiveros, Alfonso Nicolini, Humberto Escamilla, Michael TI A Genome-Wide Linkage Scan of Bipolar Disorder in Latino Families Identifies Susceptibility loci at 8q24 and 14q32 SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE genetics; family studies; Mexican; Mexican-American; Central-American; bipolar disorder ID AFFECTIVE PUERPERAL PSYCHOSIS; DNA-BINDING ACTIVITY; ASSOCIATION ANALYSIS; SLEEP DISTURBANCE; CHROMOSOME 8Q24; I DISORDER; SCHIZOAFFECTIVE DISORDER; GENETIC-HETEROGENEITY; TRANSCRIPTION FACTOR; FRONTAL-CORTEX AB A genome-wide nonparametric linkage screen was performed to localize Bipolar Disorder (BP) susceptibility loci in a sample of 3757 individuals of Latino ancestry. The sample included 963 individuals with BP phenotype (704 relative pairs) from 686 families recruited from the US, Mexico, Costa Rica, and Guatemala. Non-parametric analyses were performed over a 5 cM grid with an average genetic coverage of 0.67 cM. Multipoint analyses were conducted across the genome using non-parametric Kong & Cox LOD scores along with S-all statistics for all relative pairs. Suggestive and significant genome-wide thresholds were calculated based on 1000 simulations. Single-marker association tests in the presence of linkage were performed assuming a multiplicative model with a population prevalence of 2%. We identified two genome-wide significant susceptibly loci for BP at 8q24 and 14q32, and a third suggestive locus at 2q13-q14. Within these three linkage regions, the top associated single marker (rs1847694, P = 2.40 x 10(-5)) is located 195 Kb upstream of DPP10 in Chromosome 2. DPP10 is prominently expressed in brain neuronal populations, where it has been shown to bind and regulate Kv4-mediated A-type potassium channels. Taken together, these results provide additional evidence that 8q24, 14q32, and 2q13-q14 are susceptibly loci for BP and these regions may be involved in the pathogenesis of BP in the Latino population. (C) 2014 Wiley Periodicals, Inc. C1 [Gonzalez, Suzanne; Camarillo, Cynthia; Rodriguez, Marco; Ramirez, Mercedes; Zavala, Juan; Escamilla, Michael] Texas Tech Univ, Hlth Sci Ctr, Ctr Excellence Neurosci, Paul L Foster Sch Med, El Paso, TX 79905 USA. [Gonzalez, Suzanne; Ramirez, Mercedes; Zavala, Juan; Escamilla, Michael] Texas Tech Univ, Hlth Sci Ctr, Dept Psychiat, Paul L Foster Sch Med, El Paso, TX 79905 USA. [Armas, Regina] Univ Calif San Francisco, Langley Porter Psychiat Inst, San Francisco, CA USA. [Contreras, Salvador A.; Dassori, Albana] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Contreras, Javier; Raventos, Henriette] Univ Costa Rica, Ctr Invest Biol Celular & Mol & Escuela Biol, San Jose, Costa Rica. [Dassori, Albana] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Almasy, Laura] Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA. [Flores, Deborah] Univ Calif Los Angeles, Med Ctr, Los Angeles Biomed Res Ctr Harbor, Torrance, CA 90509 USA. [Jerez, Alvaro] Ctr Int Trastornos Afect & Conducta Adict, Guatemala City, Guatemala. [Ontiveros, Alfonso] Inst Informac & Invest Salud Mental AC, Monterrey, Nuevo Leon, Mexico. [Nicolini, Humberto] Grp Estudios Med & Familiares Carracci SC, Mexico City, DF, Mexico. [Nicolini, Humberto] Inst Nacl Med Genom, Mexico City, DF, Mexico. RP Escamilla, M (reprint author), Texas Tech Univ, Hlth Sci Ctr, Dept Psychiat, Paul L Foster Sch Med, 4800 Alberta, El Paso, TX 79905 USA. EM m.escamilla@ttuhsc.edu OI Nicolini, Humberto/0000-0003-2494-0067; Raventos, Henriette/0000-0001-9423-8308; Jerez Magana, Alvaro Antonio/0000-0002-1208-3769 FU NIMH Genetics Initiative study: Genetics of Bipolar Disorder in Latino Populations [5RO1MH069856] FX Grant sponsor: NIMH Genetics Initiative study: Genetics of Bipolar Disorder in Latino Populations; Grant number: 5RO1MH069856. NR 130 TC 4 Z9 5 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4841 EI 1552-485X J9 AM J MED GENET B JI Am. J. Med. Genet. B PD SEP PY 2014 VL 165 IS 6 BP 479 EP 491 DI 10.1002/ajmg.b.32251 PG 13 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA AN3OF UT WOS:000340497100004 PM 25044503 ER PT J AU Van Horn, DHA Rennert, L Lynch, KG McKay, JR AF Van Horn, Deborah H. A. Rennert, Lior Lynch, Kevin G. McKay, James R. TI Social Network Correlates of Participation in Telephone Continuing Care for Alcohol Dependence SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID DRINKING OUTCOMES; SUBSTANCE-ABUSE; USE DISORDERS; SUPPORT; AFTERCARE; COCAINE; PREDICTORS AB Background and Objectives: Research on face-to-face treatment for substance misuse suggests that patients' social networks may impact treatment entry and participation, but there has been no similar research on entry and participation in telephone-based continuing care. We examined whether alcohol-specific social support predicted engagement and participation in telephone continuing care for alcohol dependence, and whether treatment participation resulted in beneficial changes in participants' social networks. Methods: Participants were 252 adults (162 male) enrolled in a randomized clinical trial testing the effectiveness of telephone continuing care for alcohol dependence. Participants who completed 3 weeks of intensive outpatient treatment were randomly assigned to treatment as usual, telephone monitoring (TM; N = 83), or telephone monitoring and brief counseling (TMC; N = 83). TM and TMC included 18 months of telephone treatment. Alcohol-specific social support was measured with the Important People Inventory at baseline and 6, 12, 18, and 24-month follow-up. Results: Alcohol-specific social support did not predict entry into TM or TMC. Among those who entered telephone treatment (N = 127), participants with higher network percentage of daily drinkers, higher percentage of network members who accept drinking, and lower percentage of network members who do not accept drinking completed more continuing care calls. There was no effect of continuing care participation on alcohol-specific social support over 24 months of follow-up. Conclusion: Participants with more problematic social networks may self-select additional support in the form of telephone continuing care. Telephone continuing care does not appear to result in social network change. C1 [Van Horn, Deborah H. A.; Rennert, Lior; Lynch, Kevin G.; McKay, James R.] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. [McKay, James R.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Van Horn, DHA (reprint author), Univ Penn, Ctr Continuum Care Addict, Perelman Sch Med, Dept Psychiat, 3440 Market St,Suite 370, Philadelphia, PA 19104 USA. EM dvh@mail.med.upenn.edu FU NIAAA NIH HHS [R01 AA14850, R01 AA014850]; NIDA NIH HHS [K24 DA029062] NR 27 TC 0 Z9 0 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1055-0496 EI 1521-0391 J9 AM J ADDICTION JI Am. J. Addict. PD SEP-OCT PY 2014 VL 23 IS 5 BP 447 EP 452 DI 10.1111/j.1521-0391.2014.12128.x PG 6 WC Substance Abuse SC Substance Abuse GA AN4BR UT WOS:000340533100006 PM 24628884 ER PT J AU Irons, JG Babson, KA Bergeria, CL Bonn-Miller, MO AF Irons, Jessica G. Babson, Kimberly A. Bergeria, Cecilia L. Bonn-Miller, Marcel O. TI Physical Activity and Cannabis Cessation SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID MODERATE-INTENSITY EXERCISE; MARIJUANA USE; ACTIVITY QUESTIONNAIRE; SUBSTANCE USE; DEPENDENCE; VALIDITY; ABSTINENCE; MOTIVES; METAANALYSIS; ADOLESCENTS AB Background and Objectives: Based on recent empirical and theoretical work suggesting that physical activity (PA) activates many of the same physiological systems as cannabis, the present study sought to investigate the impact of PA level (ie, low [including none] vs. moderate/high) on a cannabis cessation attempt during the first 7 days post-quit. Methods: The present study was a 2 time-point prospective study of 84 cannabis dependent military veterans (3 female) who responded to study flyers, within a Veterans Affairs Medical Center, seeking individuals interested in engaging in a self-guided cessation attempt. All study measures were self-report. Results: Though no baseline differences between those with low and those with moderate/high levels of physical activity were observed, results revealed that participants who reported low levels of physical activity, versus moderate/high levels, were significantly more likely to report a cannabis lapse during the week following a quit attempt, particularly within the first 4 days of the cessation period. Further, individuals with low levels of PA were also more likely to report greater mean cannabis use during the first 4 days of the cessation period. Conclusions and Scientific Significance: Findings suggest that early interventions aimed at increasing physical activity may be useful among individuals with cannabis dependence who are engaged in a cessation attempt. C1 [Irons, Jessica G.] James Madison Univ, Dept Psychol, Harrisonburg, VA 22807 USA. [Babson, Kimberly A.; Bonn-Miller, Marcel O.] VA Palo Alto Hlth Care Syst, Ctr Innovat Implementat, Menlo Pk, CA USA. [Babson, Kimberly A.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Menlo Pk, CA USA. [Bergeria, Cecilia L.] Univ Vermont, Burlington, VT USA. [Bonn-Miller, Marcel O.] VA Palo Alto Hlth Care Syst, Natl Ctr PTSD, Menlo Pk, CA USA. [Bonn-Miller, Marcel O.] Philadelphia VA Med Ctr, Ctr Excellence Subst Abuse Treatment & Educ, Philadelphia, PA USA. [Bonn-Miller, Marcel O.] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Irons, JG (reprint author), James Madison Univ, Dept Psychol, MSC 7704, Harrisonburg, VA 22807 USA. EM ironsjg@jmu.edu OI Babson, Kimberly/0000-0002-9233-8230 NR 45 TC 6 Z9 6 U1 3 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1055-0496 EI 1521-0391 J9 AM J ADDICTION JI Am. J. Addict. PD SEP-OCT PY 2014 VL 23 IS 5 BP 485 EP 492 DI 10.1111/j.1521-0391.2014.12135.x PG 8 WC Substance Abuse SC Substance Abuse GA AN4BR UT WOS:000340533100012 PM 24629045 ER PT J AU Wu, GC Chan, ED Chou, YC Yu, CY Hsieh, TY Hsieh, CB Chian, CF Ke, FC Dai, YL Su, WL AF Wu, Geng-Chin Chan, Edward D. Chou, Yu-Ching Yu, Chih-Yung Hsieh, Tsai-Yuan Hsieh, Chung-Bao Chian, Chih-Feng Ke, Fu-Chang Dai, Yu-Ling Su, Wen-Lin TI Risk factors for the development of pulmonary oil embolism after transcatheter arterial chemoembolization of hepatic tumors SO ANTI-CANCER DRUGS LA English DT Article DE hepatocellular carcinoma; pulmonary oil embolism; transcatheter arterial chemoembolization ID UNRESECTABLE HEPATOCELLULAR-CARCINOMA; RESPIRATORY-DISTRESS-SYNDROME; TRANSARTERIAL CHEMOEMBOLIZATION; LIPIODOL EMBOLISM; EMBOLIZATION; COMPLICATIONS; DOXORUBICIN; INFUSION; FAILURE; SHUNT AB Pulmonary oil embolism (POE) is a rare fatal complication after transcatheter arterial embolization (TAE) and transcatheter arterial chemoembolization (TACE). As risk factors have not been clearly delineated, the aim of the present study was to identify the risk factors for development of POE after TACE. A retrospective analysis was carried out on patients with unresectable hepatocellular carcinoma who received TAE or TACE at the Tri-Service General Hospital (Taiwan) between January 2005 and December 2008. The diagnosis of TAE-induced or TACE-induced POE was based on development of respiratory signs and symptoms relatively soon after the procedure, as well as based on characteristic radiographic findings. Of the 219 enrolled patients in this study, 20 were diagnosed with POE after TAE or TACE. On univariate logistic regression analysis, patients developing POE were found to be older (67.95+/-15.95 vs. 61.44+/-12.59 years, P=0.033), with a lower serum albumin level (3.25+/-0.58 vs. 3.62+/-0.57 g/dl, P=0.009), a higher grade of liver cirrhosis as classified on the basis of Child's criteria (P<0.006), a larger tumor size (8.55+/-4.52 vs. 4.78+/-3.97 cm in diameter, P<0.001), a higher lipioidol dose (22.35+/-11.01 vs. 13.69+/-7.66 ml, P=0.003), and a higher doxorubicin dose (50.27+/-7.05 vs. 40.75+/-13.61 mg, P<0.001). Following multivariate logistic regression analysis, only lipiodol dose was found to be a significant risk factor for POE (odds ratio=1.133, 95% confidence interval: 1.004, 1.279; P=0.044). The receiver operator characteristic curve cutoff point for lipiodol dose level was 14.5 ml, with a sensitivity of 80% and a specificity of 66.3%. In conclusion, the lipiodol dose could be considered as a predictive factor for POE after TAE or TACE in hepatic malignant tumor patients. On the basis of this retrospective study, the safe lipiodol dose to minimize the risk for POE is 14.5 ml or lower; however, larger, prospective studies are needed to determine the optimally safe and yet efficacious dose. (C) 2014 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [Wu, Geng-Chin; Ke, Fu-Chang] Taoyuan Armed Forces Gen Hosp, Div Pulm Med, Dept Internal Med, Taoyuan, Taiwan. [Chou, Yu-Ching; Su, Wen-Lin] Natl Def Med Ctr, Sch Publ Hlth, Taipei, Taiwan. [Yu, Chih-Yung] Triserv Gen Hosp, Dept Radiol, Taipei, Taiwan. [Hsieh, Tsai-Yuan] Triserv Gen Hosp, Div Gastroenterol, Dept Internal Med, Taipei, Taiwan. [Hsieh, Chung-Bao] Triserv Gen Hosp, Div Organ Transplantat, Dept Surg, Taipei, Taiwan. [Chian, Chih-Feng; Dai, Yu-Ling; Su, Wen-Lin] Triserv Gen Hosp, Div Pulm & Crit Care Med, Dept Med, Taipei, Taiwan. [Su, Wen-Lin] Buddhist Tzu Chi Med Fdn, Taipei Tzu Chi Hosp, Div Pulm & Crit Care Med, Dept Med, New Taipei City 231, Taiwan. [Chan, Edward D.] Univ Colorado, Anschutz Med Ctr, Dept Med, Div Pulm Sci & Crit Care Med, Denver, CO 80202 USA. [Chan, Edward D.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Chan, Edward D.] Natl Jewish Hlth, Div Mycobacterial & Resp Infect, Dept Med, Denver, CO USA. RP Su, WL (reprint author), Buddhist Tzu Chi Med Fdn, Taipei Tzu Chi Hosp, Div Pulm & Crit Care Med, Dept Med, 289 Jianguo Rd, New Taipei City 231, Taiwan. EM williamsu2007@gmail.com NR 32 TC 1 Z9 2 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4973 EI 1473-5741 J9 ANTI-CANCER DRUG JI Anti-Cancer Drugs PD SEP PY 2014 VL 25 IS 8 BP 976 EP 981 DI 10.1097/CAD.0000000000000113 PG 6 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA AN4LD UT WOS:000340558400014 PM 24736105 ER PT J AU Bulson, R Jun, W AF Bulson, Ryan Jun, Weon TI Metastatic disease producing internuclear ophthalmolplegia: a case report SO CLINICAL AND EXPERIMENTAL OPTOMETRY LA English DT Editorial Material ID OPHTHALMOPLEGIA C1 [Bulson, Ryan] Portland VA Med Ctr, Portland, OR 97239 USA. Univ Pacific, Coll Optometry, Portland, OR USA. RP Bulson, R (reprint author), Portland VA Med Ctr, Portland, OR 97239 USA. EM ryan.bulson@pacificu.edu NR 7 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0816-4622 EI 1444-0938 J9 CLIN EXP OPTOM JI Clin. Exp. Optom. PD SEP PY 2014 VL 97 IS 5 BP 468 EP 470 DI 10.1111/cxo.12176 PG 3 WC Ophthalmology SC Ophthalmology GA AN4EU UT WOS:000340541200016 PM 24989875 ER PT J AU Northcut, TB Kienow, A AF Northcut, Terry B. Kienow, Amy TI The Trauma Trifecta of Military Sexual Trauma: A Case Study Illustrating the Integration of Mind and Body in Clinical Work with Survivors of MST SO CLINICAL SOCIAL WORK JOURNAL LA English DT Article DE Military sexual trauma; Posttraumatic stress disorder; Mindfulness; Cognitive behavioral; Self harm; Integrative psychotherapy ID DELIBERATE SELF-HARM; POSTTRAUMATIC-STRESS-DISORDER; MENTAL-HEALTH; FEMALE VETERANS; NEGATIVE AFFECT; WOMEN VETERANS; RISK-FACTORS; LIFE-COURSE; SERVICE; VICTIMIZATION AB Military sexual trauma (MST) has recently received much attention from the media in contemporary society. With the ever-increasing population of United States service members returning from the Iraq and Afghanistan wars, it is vital for any mental health practitioner to be aware of the epidemic that is sexual assault in the military, the unique trauma experiences of the MST survivor, and treatment implications incorporating multiple psychological theories. This article explores three factors, referred to as the trauma trifecta, in which the effects of MST are exacerbated: the loss of professional and personal identity, the regulatory functions of self harm behaviors, and the retraumatization that many service members endure as a result of the distinctive characteristics of the military culture and its service to veterans. A case study with clinical interventions will be utilized to demonstrate this concept of "the trauma trifecta" and the unique challenges in treating the PTSD symptoms that can result from MST in clinical therapy. Drawing from multiple theories in clinical treatment, this paper illustrates the strengths and limitations of cognitive-behavioral techniques, highlights the integration of feminist theory to illustrate the obstacles of power structures, and mind-body interventions, bridging the gap between talk therapy and body therapy. Through this unique integration of multiple therapies, the case study illustrates the veteran's reengagement with her body and the reformulation of her identity post MST. C1 [Northcut, Terry B.] Loyola Univ Chicago, Sch Social Work, Chicago, IL 60611 USA. [Kienow, Amy] US Dept Vet Affairs, Orland Pk Vet Ctr, Orland Pk, IL 60462 USA. RP Northcut, TB (reprint author), Loyola Univ Chicago, Sch Social Work, 820 N Michigan Ave, Chicago, IL 60611 USA. EM tnorthc@luc.edu; kienow.amy@gmail.com NR 78 TC 0 Z9 0 U1 1 U2 19 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0091-1674 EI 1573-3343 J9 CLIN SOC WORK J JI Clin. Soc. Work J. PD SEP PY 2014 VL 42 IS 3 SI SI BP 247 EP 259 DI 10.1007/s10615-014-0479-0 PG 13 WC Social Work SC Social Work GA AN3SB UT WOS:000340507800006 ER PT J AU Horan, W Pineda, J Wynn, J Iacoboni, M Green, M AF Horan, William P. Pineda, Jaime A. Wynn, Jonathan K. Iacoboni, Marco Green, Michael F. TI Some markers of mirroring appear intact in schizophrenia: evidence from mu suppression SO COGNITIVE AFFECTIVE & BEHAVIORAL NEUROSCIENCE LA English DT Article DE mu suppression; Schizophrenia; Mirror neuron system; Empathy ID AUTISM SPECTRUM DISORDERS; PSYCHIATRIC RATING-SCALE; BORDERLINE PERSONALITY-DISORDER; SOCIAL COGNITION; NEURON DYSFUNCTION; EMPATHIC ACCURACY; IMITATION; NEUROSCIENCE; MECHANISMS; PSYCHOSIS AB Although schizophrenia is associated with impairments in social cognition, the scope and neural correlates of these disturbances are largely unknown. In this study, we investigated whether schizophrenia patients show impaired functioning of the mirror neuron system (MNS), as indexed by electroencephalographic (EEG) mu (8-13 Hz) suppression, a hypothesized biomarker of MNS activity that is sensitive to the degree of social interaction depicted in visual stimuli. A total of 32 outpatients and 26 healthy controls completed an EEG paradigm that included six action observation or execution conditions that differed in their degrees of social interaction. Participants also completed a validated empathy questionnaire. Across both groups, we found a significant linear increase in mu suppression across the conditions involving greater levels of social engagement and interaction, but no significant group or interaction effects. Patients self-reported diminished empathic concern and perspective taking, which showed some moderate relations to mu suppression levels. Thus, the schizophrenia group showed generally intact modulation of MNS functioning at the electrophysiological level, despite self-reporting empathic disturbances. The disturbances commonly seen on self-report, performance, and neuroimaging measures of mentalizing in schizophrenia may largely reflect difficulties with higher-level inferential processes about others' emotions, rather than a basic incapacity to share in these experiences. C1 [Horan, William P.; Wynn, Jonathan K.; Green, Michael F.] Univ Calif Los Angeles, VA Greater Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Pineda, Jaime A.] Univ Calif San Diego, San Diego, CA 92103 USA. [Iacoboni, Marco] Univ Calif Los Angeles, Los Angeles, CA USA. RP Horan, W (reprint author), Univ Calif Los Angeles, VA Greater Angeles Healthcare Syst, MIRECC 210A,Bldg 210,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM horan@ucla.edu OI Wynn, Jonathan/0000-0002-1763-8540 FU Abbott Laboratories; Amgen; Cypress; Lundbeck; Teva; Otsuka; Sunovion; VA Career Development Award; NIMH [MH065707, MH43292] FX M.F.G. reports having received consulting fees from Abbott Laboratories, Amgen, Cypress, Lundbeck, and Teva. He has received speaking fees from Otsuka and Sunovion. The rest of the authors report no biomedical financial interests or potential conflicts of interest. Support for this study came from a VA Career Development Award (to W. P. H.) and from NIMH Grant Nos. MH065707 and MH43292 (M. F. G.). The authors thank Amanda Bender, Michelle Dolinsky, Crystal Gibson, Cory Tripp, and Katherine Weiner for assistance in the data collection. NR 68 TC 14 Z9 15 U1 4 U2 26 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1530-7026 EI 1531-135X J9 COGN AFFECT BEHAV NE JI Cogn. Affect. Behav. Neurosci. PD SEP PY 2014 VL 14 IS 3 BP 1049 EP 1060 DI 10.3758/s13415-013-0245-8 PG 12 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA AN3FT UT WOS:000340471500013 PM 24415272 ER PT J AU Chen, SS Seliger, SL Fried, LF AF Chen, Shan Shan Seliger, Stephen L. Fried, Linda F. TI Complete inhibition of the renin-angiotensin-aldosterone system; where do we stand? SO CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION LA English DT Review DE angiotensin receptor blocker; angiotensin-converting enzyme; cardiovascular disease; diabetic nephropathy; mineralocorticoid receptor blocker ID CONVERTING-ENZYME-INHIBITOR; CHRONIC HEART-FAILURE; LEFT-VENTRICULAR DYSFUNCTION; PRESERVED EJECTION FRACTION; RANDOMIZED CONTROLLED-TRIAL; CHRONIC RENAL-INSUFFICIENCY; TYPE-2 DIABETIC-PATIENTS; MYOCARDIAL-INFARCTION; ADDING SPIRONOLACTONE; RECEPTOR BLOCKER AB Purpose of review This review presents the role of combination therapy of renin-angiotensin-aldosterone system blockade on cardiovascular and kidney disease. Recent findings Three large randomized controlled trials comparing combination therapy of renin-angiotensin-aldosterone system blockade to monotherapy in individuals with increased cardiovascular risk, chronic kidney disease, or diabetic nephropathy have been reported. These trials - ONTARGET, ALTITUDE, and VA NEPHRON-D - demonstrated an excess risk of adverse effects [ especially acute kidney injury (AKI) and hyperkalemia] with combination therapy, without significant benefit in reducing cardiovascular and renal morbidity. Summary Current evidence supports avoiding dual renin-angiotensin-aldosterone system blockade in patients with chronic kidney disease. Subsequent studies of dual renin-angiotensin-aldosterone system blockade should examine adverse event risks and renal progression endpoints. C1 [Chen, Shan Shan; Fried, Linda F.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15213 USA. [Seliger, Stephen L.] VA Maryland Healthcare Syst, Baltimore, MD USA. [Seliger, Stephen L.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Fried, Linda F.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Chen, SS (reprint author), Univ Pittsburgh, Sch Med, Presbyterian Univ Hosp C1100, Renal Electrolyte Div, 200 Lothrop St, Pittsburgh, PA 15213 USA. EM Chens4@upmc.edu NR 61 TC 3 Z9 3 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1062-4821 EI 1473-6543 J9 CURR OPIN NEPHROL HY JI Curr. Opin. Nephrol. Hypertens. PD SEP PY 2014 VL 23 IS 5 BP 449 EP 455 DI 10.1097/MNH.0000000000000043 PG 7 WC Urology & Nephrology; Peripheral Vascular Disease SC Urology & Nephrology; Cardiovascular System & Cardiology GA AN4OG UT WOS:000340566800003 PM 25014549 ER PT J AU de Guillory, CD Schoolfield, JD Johnson, D Yeh, CK Chen, S Cappelli, DP Bober-Moken, IG Dang, H AF de Guillory, Carolina Diaz Schoolfield, John D. Johnson, Dorthea Yeh, Chih-Ko Chen, Shuo Cappelli, David P. Bober-Moken, Irene G. Dang, Howard TI Co-Relationships between glandular salivary flow rates and dental caries SO GERODONTOLOGY LA English DT Article DE caries; saliva; ageing; ethnicity ID DIFFERENT AGE-GROUPS; ROOT CARIES; HEALTH; IMPACT AB Objective: This study was designed to evaluate the relationship of age, gender, ethnicity and salivary flow rates on dental caries in an adult population using data collected from the Oral Health San Antonio Longitudinal Study of Aging (OH: SALSA). Background: Saliva is essential to maintain a healthy oral environment and diminished output can result in dental caries. Although gender and age play a role in the quantity of saliva, little is known about the interaction of age, gender and ethnicity on dental caries and salivary flow rates. Materials and methods: Data from the 1147 participants in the OH: SALSA were analysed. The dependent variables were the number of teeth with untreated coronal caries, number of teeth with root caries and the number of coronal and root surfaces with untreated caries. The independent variables were stimulated and unstimulated glandular salivary flow rates along with the age, sex and ethnicity (e. g. European or Mexican ancestry) of the participants. Results: Coronal caries experience was greater in younger participants while root surface caries experience was greater in the older participants. Coronal caries was lower in the older age groups while the root caries experience increased. Men had a statistically significant (p < 0.02) higher experience of root caries than women. Values for unstimulated and stimulated parotid salivary flow rates showed no age difference and remained constant with age, whereas the age differences in the unstimulated and stimulated submandibular/sublingual salivary flow rates were significant. The mean number of teeth with coronal and root caries was higher in Mexican-Americans than in European-Americans. Conclusions: Over one-fourth of the adults between the ages of 60 and 79 have untreated root caries over one-third having untreated coronal caries. Lower salivary flow rates play a significant role in both the number of teeth and the number of surfaces developing caries in these adults. Women and individuals of European-American ancestry experience less caries. C1 [de Guillory, Carolina Diaz; Yeh, Chih-Ko; Cappelli, David P.; Bober-Moken, Irene G.; Dang, Howard] Univ Texas Hlth Sci Ctr San Antonio, Dept Comprehens Dent, San Antonio, TX 78229 USA. [Schoolfield, John D.] Univ Texas Hlth Sci Ctr San Antonio, Dept Periodont, San Antonio, TX 78229 USA. [Johnson, Dorthea] Univ Texas Hlth Sci Ctr San Antonio, Dept Community Dent, San Antonio, TX 78229 USA. [Chen, Shuo] Univ Texas Hlth Sci Ctr San Antonio, Dept Dev Dent, San Antonio, TX 78229 USA. [Yeh, Chih-Ko] South Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. RP Dang, H (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Comprehens Dent, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM dang@uthscsa.edu FU HRSA [D13HP30016]; NIH [DE019892] FX This work was supported by grants from HRSA (D13HP30016 to DPC) and NIH (DE019892 to SC). NR 29 TC 2 Z9 2 U1 2 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0734-0664 EI 1741-2358 J9 GERODONTOLOGY JI Gerodontology PD SEP PY 2014 VL 31 IS 3 BP 210 EP 219 DI 10.1111/ger.12028 PG 10 WC Dentistry, Oral Surgery & Medicine; Geriatrics & Gerontology SC Dentistry, Oral Surgery & Medicine; Geriatrics & Gerontology GA AN3ZP UT WOS:000340527700007 ER PT J AU Park, LG Howie-Esquivel, J Dracup, K AF Park, Linda G. Howie-Esquivel, Jill Dracup, Kathleen TI A quantitative systematic review of the efficacy of mobile phone interventions to improve medication adherence SO JOURNAL OF ADVANCED NURSING LA English DT Review DE medication adherence; mobile phone; nursing; short message service (SMS); text messaging ID RANDOMIZED-CONTROLLED-TRIAL; SHORT-MESSAGE SERVICE; ANTIRETROVIRAL THERAPY; TEXT MESSAGES; PROGRAM; SMS; REMINDERS; SCHIZOPHRENIA; HIV/AIDS; MHEALTH AB Aims. To evaluate the characteristics and efficacy of mobile phone interventions to improve medication adherence. Secondary aims are to explore participants' acceptability and satisfaction with mobile phone interventions and to evaluate the selected studies in terms of study rigour, impact, cost and resource feasibility, generalizability and implications for nursing practice and research. Background. Medication non-adherence is a major global challenge. Mobile phones are the most commonly used form of technology worldwide and have the potential to promote medication adherence. Design. Guidelines from the Centre for Reviews and Dissemination were followed for this systematic review. Data Sources. A comprehensive search of databases (PubMed, Web of Science, CINAHL, PsycInfo, Google Chrome and Cochrane) and bibliographies from related articles was performed from January 2002-January 2013 to identify the included studies. Review Methods. A quantitative systematic review without meta-analysis was conducted and the selected studies were critically evaluated to extract and summarize pertinent characteristics and outcomes. Results. The literature search produced 29 quantitative research studies related to mobile phones and medication adherence. The studies were conducted for prevention purposes as well as management of acute and chronic illnesses. All of the studies used text messaging. Eighteen studies found significant improvement in medication adherence. Conclusion. While the majority of investigators found improvement in medication adherence, long-term studies characterized by rigorous research methodologies, appropriate statistical and economic analyses and the test of theory-based interventions are needed to determine the efficacy of mobile phones to influence medication adherence. C1 [Park, Linda G.] Univ Calif San Francisco, Div Geriatr, San Francisco VA Med Ctr, San Francisco, CA USA. [Howie-Esquivel, Jill; Dracup, Kathleen] Univ Calif San Francisco, Sch Nursing, San Francisco, CA 94143 USA. RP Park, LG (reprint author), Univ Calif San Francisco, Div Geriatr, San Francisco VA Med Ctr, San Francisco, CA USA. EM linda.park@ucsf.edu RI Emchi, Karma/Q-1952-2016 NR 49 TC 21 Z9 21 U1 7 U2 47 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0309-2402 EI 1365-2648 J9 J ADV NURS JI J. Adv. Nurs. PD SEP PY 2014 VL 70 IS 9 BP 1932 EP 1953 DI 10.1111/jan.12400 PG 22 WC Nursing SC Nursing GA AN2CJ UT WOS:000340390700002 PM 24689978 ER PT J AU Adams, ZW Sumner, JA Danielson, CK McCauley, JL Resnick, HS Gros, K Paul, LA Welsh, KE Ruggiero, KJ AF Adams, Zachary W. Sumner, Jennifer A. Danielson, Carla Kmett McCauley, Jenna L. Resnick, Heidi S. Groes, Kirstin Paul, Lisa A. Welsh, Kyleen E. Ruggiero, Kenneth J. TI Prevalence and predictors of PTSD and depression among adolescent victims of the Spring 2011 tornado outbreak SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Article DE Disaster; adolescents; PTSD; depression; tornadoes ID POSTTRAUMATIC STRESS SYMPTOMS; MENTAL-HEALTH RESEARCH; NEW-YORK-CITY; NATURAL DISASTER; NATIONAL SAMPLE; RISK-FACTORS; COMORBIDITY; CHILDREN; ATTACKS AB Background: Relatively few studies have examined prevalence and predictors of posttraumatic stress disorder (PTSD) or major depressive episode (MDE) in disaster-affected adolescents. Fewer still have administered diagnostic measures or studied samples exposed to tornadoes, a common type of disaster. Further, methodologic problems limit the generalizability of previous findings. This study addressed prevalence estimates and risk factors for PTSD and MDE among adolescents exposed to the Spring 2011 tornado outbreak in Alabama and Joplin, Missouri. Methods: A large (N = 2000), population-based sample of adolescents and caregivers, recruited randomly from tornado-affected communities, participated in structured telephone interviews. PTSD and MDE prevalence were estimated for the overall sample, by gender, and by age. Hierarchical logistic regression was used to identify risk factors for PTSD and MDE. Results: Overall, 6.7% of adolescents met diagnostic criteria for PTSD and 7.5% of adolescents met diagnostic criteria for MDE since the tornado. Girls were significantly more likely than boys to meet diagnostic criteria for MDE, and older adolescents were more likely than younger adolescents to report MDE since the tornado. Female gender, prior trauma exposure, and an injured family member were associated with greater risk for PTSD and MDE. Specific incident characteristics (loss of services, concern about others' safety) were associated with greater PTSD risk; prior disaster exposure was associated with lower MDE risk. Conclusions: However, most adolescents were resilient following tornado exposure, roughly 1 in 15 developed PTSD, 1 in 13 developed MDE, and many more endorsed subclinical mental health problems. Information regarding specific risk factors can guide early screening, prevention, and intervention efforts in disaster-affected communities. C1 [Adams, Zachary W.; Sumner, Jennifer A.; Danielson, Carla Kmett; McCauley, Jenna L.; Resnick, Heidi S.; Groes, Kirstin; Welsh, Kyleen E.; Ruggiero, Kenneth J.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Groes, Kirstin; Ruggiero, Kenneth J.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Paul, Lisa A.] No Illinois Univ, Dept Psychol, De Kalb, IL 60115 USA. RP Adams, ZW (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, 67 President St, Charleston, SC 29425 USA. EM adamsz@musc.edu FU National Institutes of Health [R01-MH081056]; [R21-MH086313]; [R01-DA031285]; [K12-DA031794]; [T32-MH018869] FX The National Institutes of Health (Grants R01-MH081056 to KJR) supported this study and the team of collaborators (R21-MH086313 and R01-DA031285 to C. K. D, K12-DA031794 sponsoring J.L.M, and T32-MH018869 sponsoring Z.W.A and J.A.S). All the authors declare that they have no potential or competing conflicts of interest. The authors thank the families for participating in this study. NR 33 TC 18 Z9 18 U1 9 U2 37 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9630 EI 1469-7610 J9 J CHILD PSYCHOL PSYC JI J. Child Psychol. Psychiatry PD SEP PY 2014 VL 55 IS 9 BP 1047 EP 1055 DI 10.1111/jcpp.12220 PG 9 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA AN2JD UT WOS:000340410000012 PM 24580551 ER PT J AU Benedek, G Zhu, WB Libal, N Casper, A Yu, XL Meza-Romero, R Vandenbark, AA Alkayed, NJ Offner, H AF Benedek, Gil Zhu, Wenbin Libal, Nicole Casper, Amanda Yu, Xiaolin Meza-Romero, Roberto Vandenbark, Arthur A. Alkayed, Nabil J. Offner, Halina TI A novel HLA-DR alpha 1-MOG-35-55 construct treats experimental stroke (vol 29, pg 37, 2014) SO METABOLIC BRAIN DISEASE LA English DT Correction C1 [Benedek, Gil; Yu, Xiaolin; Meza-Romero, Roberto; Vandenbark, Arthur A.; Offner, Halina] Portland VA Med Ctr, Portland, OR 97239 USA. [Zhu, Wenbin; Libal, Nicole; Casper, Amanda; Alkayed, Nabil J.; Offner, Halina] Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97201 USA. [Benedek, Gil; Yu, Xiaolin; Meza-Romero, Roberto; Vandenbark, Arthur A.; Offner, Halina] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Vandenbark, Arthur A.] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA. RP Offner, H (reprint author), Portland VA Med Ctr, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM offnerva@ohsu.edu NR 1 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0885-7490 EI 1573-7365 J9 METAB BRAIN DIS JI Metab. Brain Dis. PD SEP PY 2014 VL 29 IS 3 BP 885 EP 885 DI 10.1007/s11011-014-9518-3 PG 1 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA AN3MP UT WOS:000340492600036 ER PT J AU Wang, CC Maciejewski, ML Rao, JK Sheitman, BB Sleath, BL Farley, JF AF Wang, Chi-Chuan Maciejewski, Matthew L. Rao, Jaya K. Sheitman, Brian B. Sleath, Betsy L. Farley, Joel F. TI Examining the Relationship Between Adjunctive Psychotherapy Use and Antipsychotic Persistence and Hospitalization SO ADMINISTRATION AND POLICY IN MENTAL HEALTH AND MENTAL HEALTH SERVICES RESEARCH LA English DT Article DE Medicaid; Schizophrenia; Adjunctive psychotherapy; Adherence; Hospitalization ID IMPROVE MEDICATION ADHERENCE; RESEARCH-TEAM PORT; OUTCOMES-RESEARCH; TREATMENT RECOMMENDATIONS; PSYCHOSOCIAL TREATMENTS; NATIONAL TRENDS; CLAIMS DATA; FOLLOW-UP; SCHIZOPHRENIA; PATTERNS AB This study assessed whether the addition of adjunctive psychotherapy to antipsychotic pharmacotherapy improved antipsychotic persistence and reduced the risk of hospitalization among patients with schizophrenia using 2001-2003 Medicaid claims data from four states: Illinois, Kansas, Minnesota, and North Carolina. New antipsychotic users aged 18 or older were included. Our study showed that adjunctive psychotherapy use was associated with increased antipsychotic persistence during the first two months of treatment but was not associated with risk of hospitalization. Further research is needed to understand how to optimize the benefits of psychotherapy in terms of frequency of appointments, duration, and type. C1 [Wang, Chi-Chuan] Natl Taiwan Univ, Sch Pharm, Taipei 10051, Taiwan. [Maciejewski, Matthew L.] US Dept Vet Affairs, Ctr Hlth Serv Res Primary Care, Durham, NC USA. [Maciejewski, Matthew L.] Duke Univ, Med Ctr, Dept Med, Div Gen Internal Med, Durham, NC 27710 USA. [Rao, Jaya K.; Sleath, Betsy L.; Farley, Joel F.] Univ N Carolina, UNC Eshelman Sch Pharm, Div Pharmaceut Outcomes & Policy, Chapel Hill, NC USA. [Sheitman, Brian B.] Univ N Carolina, Sch Med, Dept Psychiat, Chapel Hill, NC USA. RP Wang, CC (reprint author), Natl Taiwan Univ, Sch Pharm, 1 Jen Ai Rd,Sect 1, Taipei 10051, Taiwan. EM chicwang@ntu.edu.tw; matthew.maciejewski@va.gov; jayarao@unc.edu; brian_sheitman@med.unc.edu; betsy_sleath@unc.edu; jffarley@unc.edu NR 48 TC 1 Z9 1 U1 3 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0894-587X EI 1573-3289 J9 ADM POLICY MENT HLTH JI Adm. Policy. Ment. Health PD SEP PY 2014 VL 41 IS 5 BP 598 EP 607 DI 10.1007/s10488-013-0503-7 PG 10 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AM6IC UT WOS:000339966800004 PM 23733044 ER PT J AU Singh, H Meyer, AND Thomas, EJ AF Singh, Hardeep Meyer, Ashley N. D. Thomas, Eric J. TI The frequency of diagnostic errors in outpatient care: estimations from three large observational studies involving US adult populations SO BMJ QUALITY & SAFETY LA English DT Article ID CANCER DIAGNOSIS; ADVERSE EVENTS; MISSED OPPORTUNITIES; MALPRACTICE CLAIMS; UNITED-STATES; FOLLOW-UP; NEGLIGENT AB Background The frequency of outpatient diagnostic errors is challenging to determine due to varying error definitions and the need to review data across multiple providers and care settings over time. We estimated the frequency of diagnostic errors in the US adult population by synthesising data from three previous studies of clinic-based populations that used conceptually similar definitions of diagnostic error. Methods Data sources included two previous studies that used electronic triggers, or algorithms, to detect unusual patterns of return visits after an initial primary care visit or lack of follow-up of abnormal clinical findings related to colorectal cancer, both suggestive of diagnostic errors. A third study examined consecutive cases of lung cancer. In all three studies, diagnostic errors were confirmed through chart review and defined as missed opportunities to make a timely or correct diagnosis based on available evidence. We extrapolated the frequency of diagnostic error obtained from our studies to the US adult population, using the primary care study to estimate rates of diagnostic error for acute conditions (and exacerbations of existing conditions) and the two cancer studies to conservatively estimate rates of missed diagnosis of colorectal and lung cancer (as proxies for other serious chronic conditions). Results Combining estimates from the three studies yielded a rate of outpatient diagnostic errors of 5.08%, or approximately 12 million US adults every year. Based upon previous work, we estimate that about half of these errors could potentially be harmful. Conclusions Our population-based estimate suggests that diagnostic errors affect at least 1 in 20 US adults. This foundational evidence should encourage policymakers, healthcare organisations and researchers to start measuring and reducing diagnostic errors. C1 [Singh, Hardeep; Meyer, Ashley N. D.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston Vet Affairs Ctr Innovat Qual Effectivenes, Houston, TX 77030 USA. [Singh, Hardeep; Meyer, Ashley N. D.] Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA. [Thomas, Eric J.] Univ Texas Med Sch Houston, Div Gen Med, Dept Med, Univ Texas Houston,Mem Hermann Ctr Healthcare Qua, Houston, TX USA. RP Singh, H (reprint author), VA Med Ctr 152, 2002 Holcombe Blvd,VAMC 152, Houston, TX 77030 USA. EM hardeeps@bcm.edu OI Meyer, Ashley/0000-0001-7993-8584 FU NIH K23 Career Development Award [K23CA125585]; VA National Center of Patient Safety; Agency for Healthcare Research and Quality [R18HS017820, R18HS17244-02]; Houston VA Center for Innovations in Quality, Effectiveness and Safety [CIN 13-413] FX Studies mentioned in this paper were supported by an NIH K23 Career Development Award (K23CA125585), the VA National Center of Patient Safety, and Agency for Healthcare Research and Quality (R18HS017820 and R18HS17244-02). HS and ANDM were supported in part by the Houston VA Center for Innovations in Quality, Effectiveness and Safety (CIN 13-413). NR 28 TC 38 Z9 38 U1 1 U2 6 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-5415 EI 2044-5423 J9 BMJ QUAL SAF JI BMJ Qual. Saf. PD SEP PY 2014 VL 23 IS 9 BP 727 EP 731 DI 10.1136/bmjqs-2013-002627 PG 5 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA AN0AR UT WOS:000340244000006 PM 24742777 ER PT J AU Long, TJ Sprenger, CC Plymate, SR Ratner, BD AF Long, Thomas J. Sprenger, Cynthia C. Plymate, Stephen R. Ratner, Buddy D. TI Prostate cancer xenografts engineered from 3D precision-porous poly(2-hydroxyethyl methacrylate) hydrogels as models for tumorigenesis and dormancy escape SO BIOMATERIALS LA English DT Article DE PolyHEMA; Scaffold; Xenograft; Prostate cancer; Dormancy; Tumor microenvironment ID PROTEIN-RELATED PROTEIN-1; MAMMARY EPITHELIAL-CELLS; IN-VITRO EVALUATION; TUMOR DORMANCY; GROWTH; PROGRESSION; CULTURE; EXPRESSION; METASTASIS; BIOLOGY AB Synthetic biomaterial scaffolds show promise for in vitro and in vivo 3D cancer models. Tumors engineered in biomaterial scaffolds have shown evidence of being more physiologically relevant than some traditional preclinical model systems, and synthetic biomaterials provide the added benefit of defined and consistent microenvironmental control. Here, we examine sphere-templated poly(2-hydroxyethyl methacrylate) (pHEMA) scaffolds as the basis for engineering xenografts from multiple human prostate cancer cell lines. pHEMA scaffolds seeded and pre-cultured with tumorigenic M12 cells prior to implantation generated tumors in athymic nude mice, demonstrating the ability of the scaffolds to be used as a synthetic vehicle for xenograft generation. pHEMA scaffolds seeded with LNCaP C4-2 cells, which require Matrigel or stromal cell support for tumor formation, were poorly tumorigenic up to 12 weeks after implantation even when Matrigel was infused into the scaffold, demonstrating a lack of necessary pro-tumorigenic signaling within the scaffolds. Finally, M12mac25 cells, which are ordinarily rendered non-tumorigenic through the expression of the tumor suppressor insulin-like growth factor binding protein 7 (IGFBP7), displayed a tumorigenic response when implanted within porous pHEMA scaffolds. These M12mac25 tumors showed significant macrophage infiltration within the scaffolds driven by the foreign body response to the materials. These findings show the potential for this biomaterials-based model system to be used in the study of prostate cancer tumorigenesis and dormancy escape. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Long, Thomas J.; Ratner, Buddy D.] Univ Washington, Dept Bioengn, Seattle, WA 98195 USA. [Sprenger, Cynthia C.; Plymate, Stephen R.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Plymate, Stephen R.] Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. RP Ratner, BD (reprint author), Univ Washington, Dept Bioengn, Box 355061,3720 15th Ave NE, Seattle, WA 98195 USA. EM ratner@uweb.engr.washington.edu FU Nanotechnology and Physical Science in Cancer Research Training Program NIH [T32CA138312]; TMEN [U54-CAl26540, P01 CA085859]; Veterans Affairs Research Service FX The authors would like to thank Shihua Sun, Colleen Irvin, Kathryn Soriano, and Gerry Hammer for technical assistance. This work was supported by the Nanotechnology and Physical Science in Cancer Research Training Program NIH T32CA138312 (TJL and BDR), TMEN U54-CAl26540 (SRP), P01 CA085859 (SRP), and the Veterans Affairs Research Service (SRP). NR 56 TC 8 Z9 8 U1 1 U2 50 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 EI 1878-5905 J9 BIOMATERIALS JI Biomaterials PD SEP PY 2014 VL 35 IS 28 BP 8164 EP 8174 DI 10.1016/j.biomaterials.2014.04.090 PG 11 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA AM3TC UT WOS:000339774700011 PM 24942815 ER PT J AU Yokoyama, JS Evans, DS Coppola, G Kramer, JH Tranah, GJ Yaffe, K AF Yokoyama, Jennifer S. Evans, Daniel S. Coppola, Giovanni Kramer, Joel H. Tranah, Gregory J. Yaffe, Kristine TI Genetic Modifiers of Cognitive Maintenance Among Older Adults SO HUMAN BRAIN MAPPING LA English DT Article DE genetics; genomics; aging; cognition; genome wide association study; neuroimaging ID GENOME-WIDE ASSOCIATION; MINI-MENTAL STATE; ALZHEIMERS-DISEASE; METABOLIC SYNDROME; OSTEOPOROTIC FRACTURES; SUSCEPTIBILITY LOCI; DECLINE; BRAIN; RISK; METAANALYSIS AB Objective: Identify genetic factors associated with cognitive maintenance in late life and assess their association with gray matter (GM) volume in brain networks affected in aging. Methods: We conducted a genome-wide association study of similar to 2.4 M markers to identify modifiers of cognitive trajectories in Caucasian participants (N=7,328) from two population-based cohorts of non-demented elderly. Standardized measures of global cognitive function (z-scores) over 10 and 6 years were calculated among participants and mixed model regression was used to determine subject-specific cognitive slopes. "Cognitive maintenance" was defined as a change in slope of >= 0 and was compared with all cognitive decliners (slope <0). In an independent cohort of cognitively normal older Caucasians adults (N=122), top association findings were then used to create genetic scores to assess whether carrying more cognitive maintenance alleles was associated with greater GM volume in specific brain networks using voxel-based morphometry. Results: The most significant association was on chromosome 11 (rs7109806, P=7.8 x 10(-8)) near RIC3. RIC3 modulates activity of alpha 7 nicotinic acetylcholine receptors, which have been implicated in synaptic plasticity and beta-amyloid binding. In the neuroimaging cohort, carrying more cognitive maintenance alleles was associated with greater volume in the right executive control network (RECN; P-FWE=0.01). Conclusions: These findings suggest that there may be genetic loci that promote healthy cognitive aging and that they may do so by conferring robustness to GM in the RECN. Future work is required to validate top candidate genes such as RIC3 for involvement in cognitive maintenance. Hum Brain Mapp 35:4556-4565, 2014. (C) 2014 The Authors. Human Brain Mapping Published by Wiley Periodicals, Inc. C1 [Yokoyama, Jennifer S.; Kramer, Joel H.; Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA 94143 USA. [Evans, Daniel S.; Tranah, Gregory J.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. [Coppola, Giovanni] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Coppola, Giovanni] Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. [Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA. RP Yokoyama, JS (reprint author), UCSF Memory & Aging Ctr, 675 Nelson Rising Ln,Suite 190, San Francisco, CA 94158 USA. EM jyokoyama@memory.ucsf.edu FU Larry L. Hillblom Foundation [2012-A-015-FEL]; National Institute on Aging (NIA) [P50-AG023501-08S1, R01 AG032289, R01 AG005407, R01 AR35582, R01 AR35583, R01 AR35584, R01 AG005394, R01 AG027574, R01 AG027576, RC1 AG035610]; National Institutes of Health (NIH) [K24 AG031155]; NIH Roadmap for Medical Research [U01 AR45580, U01 AR45614, U01 AR45632, U01 AR45647, U01 AR45654, U01 AR45583, U01 AG18197, U01-AG027810, UL1 RR024140]; National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) (GWAS in MrOS and SOF) [RC2AR058973]; National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); National Center for Research Resources (NCRR) [2007/2I] FX Contract grant sponsor: Larry L. Hillblom Foundation; Contract grant number: 2012-A-015-FEL; Contract grant sponsor: National Institute on Aging (NIA); Contract grant number: P50-AG023501-08S1; Contract grant sponsor: National Institutes of Health (NIH); Contract grant number: K24 AG031155; Contract grant sponsor: National Institute on Aging (NIA); Contract grant numbers: R01 AG032289, R01 AG005407, R01 AR35582, R01 AR35583, R01 AR35584, R01 AG005394, R01 AG027574, R01 AG027576, and RC1 AG035610; Contract grant sponsor: NIH Roadmap for Medical Research; Contract grant numbers: U01 AR45580, U01 AR45614, U01 AR45632, U01 AR45647, U01 AR45654, U01 AR45583, U01 AG18197, U01-AG027810, and UL1 RR024140; Contract grant sponsor: The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) (GWAS in MrOS and SOF); Contract grant number: RC2AR058973; Contract grant sponsor: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), and the National Center for Research Resources (NCRR); Contract grant number: 2007/2I NR 61 TC 4 Z9 4 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1065-9471 EI 1097-0193 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD SEP PY 2014 VL 35 IS 9 BP 4556 EP 4565 DI 10.1002/hbm.22494 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AM0VZ UT WOS:000339567000022 PM 24616004 ER PT J AU Lee, J Cohen, MS Engel, SA Glahn, D Nuechterlein, KH Wynn, JK Green, MF AF Lee, Junghee Cohen, Mark S. Engel, Stephen A. Glahn, David Nuechterlein, Keith H. Wynn, Jonathan K. Green, Michael F. TI Neural Substrates of Visual Masking by Object Substitution in Schizophrenia SO HUMAN BRAIN MAPPING LA English DT Article DE object substitution masking; schizophrenia; visual backward masking; fMRI ID FUNCTIONAL MRI; SEPARATING PROCESSES; OCCIPITAL CORTEX; BACKWARD-MASKING; AWARENESS; ATTENTION; FMRI; REPRESENTATION; CONSCIOUSNESS; OPTIMIZATION AB Despite a well-known behavioral finding of visual backward masking impairment in schizophrenia, its underlying neural mechanism remains obscure. This study examined neural correlates of a distinct type of visual backward masking, object substitution masking (OSM), in schizophrenia. Twenty schizophrenia patients and 26 healthy controls completed a 4-Dot OSM task and three functional localizer tasks for the lateral occipital (LO), human motion-sensitive (hMT+), and retinotopic areas in the scanner. In 4-dot masking, subjects detected a target that was followed by a mask consisting of 4 dots that surrounded a target. Stimulus-onset asynchrony (SOA) between target and mask was varied to examine the modulation of masking: (1) within three visual processing areas regions of interest (ROI) (i.e., ROI analysis) and (2) in brain regions outside the three visual processing areas (i.e., whole brain analysis). In the ROI analyses, LO and retinotopic areas showed increased peak amplitude when SOA become longer in both patients and controls. There was also an effect of ROI in that both groups showed higher activation in LO and hMT+ compared with the retinotopic areas. The whole brain analyses revealed a significantly activated area for longer SOAs vs. a short SOA in the occipital cortex in controls only, but the group contrast was not significant. Overall, this study did not find strong evidence for neural abnormalities of OSM in schizophrenia, suggesting that neural substrates of OSM in schizophrenia are not as compromised as those involved in the more common masking methods that rely on disruption of object formation. (C) 2014 Wiley Periodicals, Inc. C1 [Lee, Junghee; Cohen, Mark S.; Nuechterlein, Keith H.; Wynn, Jonathan K.; Green, Michael F.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA. [Lee, Junghee; Wynn, Jonathan K.; Green, Michael F.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Engel, Stephen A.] Univ Minnesota, Dept Psychol, Minneapolis, MN 55455 USA. [Glahn, David] Inst Living, Olin Neuropsychiat Res Ctr, Hartford, CT USA. [Glahn, David; Nuechterlein, Keith H.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. RP Lee, J (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, 760 Westwood Plaza 77-361, Los Angeles, CA 90024 USA. EM jungheelee@ucla.edu RI Lee, Junghee/C-5226-2014; Wynn, Jonathan/H-3749-2014 OI Lee, Junghee/0000-0001-9567-8700; Wynn, Jonathan/0000-0002-1763-8540 FU National Institute of Mental Health [MH43292, MH065707]; Brain Mapping Medical Research Organization; Brain Mapping Support Foundation; Pierson-Lovelace Foundation; Tamkin Foundation; Jennifer Jones-Simon Foundation; Capital Group Companies Charitable Foundation; Robson Family; Northstar Fund FX Contract grant sponsor: National Institute of Mental Health; Contract grant number: MH43292, MH065707; Contract grant sponsors: Brain Mapping Medical Research Organization, the Brain Mapping Support Foundation, the Pierson-Lovelace Foundation, the Tamkin Foundation, the Jennifer Jones-Simon Foundation, the Capital Group Companies Charitable Foundation, the Robson Family, the Northstar Fund. NR 38 TC 2 Z9 2 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1065-9471 EI 1097-0193 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD SEP PY 2014 VL 35 IS 9 BP 4654 EP 4662 DI 10.1002/hbm.22501 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AM0VZ UT WOS:000339567000029 PM 24677632 ER PT J AU Cash, TV Konig, A Eonta, AM Vrana, SR AF Cash, Therese V. Konig, Andrea Eonta, Alison M. Vrana, Scott R. TI RESPIRATORY SINUS ARRYTHMIA PREDICTS MENTAL HEALTH OUTCOMES IN AN EXPRESSIVE WRITING TASK SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 54h Annual Meeting of the Society-for-Psychophysiological-Research CY SEP 10-14, 2014 CL Atlanta, GA SP Soc Psychophysiol Res DE respiratory sinus arrhythmia; expressive writing C1 [Cash, Therese V.; Konig, Andrea; Vrana, Scott R.] Virginia Commonwealth Univ, Richmond, VA 23284 USA. [Eonta, Alison M.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0048-5772 EI 1469-8986 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD SEP PY 2014 VL 51 SU 1 SI SI MA 3-49 BP S55 EP S55 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA AL9RX UT WOS:000339479500303 ER PT J AU Jahshan, C Wynn, JK Mathis, KI Green, MF AF Jahshan, Carol Wynn, Jonathan K. Mathis, Kristopher I. Green, Michael F. TI THE NEUROPHYSIOLOGY OF BIOLOGICAL MOTION PERCEPTION IN SCHIZOPHRENIA SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 54h Annual Meeting of the Society-for-Psychophysiological-Research CY SEP 10-14, 2014 CL Atlanta, GA SP Soc Psychophysiol Res DE biological motion; electroencephalography; schizophrenia C1 VA Greater Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0048-5772 EI 1469-8986 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD SEP PY 2014 VL 51 SU 1 SI SI MA 3-17 BP S49 EP S49 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA AL9RX UT WOS:000339479500271 ER PT J AU Wangelin, BC Tuerk, PW AF Wangelin, Bethany C. Tuerk, Peter W. TI TAKING THE PULSE OF PROLONGED EXPOSURE THERAPY: CHANGES IN TRAUMA-RELATED PHYSIOLOGICAL AROUSAL ACROSS THE COURSE OF PTSD TREATMENT SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 54h Annual Meeting of the Society-for-Psychophysiological-Research CY SEP 10-14, 2014 CL Atlanta, GA SP Soc Psychophysiol Res DE PTSD; anxiety; emotion C1 [Wangelin, Bethany C.; Tuerk, Peter W.] Ralph H Johnson VAMC, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0048-5772 EI 1469-8986 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD SEP PY 2014 VL 51 SU 1 SI SI MA 4-81 BP S77 EP S77 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA AL9RX UT WOS:000339479500426 ER PT J AU Wynn, JK Roach, BJ Lee, J Horan, WP Ford, JM Jimenez, AM Weiner, K Ghermezi, L Green, MF AF Wynn, Jonathan K. Roach, Brian J. Lee, Junghee Horan, William P. Ford, Judith M. Jimenez, Amy M. Weiner, Katherine Ghermezi, Livon Green, Michael F. TI EEG FINDINGS OF REDUCED NEURAL SYNCHRONIZATION DURING VISUAL INTEGRATION IN SCHIZOPHRENIA SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 54h Annual Meeting of the Society-for-Psychophysiological-Research CY SEP 10-14, 2014 CL Atlanta, GA SP Soc Psychophysiol Res DE schizophrenia; event-related potentials; visual integration C1 [Wynn, Jonathan K.; Horan, William P.; Jimenez, Amy M.; Green, Michael F.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Wynn, Jonathan K.; Lee, Junghee; Horan, William P.; Weiner, Katherine; Ghermezi, Livon; Green, Michael F.] Univ Calif Los Angeles, Los Angeles, CA USA. [Roach, Brian J.] Vet Affairs San Francisco Med Ctr, San Francisco, CA USA. [Ford, Judith M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0048-5772 EI 1469-8986 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD SEP PY 2014 VL 51 SU 1 SI SI MA 3-16 BP S49 EP S49 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA AL9RX UT WOS:000339479500270 ER PT J AU Sher, L Grunebaum, MF Sullivan, GM Burke, AK Cooper, TB Mann, JJ Oquendo, MA AF Sher, Leo Grunebaum, Michael F. Sullivan, Gregory M. Burke, Ainsley K. Cooper, Thomas B. Mann, J. John Oquendo, Maria A. TI Association of testosterone levels and future suicide attempts in females with bipolar disorder SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Bipolar; Female; Testosterone; Suicide ID HUMAN-AGGRESSION; GONADAL AXIS; WOMEN; DEPRESSION; BEHAVIOR; ANDROGENS; SCALE; RISK; METAANALYSIS; METABOLITES AB Background: Considerable evidence suggests that testosterone may play a role in the pathophysiology of mood disorders in females. This is the first prospective study to examine whether blood testosterone levels predict suicide attempts in females with bipolar disorder. Methods: Females with a DSM-PI diagnosis of a bipolar disorder in a depressive or mixed episode with at least one past suicide attempt were enrolled. Demographic and clinical parameters were assessed and recorded. Plasma testosterone was assayed using a double antibody radioimmunoassay procedure. Patients were followed up prospectively for up to 2.5 years. Results: At baseline, testosterone levels positively correlated with the number of previous major depressive episodes and suicide attempts. Cox proportional hazards regression analysis found that higher baseline testosterone levels predicted suicide attempts during the follow-up period. Limitations: A limitation of the study is that the sample size is modest. Another limitation is that we did not have a bipolar nonattempter or healthy volunteer control group for comparison. Conclusion: Testosterone levels may predict suicidal behavior in women with bipolar disorder. Published by Elsevier B.V. C1 [Sher, Leo; Grunebaum, Michael F.; Sullivan, Gregory M.; Burke, Ainsley K.; Cooper, Thomas B.; Mann, J. John; Oquendo, Maria A.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Sher, Leo; Grunebaum, Michael F.; Sullivan, Gregory M.; Burke, Ainsley K.; Cooper, Thomas B.; Mann, J. John; Oquendo, Maria A.] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. [Sher, Leo] James J Peters Vet Adm Med Ctr, New York, NY 10468 USA. [Sher, Leo] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. RP Sher, L (reprint author), James J Peters Vet Adm Med Ctr, 130 West Kingsbridge Rd, New York, NY 10468 USA. EM Leo.Sher@mssm.edu FU NIH [R01 MH59710, P50 MH62185, R01 MH48514] FX This study was supported by grants R01 MH59710, P50 MH62185, and R01 MH48514 from the NIH. The funding source had no role in study design; data collection, analysis, or interpretation; or in writing of the manuscript and submission process. NR 54 TC 5 Z9 5 U1 3 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 EI 1573-2517 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD SEP PY 2014 VL 166 BP 98 EP 102 DI 10.1016/j.jad.2014.04.068 PG 5 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AK8UV UT WOS:000338705000014 PM 25012416 ER PT J AU Hebenstreit, C Madden, E Maguen, S AF Hebenstreit, Claire Madden, Erin Maguen, Shira TI Latent classes of PTSD symptoms in Iraq and Afghanistan female veterans SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Posttraumatic stress disorder; Women's health services; Veterans/psychology; Female ID POSTTRAUMATIC-STRESS-DISORDER; CONFIRMATORY FACTOR-ANALYSES; MENTAL-HEALTH DIAGNOSES; DISSOCIATIVE SUBTYPE; CARE; BARRIERS; VA; ETHNICITY; CONFLICTS; SERVICES AB Background: Recent studies have used latent class analysis (LCA) to identify subgroups of individuals who slut e similar patterns of PTSD symptom endorsement; however, further study is needed among Female veterans, whose PTSD symptom expression may vary from that of their male counterparts. The current study examined latent PTSD symptom classes in female veterans who returned from recent military service in Iraq and Afghanistan, and explored military and demographic variables associated with distinct PTSD symptom presentations. Methods: A retrospective analysis was conducted using existing medical records from female Iraq and Afghanistan veterans who were new users of VA mental health outpatient (MHO) care, had received a PTSD diagnosis anytime during the post-deployment period, and completed the PTSD checklist within 30 days of their first MHO visit (N=2425). Results: The LCA results identified four latent classes of PTSD symptom profiles in the sample: High Symptom, Intermediate Symptom, Intermediate Symptom with High Emotional Numbing (EN), and Low Symptom. Race/ethnicity, age, Lime since last deployment, and distance from a VA facility emerged as predictors of PTSD symptom presentation. Limitations: The current study was cross-sectional and utilized administrative data. The results may not be generalizable to female veterans from other service eras. Conclusions: Longer times between end of last deployment and initiation of MHO services were associated with more symptomatic classes. Exploration of PTSD symptom presentation may enhance our understanding of the service needs of female veterans with PTSD, and suggests potential benefits to engaging veterans in MHO soon after last deployment. Published by Elsevier B.V. C1 [Hebenstreit, Claire; Madden, Erin; Maguen, Shira] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Hebenstreit, Claire; Maguen, Shira] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Hebenstreit, C (reprint author), San Francisco VA Med Ctr, PTSD Program 116P, 4150 Clement St, San Francisco, CA 94121 USA. EM Claire.Hebenstreit@va.gov OI Hebenstreit, Claire/0000-0001-5970-2195 FU Department of Defense Award Grant [W81XWH-11-2-0189] FX This research was supported by Department of Defense Award Grant (W81XWH-11-2-0189). NR 52 TC 7 Z9 7 U1 0 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 EI 1573-2517 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD SEP PY 2014 VL 166 BP 132 EP 138 DI 10.1016/j.jad.2014.04.061 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AK8UV UT WOS:000338705000019 PM 25012421 ER PT J AU Jasinska, AJ Zorick, T Brody, AL Stein, EA AF Jasinska, Agnes J. Zorick, Todd Brody, Arthur L. Stein, Elliot A. TI Dual role of nicotine in addiction and cognition: A review of neuroimaging studies in humans SO NEUROPHARMACOLOGY LA English DT Review DE Nicotine; Tobacco; Smoking; Dopamine; PET; SPECT; fMRI; Addiction; Cognition ID CEREBRAL-BLOOD-FLOW; STRIATAL DOPAMINE RELEASE; ACETYLCHOLINE-RECEPTOR OCCUPANCY; STATE FUNCTIONAL CONNECTIVITY; POSITRON-EMISSION-TOMOGRAPHY; WORKING-MEMORY TASK; HUMAN-BRAIN; SMOKING-CESSATION; CIGARETTE-SMOKING; TOBACCO SMOKERS AB Substantial evidence demonstrates both nicotine's addiction liability and its cognition-enhancing effects. However, the neurobiological mechanisms underlying nicotine's impact on brain function and behavior remain incompletely understood. Elucidation of these mechanisms is of high clinical importance and may lead to improved therapeutics for smoking cessation as well as for a number of cognitive disorders such as schizophrenia. Neuroimaging techniques such as positron emission tomography (PET), single photon emission computed tomography (SPEC), and functional magnetic resonance imaging (fMRI), which make it possible to study the actions of nicotine in the human brain in vivo, play an increasingly important role in identifying these dual mechanisms of action. In this review, we summarize the current state of knowledge and discuss outstanding questions and future directions in human neuroimaging research on nicotine and tobacco. This research spans from receptor-level PET and SPECT studies demonstrating nicotine occupancy at nicotinic acetylcholine receptors (nAChRs) and upregulation of nAChRs induced by chronic smoking; through nicotine's interactions with the mesocorticolimbic dopamine system believed to mediate nicotine's reinforcing effects leading to dependence; to functional activity and connectivity fMRI studies documenting nicotine's complex behavioral and cognitive effects manifest by its actions on large-scale brain networks engaged both during task performance and at rest. This article is part of the Special Issue Section entitled 'Neuroimaging in Neuropharmacology'. Published by Elsevier Ltd. C1 [Jasinska, Agnes J.; Stein, Elliot A.] NIDA, Intramural Res Program, Baltimore, MD 21224 USA. [Zorick, Todd; Brody, Arthur L.] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 90095 USA. [Zorick, Todd; Brody, Arthur L.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Jasinska, AJ (reprint author), NIDA, Intramural Res Program, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM jasinskaaj@mail.nih.gov; abrody@ucla.edu; EStein@intra.nida.nih.gov FU Intramural Research Program of NIDA; National Institute on Drug Abuse [R01 DA20872]; Tobacco-Related Disease Research Program [19XT-0135]; Merit Review Award from the Department of Veterans Affairs, Office of Research and Development FX Supported by the Intramural Research Program of NIDA (E.A.S., NJ.) and grants R01 DA20872 from the National Institute on Drug Abuse (A.L.B.), 19XT-0135 from the Tobacco-Related Disease Research Program (A.L.B.), and a Merit Review Award from the Department of Veterans Affairs, Office of Research and Development (A.L.B.). NR 156 TC 24 Z9 27 U1 3 U2 55 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 EI 1873-7064 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD SEP PY 2014 VL 84 SI SI BP 111 EP 122 DI 10.1016/j.neuropharm.2013.02.015 PG 12 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA AK7OC UT WOS:000338616600012 PM 23474015 ER PT J AU Koppel, J Acker, C Davies, P Lopez, OL Jimenez, H Azose, M Greenwald, BS Murray, PS Kirkwood, CM Kofler, J Sweet, RA AF Koppel, Jeremy Acker, Chris Davies, Peter Lopez, Oscar L. Jimenez, Heidy Azose, Miriam Greenwald, Blaine S. Murray, Patrick S. Kirkwood, Caitlin M. Kofler, Julia Sweet, Robert A. TI Psychotic Alzheimer's disease is associated with gender-specific tau phosphorylation abnormalities SO NEUROBIOLOGY OF AGING LA English DT Article DE Alzheimer's disease; Psychosis; Tau; Dementia with Lewy bodies; Alpha-synuclein; Neurofibrillary tangles ID INCREASED FAMILIAL RISK; NEUROFIBRILLARY TANGLES; ATYPICAL ANTIPSYCHOTICS; LEWY BODY; DEMENTIA; DELUSIONS; HALLUCINATIONS; CONSORTIUM; EPIDEMIOLOGY; TRAJECTORIES AB Converging evidence suggests that psychotic Alzheimer's disease (AD + P) is associated with an acceleration of frontal degeneration, with tau pathology playing a primary role. Previous histopathologic and biomarker studies have specifically implicated tau pathology in this condition. To precisely quantify tau abnormalities in the frontal cortex in AD + P, we used a sensitive biochemical assay of total tau and 4 epitopes of phospho-tau relevant in AD pathology in a postmortem sample of AD + P and AD - P. Samples of superior frontal gyrus from 26 AD subjects without psychosis and 45 AD + P subjects with psychosis were analyzed. Results of enzyme-linked immunosorbent assay demonstrate that AD + P females, but not males, had significantly higher levels of phosphorylated tau in the frontal cortex. In males, but not females, AD + P was associated with the presence of alpha-synuclein pathology. These results support a gender dissociation of pathology in AD + P. The design of future studies aimed at the elucidation of cognitive and/or functional outcomes; regional brain metabolic deficits; or genetic correlates of AD + P should take gender into consideration. (C) 2014 Elsevier Inc. All rights reserved. C1 [Koppel, Jeremy; Acker, Chris; Davies, Peter; Jimenez, Heidy; Sweet, Robert A.] Feinstein Inst Med Res, Litwin Zucker Res Ctr Study Alzheimers Dis, Manhasset, NY USA. [Koppel, Jeremy; Greenwald, Blaine S.] North Shore LIJ Hlth Syst, Zucker Hillside Hosp, Glen Oaks, NY USA. [Lopez, Oscar L.; Murray, Patrick S.; Kirkwood, Caitlin M.; Kofler, Julia; Sweet, Robert A.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Lopez, Oscar L.; Murray, Patrick S.; Kirkwood, Caitlin M.; Kofler, Julia; Sweet, Robert A.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. [Azose, Miriam] Touro Coll, Brooklyn, NY USA. VA Pittsburgh Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr MIRECC Q2, Pittsburgh, PA USA. RP Koppel, J (reprint author), Zucker Hillside Hosp, Litwin Zucker Res Ctr Study Alzheimers Dis, 350 Community Dr, Manhasset, NY 11030 USA. EM jkoppel@nshs.edu OI Murray, Patrick/0000-0002-6525-2888 FU Veterans Health Administration [BX000452]; National Institute on Aging [AG005133, AG027224] FX This work was supported by the Veterans Health Administration (BX000452 to Robert A. Sweet) and the National Institute on Aging (AG005133 to Oscar L. Lopez, AG027224 to Robert A. Sweet). The content is solely the responsibility of the authors and does not necessarily represent the official views of the Department of Veterans Affairs, the National Institutes of Health, or the United States Government. NR 52 TC 10 Z9 10 U1 3 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 EI 1558-1497 J9 NEUROBIOL AGING JI Neurobiol. Aging PD SEP PY 2014 VL 35 IS 9 BP 2021 EP 2028 DI 10.1016/j.neurobiolaging.2014.03.003 PG 8 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA AK1SB UT WOS:000338195100011 PM 24731519 ER PT J AU Liang, S Salas, T Gencaslan, E Li, BJ Habib, SL AF Liang, Sitai Salas, Tiffanie Gencaslan, Emre Li, Baojie Habib, Samy L. TI Tuberin-deficiency downregulates N-cadherin and upregulates vimentin in kidney tumor of TSC patients SO ONCOTARGET LA English DT Article DE N-cadherin; vimentin; Akt; tuberin; mTOR and angiomyolipomas ID REPAIR ENZYME OGG1; SCLEROSIS COMPLEX; MESENCHYMAL-TRANSITION; 3-KINASE/AKT PATHWAY; GAP ACTIVITY; EXPRESSION; GENE; ANGIOMYOLIPOMAS; DISEASE; TISSUES AB Angiomyolipomas (AMLs) are associated with cell fibrosis in kidney of Tuberous Sclerosis Complex patients. The mechanism by which the fibrotic proteins accumulated in AMLs has not been explored. In the present study, we investigated the role of Akt/tuberin/mTOR pathway in the regulation cell fibrosis proteins. AML cells that expressed low levels of tuberin showed less expression of N-cadherin and higher of vimentin proteins compared to HEK293 cells. AML cells infected with Ad-tuberin showed a significant decrease in vimentin and an increase in N-cadherin protein expression. In addition, cells treated with rapamycin showed a significant increase in p-Akt and a decrease in p-p70S6K that was associated with a decrease expression of vimentin and a slight increase expression in N-cadherin. On the other hand, cells treated with Akt inhibitor revealed a significant decrease in p-Akt and p-p70S6K that was associated with a significant decrease in vimentin and an increase in N-cadherin expression. In addition, cells transfected with DN-Akt or DN-S6K show significant increase expression in N-cadherin and a decrease in vimentin. Moreover, cells transfected with siRNA against rictor or siRNA against raptor resulted in a decrease in vimentin and an increase N-cadherin expression. Kidney tumors from TSC patients showed significant decrease in N-cadherin and significant increased in vimentin protein expression compared to control kidney tissues. These data comprise the first report to provide the role of Akt/tuberin/mTORC1/2 in the regulation of N-cadherin and vimentin that are involved in the progression of fibrosis in kidney tumor of TSC patients. C1 [Liang, Sitai; Salas, Tiffanie; Habib, Samy L.] South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Gencaslan, Emre] Akdeniz Univ, Sch Med, TR-07058 Antalya, Turkey. [Li, Baojie] Shanghai Jiao Tong Univ, Minist Educ, Key Lab Genet Dev & Neuropsychiatr Disorders, BioX Inst, Shanghai 200030, Peoples R China. [Habib, Samy L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. RP Habib, SL (reprint author), South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. EM habib@uthscsa.edu FU American Heart Association; Merit Review Award from South Texas Veterans Healthcare System FX This work was supported in part by grants from the American Heart Association, and Merit Review Award from South Texas Veterans Healthcare System (to S.L.H.). NR 39 TC 3 Z9 4 U1 1 U2 3 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD AUG 30 PY 2014 VL 5 IS 16 BP 6936 EP 6946 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA AZ0EX UT WOS:000347920100034 PM 25149531 ER PT J AU Shanmugasundaram, K Nayak, B Shim, EH Livi, CB Block, K Sudarshan, S AF Shanmugasundaram, Karthigayan Nayak, Bijaya Shim, Eun-Hee Livi, Carolina B. Block, Karen Sudarshan, Sunil TI The Oncometabolite Fumarate Promotes Pseudohypoxia Through Noncanonical Activation of NF-kappa B Signaling SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article DE Cancer Biology; Cell Metabolism; Hypoxia-inducible Factor (HIF); NF-B (NF-KB); Small Molecule; Small ID RENAL-CELL CANCER; PROLINE HYDROXYLATION; PROLYL HYDROXYLATION; KIDNEY CANCER; HIF-ALPHA; HYPOXIA; HYDRATASE; HEREDITARY; KINASES; TBK1 AB Background: We examined alternative mechanisms by which fumarate levels contribute to hypoxia inducible factor (HIF)-1 accumulation and fumarate hydratase (FH)-deficient renal carcinogenesis. Results: Fumarate promotes HIF-1 transcription through Tank binding kinase 1 (TBK1)-dependent noncannonical activation of NF-B signaling. Conclusion: Fumarate-mediated, TBK-dependent accumulation of HIF-1 mediates cell invasion in FH-deficient RCC. Significance: TBK is a novel putative therapeutic target for the treatment of aggressive fumarate-driven tumors. Inactivating mutations of the gene encoding the tricarboxylic acid cycle enzyme fumarate hydratase (FH) have been linked to an aggressive variant of hereditary kidney cancer (hereditary leiomyomatosis and renal cell cancer). These tumors accumulate markedly elevated levels of fumarate. Fumarate is among a growing list of oncometabolites identified in cancers with mutations of genes involved in intermediary metabolism. FH-deficient tumors are notable for their pronounced accumulation of the transcription factor hypoxia inducible factor-1 (HIF-1) and aggressive behavior. To date, HIF-1 accumulation in hereditary leiomyomatosis and renal cell cancer tumors is thought to result from fumarate-dependent inhibition of prolyl hydroxylases and subsequent evasion from von Hippel-Lindau-dependent degradation. Here, we demonstrate a novel mechanism by which fumarate promotes HIF-1 mRNA and protein accumulation independent of the von Hippel-Lindau pathway. Here we demonstrate that fumarate promotes p65 phosphorylation and p65 accumulation at the HIF-1 promoter through non-canonical signaling via the upstream Tank binding kinase 1 (TBK1). Consistent with these data, inhibition of the TBK1/p65 axis blocks HIF-1 accumulation in cellular models of FH loss and markedly reduces cell invasion of FH-deficient RCC cancer cells. Collectively, our data demonstrate a novel mechanism by which pseudohypoxia is promoted in FH-deficient tumors and identifies TBK1 as a novel putative therapeutic target for the treatment of aggressive fumarate-driven tumors. C1 [Shanmugasundaram, Karthigayan; Nayak, Bijaya; Block, Karen] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Livi, Carolina B.] Univ Texas Hlth Sci Ctr San Antonio, Dept Mol Med, San Antonio, TX 78229 USA. [Shim, Eun-Hee; Sudarshan, Sunil] Univ Alabama Birmingham, Dept Urol, Birmingham, AL 35294 USA. [Block, Karen] South Texas Vet Hlth Care Syst, Audie L Murphy Mem Hosp Div, San Antonio, TX 78229 USA. RP Block, K (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM block@uthscsa.edu; sudarshan@uab.edu FU National Institutes of Health [K08 CA138774]; Urology Care Foundation; Astellas Pharma Rising Star Award; America Cancer Society [RSG-12-127-01 CNE]; Veterans Affairs Merit Grants [CPRIT RP120190, P30CA054174] FX This work was supported, in whole or in part, by National Institutes of Health Grant K08 CA138774 (to S. S.), Urology Care Foundation and Astellas Pharma Rising Star Award, and America Cancer Society RSG-12-127-01 CNE (to S. S.) and Veterans Affairs Merit Grants CPRIT RP120190 and P30CA054174 (to K. B). NR 35 TC 8 Z9 9 U1 0 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 29 PY 2014 VL 289 IS 35 BP 24691 EP 24699 DI 10.1074/jbc.M114.568162 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AO7AY UT WOS:000341505600058 PM 25028521 ER PT J AU Zhang, H Singh, KK AF Zhang, Hengshan Singh, Keshav K. TI Global Genetic Determinants of Mitochondrial DNA Copy Number SO PLOS ONE LA English DT Article ID CONGENITAL MUSCULAR-DYSTROPHY; RENAL-CELL CARCINOMA; SACCHAROMYCES-CEREVISIAE; THYMIDINE KINASE; GASTRIC-CANCER; LARGE SUBUNIT; HUMAN-DISEASE; MUTATIONS; DEPLETION; EXPRESSION AB Many human diseases including development of cancer is associated with depletion of mitochondrial DNA (mtDNA) content. These diseases are collectively described as mitochondrial DNA depletion syndrome (MDS). High similarity between yeast and human mitochondria allows genomic study of the budding yeast to be used to identify human disease genes. In this study, we systematically screened the pre-existing respiratory-deficient Saccharomyces cerevisiae yeast strains using fluorescent microscopy and identified 102 nuclear genes whose deletions result in a complete mtDNA loss, of which 52 are not reported previously. Strikingly, these genes mainly encode protein products involved in mitochondrial protein biosynthesis process (54.9%). The rest of these genes either encode protein products associated with nucleic acid metabolism (14.7%), oxidative phosphorylation (3.9%), or other protein products (13.7%) responsible for bud-site selection, mitochondrial intermembrane space protein import, assembly of cytochrome-c oxidase, vacuolar protein sorting, protein-nucleus import, calcium-mediated signaling, heme biosynthesis and iron homeostasis. Thirteen (12.7%) of the genes encode proteins of unknown function. We identified human orthologs of these genes, conducted the interaction between the gene products and linked them to human mitochondrial disorders and other pathologies. In addition, we screened for genes whose defects affect the nuclear genome integrity. Our data provide a systematic view of the nuclear genes involved in maintenance of mitochondrial DNA. Together, our studies i) provide a global view of the genes regulating mtDNA content; ii) provide compelling new evidence toward understanding novel mechanism involved in mitochondrial genome maintenance and iii) provide useful clues in understanding human diseases in which mitochondrial defect and in particular depletion of mitochondrial genome plays a critical role. C1 [Zhang, Hengshan] Fujian Med Univ, Affiliated Hosp 1, Dept Cent Lab, Fuzhou, Peoples R China. [Singh, Keshav K.] Univ Alabama Birmingham, Dept Genet, Ctr Free Radical Biol, Ctr Aging, Birmingham, AL 35294 USA. [Singh, Keshav K.] Univ Alabama Birmingham, UAB Comprehens Canc Ctr, Birmingham, AL USA. [Singh, Keshav K.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Singh, KK (reprint author), Univ Alabama Birmingham, Dept Genet, Ctr Free Radical Biol, Ctr Aging, Birmingham, AL 35294 USA. EM kksingh@uab.edu FU Veterans Administration [1I01BX001716]; National Institutes of Health (NIH) [R01CA121904] FX Studies reported in this manuscript were supported in part by Veterans Administration grant 1I01BX001716 and National Institutes of Health (NIH) R01CA121904 (to KKS). Funding agencies has no role in design or data collection. NR 51 TC 3 Z9 3 U1 0 U2 10 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD AUG 29 PY 2014 VL 9 IS 8 AR e105242 DI 10.1371/journal.pone.0105242 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AO2EE UT WOS:000341127500037 PM 25170845 ER PT J AU Pevnick, JM Li, N Asch, SM Jackevicius, CA Bell, DS AF Pevnick, Joshua M. Li, Ning Asch, Steven M. Jackevicius, Cynthia A. Bell, Douglas S. TI Effect of electronic prescribing with formulary decision support on medication tier, copayments, and adherence SO BMC MEDICAL INFORMATICS AND DECISION MAKING LA English DT Article DE Clinical decision support; Electronic prescribing; Medication adherence ID DRUG-THERAPY; HEALTH; IMPACT; CARE; INTERVENTIONS; PERSISTENCE; ADOPTION; RECORDS; ASTHMA; COST AB Background: Medication non-adherence is prevalent. We assessed the effect of electronic prescribing (e-prescribing) with formulary decision support on preferred formulary tier usage, copayment, and concomitant adherence. Methods: We retrospectively analyzed 14,682 initial pharmaceutical claims for angiotensin receptor blocker and inhaled steroid medications among 14,410 patients of 2189 primary care physicians (PCPs) who were offered e-prescribing with formulary decision support, including 297 PCPs who adopted it. Formulary decision support was initially non-interruptive, such that formulary tier symbols were displayed adjacent to medication names. Subsequently, interruptive formulary decision support alerts also interrupted e-prescribing when preferred-tier alternatives were available. A difference in differences design was used to compare the pre-post differences in medication tier for each new prescription attributed to non-adopters, low user (<30% usage rate), and high user PCPs (>30% usage rate). Second, we modeled the effect of formulary tier on prescription copayment. Last, we modeled the effect of copayment on adherence (proportion of days covered) to each new medication. Results: Compared with non-adopters, high users of e-prescribing were more likely to prescribe preferred-tier medications (vs. non-preferred tier) when both non-interruptive and interruptive formulary decision support were in place (OR 1.9 [95% CI 1.0-3.4], p = 0.04), but no more likely to prescribe preferred-tier when only non-interruptive formulary decision support was in place (p = 0.90). Preferred-tier claims had only slightly lower mean monthly copayments than non-preferred tier claims (angiotensin receptor blocker: $ 10.60 versus $ 11.81, inhaled steroid: $ 14.86 versus $ 16.42, p < 0.0001). Medication possession ratio was 8% lower for each $ 1.00 increase in monthly copayment to the one quarter power (p < 0.0001). However, we detected no significant direct association between formulary decision support usage and adherence. Conclusion: Interruptive formulary decision support shifted prescribing toward preferred tiers, but these medications were only minimally less expensive in the studied patient population. In this context, formulary decision support did not significantly increase adherence. To impact cost-related non-adherence, formulary decision support will likely need to be paired with complementary drug benefit design. Formulary decision support should be studied further, with particular attention to its effect on adherence in the setting of different benefit designs. C1 [Pevnick, Joshua M.] Cedars Sinai Hlth Syst, Dept Med, Div Gen Internal Med, Los Angeles, CA 90048 USA. [Pevnick, Joshua M.; Bell, Douglas S.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Li, Ning] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biomath, Los Angeles, CA 90095 USA. [Asch, Steven M.] Stanford Sch Med, Palo Alto, CA USA. [Asch, Steven M.] Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Jackevicius, Cynthia A.] Inst Clin Evaluat Sci, Toronto, ON, Canada. [Jackevicius, Cynthia A.] Univ Hlth Network, Toronto, ON, Canada. [Jackevicius, Cynthia A.] Univ Toronto, Fac Med, Dept Hlth Policy Management & Evaluat, Toronto, ON, Canada. [Jackevicius, Cynthia A.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Jackevicius, Cynthia A.] Western Univ Hlth Sci, Coll Pharm, Dept Pharm Practice & Adm, Pomona, CA USA. [Bell, Douglas S.] RAND Hlth, Santa Monica, CA USA. RP Pevnick, JM (reprint author), Cedars Sinai Hlth Syst, Dept Med, Div Gen Internal Med, 8700 Beverly Blvd,PACT 400-8G, Los Angeles, CA 90048 USA. EM jpevnick@gmail.com FU Agency for Healthcare Research and Quality [1U18HS016391-01]; Burns and Allen Research Institute at Cedars-Sinai Medical Center; National Center for Advancing Translational Science [UL1TR000124] FX This data was initially gathered during work on grant 1U18HS016391-01 funded by the Agency for Healthcare Research and Quality as part of a larger set of e-prescribing pilot studies (Dr. Bell). This work was also supported by a Clinical Scholars Research Grant from the Burns and Allen Research Institute at Cedars-Sinai Medical Center (Dr. Pevnick), and by the National Center for Advancing Translational Science, Grant UL1TR000124 (Drs. Bell and Pevnick). The authors have no conflicts of interest to disclose. NR 30 TC 2 Z9 2 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6947 J9 BMC MED INFORM DECIS JI BMC Med. Inform. Decis. Mak. PD AUG 28 PY 2014 VL 14 AR 79 DI 10.1186/1472-6947-14-79 PG 12 WC Medical Informatics SC Medical Informatics GA AS2KJ UT WOS:000344108600001 PM 25167807 ER PT J AU Papay, K Xie, SX Stern, M Hurtig, H Siderowf, A Duda, JE Minger, J Weintraub, D AF Papay, Kimberly Xie, Sharon X. Stern, Matthew Hurtig, Howard Siderowf, Andrew Duda, John E. Minger, James Weintraub, Daniel TI Naltrexone for impulse control disorders in Parkinson disease A placebo-controlled study SO NEUROLOGY LA English DT Article ID ALZHEIMER-DISEASE; LONGITUDINAL DATA; DEPRESSION; BEHAVIORS; TRIAL; ANTAGONIST; AMANTADINE; DEPENDENCE; SYMPTOMS; MODELS AB Objective: Impulse control disorders (ICDs) in Parkinson disease (PD) are common and can be difficult to manage. The objective of this study was to determine the efficacy and tolerability of naltrexone, an opioid antagonist, for the treatment of ICDs in PD. Methods: Patients with PD (n = 50) and an ICD were enrolled in an 8-week, randomized (1: 1), double-blind, placebo-controlled study of naltrexone 50-100 mg/d (flexible dosing). The primary outcome measure was response based on the Clinical Global Impression-Change score, and the secondary outcome measure was change in symptom severity using the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) ICD score. Results: Forty-five patients (90%) completed the study. The Clinical Global Impression-Change response rate difference favoring naltrexone in completers was 19.8%(95% confidence interval [CI] -8.7% to 44.2%). While this difference was not significant (odds ratio = 1.6, 95% CI 0.5-5.2, Wald x(2) [df] = 0.5 [1], p = 0.5), naltrexone treatment led to a significantly greater decrease in QUIP-RS ICD score over time compared with placebo (regression coefficient for interaction term in linear mixed-effects model = 27.37, F[df] = 4.3 [1, 49], p = 0.04). The estimated changes in QUIP-RS ICD scores from baseline to week 8 were 14.9 points (95% CI 9.9-19.9) for naltrexone and 7.5 points (95% CI 2.5-12.6) for placebo. Conclusions: Naltrexone treatment was not efficacious for the treatment of ICDs in PD using a global assessment of response, but findings using a PD-specific ICD rating scale support further evaluation of opioid antagonists for the treatment of ICD symptoms in PD. Classification of evidence: This study provides Class I evidence that in patients with PD and an ICD, naltrexone does not significantly increase the probability of achieving response. However, the study lacked the precision to exclude an important difference in response rates. C1 [Papay, Kimberly; Weintraub, Daniel] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Xie, Sharon X.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Stern, Matthew; Hurtig, Howard; Duda, John E.; Minger, James] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Siderowf, Andrew] Avid Radiopharmaceut, Philadelphia, PA USA. [Duda, John E.; Weintraub, Daniel] Philadelphia Vet Affairs Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA USA. RP Weintraub, D (reprint author), Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. EM daniel.weintraub@uphs.upenn.edu FU Clinical Intervention Award from the Michael J. Fox Foundation for Parkinson's Research [NCT1052831] FX This study was funded by a Clinical Intervention Award from the Michael J. Fox Foundation for Parkinson's Research (D.W., NCT1052831). NR 39 TC 14 Z9 15 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD AUG 26 PY 2014 VL 83 IS 9 BP 826 EP 833 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA AO1SY UT WOS:000341096100012 PM 25037206 ER PT J AU Stefan, M Wei, CG Lombardi, A Li, CW Concepcion, ES Inabnet, WB Owen, R Zhang, WJ Tomer, Y AF Stefan, Mihaela Wei, Chengguo Lombardi, Angela Li, Cheuk Wun Concepcion, Erlinda S. Inabnet, William B., III Owen, Randall Zhang, Weijia Tomer, Yaron TI Genetic-epigenetic dysregulation of thymic TSH receptor gene expression triggers thyroid autoimmunity SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE histone modifications; interferon; thyroiditis ID INTERFERON-INDUCED THYROIDITIS; GRAVES-DISEASE; CHROMATIN-STRUCTURE; ALPHA; TRANSCRIPTION; ASSOCIATION; BINDING; CELLS; SUSCEPTIBILITY; TOLERANCE AB Graves disease (GD) is an autoimmune condition caused by interacting genetic and environmental factors. Genetic studies have mapped several single-nucleotide polymorphisms (SNPs) that are strongly associated with GD, but the mechanisms by which they trigger disease are unknown. We hypothesized that epigenetic modifications induced by microenvironmental influences of cytokines can reveal the functionality of GD-associated SNPs. We analyzed genome-wide histone H3 lysine 4 methylation and gene expression in thyroid cells induced by IFN alpha, a key cytokine secreted during viral infections, and overlapped them with known GD-associated SNPs. We mapped an open chromatin region overlapping two adjacent GD-associated SNPs (rs12101255 and rs12101261) in intron 1 of the thyroid stimulating hormone receptor (TSHR) gene. We then demonstrated that this region functions as a regulatory element through binding of the transcriptional repressor promyelocytic leukemia zinc finger protein (PLZF) at the rs12101261 site. Repression by PLZF depended on the rs12101261 disease susceptibility allele and was increased by IFNa. Intrathymic TSHR expression was decreased in individuals homozygous for the rs12101261 disease-associated genotype compared with carriers of the disease-protective allele. Our studies discovered a genetic-epigenetic interaction involving a noncoding SNP in the TSHR gene that regulates thymic TSHR gene expression and facilitates C1 [Stefan, Mihaela; Lombardi, Angela; Li, Cheuk Wun; Concepcion, Erlinda S.; Tomer, Yaron] Icahn Sch Med Mt Sinai, Div Endocrinol, New York, NY 10029 USA. [Stefan, Mihaela; Tomer, Yaron] James J Peters Vet Adm Med Ctr, Bronx, NY 10468 USA. [Wei, Chengguo; Zhang, Weijia] Icahn Sch Med Mt Sinai, Dept Med Bioinformat Core, New York, NY 10029 USA. [Inabnet, William B., III; Owen, Randall] Icahn Sch Med Mt Sinai, Dept Surg, New York, NY 10029 USA. RP Tomer, Y (reprint author), Icahn Sch Med Mt Sinai, Div Endocrinol, New York, NY 10029 USA. EM yaron.tomer@mssm.edu FU National Institute of Diabetes and Digestive and Kidney Diseases [DK061659, DK067555, DK073681]; Department of Veterans Affairs (VA), Office of Research and Development; VA Biomedical Laboratory Research and Development Merit Award [1I01BX002031] FX We thank Dr. Rauf Latif for helpful advice. This work was supported in part by Grants DK061659, DK067555, and DK073681 from the National Institute of Diabetes and Digestive and Kidney Diseases (to Y.T.). In addition, this material is based upon work supported in part by the Department of Veterans Affairs (VA), Office of Research and Development, and by VA Biomedical Laboratory Research and Development Merit Award 1I01BX002031 (to Y.T.). NR 36 TC 18 Z9 21 U1 1 U2 15 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 26 PY 2014 VL 111 IS 34 BP 12562 EP 12567 DI 10.1073/pnas.1408821111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AN7LA UT WOS:000340780300065 PM 25122677 ER PT J AU Marshall, KM He, SQ Zhong, Z Atkinson, C Tomlinson, S AF Marshall, Keely M. He, Songqing Zhong, Zhi Atkinson, Carl Tomlinson, Stephen TI Dissecting the complement pathway in hepatic injury and regeneration with a novel protective strategy SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID MEMBRANE ATTACK COMPLEX; ISCHEMIA-REPERFUSION INJURY; C5A RECEPTOR ANTAGONIST; LIVER-REGENERATION; ISCHEMIA/REPERFUSION INJURY; MONOCLONAL-ANTIBODY; PARTIAL-HEPATECTOMY; NLRP3 INFLAMMASOME; KUPFFER CELLS; MICE AB Liver resection is commonly performed under ischemic conditions, resulting in two types of insult to the remnant liver: ischemia reperfusion injury (IRI) and loss of liver mass. Complement inhibition is recognized as a potential therapeutic modality for IRI, but early complement activation products are also essential for liver regeneration. We describe a novel site-targeted murine complement inhibitor, CR2-CD59, which specifically inhibits the terminal membrane attack complex (MAC), and we use this protein to investigate the complement-dependent balance between liver injury and regeneration in a clinical setting of pharmacological inhibition. CR2-CD59 did not impact in vivo generation of C3 and C5 activation products but was as effective as the C3 activation inhibitor CR2-Crry at ameliorating hepatic IRI, indicating that the MAC is the principle mediator of hepatic IRI. Furthermore, unlike C3 or C5 inhibition, CR2-CD59 was not only protective but significantly enhanced hepatocyte proliferation after partial hepatectomy, including when combined with ischemia and reperfusion. Remarkably, CR2-CD59 also enhanced regeneration after 90% hepatectomy and improved long-term survival from 0 to 70%. CR2-CD59 functioned by increasing hepatic TNF and IL-6 levels with associated STAT3 and Akt activation, and by preventing mitochondrial depolarization and allowing recovery of ATP stores. C1 [Marshall, Keely M.; He, Songqing; Atkinson, Carl; Tomlinson, Stephen] Med Univ S Carolina, Darby Childrens Res Inst, Dept Microbiol & Immunol, Charleston, SC 29425 USA. [Zhong, Zhi] Med Univ S Carolina, Dept Drug Discovery & Biomed Sci, Charleston, SC 29425 USA. [He, Songqing] Guilin Med Univ, Affiliated Hosp, Dept Hepatobiliary Surg, Guilin 541001, Guangxi, Peoples R China. [Tomlinson, Stephen] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. RP Tomlinson, S (reprint author), Med Univ S Carolina, Darby Childrens Res Inst, Dept Microbiol & Immunol, Charleston, SC 29425 USA. EM tomlinss@musc.edu FU National Institutes of Health [R56 AI095657, R01 HL86576, R01 HL082485]; National Natural Science Foundation of China [81160066, 31370917]; Guangxi Natural Science Foundation [2013GXNSFCA019012]; Science & Technology Planning Project of Guangxi Province [1140003-79]; Science & Technology Planning Project of Guilin City [20110119-1-8] FX This work was supported by grants from the National Institutes of Health (R56 AI095657, R01 HL86576, and R01 HL082485), the National Natural Science Foundation of China (81160066 and 31370917), Guangxi Natural Science Foundation (2013GXNSFCA019012), the Science & Technology Planning Project of Guangxi Province (1140003-79), and the Science & Technology Planning Project of Guilin City (20110119-1-8). NR 55 TC 11 Z9 13 U1 3 U2 9 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 EI 1540-9538 J9 J EXP MED JI J. Exp. Med. PD AUG 25 PY 2014 VL 211 IS 9 BP 1793 EP 1805 DI 10.1084/jem.20131902 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA AQ4EA UT WOS:000342744500010 PM 25113972 ER PT J AU Simmons, DA Knowles, JK Belichenko, NP Banerjee, G Finkle, C Massa, SM Longo, FM AF Simmons, Danielle A. Knowles, Juliet K. Belichenko, Nadia P. Banerjee, Gargi Finkle, Carly Massa, Stephen M. Longo, Frank M. TI A Small Molecule p75(NTR) Ligand, LM11A-31, Reverses Cholinergic Neurite Dystrophy in Alzheimer's Disease Mouse Models with Mid- to Late-Stage Disease Progression SO PLOS ONE LA English DT Article ID P75 NEUROTROPHIN RECEPTOR; NERVE GROWTH-FACTOR; AMYLOID PRECURSOR PROTEIN; BASAL FOREBRAIN NEURONS; TRANSGENIC MICE; COGNITIVE IMPAIRMENT; BETA PROTEIN; EXPRESSION; BRAIN; DEFICITS AB Degeneration of basal forebrain cholinergic neurons contributes significantly to the cognitive deficits associated with Alzheimer's disease (AD) and has been attributed to aberrant signaling through the neurotrophin receptor p75 (p75(NTR)). Thus, modulating p75(NTR) signaling is considered a promising therapeutic strategy for AD. Accordingly, our laboratory has developed small molecule p75(NTR) ligands that increase survival signaling and inhibit amyloid-beta-induced degenerative signaling in in vitro studies. Previous work found that a lead p75(NTR) ligand, LM11A-31, prevents degeneration of cholinergic neurites when given to an AD mouse model in the early stages of disease pathology. To extend its potential clinical applications, we sought to determine whether LM11A-31 could reverse cholinergic neurite atrophy when treatment begins in AD mouse models having mid-to late stages of pathology. Reversing pathology may have particular clinical relevance as most AD studies involve patients that are at an advanced pathological stage. In this study, LM11A-31 (50 or 75 mg/kg) was administered orally to two AD mouse models, Thy-1 hAPP(Lond/Swe) (APP(L/S)) and Tg2576, at age ranges during which marked AD-like pathology manifests. In mid-stage male APP(L/S) mice, LM11A-31 administered for 3 months starting at 6-8 months of age prevented and/or reversed atrophy of basal forebrain cholinergic neurites and cortical dystrophic neurites. Importantly, a 1 month LM11A-31 treatment given to male APP(L/S) mice (12-13 months old) with late-stage pathology reversed the degeneration of cholinergic neurites in basal forebrain, ameliorated cortical dystrophic neurites, and normalized increased basal forebrain levels of p75(NTR). Similar results were seen in female Tg2576 mice. These findings suggest that LM11A-31 can reduce and/or reverse fundamental AD pathologies in late-stage AD mice. Thus, targeting p75(NTR) is a promising approach to reducing AD-related degenerative processes that have progressed beyond early stages. C1 [Simmons, Danielle A.; Knowles, Juliet K.; Belichenko, Nadia P.; Banerjee, Gargi; Finkle, Carly; Longo, Frank M.] Stanford Univ, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA. [Knowles, Juliet K.; Longo, Frank M.] Univ N Carolina, Dept Neurol, Chapel Hill, NC USA. [Massa, Stephen M.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Massa, Stephen M.] Univ Calif San Francisco, Lab Computat Neurochem & Drug Discovery, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. RP Longo, FM (reprint author), Stanford Univ, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA. EM longo@stanford.edu FU Veteran's Administration; [NIA UO1 AG032225]; [NINDS F30 NA051971] FX This work was supported by grants NIA UO1 AG032225 (FML), NINDS F30 NA051971 (JKK) and the Veteran's Administration (SMM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 56 TC 10 Z9 10 U1 1 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD AUG 25 PY 2014 VL 9 IS 8 AR e102136 DI 10.1371/journal.pone.0102136 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AN9TR UT WOS:000340952200004 PM 25153701 ER PT J AU Gallun, FJ Diedesch, AC Kampel, SD Jakien, KM AF Gallun, Frederick J. Diedesch, Anna C. Kampel, Sean D. Jakien, Kasey M. TI Independent impacts of age and hearing loss on spatial release in a complex auditory environment (vol 8, pg 264, 2014) SO FRONTIERS IN NEUROSCIENCE LA English DT Correction DE spatial hearing; aging; hearing loss; virtual spatial array; sensation level C1 [Gallun, Frederick J.; Kampel, Sean D.] Portland VA Med Ctr, Natl Ctr Rehabil Auditory Res, Dept Vet Affairs, Portland, OR 97239 USA. [Gallun, Frederick J.; Jakien, Kasey M.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Diedesch, Anna C.] Vanderbilt Univ, Nashville, TN 37235 USA. RP Gallun, FJ (reprint author), Portland VA Med Ctr, Natl Ctr Rehabil Auditory Res, Dept Vet Affairs, Portland, OR 97239 USA. EM frederick.gallun@va.gov NR 2 TC 0 Z9 0 U1 1 U2 1 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-453X J9 FRONT NEUROSCI-SWITZ JI Front. Neurosci. PD AUG 22 PY 2014 VL 8 AR 264 DI 10.3389/fnins.2014.00264 PG 1 WC Neurosciences SC Neurosciences & Neurology GA AW8KY UT WOS:000346511900001 ER PT J AU Shen, KZ Yakhnitsa, V Munhall, AC Johnson, SW AF Shen, K. -Z. Yakhnitsa, V. Munhall, A. C. Johnson, S. W. TI AMP KINASE REGULATES K-ATP CURRENTS EVOKED BY NMDA RECEPTOR STIMULATION IN RAT SUBTHALAMIC NUCLEUS NEURONS SO NEUROSCIENCE LA English DT Article DE AMP kinase; NMDA; Subthalamic nucleus; Brain slice; K-ATP; Patch-clamp ID ACTIVATED PROTEIN-KINASE; SENSITIVE POTASSIUM CHANNELS; CENTRAL-NERVOUS-SYSTEM; INSULIN-SECRETION; IN-VITRO; GLOBUS-PALLIDUS; CELLULAR-ENERGY; ARCUATE NUCLEUS; NEUROPEPTIDE-Y; BASAL GANGLIA AB Our lab recently showed that N-methyl-D-aspartate (NMDA) evokes ATP-sensitive K+ (K-ATP) currents in subthalamic nucleus (STN) neurons in slices of the rat brain. Both K-ATP channels and 5'-adenosine monophosphate-activated protein kinase (AMPK) are considered cellular energy sensors because their activities are influenced by the phosphorylation state of adenosine nucleotides. Moreover, AMPK has been shown to regulate K-ATP function in a variety of tissues including pancreas, cardiac myocytes, and hypothalamus. We used whole-cell patch clamp recordings to study the effect of AMPK activation on K-ATP channel function in STN neurons in slices of the rat brain. We found that bath or intracellular application of the AMPK activators A769662 and PT1 augmented tolbutamide-sensitive K-ATP currents evoked by NMDA receptor stimulation. The effect of AMPK activators was blocked by the AMPK inhibitor dorsomorphin (compound C), and by STO609, an inhibitor of the upstream AMPK activator CaMKK beta. AMPK augmentation of NMDA-induced K-ATP current was also blocked by intracellular BAPTA and by inhibitors of nitric oxide synthase and guanylyl cyclase. However, A769662 did not augment currents evoked by the K-ATP channel opener diazoxide. In the presence of NMDA, A769662 inhibited depolarizing plateau potentials and burst firing, both of which could be antagonized by tolbutamide or dorsomorphin. These studies show that AMPK augments NMDA-induced K-ATP currents by a Ca2+-dependent process that involves nitric oxide and cGMP. By augmenting K-ATP currents, AMPK activation would be expected to dampen the excitatory effect of glutamate-mediated transmission in the STN. Published by Elsevier Ltd. on behalf of IBRO. C1 [Shen, K. -Z.; Yakhnitsa, V.; Munhall, A. C.; Johnson, S. W.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. [Johnson, S. W.] Portland VA Med Ctr, Portland, OR 97207 USA. RP Johnson, SW (reprint author), Portland VA Med Ctr, Portland, OR 97207 USA. EM johnsost@ohsu.edu FU NIH [NS038715]; Portland Veterans Affairs Parkinson's Disease Research, Education, and Clinical Center FX This work was supported by NIH grant NS038715 and by the Portland Veterans Affairs Parkinson's Disease Research, Education, and Clinical Center. NR 59 TC 5 Z9 5 U1 0 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 EI 1873-7544 J9 NEUROSCIENCE JI Neuroscience PD AUG 22 PY 2014 VL 274 BP 138 EP 152 DI 10.1016/j.neuroscience.2014.05.031 PG 15 WC Neurosciences SC Neurosciences & Neurology GA AK8XO UT WOS:000338712300014 PM 24875176 ER PT J AU Woo, JH Wang, SM Melhem, ER Gee, JC Cucchiara, A McCluskey, L Elman, L AF Woo, John H. Wang, Sumei Melhem, Elias R. Gee, James C. Cucchiara, Andrew McCluskey, Leo Elman, Lauren TI Linear Associations between Clinically Assessed Upper Motor Neuron Disease and Diffusion Tensor Imaging Metrics in Amyotrophic Lateral Sclerosis SO PLOS ONE LA English DT Article ID CORTICOSPINAL TRACT; WHITE-MATTER; MRI; ALS; REGISTRATION; TRACTOGRAPHY; INVOLVEMENT; ATLAS; TOOL AB Objective: To assess the relationship between clinically assessed Upper Motor Neuron (UMN) disease in Amyotrophic Lateral Sclerosis (ALS) and local diffusion alterations measured in the brain corticospinal tract (CST) by a tractography-driven template-space region-of-interest (ROI) analysis of Diffusion Tensor Imaging (DTI). Methods: This cross-sectional study included 34 patients with ALS, on whom DTI was performed. Clinical measures were separately obtained including the Penn UMN Score, a summary metric based upon standard clinical methods. After normalizing all DTI data to a population-specific template, tractography was performed to determine a region-of-interest (ROI) outlining the CST, in which average Mean Diffusivity (MD) and Fractional Anisotropy (FA) were estimated. Linear regression analyses were used to investigate associations of DTI metrics (MD, FA) with clinical measures (Penn UMN Score, ALSFRS-R, duration-of-disease), along with age, sex, handedness, and El Escorial category as covariates. Results: For MD, the regression model was significant (p = 0.02), and the only significant predictors were the Penn UMN Score (p = 0.005) and age (p = 0.03). The FA regression model was also significant (p = 0.02); the only significant predictor was the Penn UMN Score (p = 0.003). Conclusions: Measured by the template-space ROI method, both MD and FA were linearly associated with the Penn UMN Score, supporting the hypothesis that DTI alterations reflect UMN pathology as assessed by the clinical examination. C1 [Woo, John H.; Wang, Sumei; Gee, James C.] Univ Penn, Dept Radiol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Cucchiara, Andrew] Univ Penn, Dept Biostat & Epidemiol, Perelman Sch Med, Philadelphia, PA 19104 USA. [McCluskey, Leo; Elman, Lauren] Univ Penn, Dept Neurol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Woo, John H.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Melhem, Elias R.] Univ Maryland, Dept Radiol, Baltimore, MD 21201 USA. RP Woo, JH (reprint author), Univ Penn, Dept Radiol, Perelman Sch Med, Philadelphia, PA 19104 USA. EM john.woo@uphs.upenn.edu FU National Institutes of Health [NS063111, NS065347, DA022807, NS045839, AG032953]; Greater Philadelphia Chapter of the ALS Association; Philadelphia Veterans Affairs Medical Center; National Center for Advancing Translational Sciences (NCATS) of the NIH [UL1TR000003] FX The authors acknowledge the financial support of the following institutions: National Institutes of Health (NS063111, NS065347, DA022807, NS045839, AG032953), the Greater Philadelphia Chapter of the ALS Association, and the Philadelphia Veterans Affairs Medical Center. This project was also supported by Grant Number UL1TR000003 from the National Center for Advancing Translational Sciences (NCATS) of the NIH. The content is solely the responsibility of the authors and does not necessarily represent the official view of NCATS or the NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 22 TC 3 Z9 3 U1 1 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD AUG 21 PY 2014 VL 9 IS 8 AR e105753 DI 10.1371/journal.pone.0105753 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AO1WL UT WOS:000341106100118 PM 25144708 ER PT J AU McDougal, SJ Alexander, J Dhanireddy, S Harrington, RD Stekler, JD AF McDougal, Sarah J. Alexander, Jeremiah Dhanireddy, Shireesha Harrington, Robert D. Stekler, Joanne D. TI Non-Occupational Post-Exposure Prophylaxis for HIV: 10-Year Retrospective Analysis in Seattle, Washington SO PLOS ONE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; INJECTION-DRUG EXPOSURE; SEXUAL EXPOSURE; COST-EFFECTIVENESS; ZIDOVUDINE TREATMENT; UNITED-STATES; INFECTION; RISK; MEN; TRANSMISSION AB Despite treatment guidelines in place since 2005, non-occupational post-exposure HIV prophylaxis (nPEP) remains an underutilized prevention strategy. We conducted a retrospective chart review of patients presenting to a publicly-funded HIV clinic in Seattle, Washington for nPEP between 2000 and 2010 (N = 360). nPEP prescriptions were provided for 324 (90%) patients; 83% of prescription decisions were appropriate according to Centers for Disease Control and Prevention guidelines, but only 31% (N = 111/360) of patients were considered "high risk.'' In order to use limited resources most efficiently, public health agencies should target messaging for this high-cost intervention to individuals with high-risk HIV exposures. C1 [McDougal, Sarah J.; Alexander, Jeremiah; Dhanireddy, Shireesha; Harrington, Robert D.; Stekler, Joanne D.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Stekler, Joanne D.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Alexander, Jeremiah] Vet Affairs Puget Sound, Gen Med Serv, Seattle, WA USA. RP McDougal, SJ (reprint author), Univ Washington, Dept Med, Seattle, WA 98195 USA. EM sjmcd13@uw.edu NR 36 TC 4 Z9 4 U1 3 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD AUG 20 PY 2014 VL 9 IS 8 AR e105030 DI 10.1371/journal.pone.0105030 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AQ3JB UT WOS:000342687200048 PM 25140868 ER PT J AU Tsai, J Elhai, JD Pietrzak, RH Hoff, RA Harpaz-Rotem, I AF Tsai, Jack Elhai, Jon D. Pietrzak, Robert H. Hoff, Rani A. Harpaz-Rotem, Ilan TI Comparing four competing models of depressive symptomatology: A confirmatory factor analytic study of 986,647 US veterans SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Depression; Veterans; Confirmatory factor analyses ID SPINAL-CORD-INJURY; PATIENT HEALTH QUESTIONNAIRE-9; NATIONAL-COMORBIDITY-SURVEY; OF-FIT INDEXES; MAJOR DEPRESSION; PRIMARY-CARE; SYMPTOMS; EPIDEMIOLOGY; ANXIETY; INVARIANCE AB Background: Few rigorous studies have examined the factor structure of major depression symptoms as assessed by current diagnostic systems. This study evaluated four competing models of depressive symptomatology among a large, heterogeneous sample of U.S. veterans. Methods: To determine the best fitting model of major depressive symptoms among four competing models, this study conducted a series of confirmatory factor analyses on a national sample of 986,647 U.S. veterans. Results: A two-factor model first reported by Krause, Reed, and McArdle (2010) provided superior fit to symptom-level data compared to three other models. The optimal model consists of a somatic factor including anhedonia, sleep difficulties, fatigue, appetite changes, concentration difficulties, and psychomotor agitation; and a non-somatic factor including depressed mood, feelings of worthlessness, and thoughts of death. Factorial invariance testing found this model to be invariant by gender and major depression diagnosis. Limitations: A widely used self-report measure of depression was used and the sample consisted solely of veterans so further study is needed with clinician-administered measures and non-veteran samples. Conclusions: Together, these findings support separating symptoms of major depression into somatic and non-somatic factors which may have clinical relevance, and help clarify debates about the factor structure of depressive symptoms. Published by Elsevier B.V. C1 [Tsai, Jack] US Dept Vet Affairs, New England Mental Illness Res Educ & Clin Ctr, West Haven, CT 06516 USA. [Tsai, Jack; Pietrzak, Robert H.; Hoff, Rani A.; Harpaz-Rotem, Ilan] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06510 USA. [Elhai, Jon D.] Univ Toledo, Dept Psychol, Toledo, OH 43606 USA. [Elhai, Jon D.] Univ Toledo, Dept Psychiat, Toledo, OH 43606 USA. [Pietrzak, Robert H.; Harpaz-Rotem, Ilan] VA Connecticut Healthcare Syst, US Dept Vet Affairs, Natl Ctr Posttraumat Stress Disorder, Clin Neurosci Div, West Haven, CT 06516 USA. [Hoff, Rani A.] Vet Affairs Northeast Program Evaluat Ctr, West Haven, CT 06516 USA. RP Tsai, J (reprint author), US Dept Vet Affairs, New England Mental Illness Res Educ & Clin Ctr, 950 Campbell Ave,151D, West Haven, CT 06516 USA. EM Jack.Tsai@yale.edu OI Tsai, Jack/0000-0002-0329-648X FU Bristol Meyers Squibb Foundation; United States Department of Veterans Affairs, Office of Research and Development FX None of the authors report any conflicts of interest related to this work. Dr. Tsai has received funding from the Bristol Meyers Squibb Foundation, which had no influence on this work. This work was supported by the United States Department of Veterans Affairs, Office of Research and Development. The views presented here are those of the authors alone and do not represent the position of any federal agency or of the United States Government. NR 24 TC 6 Z9 6 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 EI 1573-2517 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD AUG 20 PY 2014 VL 165 BP 166 EP 169 DI 10.1016/j.jad.2014.04.075 PG 4 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AJ7FF UT WOS:000337861900026 PM 24882195 ER PT J AU Kansagara, D Papak, J Pasha, AS O'Neil, M Freeman, M Relevo, R Quinones, A Motu'apuaka, M Jou, JH AF Kansagara, Devan Papak, Joel Pasha, Amirala S. O'Neil, Maya Freeman, Michele Relevo, Rose Quinones, Ana Motu'apuaka, Makalapua Jou, Janice H. TI Screening for Hepatocellular Carcinoma in Chronic Liver Disease A Systematic Review SO ANNALS OF INTERNAL MEDICINE LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; CHRONIC VIRAL-HEPATITIS; CIRRHOTIC-PATIENTS; PATIENT SURVIVAL; NATURAL-HISTORY; SURVEILLANCE PROGRAM; COST-EFFECTIVENESS; CLINICAL-PRACTICE; CANCER INCIDENCE; EARLY-DIAGNOSIS AB Background: Guidelines recommend routine screening for hepatocellular carcinoma (HCC) in high-risk patients, but the strength of evidence supporting these recommendations is unclear. Purpose: To review the benefits and harms of HCC screening in patients with chronic liver disease. Data Sources: MEDLINE, PsycINFO, and ClinicalTrials.gov from inception to April 2014; Cochrane databases to June 2013; reference lists; and technical advisors. Study Selection: English-language trials and observational studies comparing screening versus no screening, studies of harms, and trials comparing different screening intervals. Data Extraction: Mortality and adverse events were the outcomes of interest. Individual-study quality and the overall strength of evidence were dual-reviewed using published criteria. Data Synthesis: Of 13 801 citations, 22 studies met inclusion criteria. The overall strength of evidence on the effects of screening was very low. One large trial of patients with hepatitis B found decreased HCC mortality with periodic ultrasonographic screening (rate ratio, 0.63 [95% CI, 0.41 to 0.98]), but the study was limited by methodological flaws. Another trial in patients with hepatitis B found no survival benefit with periodic alpha-fetoprotein screening. In 18 observational studies, screened patients had earlier-stage HCC than clinically diagnosed patients, but lead- and length-time biases confounded the effects on mortality. Two trials found no survival differences between shorter (3- to 4-month) and longer (6- to 12-month) screening intervals. Harms of screening were not well-studied. Limitations: Only English-language studies were included. The evidence base is limited by methodological issues and a paucity of trials. Conclusion: There is very-low-strength evidence about the effects of HCC screening on mortality in patients with chronic liver disease. Screening tests can identify early-stage HCC, but whether systematic screening leads to a survival advantage over clinical diagnosis is uncertain. C1 [Kansagara, Devan; O'Neil, Maya; Freeman, Michele; Relevo, Rose] Portland VA Med Ctr, Portland, OR 97239 USA. [Papak, Joel; Jou, Janice H.] Portland VA Med Ctr, Dept Med, Portland, OR 97239 USA. [Pasha, Amirala S.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97239 USA. [Quinones, Ana] Oregon Hlth & Sci Univ, Portland, OR 97239 USA. [Motu'apuaka, Makalapua] Oregon Evidence Based Practice Ctr, Portland, OR 97233 USA. RP Kansagara, D (reprint author), Portland VA Med Ctr, RD71,3710 SW US Veterans Hosp Rd, Portland, OR 97239 USA. EM kansagar@ohsu.edu FU U.S. Department of Veterans Affairs Quality Enhancement Research Initiative FX U.S. Department of Veterans Affairs Quality Enhancement Research Initiative. NR 56 TC 38 Z9 39 U1 2 U2 8 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD AUG 19 PY 2014 VL 161 IS 4 BP 261 EP + DI 10.7326/M14-0558 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA AP8RU UT WOS:000342347300016 PM 24934699 ER PT J AU Zipkin, DA Umscheid, CA Keating, NL Allen, E Aung, K Beyth, R Kaatz, S Mann, DM Sussman, JB Korenstein, D Schardt, C Nagi, A Sloane, R Feldstein, DA AF Zipkin, Daniella A. Umscheid, Craig A. Keating, Nancy L. Allen, Elizabeth Aung, Koko Beyth, Rebecca Kaatz, Scott Mann, Devin M. Sussman, Jeremy B. Korenstein, Deborah Schardt, Connie Nagi, Avishek Sloane, Richard Feldstein, David A. TI Evidence-Based Risk Communication A Systematic Review SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; BREAST-CANCER RISKS; DECISION-MAKING; PRESENTING RISK; DIFFERENT FORMATS; RELATIVE RISK; QUANTITATIVE INFORMATION; FRAMING INFORMATION; INFORMING PATIENTS; TREATMENT CHOICES AB Background: Effective communication of risks and benefits to patients is critical for shared decision making. Purpose: To review the comparative effectiveness of methods of communicating probabilistic information to patients that maximize their cognitive and behavioral outcomes. Data Sources: PubMed (1966 to March 2014) and CINAHL, EMBASE, and the Cochrane Central Register of Controlled Trials (1966 to December 2011) using several keywords and structured terms. Study Selection: Prospective or cross-sectional studies that recruited patients or healthy volunteers and compared any method of communicating probabilistic information with another method. Data Extraction: Two independent reviewers extracted study characteristics and assessed risk of bias. Data Synthesis: Eighty-four articles, representing 91 unique studies, evaluated various methods of numerical and visual risk display across several risk scenarios and with diverse outcome measures. Studies showed that visual aids (icon arrays and bar graphs) improved patients' understanding and satisfaction. Presentations including absolute risk reductions were better than those including relative risk reductions for maximizing accuracy and seemed less likely than presentations with relative risk reductions to influence decisions to accept therapy. The presentation of numbers needed to treat reduced understanding. Comparative effects of presentations of frequencies (such as 1 in 5) versus event rates (percentages, such as 20%) were inconclusive. Limitation: Most studies were small and highly variable in terms of setting, context, and methods of administering interventions. Conclusion: Visual aids and absolute risk formats can improve patients' understanding of probabilistic information, whereas numbers needed to treat can lessen their understanding. Due to study heterogeneity, the superiority of any single method for conveying probabilistic information is not established, but there are several good options to help clinicians communicate with patients. C1 [Zipkin, Daniella A.] Duke Univ, Med Ctr, Durham, NC 27710 USA. [Umscheid, Craig A.] Univ Penn, Ctr Evidence Based Practice, Philadelphia, PA 19104 USA. [Keating, Nancy L.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Allen, Elizabeth] Portland VA Med Ctr, Portland, OR 97207 USA. [Aung, Koko] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Beyth, Rebecca] North Florida South Georgia Vet Hlth Syst, Geriatric Res Educ & Clin Ctr T2 182, Gainesville, FL 32608 USA. [Kaatz, Scott] Hurley Med Ctr, Flint, MI 48503 USA. [Mann, Devin M.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Sussman, Jeremy B.] Ctr Clin Management Res, Ann Arbor, MI 48109 USA. [Korenstein, Deborah] Amer Coll Physicians, Philadelphia, PA 19106 USA. [Schardt, Connie] Univ N Carolina, Sch Lib & Informat Sci, Chapel Hill, NC 27599 USA. [Nagi, Avishek] Vet Affairs Med Ctr, Durham, NC 27705 USA. [Sloane, Richard] Duke Univ, Med Ctr, Ctr Study Aging, Durham, NC 27710 USA. [Feldstein, David A.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI 53705 USA. RP Zipkin, DA (reprint author), Duke Univ, Med Ctr, Box 2992, Durham, NC 27710 USA. EM daniella.zipkin@duke.edu OI Mann, Devin/0000-0002-2099-0852 NR 103 TC 41 Z9 41 U1 6 U2 32 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD AUG 19 PY 2014 VL 161 IS 4 BP 270 EP + DI 10.7326/M14-0295 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA AP8RU UT WOS:000342347300017 PM 25133362 ER PT J AU Liu, J Wang, PP Zou, LY Qu, J Litovsky, S Umeda, P Zhou, LF Chatham, J Marsh, SA Dell'Italia, LJ Lloyd, SG AF Liu, Jian Wang, Peipei Zou, Luyun Qu, Jing Litovsky, Silvio Umeda, Patrick Zhou, Lufang Chatham, John Marsh, Susan A. Dell'Italia, Louis J. Lloyd, Steven G. TI High-fat, low-carbohydrate diet promotes arrhythmic death and increases myocardial ischemia-reperfusion injury in rats SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE diet; myocardial ischemia; reperfusion injury; mitochondria; arrhythmia ID ACID OXIDATION; CARDIAC-FUNCTION; GENE-EXPRESSION; VENTRICULAR-FIBRILLATION; MITOCHONDRIAL DYNAMICS; LIPID-ACCUMULATION; HEART-DISEASE; HIGH-PROTEIN; DYSFUNCTION; ARRHYTHMOGENESIS AB High-fat, low-carbohydrate diets (HFLCD) are often eaten by humans for a variety of reasons, but the effects of such diets on the heart are incompletely understood. We evaluated the impact of HFLCD on myocardial ischemia/reperfusion (I/R) using an in vivo model of left anterior descending coronary artery ligation. Sprague-Dawley rats (300 g) were fed HFLCD (60% calories fat, 30% protein, 10% carbohydrate) or control (CONT; 16% fat, 19% protein, 65% carbohydrate) diet for 2 wk and then underwent open chest I/R. At baseline (preischemia), diet did not affect left ventricular (LV) systolic and diastolic function. Oil red O staining revealed presence of lipid in the heart with HFLCD but not in CONT. Following I/R, recovery of LV function was decreased in HFLCD. HFLCD hearts exhibited decreased ATP synthase and increased uncoupling protein-3 gene and protein expression. HFLCD downregulated mitochondrial fusion proteins and upregulated fission proteins and store-operated Ca2+ channel proteins. HFLCD led to increased death during I/R; 6 of 22 CONT rats and 16 of 26 HFLCD rats died due to ventricular arrhythmias and hemodynamic shock. In surviving rats, HFLCD led to larger infarct size. We concluded that in vivo HFLCD does not affect nonischemic LV function but leads to greater myocardial injury during I/R, with increased risk of death by pump failure and ventricular arrhythmias, which might be associated with altered cardiac energetics, mitochondrial fission/fusion dynamics, and store-operated Ca2+ channel expression. C1 [Liu, Jian; Qu, Jing; Umeda, Patrick; Zhou, Lufang; Dell'Italia, Louis J.; Lloyd, Steven G.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Zou, Luyun; Litovsky, Silvio; Chatham, John] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. [Wang, Peipei] Natl Univ Singapore, Natl Univ Hlth Syst, Cardiovasc Res Inst, Singapore 117548, Singapore. [Marsh, Susan A.] Washington State Univ, Dept Clin Pharmacol, Pullman, WA 99164 USA. [Dell'Italia, Louis J.; Lloyd, Steven G.] Birmingham VA Med Ctr, Birmingham, AL USA. RP Lloyd, SG (reprint author), Univ Alabama Birmingham, Dept Med, Div Cardiovasc Dis, D-101 Cardiac MRI,1808 7th Ave South, Birmingham, AL 35294 USA. EM sglloyd@uab.edu RI Marsh, Sue/J-3711-2014 OI Marsh, Sue/0000-0002-7530-0417 FU American Heart Association (Scientist Development Grant) [0735212N]; National Institutes of Health [P30DK056336] FX This work was supported in part by the American Heart Association (Scientist Development Grant 0735212N) and by the National Institutes of Health (P30DK056336). NR 65 TC 3 Z9 3 U1 1 U2 13 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 EI 1522-1539 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD AUG 15 PY 2014 VL 307 IS 4 BP H598 EP H608 DI 10.1152/ajpheart.00058.2014 PG 11 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA AN8FZ UT WOS:000340840200013 PM 24929857 ER PT J AU Smith, JA Stallons, LJ Schnellmann, RG AF Smith, Joshua A. Stallons, L. Jay Schnellmann, Rick G. TI Renal cortical hexokinase and pentose phosphate pathway activation through the EGFR/Akt signaling pathway in endotoxin-induced acute kidney injury SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE lipopolysaccharide; acute kidney injury; hexokinase; EGFR; pentose phosphate pathway ID GROWTH-FACTOR RECEPTOR; GLYCOGEN-SYNTHESIS PATHWAY; OXIDATIVE STRESS; IN-VIVO; MITOCHONDRIAL HEXOKINASE; OXYGEN-CONSUMPTION; AKT INHIBITOR; FAILURE; METABOLISM; CELLS AB While disruption of energy production is an important contributor to renal injury, metabolic alterations in sepsis-induced AKI remain understudied. We assessed changes in renal cortical glycolytic metabolism in a mouse model of sepsis-induced AKI. A specific and rapid increase in hexokinase (HK) activity (similar to 2-fold) was observed 3 h after LPS exposure and maintained up to 18 h, in association with a decline in renal function as measured by blood urea nitrogen (BUN). LPS-induced HK activation occurred independently of HK isoform expression or mitochondrial localization. No other changes in glycolytic enzymes were observed. LPS-mediated HK activation was not sufficient to increase glycolytic flux as indicated by reduced or unchanged pyruvate and lactate levels in the renal cortex. LPS-induced HK activation was associated with increased glucose-6-phosphate dehydrogenase activity but not glycogen production. Mechanistically, LPS-induced HK activation was attenuated by pharmacological inhibitors of the EGF receptor (EGFR) and Akt, indicating that EGFR/phosphatidylinositol 3-kinase/Akt signaling is responsible. Our findings reveal LPS rapidly increases renal cortical HK activity in an EGFR-and Akt-dependent manner and that HK activation is linked to increased pentose phosphate pathway activity. C1 [Smith, Joshua A.; Stallons, L. Jay; Schnellmann, Rick G.] Med Univ S Carolina, Dept Drug Discovery & Biomed Sci, Charleston, SC 29425 USA. [Schnellmann, Rick G.] Ralph H Johnson Vet Adm Med Ctr, Charleston, SC USA. RP Schnellmann, RG (reprint author), Med Univ S Carolina, Dept Drug Discovery & Biomed Sci, 280 Calhoun St,MSC140, Charleston, SC 29425 USA. EM schnell@musc.edu FU National Institute of General Medical Sciences [GM084147, P20GM103542-02]; National Center for Research Resources [UL1-RR029882, C06-RR015455]; Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs [5I01 BX-000851]; South Carolina Clinical and Translational Research Institute at the Medical University of South Carolina FX This material is based on work supported in part by National Institute of General Medical Sciences Grants GM084147 (to R. G. Schnellmann) and P20GM103542-02 (to South Carolina COBRE in Oxidants, Redox Balance, and Stress Signaling); National Center for Research Resources Grant UL1-RR029882; the Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs [Grant 5I01 BX-000851 (to R. G. Schnellmann)], and the South Carolina Clinical and Translational Research Institute at the Medical University of South Carolina. Animal facilities were funded by National Center for Research Resources Grant C06-RR015455. NR 75 TC 4 Z9 4 U1 1 U2 9 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X EI 1522-1466 J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD AUG 15 PY 2014 VL 307 IS 4 BP F435 EP F444 DI 10.1152/ajprenal.00271.2014 PG 10 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA AO1PN UT WOS:000341085600008 PM 24990892 ER PT J AU Moser, R Xu, C Kao, M Annis, J Lerma, LA Schaupp, CM Gurley, KE Jang, IS Biktasova, A Yarbrough, WG Margolin, AA Grandori, C Kemp, CJ Mendez, E AF Moser, Russell Xu, Chang Kao, Michael Annis, James Lerma, Luisa Angelica Schaupp, Christopher M. Gurley, Kay E. Jang, In Sock Biktasova, Asel Yarbrough, Wendell G. Margolin, Adam A. Grandori, Carla Kemp, Christopher J. Mendez, Eduardo TI Functional Kinomics Identifies Candidate Therapeutic Targets in Head and Neck Cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID SQUAMOUS-CELL CARCINOMA; GROWTH-FACTOR RECEPTOR; FOCAL-ADHESION KINASE; LOCALLY ADVANCED HEAD; DNA-DAMAGING AGENTS; SRC FAMILY KINASES; MALIGNANT PROGRESSION; TYROSINE KINASE; TUMOR-CELLS; WEE1 KINASE AB Purpose: To identify novel therapeutic drug targets for p53-mutant head and neck squamous cell carcinoma (HNSCC). Experimental Design: RNAi kinome viability screens were performed on HNSCC cells, including autologous pairs from primary tumor and recurrent/metastatic lesions, and in parallel on murine squamous cell carcinoma (MSCC) cells derived from tumors of inbred mice bearing germline mutations in Trp53, and p53 regulatory genes: Atm, Prkdc, and p19(Arf). Cross-species analysis of cell lines stratified by p53 mutational status and metastatic phenotype was used to select 38 kinase targets. Both primary and secondary RNAi validation assays were performed on additional HNSCC cell lines to credential these kinase targets using multiple phenotypic endpoints. Kinase targets were also examined via chemical inhibition using a panel of kinase inhibitors. A preclinical study was conducted on the WEE1 kinase inhibitor, MK-1775. Results: Our functional kinomics approach identified novel survival kinases in HNSCC involved in G(2)-M cell-cycle checkpoint, SFK, PI3K, and FAK pathways. RNAi-mediated knockdown and chemical inhibition of the WEE1 kinase with a specific inhibitor, MK-1775, had a significant effect on both viability and apoptosis. Sensitivity to the MK-1775 kinase inhibitor is in part determined by p53 mutational status, and due to unscheduled mitotic entry. MK-1775 displays single-agent activity and potentiates the efficacy of cisplatin in a p53-mutant HNSCC xenograft model. Conclusions: WEE1 kinase is a potential therapeutic drug target for HNSCC. This study supports the application of a functional kinomics strategy to identify novel therapeutic targets for cancer. (C) 2014 AACR. C1 [Moser, Russell; Gurley, Kay E.; Grandori, Carla; Kemp, Christopher J.] Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98109 USA. [Xu, Chang; Kao, Michael; Lerma, Luisa Angelica; Mendez, Eduardo] Univ Washington, Med Ctr, Dept Otolaryngol Head & Neck Surg, Seattle, WA 98195 USA. [Xu, Chang; Mendez, Eduardo] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Annis, James; Grandori, Carla] Univ Washington Med Res, Inst Stem Cell & Regenerat Med, Quellos High Throughput Facil, Seattle, WA USA. [Schaupp, Christopher M.] Univ Washington, Dept Environm & Occupat Hlth Sci, Toxicol Program, Seattle, WA 98195 USA. [Jang, In Sock; Margolin, Adam A.] Sage Bionetworks, Seattle, WA USA. [Biktasova, Asel; Yarbrough, Wendell G.] Yale Univ, Sch Med, Dept Surg Otolaryngol Head & Neck Surg, New Haven, CT USA. [Mendez, Eduardo] VA Puget Sound Hlth Care Syst, Surg & Perioperat Care Serv, Seattle, WA USA. RP Mendez, E (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave North, Seattle, WA 98109 USA. EM cjkemp@fhcrc.org; edmendez@u.washington.edu FU FHCRC/UW Cancer Consortium Pilot grants from the NIH [P30CA015704]; National Center for Research Resources [5KL2RR025015]; Howard Hughes Medical Institute Early Physician-Scientist Career Development Award; American Cancer Society [RSG TBG-123653]; Mouse Models of Human Cancer Consortium [U01 CA141550]; National Institute of Environmental Health Science [ES020116]; Integrated Cancer Biology Program [54CA149237]; National Cancer Institute [U01 CA176303]; Department of Otolaryngology/Head and Neck Surgery at the University of Washington; VA Puget Sound Health Care System FX This work was supported by two FHCRC/UW Cancer Consortium Pilot grants from the NIH (P30CA015704); the National Center for Research Resources (5KL2RR025015); the Howard Hughes Medical Institute Early Physician-Scientist Career Development Award; American Cancer Society grant (RSG TBG-123653); the Mouse Models of Human Cancer Consortium (U01 CA141550); the National Institute of Environmental Health Science (ES020116); the Integrated Cancer Biology Program (54CA149237); National Cancer Institute grant (U01 CA176303); and center funds from the Department of Otolaryngology/Head and Neck Surgery at the University of Washington and VA Puget Sound Health Care System NR 50 TC 14 Z9 14 U1 1 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD AUG 15 PY 2014 VL 20 IS 16 BP 4274 EP 4288 DI 10.1158/1078-0432.CCR-13-2858 PG 15 WC Oncology SC Oncology GA AO2WB UT WOS:000341186100012 PM 25125259 ER PT J AU Singhi, AD Nikiforova, MN Fasanella, KE McGrath, KM Pai, RK Ohori, NP Bartholow, TL Brand, RE Chennat, JS Lu, X Papachristou, GI Slivka, A Zeh, HJ Zureikat, AH Lee, KK Tsung, A Mantha, GS Khalid, A AF Singhi, Aatur D. Nikiforova, Marina N. Fasanella, Kenneth E. McGrath, Kevin M. Pai, Reetesh K. Ohori, N. Paul Bartholow, Tanner L. Brand, Randall E. Chennat, Jennifer S. Lu, Xuong Papachristou, Georgios I. Slivka, Adam Zeh, Herbert J. Zureikat, Amer H. Lee, Kenneth K. Tsung, Allan Mantha, Geeta S. Khalid, Asif TI Preoperative GNAS and KRAS Testing in the Diagnosis of Pancreatic Mucinous Cysts SO CLINICAL CANCER RESEARCH LA English DT Article ID INTERNATIONAL CONSENSUS GUIDELINES; FINE-NEEDLE-ASPIRATION; DNA ANALYSIS; MUTATIONS; MANAGEMENT; LESIONS; NEOPLASMS; CANCER; PRECURSORS; CYTOLOGY AB Purpose: Management guidelines for pancreatic intraductal papillary mucinous neoplasms (IPMN) and mucinous cystic neoplasms (MCN) are based on the assumption that mucinous cysts can be accurately distinguished from other pancreatic cystic lesions. Previous studies using surgical material have identified recurrent mutations in GNAS and KRAS in pancreatic mucinous neoplasms. Yet, the diagnostic utility of testing for both genes in pancreatic cyst fluid obtained by endoscopic ultrasound-fine-needle aspiration (EUS-FNA) remains unclear. Experimental Design: GNAS and KRAS testing was performed on EUS-FNA pancreatic cyst fluid from 91 pancreatic cysts: 41 IPMNs, 9 IPMNs with adenocarcinoma, 16 MCNs, 10 cystic pancreatic neuroendocrine tumors (PanNET), 9 serous cystadenomas (SCA), 3 retention cysts, 2 pseudocysts, and 1 lymphoepithelial cyst. Results: Mutations in GNAS were detected in 16 (39%) IPMNs and 2 (22%) IPMNs with adenocarcinoma. KRAS mutations were identified in 28 (68%) IPMNs, 7 (78%) IPMNs with adenocarcinoma, and 1 (6%) MCN. Mutations in either gene were present in 34 (83%) IPMNs, 8 (89%) IPMNs with adenocarcinoma, and 1 (6%) MCN. No mutations were found in cystic PanNETs, SCAs, retention cysts, pseudocysts, and a lymphoepithelial cyst. GNAS and KRAS mutations had 100% specificity [95% confidence interval (CI), 0.83-1.00] but 65% sensitivity (95% CI, 0.52-0.76) for mucinous differentiation. Among IPMNs, mutations in either gene had 98% specificity (95% CI, 0.86-1.00) and 84% sensitivity (95% CI, 0.70-0.92). Conclusions: The combination of GNAS and KRAS testing was highly specific and sensitive for IPMNs; however, the lack of sensitivity for MCNs highlights the need for additional markers to improve the detection of pancreatic mucinous neoplasms. (C)2014 AACR. C1 [Singhi, Aatur D.; Nikiforova, Marina N.; Pai, Reetesh K.; Ohori, N. Paul; Bartholow, Tanner L.; Mantha, Geeta S.] Univ Pittsburgh, Med Ctr, Dept Pathol, Pittsburgh, PA 15213 USA. [Fasanella, Kenneth E.; McGrath, Kevin M.; Brand, Randall E.; Chennat, Jennifer S.; Lu, Xuong; Papachristou, Georgios I.; Slivka, Adam; Khalid, Asif] Univ Pittsburgh, Med Ctr, Dept Med, Pittsburgh, PA 15213 USA. [Zeh, Herbert J.; Zureikat, Amer H.; Lee, Kenneth K.; Tsung, Allan] Univ Pittsburgh, Med Ctr, Dept Surg, Pittsburgh, PA 15213 USA. [Papachristou, Georgios I.; Khalid, Asif] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Singhi, AD (reprint author), Univ Pittsburgh, Med Ctr, Presbyterian Hosp, Scaife Hall,Room 616-2,200 Lothrop St, Pittsburgh, PA 15213 USA. EM singhiad@upmc.edu FU National Pancreas Foundation, Western Pennsylvania Chapter FX This study was supported in part by a grant from the National Pancreas Foundation, Western Pennsylvania Chapter (to A.D. Singhi). NR 26 TC 27 Z9 27 U1 0 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD AUG 15 PY 2014 VL 20 IS 16 BP 4381 EP 4389 DI 10.1158/1078-0432.CCR-14-0513 PG 9 WC Oncology SC Oncology GA AO2WB UT WOS:000341186100021 PM 24938521 ER PT J AU Xiong, GX Elkind, JA Kundu, S Smith, CJ Antunes, MB Tamashiro, E Kofonow, JM Mitala, CM Stein, SC Grady, MS Einhorn, E Cohen, NA Cohen, AS AF Xiong, Guoxiang Elkind, Jaclynn A. Kundu, Suhali Smith, Colin J. Antunes, Marcelo B. Tamashiro, Edwin Kofonow, Jennifer M. Mitala, Christina. M. Stein, Sherman C. Grady, M. Sean Einhorn, Eugene Cohen, Noam A. Cohen, Akiva S. TI Traumatic Brain Injury-Induced Ependymal Ciliary Loss Decreases Cerebral Spinal Fluid Flow SO JOURNAL OF NEUROTRAUMA LA English DT Article DE beta-tubulin; basal body; hydrocephalus; lateral fluid percussion; particle tracking ID POSTTRAUMATIC HYDROCEPHALUS; CEREBROSPINAL-FLUID; ALZHEIMERS-DISEASE; BEAT FREQUENCY; CHOROID-PLEXUS; MICE; DYSFUNCTION; DYSKINESIA; MOTILITY; SLEEP AB Traumatic brain injury (TBI) afflicts up to 2 million people annually in the United States and is the primary cause of death and disability in young adults and children. Previous TBI studies have focused predominantly on the morphological, biochemical, and functional alterations of gray matter structures, such as the hippocampus. However, little attention has been given to the brain ventricular system, despite the fact that altered ventricular function is known to occur in brain pathologies. In the present study, we investigated anatomical and functional alterations to mouse ventricular cilia that result from mild TBI. We demonstrate that TBI causes a dramatic decrease in cilia. Further, using a particle tracking technique, we demonstrate that cerebrospinal fluid flow is diminished, thus potentially negatively affecting waste and nutrient exchange. Interestingly, injury-induced ventricular system pathology resolves completely by 30 days after injury as ependymal cell ciliogenesis restores cilia density to uninjured levels in the affected lateral ventricle. C1 [Xiong, Guoxiang; Elkind, Jaclynn A.; Kundu, Suhali; Smith, Colin J.; Mitala, Christina. M.; Cohen, Akiva S.] Childrens Hosp Philadelphia, Div Neurol, Philadelphia, PA 19104 USA. [Antunes, Marcelo B.; Tamashiro, Edwin; Kofonow, Jennifer M.; Cohen, Noam A.] Univ Penn, Perelman Sch Med, Dept Otorhinolaryngol Head & Neck Surg, Philadelphia, PA 19104 USA. [Stein, Sherman C.; Grady, M. Sean] Univ Penn, Perelman Sch Med, Dept Neurosurg, Philadelphia, PA 19104 USA. [Cohen, Akiva S.] Univ Penn, Perelman Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. [Einhorn, Eugene; Cohen, Noam A.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Cohen, AS (reprint author), Univ Penn, Perelman Sch Med, Dept Pediat, 3615 Civ Ctr Blvd,816-H ARC, Philadelphia, PA 19104 USA. EM cohena@email.chop.edu RI Tamashiro, Edwin/C-5062-2012 OI Tamashiro, Edwin/0000-0002-3153-6292 FU National Institutes of Health [R01HD059288, R01NS069629] FX The authors thank Michael Schell for critiquing an earlier draft of the manuscript and Kathleen Joy Propert for statistical guidance. This study was supported in part by National Institutes of Health grants (R01HD059288 and R01NS069629; to A.S.C.). NR 59 TC 5 Z9 5 U1 0 U2 5 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 EI 1557-9042 J9 J NEUROTRAUM JI J. Neurotrauma PD AUG 15 PY 2014 VL 31 IS 16 BP 1396 EP 1404 DI 10.1089/neu.2013.3110 PG 9 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA AN4DB UT WOS:000340536700003 PM 24749541 ER PT J AU Bodhankar, S Chen, YX Lapato, A Vandenbark, AA Murphy, SJ Offner, H AF Bodhankar, Sheetal Chen, Yingxin Lapato, Andrew Vandenbark, Arthur A. Murphy, Stephaine J. Offner, Halina TI Targeting immune co-stimulatory effects of PD-L1 and PD-L2 might represent an effective therapeutic strategy n stroke SO FRONTIERS IN CELLULAR NEUROSCIENCE LA English DT Article DE MCAO; co-stimulatory pathway; programmed death ligand-1 and 2; T-cells; regulatory B cells ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; PROGRAMMED DEATH-1 PD-1; T-CELL PROLIFERATION; ISCHEMIC-STROKE; INFARCT SIZE; IMMUNOLOGICAL-TOLERANCE; CEREBRAL-ISCHEMIA; CNS INFLAMMATION; DEFICIENT MICE; REGULATORY T AB Stroke outcome is worsened by the infiltration of inflammatory immune cells into ischemic brains. Our recent study demonstrated that PD-L1- and to a lesser extent PD-L2-deficient mice had smaller brain infarcts and fewer brain-infiltrating cells vs. wild-type (WI) mice, suggesting a pathogenic role for PD-ligands in experimental stroke. We sought to ascertain PD-L1 and PD-L2-expressing cell types that affect T-cell activation, post-stroke in the context of other known co-stimulatory molecules. Thus, cells from male WT and PD-1, deficient mice undergoing 60 min of middle cerebral artery occlusion (MCAO) followed by 96 h of reperfusion were treated with neutralizing antibodies to study co-stimulatory and co-inhibitory interactions between CD80, cytotoxic T-lymphocyte antigen-4 (CTLA-4), PD-1, and PD-Ls that regulate CD8+ and CD4+ T-cell activation. We found that antibody neutralization of PD-1 and CTLA-4 signaling post-MCAO resulted in higher proliferation in WT CD8+ and CD4+ T-cells, confirming an inhibitory role of PD-1 and CTLA-4 on Tcell activation. Also, CD80/CD28 interactions played a prominent regulatory role for the CD8+ T-cells and the PD-1/PD-L2 interactions were dominant in controlling the CD4+ T-cell responses in WT mice after stroke. A suppressive phenotype in PD-L1-deficient mice was attributed to CD80/CTLA-4 and PD-1/PD-L2 interactions. PD-L2 was crucial in modulating CD4+T-cell responses, whereas PD-L1 regulated both CD8+ and CD4+ T-cells. To establish the contribution of PD-L1 and PD-L2 on regulatory B-cells (Bregs), infarct volumes were evaluated in male PD-L1- and PD-L2-deficient mice receiving IL-10+ B-cells 4h post-MCAO. PD-L2- but not PD-L1-deficient recipients of IL-10+ B-cells had markedly reduced infarct volumes, indicating a regulatory role of PD-L2 on Bregs. These results imply that PDL1 and PD-L2 differentially control induction of T- and Breg-cell responses after MCAO, thus suggesting that selective targeting of PD-L1 and PD-L2 might represent a valuable therapeutic strategy in stroke. C1 [Bodhankar, Sheetal; Lapato, Andrew; Vandenbark, Arthur A.; Offner, Halina] Portland VA Med Ctr, Portland, OR 97239 USA. [Bodhankar, Sheetal; Lapato, Andrew; Vandenbark, Arthur A.; Offner, Halina] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR USA. [Chen, Yingxin; Murphy, Stephaine J.; Offner, Halina] Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR USA. [Vandenbark, Arthur A.] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR USA. RP Offner, H (reprint author), Portland VA Med Ctr, R&D-31,3710 SW,US Vet Hosp Rd, Portland, OR 97239 USA. EM offnerva@ohsu.edu FU NIH/NINDS [1R01 NS075887]; Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development; Biomedical Laboratory Research and Development FX The authors wish to thank Gail Kent for assistance in manuscript submission. This work was supported by NIH/NINDS 1R01 NS075887. This material is based upon work supported in part by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development. The contents do not represent the views of the Department of Veterans Affairs or the United States Government. NR 69 TC 1 Z9 1 U1 1 U2 12 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-5102 J9 FRONT CELL NEUROSCI JI Front. Cell. Neurosci. PD AUG 11 PY 2014 VL 8 AR 228 DI 10.3389/fncel.2014.00228 PG 14 WC Neurosciences SC Neurosciences & Neurology GA AM7EH UT WOS:000340027000001 PM 25157219 ER PT J AU Abad, CL Moseley, RH Crnich, CJ Saint, S Safdar, N AF Abad, Cybele L. Moseley, Richard H. Crnich, Christopher J. Saint, Sanjay Safdar, Nasia TI A Gut Instinct SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID TUBERCULOSIS INFECTION; ABDOMINAL-PAIN C1 [Abad, Cybele L.; Crnich, Christopher J.; Safdar, Nasia] Univ Wisconsin, Sch Med, Dept Med, Madison, WI 53706 USA. [Crnich, Christopher J.; Safdar, Nasia] William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. [Moseley, Richard H.; Saint, Sanjay] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI USA. [Moseley, Richard H.; Saint, Sanjay] Ann Arbor Healthcare Syst & Hlth Serv Res & Dev C, Dept Vet Affairs, Ann Arbor, MI USA. RP Safdar, N (reprint author), William S Middleton Mem Vet Adm Med Ctr, 2500 Overlook Terrace, Madison, WI 53705 USA. EM ns2@medicine.wisc.edu FU Covance; Doximity; Jvion FX Dr. Moseley reports providing expert testimony in a case related to chronic hepatitis B virus infection; Dr. Crnich, receiving fees for serving on a data and safety monitoring board from Covance; and Dr. Saint, receiving fees for board membership from Doximity and Jvion. No other potential conflict of interest relevant to this article was reported. NR 12 TC 1 Z9 1 U1 0 U2 3 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 7 PY 2014 VL 371 IS 6 BP 560 EP 564 DI 10.1056/NEJMcps1202137 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA AM5LE UT WOS:000339899100012 PM 25099581 ER PT J AU Elvington, M Scheiber, M Yang, XF Lyons, K Jacqmin, D Wadsworth, C Marshall, D Vanek, K Tomlinson, S AF Elvington, Michelle Scheiber, Melissa Yang, Xiaofeng Lyons, Katherine Jacqmin, Dustin Wadsworth, Casey Marshall, David Vanek, Kenneth Tomlinson, Stephen TI Complement-Dependent Modulation of Antitumor Immunity following Radiation Therapy SO CELL REPORTS LA English DT Article ID CD8(+) T-CELLS; APOPTOTIC CELLS; NEUTROPHIL RECRUITMENT; DOSE RADIOTHERAPY; MURINE MODEL; TUMOR-GROWTH; CANCER; INHIBITION; INTERLEUKIN-10; MELANOMA AB Complement is traditionally thought of as a proinflammatory effector mechanism of antitumor immunity. However, complement is also important for effective clearance of apoptotic cells, which can be an anti-inflammatory and tolerogenic process. We show that localized fractionated radiation therapy (RT) of subcutaneous murine lymphoma results in tumor cell apoptosis and local complement activation. Cotreatment of mice with tumor-targeted complement inhibition markedly improved therapeutic outcome of RT, an effect linked to early increases in apoptotic cell numbers and increased inflammation. Improved outcome was dependent on an early neutrophil influx and was characterized by increased numbers of mature dendritic cells and the subsequent modulation of T cell immunity. Appropriate complement inhibition may be a promising strategy to enhance a mainstay of treatment for cancer. C1 [Elvington, Michelle; Scheiber, Melissa; Yang, Xiaofeng; Wadsworth, Casey; Tomlinson, Stephen] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. [Lyons, Katherine; Jacqmin, Dustin; Marshall, David; Vanek, Kenneth] Med Univ S Carolina, Dept Radiat Oncol, Charleston, SC 29425 USA. [Tomlinson, Stephen] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. RP Tomlinson, S (reprint author), Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. EM tomlinss@musc.edu FU NIH [RO1CA158179] FX This work was supported by a grant from the NIH (RO1CA158179). We thank Ms. Emily Paulling for expert technical assistance. S.T. holds licensed patents for CR2-targeted complement inhibitors. NR 44 TC 7 Z9 7 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2211-1247 J9 CELL REP JI Cell Reports PD AUG 7 PY 2014 VL 8 IS 3 BP 818 EP 830 DI 10.1016/j.celrep.2014.06.051 PG 13 WC Cell Biology SC Cell Biology GA AO7ZR UT WOS:000341572200018 PM 25066124 ER PT J AU Bakaeen, FG Blaustein, A Kibbe, MR AF Bakaeen, Faisal G. Blaustein, Alvin Kibbe, Melina R. TI Health Care at the VA Recommendations for Change SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 [Bakaeen, Faisal G.] Texas Heart Inst, Div Cardiovasc Surg, Michael E DeBakey Vet Affairs Med Ctr, Dept Cardiovasc Surg, Houston, TX 77025 USA. [Bakaeen, Faisal G.] Baylor Coll Med, Div Cardiothorac Surg, Michael E DeBakey Dept Surg, Houston, TX 77030 USA. [Blaustein, Alvin] Michael E DeBakey VA Med Ctr, Div Cardiol, Houston, TX 77030 USA. [Blaustein, Alvin] Baylor Coll Med, Dept Med, Div Cardiol, Houston, TX 77030 USA. [Kibbe, Melina R.] Jesse Brown Vet Affairs Med Ctr, Surg Serv, Chicago, IL USA. [Kibbe, Melina R.] Northwestern Univ, Dept Surg, Feinberg Sch Med, Chicago, IL 60611 USA. RP Bakaeen, FG (reprint author), Michael E DeBakey VA Med Ctr, OCL 112,2002 Holcombe Blvd, Houston, TX 77030 USA. EM fbakaeen@bcm.edu NR 6 TC 5 Z9 5 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 6 PY 2014 VL 312 IS 5 BP 481 EP 482 DI 10.1001/jama.2014.8054 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA AM4FL UT WOS:000339808600012 PM 24945974 ER PT J AU Anderson, TS Good, CB Gellad, WF AF Anderson, Timothy S. Good, Chester B. Gellad, Walid F. TI Potential Conflicts of Interest for Academic Medical Center Leaders Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 [Anderson, Timothy S.] Univ Pittsburgh, Med Ctr, Dept Internal Med, Pittsburgh, PA USA. [Good, Chester B.; Gellad, Walid F.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA 15240 USA. RP Gellad, WF (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, 151C Univ Dr, Pittsburgh, PA 15240 USA. EM wfg3@pitt.edu NR 4 TC 0 Z9 0 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 6 PY 2014 VL 312 IS 5 BP 558 EP 559 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA AM4FL UT WOS:000339808600031 PM 25096702 ER PT J AU Han, S Mallampalli, RK AF Han, SeungHye Mallampalli, Rama K. TI Sizing up Surfactant Synthesis SO CELL METABOLISM LA English DT Editorial Material ID LYSOPHOSPHATIDYLCHOLINE ACYLTRANSFERASE; II CELLS; PHOSPHOLIPIDS; LPCAT1 AB Phosphatidylcholine is generated through de novo synthesis and remodeling involving a lysophospholipid. In this issue of Cell Metabolism, research from the Shimizu lab (Harayama et al., 2014) demonstrates the highly selective enzymatic behavior of lysophospholipid acyltransferases. The authors present an enzymatic model for phosphatidylcholine molecular species diversification that impacts surfactant formation. C1 [Han, SeungHye; Mallampalli, Rama K.] Univ Pittsburgh, Dept Med, Acute Lung Injury Ctr Excellence, Pittsburgh, PA 15213 USA. [Mallampalli, Rama K.] Univ Pittsburgh, Dept Cell Biol & Physiol, Pittsburgh, PA 15213 USA. [Mallampalli, Rama K.] Vet Affairs Pittsburgh Healthcare Syst, Med Specialty Serv Line, Pittsburgh, PA 15240 USA. RP Mallampalli, RK (reprint author), Univ Pittsburgh, Dept Med, Acute Lung Injury Ctr Excellence, 930 Scaife Hall, Pittsburgh, PA 15213 USA. EM mallampallirk@upmc.edu FU BLRD VA [I01 BX002200]; NHLBI NIH HHS [R01 HL098174, R01 HL096376, R01 HL081784, UH2 HL123502, P01 HL114453, R01 HL097376] NR 11 TC 0 Z9 0 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 EI 1932-7420 J9 CELL METAB JI Cell Metab. PD AUG 5 PY 2014 VL 20 IS 2 BP 195 EP 196 DI 10.1016/j.cmet.2014.07.015 PG 2 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA AO5RJ UT WOS:000341402500002 PM 25100056 ER PT J AU Wong, CA Asch, DA Vinoya, CM Ford, CA Baker, T Town, R Merchant, RM AF Wong, Charlene A. Asch, David A. Vinoya, Cjloe M. Ford, Carol A. Baker, Tom Town, Robert Merchant, Raina M. TI The Experience of Young Adults on HealthCare.gov: Suggestions for Improvement SO ANNALS OF INTERNAL MEDICINE LA English DT Letter C1 [Wong, Charlene A.; Vinoya, Cjloe M.; Ford, Carol A.; Merchant, Raina M.] Univ Penn, Philadelphia, PA 19104 USA. [Wong, Charlene A.; Ford, Carol A.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Asch, David A.; Town, Robert] Univ Penn, Wharton Sch, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Asch, David A.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Baker, Tom] Univ Penn, Sch Law, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. RP Wong, CA (reprint author), Univ Penn, Philadelphia, PA 19104 USA. FU NHLBI NIH HHS [K23 HL109083] NR 5 TC 10 Z9 10 U1 1 U2 2 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD AUG 5 PY 2014 VL 161 IS 3 BP 231 EP U107 DI 10.7326/L14-0287 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA AN3KH UT WOS:000340486000013 PM 25004086 ER PT J AU Boekholdt, SM Hovingh, GK Mora, S Arsenault, BJ Amarenco, P Pedersen, TR LaRosa, JC Waters, DD DeMicco, DA Simes, RJ Keech, AC Colquhoun, D Hitman, GA Betteridge, J Clearfield, MB Downs, JR Colhoun, HM Gotto, AM Ridker, PM Grundy, SM Kastelein, JJP AF Boekholdt, S. Matthijs Hovingh, G. Kees Mora, Samia Arsenault, Benoit J. Amarenco, Pierre Pedersen, Terje R. LaRosa, John C. Waters, David D. DeMicco, David A. Simes, R. John Keech, Antony C. Colquhoun, David Hitman, Graham A. Betteridge, John Clearfield, Michael B. Downs, John R. Colhoun, Helen M. Gotto, Antonio M., Jr. Ridker, Paul M. Grundy, Scott M. Kastelein, John J. P. TI Very Low Levels of Atherogenic Lipoproteins and the Risk for Cardiovascular Events A Meta-Analysis of Statin Trials SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE apolipoprotein B; LDL-cholesterol; meta-analysis; non-HDL-cholesterol ID LOW-DENSITY-LIPOPROTEIN; CORONARY-HEART-DISEASE; SCANDINAVIAN SIMVASTATIN SURVIVAL; HIGH-DOSE ATORVASTATIN; CHOLESTEROL REDUCTION; PRIMARY PREVENTION; LDL CHOLESTEROL; LIPID TRIAL; TARGETS TNT; THERAPY AB BACKGROUND Levels of atherogenic lipoproteins achieved with statin therapy are highly variable, but the consequence of this variability for cardiovascular disease risk is not well-documented. OBJECTIVES The aim of this meta-analysis was to evaluate: 1) the interindividual variability of reductions in low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), or apolipoprotein B (apoB) levels achieved with statin therapy; 2) the proportion of patients not reaching guideline-recommended lipid levels on high-dose statin therapy; and 3) the association between very low levels of atherogenic lipoproteins achieved with statin therapy and cardiovascular disease risk. METHODS This meta-analysis used individual patient data from 8 randomized controlled statin trials, in which conventional lipids and apolipoproteins were determined in all study participants at baseline and at 1-year follow-up. RESULTS Among 38,153 patients allocated to statin therapy, a total of 6,286 major cardiovascular events occurred in 5,387 study participants during follow-up. There was large interindividual variability in the reductions of LDL-C, non-HDL-C, and apoB achieved with a fixed statin dose. More than 40% of trial participants assigned to high-dose statin therapy did not reach an LDL-C target < 70 mg/dl. Compared with patients who achieved an LDL-C > 175 mg/dl, those who reached an LDL-C 75 to < 100 mg/dl, 50 to < 75 mg/dl, and < 50 mg/dl had adjusted hazard ratios for major cardiovascular events of 0.56 (95% confidence interval [CI]: 0.46 to 0.67), 0.51 (95% CI: 0.42 to 0.62), and 0.44 (95% CI: 0.35 to 0.55), respectively. Similar associations were observed for non-HDL-C and apoB. CONCLUSIONS The reductions of LDL-C, non-HDL-C, and apoB levels achieved with statin therapy displayed large interindividual variation. Among trial participants treated with high-dose statin therapy, > 40% did not reach an LDL-C target < 70 mg/dl. Patients who achieve very low LDL-C levels have a lower risk for major cardiovascular events than do those achieving moderately low levels. (C) 2014 by the American College of Cardiology Foundation. C1 [Boekholdt, S. Matthijs] Acad Med Ctr, Dept Cardiol, NL-1105 AZ Amsterdam, Netherlands. [Hovingh, G. Kees; Arsenault, Benoit J.; Gotto, Antonio M., Jr.] Acad Med Ctr, Dept Vasc Med, NL-1105 AZ Amsterdam, Netherlands. [Mora, Samia] Brigham & Womens Hosp, Ctr Cardiovasc Dis Prevent, Boston, MA 02115 USA. [Amarenco, Pierre] Hop Xavier Bichat, Dept Neurol & Stroke Ctr, Paris, France. [Pedersen, Terje R.] Ulleval & Univ Oslo, Oslo Univ Hosp, Ctr Prevent Med, Oslo, Norway. [LaRosa, John C.] State Univ New York, Hlth Sci Ctr, Brooklyn, NY USA. [Waters, David D.] Univ Calif San Francisco, San Francisco Gen Hosp, Div Cardiol, San Francisco, CA 94143 USA. [DeMicco, David A.] Pfizer Inc, New York, NY USA. [Simes, R. John; Keech, Antony C.] Univ Sydney, NHMRC, Clin Trials Ctr, Sydney, NSW 2006, Australia. [Simes, R. John; Keech, Antony C.] Wesley Hosp, Brisbane, Qld, Australia. [Hitman, Graham A.] Univ London Queen Mary, Barts & London Sch Med & Dent, Ctr Diabet, London, England. [Betteridge, John] Univ Coll London Hosp, Dept Endocrinol & Diabet, London, England. [Clearfield, Michael B.] Touro Univ, Mare Island, CA USA. [Downs, John R.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Downs, John R.] South Texas Vet Hlth Care Syst, VERDICT, San Antonio, TX USA. [Colhoun, Helen M.] Univ Dundee, Inst Med Res, Dundee, Scotland. [Gotto, Antonio M., Jr.] Weill Cornell Med Coll, New York, NY USA. [Grundy, Scott M.] Univ Texas Dallas, Ctr Human Nutr, SW Med Ctr, Dallas, TX 75230 USA. RP Kastelein, JJP (reprint author), Acad Med Ctr, Dept Vasc Med, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands. EM j.j.kastelein@amc.uva.nl RI Simes, Robert/P-1497-2014; Colquhoun, David/F-9078-2013; Boekholdt, Matthijs/G-7562-2014 OI Colhoun, Helen/0000-0002-8345-3288 FU Netherlands Organisation for Scientific Research [91612122]; Pfizer Inc.; Atherotech Diagnostics; AstraZeneca Pharma U.S., Inc.; National Heart, Lung, and Blood Institute [HL117861]; Cerenis Therapeutics; Genzyme Corporation; Quest Diagnostics Inc.; AstraZeneca France; Bayer S.A.S.; Boehringer France S.A.S.; Boston Scientific-France; Bristol-Myers Squibb Agen; Daiichi Sankyo France S.A.S.; Edwards Lifesciences S.A.S.; Kowa Europe GmbH; H. Lundbeck A/S; Merck KGaA; Amgen Inc.; Merck Sharp & Dohme Corporation; Roche Therapeutics Inc.; Anthera Pharmaceuticals Inc.; Genentech U.S.A., Inc.; Laboratoires Servier; Aegerion Pharmaceuticals, Inc.; BioSante Pharmaceuticals, Inc.; Merck Co., Inc.; Sanofi-Aventis; Abbott Australasia Pty. Ltd.; AstraZeneca Australia; Bristol-Myers Squibb Australia; Eli Lilly Australia; Novartis A.G.; Roche Products Pty. Ltd.; Solvay Interox Pty.; AstraZeneca; Eli Lilly and Co. Ltd.; GlaxoSmithKline plc.; Merck Sharp Dohme Ltd.; Novo Nordisk Ltd.; OSI Pharmaceuticals Ltd.; Takeda U.K. Ltd.; Parke-Davis; Eli Lilly and Co., Ltd.; E.U. Innovative Medicines Initiative from AstraZeneca; Boehringer Ingelheim Ltd. U.K.; JRDF; Roche Products Ltd.; Novartis Pharmaceuticals U.K. Ltd.; Janssen Pharmaceuticals, Inc.; Kowa Pharmaceuticals America, Inc.; Abbott Laboratories; Boehringer-Ingelheim Pharmaceuticals; Isis Pharmaceuticals, Inc.; Vascular Biogenics Ltd. FX This meta-analysis was not supported by any funding. The contributing trials were funded by their respective sponsors and provided the requested data. They did not play any role in the statistical analysis, interpretation of the data, writing of the manuscript, or the decision to submit the manuscript. Dr. Hovingh is funded by a Veni grant (project number 91612122) from the Netherlands Organisation for Scientific Research. Drs. Boekholdt, Hovingh, and Arsenault have received consulting fees from Pfizer Inc. Dr. Hovingh has served on the speakers' bureaus of Amgen Europe B.V., Genzyme Netherlands, Merck Sharp & Dohme Corporation, Pfizer B.V., Roche Nederland B.V., and Sanofi-Aventis Netherlands B.V. Dr. Mora has received honoraria grants through her institution from Atherotech Diagnostics, AstraZeneca Pharma U.S., Inc., and the National Heart, Lung, and Blood Institute (HL117861); consulting fees from Cerenis Therapeutics, Genzyme Corporation, Pfizer Inc., and Quest Diagnostics Inc.; and travel accommodations/meeting expenses from Pfizer Inc.; and has served on the speakers' bureaus of Abbott Laboratories and AstraZeneca Pharma U.S., Inc. Dr. Amarenco has served on the speakers' bureaus of AstraZeneca France, Boehringer Ingelheim France S.A.S., Merck KGaA, Pfizer Inc., Sanofi-Aventis, and the government of France; and has received consulting fees from AstraZeneca France, Bayer S.A.S., Boehringer France S.A.S., Boston Scientific-France, Bristol-Myers Squibb Agen, Daiichi Sankyo France S.A.S., Edwards Lifesciences S.A.S., Kowa Europe GmbH, H. Lundbeck A/S, Merck KGaA, and Pfizer Inc. Dr. LaRosa has received consulting fees from Amgen Inc. and Pfizer Inc.; and travel expenses from Pfizer Inc. Dr. Pedersen has received honoraria grants and/or served on the speakers' bureaus of AstraZeneca Pharma U.S., Inc., Merck Sharp & Dohme Corporation, Pfizer Inc., and Roche Therapeutics Inc. Dr. Waters has received consulting fees from Anthera Pharmaceuticals Inc., Genentech U.S.A., Inc., Pfizer Inc., Roche Therapeutics Inc., and Laboratoires Servier; has served on the speakers' bureaus of Pfizer Inc. and Zydus Cadila Healthcare Ltd. (Medica); and has participated in committees of clinical trials sponsored by Aegerion Pharmaceuticals, Inc., BioSante Pharmaceuticals, Inc., Merck & Co., Inc., Pfizer Inc., and Sanofi-Aventis. Dr. DeMicco is an employee of, and holds stock options in, Pfizer Inc. Prof. Keech has received honoraria grants from and/or served on the speakers' bureaus and/or advisory boards of Abbott Australasia Pty. Ltd., AstraZeneca Australia, Bristol-Myers Squibb Australia, Eli Lilly Australia, Merck KGaA, Novartis A.G., Pfizer Inc., Roche Products Pty. Ltd., and Solvay Interox Pty. Ltd. Dr. Hitman has received consulting fees from and/or served on the speakers' bureaus of AstraZeneca, Eli Lilly and Co. Ltd., GlaxoSmithKline plc., Merck Sharp & Dohme Ltd., Novo Nordisk Ltd., OSI Pharmaceuticals Ltd., Pfizer Inc., and Takeda U.K. Ltd.; and has received honoraria grants from Parke-Davis and Eli Lilly and Co., Ltd. Dr. Betteridge has served on the speakers' bureaus and/or advisory boards for Aegerion Pharmaceuticals, Inc., Amgen Europe B.V., AstraZeneca, Janssen Ltd., Kowa Europe GmbH, Merck Sharp & Dohme Ltd., Pfizer Inc., Roche Products Ltd., Sanofi-Synthelabo Ltd., and Takeda U.K. Ltd. Dr. Clearfield has received honoraria for consulting on the advisory boards for AstraZeneca Pharma U.S., Inc., and Merck Sharp & Dohme Corporation. Dr. Colhoun has received honoraria grants through the E.U.; Innovative Medicines Initiative from AstraZeneca, Boehringer Ingelheim Ltd. U.K., Eli Lilly and Co., Ltd., JRDF, Pfizer Inc., Roche Products Ltd., and Sanofi-Aventis; consulting fees from Eli Lilly and Co., Ltd., Novartis Pharmaceuticals U.K. Ltd., Pfizer Inc., and Sanofi-Aventis; has served on the speakers' bureaus of, and received travel expenses from, Pfizer Inc.; served on the advisory boards of Eli Lilly and Co., Ltd., Novartis Pharmaceuticals U.K. Ltd., Pfizer Inc., and Sanofi-Aventis; holds stock options in Roche Products Ltd.; and has participated in committees of clinical trials sponsored by Eli Lilly and Co., Ltd., JDRF, Novartis Pharmaceuticals U.K. Ltd., and Sanofi-Aventis. Dr. Gotto has received consulting fees from Roche Products Ltd., Janssen Pharmaceuticals, Inc., Kowa Pharmaceuticals America, Inc., Merck & Co., Inc., and Roche Therapeutics Inc.; has been a member of the boards of directors for Aegerion Pharmaceuticals, Inc. and Arisaph Pharmaceuticals, Inc.; and has been a member of the scientific advisory boards for DuPont, Haptocure Ltd., vascuVis Inc., and Vatera Healthcare Partners. Dr. Ridker has received honoraria grants from AstraZeneca Pharma U.S., Inc., Novartis A.G., and Pfizer Inc.; consulting fees from Abbott Laboratories, Boehringer-Ingelheim Pharmaceuticals, Isis Pharmaceuticals, Inc., Merck Sharp & Dohme Corporation, and Vascular Biogenics Ltd.; has been a member of the scientific advisory board for Boston Heart Diagnostics Corporation, Janssen Pharmaceuticals, Inc., Isis Pharmaceuticals, Inc., Merck Sharp & Dohme Corporation, and Pfizer Inc.; has received honoraria grants to his institution from Amgen Inc.; and is listed as a co-inventor on patents held by the Brigham and Women's Hospital that relate to the use of inflammatory biomarkers in cardiovascular disease and diabetes and that have been licensed to AstraZeneca Pharma U.S., Inc. and Siemens Corporation. Dr. Kastelein has received honoraria for serving on the speakers' bureaus of AstraZeneca, Genzyme Australia, Labortoires Isispharma, Kowa Australia Pty. Ltd., Merck Sharp & Dohme Pty. Ltd., Novartis Pharmaceuticals Australia Pty. Ltd., Pfizer Inc., and Roche Products Pty. Ltd. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 34 TC 121 Z9 127 U1 0 U2 16 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD AUG 5 PY 2014 VL 64 IS 5 BP 485 EP 494 DI 10.1016/j.jacc.2014.02.615 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AM9ZR UT WOS:000340241100011 PM 25082583 ER PT J AU Wong, ES Maciejewski, ML Hebert, PL Bryson, CL Liu, CF AF Wong, Edwin S. Maciejewski, Matthew L. Hebert, Paul L. Bryson, Christopher L. Liu, Chuan-Fen TI Massachusetts Health Reform and Veterans Affairs Health System Enrollment SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID AFFORDABLE CARE ACT; MEDICARE; COVERAGE; IMPACTS; ACCESS; RATES AB Objectives Veterans Health Administration (VA) operates the largest integrated health system in the nation. The Affordable Care Act (ACA) does not require any changes to VA, but the individual mandate and expanded health insurance options may change veterans' preferences for coverage. We examined the impact of healthcare reform in Massachusetts, which also included these policy changes, on veterans' enrollment in VA, private insurance, and Medicaid. Study Design Massachusetts' healthcare reform in June 2006 served as a natural experiment. Using data from the 2004-2013 Current Population Surveys, we examined enrollment in VA, private insurance, and Medicaid, comparing veterans residing in Massachusetts with veterans residing in neighboring New England states that did not undergo health reform. Methods We estimated the probability of being enrolled in VA, private insurance, and Medicaid before and after healthcare reform, using multivariate probit models while adjusting for individual characteristics. Using a difference-in-difference approach, we compared pre-post changes in enrollment probability among Massachusetts and non-Massachusetts veterans, respectively. Results Compared with other New England veterans, Massachusetts veterans decreased their enrollment in VA and private insurance by 0.2 (P =.857) and 0.9 (P = .666) percentage points, respectively, following health reform. In contrast, Medicaid enrollment increased by 2.5 percentage points (P = .038). Conclusions Healthcare reform in Massachusetts was associated with greater Medicaid enrollment, but was not significantly associated with VA and private insurance enrollment. Our results are significant for informing VA fiscal planning in the post ACA era. C1 [Wong, Edwin S.; Hebert, Paul L.; Bryson, Christopher L.; Liu, Chuan-Fen] VA Puget Sound Hlth Care Syst, Northwest Ctr Outcomes Res Older Adults, Seattle, WA USA. [Wong, Edwin S.; Hebert, Paul L.; Liu, Chuan-Fen] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Maciejewski, Matthew L.] Durham VA Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC USA. [Maciejewski, Matthew L.] Duke Univ, Dept Med, Div Gen Internal Med, Durham, NC USA. [Bryson, Christopher L.] Univ Washington, Dept Med, Seattle, WA USA. RP Wong, ES (reprint author), Ctr Innovat Vet Ctr & Value Driven Care, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM edwin.wong@va.gov FU VA Health Services Research and Development Career Development Award [CDA 13-024] FX Dr Wong is supported by a VA Health Services Research and Development Career Development Award (CDA 13-024). Dr Maciejewski is a VA Research Career Scientist (RCS 10-391). The views expressed are those of the authors and do not necessarily reflect the views of the Department of Veterans Affairs, the University of Washington, and Duke University. NR 25 TC 1 Z9 1 U1 0 U2 1 PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC PI PLAINSBORO PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD AUG PY 2014 VL 20 IS 8 BP 629 EP 636 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CD3PK UT WOS:000350990800011 PM 25295677 ER PT J AU Kimbro, LB Li, JN Turk, N Ettner, SL Moin, T Mangione, CM Duru, OK AF Kimbro, Lindsay B. Li, Jinnan Turk, Norman Ettner, Susan L. Moin, Tannaz Mangione, Carol M. Duru, O. Kenrik TI Optimizing Enrollment in Employer Health Programs: A Comparison of Enrollment Strategies in the Diabetes Health Plan SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID MEXICAN-AMERICANS; MEDICAL-CARE; INSURANCE; ACCULTURATION; ADHERENCE; SERVICES; ACCESS AB Background Many health programs struggle with low enrollment rates. Objectives To compare the characteristics of populations enrolled in a new health plan when employer groups implement voluntary versus automatic enrollment approaches. Study Design We analyzed enrollment rates resulting from 2 different strategies: voluntary and automatic enrollment. We used regression modeling to estimate the associations of patient characteristics with the probability of enrolling within each strategy. The subjects were 5014 eligible employees from 11 self-insured employers who had purchased the Diabetes Health Plan (DHP), which offers free or discounted copayments for diabetes related medications, testing supplies, and physician visits. Six employers used voluntary enrollment while five5 used automatic enrollment. The main outcome of interest was enrollment into the DHP. Predictors were gender, age, race/ethnicity, dependent status, household income, education level, number of comorbidities, and employer group. Results Overall, the proportion of eligible members who were enrolled within the automatic enrollment strategy was 91%, compared with 35% for voluntary enrollment. Income was a significant predictor for voluntary enrollment but not for automatic enrollment. Within automatic enrollment, covered dependents, Hispanics, and persons with 1 nondiabetes comorbidity were more likely to enroll than other subgroups. Employer group was also a significant correlate of enrollment. Notably, all demographic groups had higher DHP enrollment rates under automatic enrollment than under voluntary enrollment. Conclusions For employer-based programs that struggle with low enrollment rates, especially among certain employee subgroups, an automatic enrollment strategy may not only increase the total number of enrollees but may also decrease some enrollment disparities. C1 [Kimbro, Lindsay B.; Li, Jinnan; Turk, Norman; Ettner, Susan L.; Mangione, Carol M.; Duru, O. Kenrik] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Ettner, Susan L.; Mangione, Carol M.] Univ Calif Los Angeles, Jonathan & Karin Fielding Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA USA. [Moin, Tannaz] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA USA. [Moin, Tannaz] Vet Affairs Greater Los Angeles Healthcare Syst, HSR&D Ctr Excellence Study Healthcare Provider Be, Los Angeles, CA USA. RP Kimbro, LB (reprint author), 10940 Wilshire Blvd,Ste 700, Los Angeles, CA 90095 USA. EM lkimbro@mednet.ucla.edu FU Centers for Disease Control and Prevention; National Institute of Diabetes and Digestive and Kidney Diseases as part of the Natural Experiments for the Translation of Diabetes (NEXT-D) Study [DP002722]; VA Office of Academic Affiliations, Health Services Research and Development through the Health Services Fellowship Training Program [TPM65-010]; VA Greater Los Angeles Healthcare System; University of California, Los Angeles; Resource Centers for Minority Aging Research Center for Health Improvement of Minority Elderly (RCMAR/CHIME) under NIH/NIA [P30-AG021684]; [K08 AG033630] FX Funding received from the Centers for Disease Control and Prevention and the National Institute of Diabetes and Digestive and Kidney Diseases as part of the Natural Experiments for the Translation of Diabetes (NEXT-D) Study (Grant number DP002722). Dr Moin is supported by VA Office of Academic Affiliations, Health Services Research and Development, through the Health Services Fellowship Training Program (TPM65-010), VA Greater Los Angeles Healthcare System. Dr Mangione and Dr Duru are supported in part by the University of California, Los Angeles, Resource Centers for Minority Aging Research Center for Health Improvement of Minority Elderly (RCMAR/CHIME) under NIH/NIA Grant P30-AG021684. Dr Duru is supported in part by the Career Development award K08 AG033630. NR 19 TC 1 Z9 1 U1 0 U2 1 PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC PI PLAINSBORO PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD AUG PY 2014 VL 20 IS 8 BP E311 EP E319 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CD3PK UT WOS:000350990800004 PM 25295794 ER PT J AU Conner, JD Wolden-Hanson, T Quinn, LS AF Conner, Jennifer D. Wolden-Hanson, Tami Quinn, LeBris S. TI Assessment of Murine Exercise Endurance Without the Use of a Shock Grid: An Alternative to Forced Exercise SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS LA English DT Article DE Behavior; Issue 90; Exercise; Mouse; Treadmill; Endurance; Refinement ID PHYSICAL-ACTIVITY; MICE; PGC-1-ALPHA; RECEPTOR; OBESITY; INFLAMMATION; PERFORMANCE; METABOLISM; EXPRESSION; SPEED AB Using laboratory mouse models, the molecular pathways responsible for the metabolic benefits of endurance exercise are beginning to be defined. The most common method for assessing exercise endurance in mice utilizes forced running on a motorized treadmill equipped with a shock grid. Animals who quit running are pushed by the moving treadmill belt onto a grid that delivers an electric foot shock; to escape the negative stimulus, the mice return to running on the belt. However, avoidance behavior and psychological stress due to use of a shock apparatus can interfere with quantitation of running endurance, as well as confound measurements of postexercise serum hormone and cytokine levels. Here, we demonstrate and validate a refined method to measure running endurance in naive C57BL/6 laboratory mice on a motorized treadmill without utilizing a shock grid. When mice are preacclimated to the treadmill, they run voluntarily with gait speeds specific to each mouse. Use of the shock grid is replaced by gentle encouragement by a human operator using a tongue depressor, coupled with sensitivity to the voluntary willingness to run on the part of the mouse. Clear endpoints for quantifying running time-to-exhaustion for each mouse are defined and reflected in behavioral signs of exhaustion such as splayed posture and labored breathing. This method is a humane refinement which also decreases the confounding effects of stress on experimental parameters. C1 [Conner, Jennifer D.; Wolden-Hanson, Tami; Quinn, LeBris S.] VA Puget Sound Hlth Care Syst, Res Serv, Seattle, WA 98108 USA. [Conner, Jennifer D.] Seattle Inst Biomed & Clin Res, Seattle, WA USA. [Quinn, LeBris S.] Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA. [Quinn, LeBris S.] VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. RP Quinn, LS (reprint author), VA Puget Sound Hlth Care Syst, Res Serv, Seattle, WA 98108 USA. EM quinnL@uw.edu FU Department of Veterans Affairs [BX001026]; NIA [5P30AG-013280]; University of Washington Diabetes Endocrinology Research Center (NIH) [P30 DK-17047] FX Supported by Merit Review #BX001026 from the Department of Veterans Affairs (LSQ), and use of resources and facilities at VA Puget Sound Health Care System, the Transgenic Resource Core at the University of Washington Nathan Shock Center of Excellence in the Basic Biology of Aging (NIA #5P30AG-013280), and the University of Washington Diabetes Endocrinology Research Center (NIH #P30 DK-17047). We thank Cynthia Pekow DVM and Kari L. Koszdin DVM, VA Puget Sound, provided helpful comments on the manuscript. NR 25 TC 0 Z9 0 U1 2 U2 6 PU JOURNAL OF VISUALIZED EXPERIMENTS PI CAMBRIDGE PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA SN 1940-087X J9 JOVE-J VIS EXP JI J. Vis. Exp. PD AUG PY 2014 IS 90 AR e51846 DI 10.3791/51846 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CB0EV UT WOS:000349299200068 PM 25145813 ER PT J AU Wood, KH Hoef, LWV Knight, DC AF Wood, Kimberly H. Hoef, Lawrence W. Ver Knight, David C. TI The Amygdala Mediates the Emotional Modulation of Threat-Elicited Skin Conductance Response SO EMOTION LA English DT Article DE fMRI; emotion; threat; amygdala; skin conductance ID FEAR-POTENTIATED STARTLE; FACIAL EXPRESSIONS; INDIVIDUAL-DIFFERENCES; TRAIT ANXIETY; CONDITIONED DIMINUTION; NEURAL RESPONSES; VIETNAM VETERANS; FUNCTIONAL MRI; LONG-TERM; ACTIVATION AB The ability to respond adaptively to threats in a changing environment is an important emotional function. The amygdala is a critical component of the neural circuit that mediates many emotion-related processes, and thus likely plays an important role in modulating the peripheral emotional response to threat. However, prior research has largely focused on the amygdala's response to stimuli that signal impending threat, giving less attention to the amygdala's response to the threat itself. From a functional perspective, however, it is the response to the threat itself that is most biologically relevant. Thus, understanding the factors that influence the amygdala's response to threat is critical for a complete understanding of adaptive emotional processes. Therefore, we used functional MRI to investigate factors (i.e., valence and arousal of co-occurring visual stimuli) that influence the amygdala's response to threat (loud white noise). We also assessed whether changes in amygdala activity varied with the peripheral expression of emotion (indexed via skin conductance response; SCR). The results showed that threat-elicited amygdala activation varied with the arousal, not valence, of emotional images. More specifically, threat-elicited amygdala activation was larger to the threat when presented during high-arousal (i.e., negative and positive) versus low-arousal (i.e., neutral) images. Further, the threat-elicited amygdala response was positively correlated with threat-elicited SCR. These findings indicate the amygdala's response to threat is modified by the nature (e.g., arousal) of other stimuli in the environment. In turn, the amygdala appears to mediate important aspects of the peripheral emotional response to threat. C1 [Wood, Kimberly H.; Knight, David C.] Univ Alabama Birmingham, Dept Psychol, Birmingham, AL 35233 USA. [Hoef, Lawrence W. Ver] Univ Alabama Birmingham, Sch Med, Dept Neurol, Birmingham, AL 35233 USA. [Hoef, Lawrence W. Ver] Birmingham VA Med Ctr, Dept Neurol, Birmingham, AL USA. RP Knight, DC (reprint author), Univ Alabama Birmingham, CIRC 235H,1720 2nd Ave South, Birmingham, AL 35233 USA. EM knightdc@uab.edu FU NIMH NIH HHS [R01 MH098348, MH098348] NR 68 TC 9 Z9 9 U1 5 U2 20 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1528-3542 EI 1931-1516 J9 EMOTION JI Emotion PD AUG PY 2014 VL 14 IS 4 BP 693 EP 700 DI 10.1037/a0036636 PG 8 WC Psychology, Experimental SC Psychology GA CA9CS UT WOS:000349218600006 PM 24866521 ER PT J AU Sarver, NW Gros, DF AF Sarver, Nina Wong Gros, Daniel F. TI A Modern Behavioral Treatment to Address Fetishism and Associated Functional Impairment SO CLINICAL CASE STUDIES LA English DT Article DE behavioral treatment; behavioral activation; sensate focused therapy; fetishism; paraphilias ID TERM PSYCHODYNAMIC PSYCHOTHERAPY; ACTIVATION TREATMENTS; SEXUAL DYSFUNCTION; DSM-IV; METAANALYSIS; THERAPY; AVERSION; INTERVENTIONS; SENSITIZATION; PARAPHILIAS AB The clinical research and treatment options for sexual paraphilias are scant and have generally been limited to psychodynamic and early behavioral approaches. This article highlights the application of two existing evidence-based modern behavioral interventions, specifically behavioral activation and sensate focused therapy, to treat foot fetishism/sexual impulses and co-occurring mood/anxiety symptoms in a 57-year-old male Vietnam War veteran. This brief 6-week treatment addressed the patient's complicating psychosocial factors and medical conditions, and focused on targeting behavioral avoidance symptoms associated with fetishism and depression (e.g., increasing socially and sexually appropriate and positive reinforcing behaviors in his environment). The patient no longer met diagnostic criteria for fetishism and endorsed significant reductions in depressed mood, anxiety, and stress at post-treatment and 1-month follow-up. This case illustrated how current behavioral treatments may be used to successfully treat patients with rare symptom presentations who may otherwise be neglected within a medical system. C1 [Sarver, Nina Wong] Boston Univ, Boston, MA 02215 USA. [Gros, Daniel F.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. [Gros, Daniel F.] Med Univ S Carolina, Charleston, SC USA. RP Gros, DF (reprint author), Ralph H Johnson Vet Affairs Med Ctr, Mental Hlth Serv 116, 109 Bee St, Charleston, SC 29401 USA. EM grosd@musc.edu NR 64 TC 0 Z9 0 U1 2 U2 11 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1534-6501 EI 1552-3802 J9 CLIN CASE STUD JI Clin. Case Stud. PD AUG PY 2014 VL 13 IS 4 BP 336 EP 351 DI 10.1177/1534650113512020 PG 16 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AW9PK UT WOS:000346589300004 ER PT J AU Walters, PR Zuckerbraun, BS AF Walters, Pamela R. Zuckerbraun, Brian S. TI Clostridium difficile Infection Clinical Challenges and Management Strategies SO CRITICAL CARE NURSE LA English DT Article ID POLYMERASE-CHAIN-REACTION; HEALTH-CARE SETTINGS; HOSPITALIZED-PATIENTS; SURGICAL-MANAGEMENT; DISEASE; DIARRHEA; COLITIS; EPIDEMIOLOGY; COLECTOMY; VANCOMYCIN AB Clostridium difficile has become the leading cause of nosocomial diarrhea in adults. A substantial increase has occurred in morbidity and mortality associated with disease caused by C difficile and in the identification of new hypervirulent strains, warranting a high clinical index of suspicion for infections due to this organism. Prevention of infection requires a multidisciplinary approach, including early recognition of disease, effective contact isolation precautions, adherence to disinfectant policies, and judicious use of antibiotics. Current treatment approaches are based on the severity of illness. As hypervirulent strains evolve, unsuccessful treatments are more common. Complicated colitis caused by C difficile may benefit from surgical intervention. Subtotal colectomy and end ileostomy have been the procedures of choice, but are associated with a high mortality rate because of late surgical consultation and use of surgery as a salvage therapy. A promising surgical alternative is creation of a diverting loop ileostomy with colonic lavage. C1 [Walters, Pamela R.] Univ Pittsburgh, Ctr Sports Med, Pittsburgh, PA 15213 USA. [Zuckerbraun, Brian S.] Univ Pittsburgh, Pittsburgh, PA 15213 USA. [Zuckerbraun, Brian S.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Walters, PR (reprint author), Univ Pittsburgh, Med Ctr, 200 Lothrop St, Pittsburgh, PA 15213 USA. EM pamelarwalters@gmail.com NR 58 TC 5 Z9 5 U1 0 U2 0 PU AMER ASSOC CRITICAL CARE NURSES PI ALISO VIEJO PA 101 COLUMBIA, ALISO VIEJO, CA 92656 USA SN 0279-5442 EI 1940-8250 J9 CRIT CARE NURSE JI Crit. Care Nurse PD AUG PY 2014 VL 34 IS 4 BP 24 EP 33 DI 10.4037/ccn2014822 PG 10 WC Critical Care Medicine; Nursing SC General & Internal Medicine; Nursing GA AW8WF UT WOS:000346538700003 PM 25086091 ER PT J AU Williams, NR Taylor, JJ Kerns, S Short, EB Kantor, EM George, MS AF Williams, Nolan R. Taylor, Joseph J. Kerns, Suzanne Short, E. Baron Kantor, Edward M. George, Mark S. TI Interventional Psychiatry: Why Now? SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Letter ID DEEP BRAIN-STIMULATION; OBSESSIVE-COMPULSIVE DISORDER; TRANSCRANIAL MAGNETIC STIMULATION; TREATMENT-RESISTANT DEPRESSION; RANDOMIZED CONTROLLED-TRIAL; ELECTROCONVULSIVE-THERAPY; CLINICAL NEUROSCIENCE; MAJOR DEPRESSION; NEURAL CIRCUITS; EFFICACY C1 [Williams, Nolan R.; Taylor, Joseph J.; Kerns, Suzanne; Short, E. Baron; Kantor, Edward M.; George, Mark S.] Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. [Williams, Nolan R.; Taylor, Joseph J.; George, Mark S.] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. [George, Mark S.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Williams, NR (reprint author), Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. EM willianr@musc.edu OI Williams, Nolan/0000-0003-4368-3203 FU NIDA NIH HHS [R25 DA020537, F30 DA033748] NR 57 TC 2 Z9 2 U1 2 U2 3 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD AUG PY 2014 VL 75 IS 8 BP 895 EP 897 DI 10.4088/JCP.13l08745 PG 3 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AU3RC UT WOS:000345530300019 PM 25191910 ER PT J AU Charles, R Sakurai, T Takahashi, N Elder, GA Sosa, MAG Young, LJ Buxbaum, JD AF Charles, Rhonda Sakurai, Takeshi Takahashi, Nagahide Elder, Gregory A. Sosa, Miguel A. Gama Young, Larry J. Buxbaum, Joseph D. TI Introduction of the human AVPR1A gene substantially alters brain receptor expression patterns and enhances aspects of social behavior in transgenic mice SO DISEASE MODELS & MECHANISMS LA English DT Article DE AVPR1A; Humanized mouse; Social behavior; Species-specific; Microsatellite; Autism ID ANXIETY-RELATED BEHAVIOR; VASOPRESSIN RECEPTOR; KNOCKOUT MICE; PREPULSE INHIBITION; PROMOTER REGION; PSYCHIATRIC-DISORDERS; MONOGAMOUS VOLE; BINDING-SITES; MESSENGER-RNA; V-1A RECEPTOR AB Central arginine vasopressin receptor 1A(AVPR1A) modulates a wide range of behaviors, including stress management and territorial aggression, as well as social bonding and recognition. Inter- and intra-species variations in the expression pattern of AVPR1A in the brain and downstream differential behavioral phenotypes have been attributed to differences in the non-coding regions of the AVPR1A gene, including polymorphic elements within upstream regulatory areas. Gene association studies have suggested a link between AVPR1A polymorphisms and autism, and AVPR1A has emerged as a potential pharmacological target for treatment of social cognitive impairments and mood and anxiety disorders. To further investigate the genetic mechanism giving rise to species differences in AVPR1A expression patterns and associated social behaviors, and to create a preclinical mouse model useful for screening drugs targeting AVPR1A, we engineered and extensively characterized bacterial artificial chromosome(BAC) transgenic mice harboring the entire human AVPR1A locus with the surrounding regulatory elements. Compared with wild-type animals, the humanized mice displayed a more widely distributed ligand-AVPR1A binding pattern, which overlapped with that of primates. Furthermore, humanized AVPR1A mice displayed increased reciprocal social interactions compared with wild-type animals, but no differences in social approach and preference for social novelty were observed. Aspects of learning and memory, specifically novel object recognition and spatial relocation recognition, were unaffected. The biological alterations in humanized AVPR1A mice resulted in the rescue of the prepulse inhibition impairments that were observed in knockout mice, indicating conserved functionality. Although further behavioral paradigms and additional cohorts need to be examined in humanized AVPR1A mice, the results demonstrate that species-specific variations in the genomic content of regulatory regions surrounding the AVPR1A locus are responsible for differential receptor protein expression patterns across species and that they are likely to contribute to species-specific behavioral variation. The humanized AVPR1A mouse is a potential preclinical model for further understanding the regulation of receptor gene expression and the impact of variation in receptor expression on behaviors, and should be useful for screening drugs targeting human AVPR1A, taking advantage of the expression of human AVPR1A in human-relevant brain regions. C1 [Charles, Rhonda; Sakurai, Takeshi; Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Seaver Autism Ctr Res & Treatment, New York, NY 10029 USA. [Charles, Rhonda; Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA. [Sakurai, Takeshi; Takahashi, Nagahide; Elder, Gregory A.; Sosa, Miguel A. Gama; Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Elder, Gregory A.] Icahn Sch Med Mt Sinai, Dept Neurol, New York, NY 10029 USA. [Elder, Gregory A.] James J Peters VA Med Ctr, Neurol Serv, Bronx, NY 10468 USA. [Sosa, Miguel A. Gama] James J Peters VA Med Ctr, Res & Dev Serv, Bronx, NY 10468 USA. [Young, Larry J.] Emory Univ, Yerkes Natl Primate Res Ctr, Dept Psychiat & Behav Sci, Ctr Translat Social Neurosci, Atlanta, GA 30329 USA. [Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY 10029 USA. [Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA. [Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA. RP Buxbaum, JD (reprint author), Icahn Sch Med Mt Sinai, Seaver Autism Ctr Res & Treatment, New York, NY 10029 USA. EM joseph.buxbaum@mssm.edu OI Buxbaum, Joseph/0000-0001-8898-8313 FU Seaver Foundation; Autism Science Foundation; National Institutes of Health [MH056897, MH064692, P51OD11132] FX This work was supported by the Seaver Foundation and a predoctoral fellowship from the Autism Science Foundation to R. C. Additional support was provided by National Institutes of Health grants [MH056897 and MH064692 to L.J.Y. and P51OD11132 to Yerkes National Primate Research Center]. NR 55 TC 3 Z9 3 U1 0 U2 15 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 1754-8403 EI 1754-8411 J9 DIS MODEL MECH JI Dis. Model. Mech. PD AUG PY 2014 VL 7 IS 8 BP 1013 EP 1022 DI 10.1242/dmm.017053 PG 10 WC Cell Biology; Pathology SC Cell Biology; Pathology GA AT5TF UT WOS:000345004200009 PM 24924430 ER PT J AU Sher, L Landers, S AF Sher, Leo Landers, Sean TI Bipolar disorder, testosterone administration, and homicide: A case report SO INTERNATIONAL JOURNAL OF PSYCHIATRY IN CLINICAL PRACTICE LA English DT Article DE Bipolar disorder; testosterone; homicide ID STEROID USE; OFFENDERS AB Objective. Homicide is a major public health and social concern in the United States. Studies have found higher rates of psychiatric disorders in homicide off enders than in the general population. The aim of this article is to report and to discuss a case of a patient with bipolar disorder and hypogonadism who murdered his wife shortly aft er a testosterone injection. Methods. A case study and a review of the relevant literature. Results. Our case study as well as several case reports in the literature suggests that testosterone administration or high testosterone levels may be associated with homicidal behavior. Conclusion. Further studies of the role of testosterone in the neurobiology of violent and homicidal behavior may lead to improvements in the prevention of homicides. C1 [Sher, Leo] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Sher, Leo] James J Peters Vet Adm Med Ctr, New York, NY USA. [Landers, Sean] Ninth Judicial Circuit, Orlando, FL USA. RP Sher, L (reprint author), James J Peters Vet Adm, Icahn Sch Med Mt Sinai, Med Ctr, 130 West Kingsbridge Rd, Bronx, NY 10468 USA. EM DrLeoSher@gmail.com NR 13 TC 1 Z9 1 U1 0 U2 7 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1365-1501 EI 1471-1788 J9 INT J PSYCHIAT CLIN JI Int. J. Psychiat. Clin. PD AUG PY 2014 VL 18 IS 3 BP 215 EP 216 DI 10.3109/13651501.2014.894075 PG 2 WC Psychiatry SC Psychiatry GA AS8AO UT WOS:000344473100011 PM 24527885 ER PT J AU Lytle, MC De Luca, SM Blosnich, JR AF Lytle, Megan C. De Luca, Susan M. Blosnich, John R. TI The Influence of Intersecting Identities on Self-Harm, Suicidal Behaviors, and Depression among Lesbian, Gay, and Bisexual Individuals SO SUICIDE AND LIFE-THREATENING BEHAVIOR LA English DT Article ID SEXUAL ORIENTATION; RISK-FACTORS; DISORDERS; IDEATION; ADULTS; LATINO AB Individuals with lesbian, gay, and bisexual (LGB) identities have higher prevalence of self-directed violence, but very little is known about racial/ethnic differences between LGB populations. This study aimed to examine racial/ethnic differences in self-harm, suicidal ideation, suicide attempt, and depression among LGB and heterosexual emerging adults. Data are compiled from the Fall 2008 and Spring 2009 National College Health Assessment and limited to respondents within emerging adulthood (ages 18-24) who indicated their sexual orientation and racial/ethnic identities (n = 89,199). Within each racial/ethnic group, LGB individuals were significantly more likely to report self-harm, suicidal ideation, suicide attempt, and depression than non-LGB individuals. C1 [Lytle, Megan C.] Univ Rochester, Med Ctr, Dept Psychiat, Rochester, NY 14642 USA. [De Luca, Susan M.] Univ Texas Austin, Sch Social Work, Austin, TX 78712 USA. [Blosnich, John R.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. RP Lytle, MC (reprint author), Univ Rochester, Med Ctr, Dept Psychiat, 300 Crittenden Blvd, Rochester, NY 14642 USA. EM megan_lytle@urmc.rochester.edu FU NCATS NIH HHS [KL2 TR000095]; NIMH NIH HHS [T32 MH020061] NR 22 TC 5 Z9 5 U1 3 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0363-0234 EI 1943-278X J9 SUICIDE LIFE-THREAT JI Suicide Life-Threat. Behav. PD AUG PY 2014 VL 44 IS 4 BP 384 EP 391 DI 10.1111/sltb.12083 PG 8 WC Psychiatry; Psychology, Multidisciplinary SC Psychiatry; Psychology GA AS3LI UT WOS:000344178900004 PM 25250405 ER PT J AU Walter, KH Varkovitzky, RL Owens, GP Lewis, J Chard, KM AF Walter, Kristen H. Varkovitzky, Ruth L. Owens, Gina P. Lewis, Jennifer Chard, Kathleen M. TI Cognitive Processing Therapy for Veterans With Posttraumatic Stress Disorder: A Comparison Between Outpatient and Residential Treatment SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article DE posttraumatic stress disorder; cognitive processing therapy; outpatient treatment; residential treatment; veterans ID ADMINISTERED PTSD SCALE; PSYCHOMETRIC PROPERTIES; BEHAVIORAL THERAPY; PROLONGED EXPOSURE; AFGHANISTAN; IRAQ; PROGRAM; TRIAL; CARE AB Objective: Across the Veterans Affairs (VA) Healthcare System, outpatient and residential posttraumatic stress disorder (PTSD) treatment programs are available to veterans of all ages and both genders; however, no research to date has compared these treatment options. This study compared veterans who received outpatient (n = 514) to those who received residential treatment (n = 478) within a VA specialty clinic on demographic and pretreatment symptom variables. Further, the study examined pre- to posttreatment symptom trajectories across the treatment programs. Method: All 992 veterans met diagnostic criteria for PTSD and attended at least 1 session of cognitive processing therapy (CPT) in either the outpatient or residential program. Bivariate analyses were utilized to investigate differences between samples on demographic variables and severity of pretreatment symptoms. Multilevel modeling (MLM) was used to investigate the change in symptomatology between the 2 samples from pre- to posttreatment. Results: Analyses indicated that the samples differed on all demographic and pretreatment symptom variables, with residential patients reporting higher scores on all assessment measures. MLM results demonstrated that symptom scores improved for all veterans across time, with outpatients consistently reporting fewer symptoms at both time points. The time by program interaction was significant for PTSD-related symptom trajectories, but not for the depression-related symptom trajectory. Conclusion: This is the 1st study to compare pretreatment characteristics and treatment outcome between veterans receiving outpatient and residential PTSD treatment. Findings may help clinicians select appropriate care for their patients by identifying relevant pretreatment characteristics and generally informing expectations of treatment outcome. C1 [Walter, Kristen H.] Vet Med Res Fdn, San Diego, CA 92161 USA. [Walter, Kristen H.] Vet Affairs San Diego Healthcare Syst, Res Serv, San Diego, CA USA. [Varkovitzky, Ruth L.] Vet Affairs Puget Sound Healthcare Syst, Amer Lake Div, PTSD Outpatient Clin, Tacoma, WA USA. [Owens, Gina P.] Univ Tennessee, Dept Psychol, Knoxville, TN 37996 USA. [Lewis, Jennifer; Chard, Kathleen M.] Cincinnati Vet Affairs Med Ctr, Trauma Recovery Ctr, Cincinnati, OH USA. [Chard, Kathleen M.] Univ Cincinnati, Dept Psychiat, Cincinnati, OH 45221 USA. RP Walter, KH (reprint author), Vet Med Res Fdn, 3350 La Jolla Village Dr,111N-1,Bldg 13, San Diego, CA 92161 USA. EM Kristen.Walter@va.gov NR 37 TC 3 Z9 3 U1 3 U2 16 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X EI 1939-2117 J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD AUG PY 2014 VL 82 IS 4 BP 551 EP 561 DI 10.1037/a0037075 PG 11 WC Psychology, Clinical SC Psychology GA AS3FY UT WOS:000344164000001 PM 24911422 ER PT J AU Shah, A Carreno, FR Frazer, A AF Shah, Aparna Carreno, Flavia Regina Frazer, Alan TI Therapeutic Modalities for Treatment Resistant Depression: Focus on Vagal Nerve Stimulation and Ketamine SO CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE LA English DT Review DE Depression; Vagal nerve stimulation; Ketamine; TrkB ID D-ASPARTATE ANTAGONIST; PHARMACOLOGICALLY DIVERSE ANTIDEPRESSANTS; TRANSCRANIAL MAGNETIC STIMULATION; COGNITIVE-BEHAVIORAL THERAPY; NEUROTROPHIC FACTOR-RECEPTOR; DELTA-FOSB IMMUNOREACTIVITY; RANDOMIZED CONTROLLED-TRIAL; VAGUS NERVE; MAJOR DEPRESSION; RAT-BRAIN AB Treatment resistant depression (TRD) is a global health concern affecting a large proportion of depressed patients who then require novel therapeutic options. One such treatment option that has received some attention in the past several years. is vagal nerve stimulation (VNS). The present review briefly describes the relevance of this treatment in the light of other existing pharmacological and non-pharmacological options, It then summarizes clinical findings with respect to the efficacy of VNS. The anatomical rationale for its efficacy and other potential mechanisms of its antidepressant effects as compared to those employed by classical antidepressant drugs are discussed. VNS has been approved in some countries and has been used for patients with TRD for quite some time, A newer, fast-acting, non-invasive pharmacological option called ketamine is currently in the limelight with reference to TRD. This drug is currently in the investigational phase but shows promise. The clinical and preclinical findings related to ketamine have also been summarized and compared with those for VNS. The role of neurotrophin factors, specifically brain derived neurotrophic factor and its receptor, in the beneficial effects of both VNS and ketamine have been highlighted. It can be concluded that both these therapeutic modalities, while effective, need further research that can reveal specific targets for intervention by novel drugs and address concerns related to side-effects, especially those seen with ketamine. C1 [Shah, Aparna; Carreno, Flavia Regina; Frazer, Alan] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA. [Shah, Aparna; Carreno, Flavia Regina; Frazer, Alan] Univ Texas Hlth Sci Ctr San Antonio, Ctr Biomed Neurosci, San Antonio, TX 78229 USA. [Frazer, Alan] South Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. RP Shah, A (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, 7703 Floyd Curl Dr,Mail Code 7764, San Antonio, TX 78229 USA. EM shahap@uthscsa.edu FU Lundbeck; Takeda Pharmaceuticals International, Inc.; Eli Lilly and Co. FX Dr. Frazer has served on advisory boards for Lundbeck and for Takeda Pharmaceuticals International, Inc. and Eli Lilly and Co. Previously, Dr. Frazer had received financial compensation as a consultant for Cyberonics Inc. and had also obtained grant support from them for a preclinical study. NR 126 TC 9 Z9 9 U1 1 U2 10 PU KOREAN COLL NEUROPSYCHOPHARMACOLOGY PI SEOUL PA RN 1003 OFFICETEL 40, 63-RO YEONGDEUNGPO-GU, SEOUL, 150-731, SOUTH KOREA SN 1738-1088 EI 2093-4327 J9 CLIN PSYCHOPHARM NEU JI Clin. Psychopharmacol. Neurosci. PD AUG PY 2014 VL 12 IS 2 BP 83 EP 93 DI 10.9758/cpn.2014.12.2.83 PG 11 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA AQ5NK UT WOS:000342855700002 PM 25191499 ER PT J AU Shalaby, AA Brumberg, GE Pointer, L Bekelman, DB Rumsfeld, JS Yang, YF Pellegrini, CN Heidenreich, PA Keung, E Massie, BM Varosy, PD AF Shalaby, Alaa A. Brumberg, Genevieve E. Pointer, Lauren Bekelman, David B. Rumsfeld, John S. Yang, Yanfei Pellegrini, Cara N. Heidenreich, Paul A. Keung, Edmund Massie, Barry M. Varosy, Paul D. TI Depression and Outcome among Veterans with Implantable Cardioverter Defibrillators with or without Cardiac Resynchronization Therapy Capability SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Article DE depression; implantable cardiac defibrillator; mortality; heart failure ID CHRONIC HEART-FAILURE; MYOCARDIAL-INFARCTION; COLLABORATIVE CARE; SYMPTOMS; RISK; MORTALITY; PREVALENCE; LIFE AB Background: The impact of depression on outcome in implantable cardioverter defibrillator (ICD) recipients has not been fully appreciated. We assessed the prevalence of depression and its association with heart failure (HF) outcome among veterans with ICDs. Methods and Results: Patients enrolled between January 2005 and January 2010 in the Outcomes among Veterans with Implantable Defibrillators Registry were studied. We examined the cross-sectional association of depression with severity of HF functional class as well as the association of depression with the composite outcome of mortality or HF hospitalization over a mean follow-up time of 2.7 years. There were 3,862 patients enrolled. Patients with depression (1,162, 43%) were younger (63.1 +/- 9.4 years vs 66.6 +/- 9.9 years, P<0.001), more likely to have a history of tobacco or alcohol abuse (P<0.0001) or atrial fibrillation (P=0.05) while having a higher ejection fraction (28.3% vs 27.4%, P=0.03). Depression was associated with advanced HF class at time of implant; odds ratio (OR; vs class I) for class III: 1.65 (confidence interval [CI] 1.17-2.33), class IV: 1.73 (95% CI 1.08-2.76). Death or HF hospitalization was more likely to occur in patients with depression (35.2% vs 32.0%, HR: 1.15 [95% CI 0.99-1.33]). The predictive value of depression was stronger after multivariable adjustment; HR: 1.25 (95% CI 1.05-1.49). Conclusion: Depression was prevalent among veterans with ICDs. Depression was associated with severity of HF. The predictive value of associated depression was significant after multivariable adjustment. C1 [Shalaby, Alaa A.; Brumberg, Genevieve E.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15240 USA. [Shalaby, Alaa A.; Brumberg, Genevieve E.] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Pointer, Lauren; Bekelman, David B.; Rumsfeld, John S.; Varosy, Paul D.] Vet Affairs Eastern Colorado Hlth Care Syst, Denver, CO USA. [Pointer, Lauren; Bekelman, David B.; Rumsfeld, John S.; Varosy, Paul D.] Univ Colorado, Colorado Cardiovasc Outcomes Res, Denver, CO 80202 USA. [Yang, Yanfei; Heidenreich, Paul A.] Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Yang, Yanfei; Heidenreich, Paul A.] Stanford Univ, Palo Alto, CA 94304 USA. [Pellegrini, Cara N.; Keung, Edmund; Massie, Barry M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Pellegrini, Cara N.; Keung, Edmund; Massie, Barry M.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Shalaby, AA (reprint author), Univ Pittsburgh, Sch Med, VA Pittsburgh Healthcare Syst, Div Cardiol, 111 C Univ Dr, Pittsburgh, PA 15240 USA. EM Alaa.Shalaby@va.gov OI Heidenreich, Paul/0000-0001-7730-8490 NR 37 TC 2 Z9 2 U1 3 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0147-8389 EI 1540-8159 J9 PACE JI PACE-Pacing Clin. Electrophysiol. PD AUG PY 2014 VL 37 IS 8 BP 994 EP 1001 DI 10.1111/pace.12361 PG 8 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA AQ5FL UT WOS:000342831900011 PM 24520992 ER PT J AU Deyo, RA Dworkin, SF Amtmann, D Andersson, G Borenstein, D Carragee, E Carrino, J Chou, R Cook, K DeLitto, A Goertz, C Khalsa, P Loeser, J Mackey, S Panagis, J Rainville, J Tosteson, T Turk, D Von Korff, M Weiner, DK AF Deyo, Richard A. Dworkin, Samuel F. Amtmann, Dagmar Andersson, Gunnar Borenstein, David Carragee, Eugene Carrino, John Chou, Roger Cook, Karon DeLitto, Anthony Goertz, Christine Khalsa, Partap Loeser, John Mackey, Sean Panagis, James Rainville, James Tosteson, Tor Turk, Dennis Von Korff, Michael Weiner, Debra K. TI Report of the NIH Task Force on Research Standards for Chronic Low Back Pain SO PAIN MEDICINE LA English DT Article DE Low Back Pain; Chronic Low Back Pain; Research Standards; Minimum Dataset; NIH Task Force ID CLINICAL-PRACTICE GUIDELINE; DEFINING CHRONIC PAIN; INFORMATION-SYSTEM PROMIS; FUNCTION ITEM BANK; QUALITY-OF-LIFE; PRIMARY-CARE; PROGNOSTIC APPROACH; SCREENING TOOL; START BACK; OUTCOME MEASURES AB Objective. Despite rapidly increasing intervention, functional disability due to chronic low back pain (cLBP) has increased in recent decades. We often cannot identify mechanisms to explain the major negative impact cLBP has on patients' lives. Such cLBP is often termed non-specific, and may be due to multiple biologic and behavioral etiologies. Researchers use varied inclusion criteria, definitions, baseline assessments, and outcome measures, which impede comparisons and consensus. Design. Expert panel and preliminary evaluation of key recommendations. Methods. The NIH Pain Consortium charged a Research Task Force (RTF) to draft standards for research on cLBP. The resulting multidisciplinary panel developed a 3-stage process, each with a 2-day meeting. Results. The panel recommended using 2 questions to define cLBP; classifying cLBP by its impact (defined by pain intensity, pain interference, and physical function); use of a minimal data set to describe research subjects (drawing heavily on the PROMIS methodology); reporting "responder analyses" in addition to mean outcome scores; and suggestions for future research and dissemination. The Pain Consortium has approved the recommendations, which investigators should incorporate into NIH grant proposals. Conclusion. The RTF believes these recommendations will advance the field, help to resolve controversies, and facilitate future research addressing the genomic, neurologic, and other mechanistic substrates of chronic low back pain. Greater consistency in reporting should facilitate comparisons among studies and the development of phenotypes. We expect the RTF recommendations will be come a dynamic document, and undergo continual improvement. Perspective. A task force was convened by the NIH Pain Consortium with the goal of developing research standards for chronic low back pain. The results included recommendations for definitions, a minimum dataset, reporting outcomes, and future research. Greater consistency in reporting should facilitate comparisons among studies and the development of phenotypes. C1 [Deyo, Richard A.; Chou, Roger] Oregon Hlth & Sci Univ, Portland, OR 97239 USA. [Dworkin, Samuel F.; Amtmann, Dagmar; Loeser, John; Turk, Dennis] Univ Washington, Seattle, WA 98195 USA. [Von Korff, Michael] Grp Hlth Res Inst, Seattle, WA USA. [Andersson, Gunnar] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Cook, Karon; Weiner, Debra K.] Northwestern Univ, Evanston, IL USA. [Borenstein, David] George Washington Univ, Washington, DC USA. [Carragee, Eugene; Mackey, Sean] Stanford Univ, Stanford, CA 94305 USA. [Carrino, John] Johns Hopkins Univ, Baltimore, MD USA. [Khalsa, Partap] Natl Ctr Complementary & Alternat Med, Bethesda, MD USA. [Panagis, James] NIAMSD, Bethesda, MD 20892 USA. [DeLitto, Anthony] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [DeLitto, Anthony] Univ Pittsburgh, Pittsburgh, PA USA. [Goertz, Christine] Palmer Coll Chiropract, Davenport, IA USA. [Rainville, James] New England Baptist Hosp, Roxbury Crossing, MA USA. [Tosteson, Tor] Dartmouth Coll, Hanover, NH USA. RP Deyo, RA (reprint author), Oregon Hlth & Sci Univ, 3181 SW Sam Jackson Pk Rd,Mail Code FM, Portland, OR 97239 USA. EM deyor@ohsu.edu FU National Center for Complementary and Alternative Medicine; National Institute for Arthritis, Musculoskeletal, and Skin Diseases FX This study was supported by the National Center for Complementary and Alternative Medicine and the National Institute for Arthritis, Musculoskeletal, and Skin Diseases. NR 126 TC 12 Z9 13 U1 8 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1526-2375 EI 1526-4637 J9 PAIN MED JI Pain Med. PD AUG PY 2014 VL 15 IS 8 BP 1249 EP 1267 DI 10.1111/pme.12538 PG 19 WC Medicine, General & Internal SC General & Internal Medicine GA AQ2PW UT WOS:000342630800004 PM 25132307 ER PT J AU Allen, JL Kautz, SA Neptune, RR AF Allen, Jessica L. Kautz, Steven A. Neptune, Richard R. TI Forward propulsion asymmetry is indicative of changes in plantarflexor coordination during walking in individuals with post-stroke hemiparesis SO CLINICAL BIOMECHANICS LA English DT Article DE Forward dynamic simulations; Gait; Post-stroke hemiparesis; Rehabilitation ID GROUND REACTION FORCES; BODY-WEIGHT SUPPORT; MECHANICAL-PROPERTIES; STROKE SURVIVORS; GAIT ANALYSIS; PARETIC LEG; ENERGY-COST; MUSCLE; SPEED; PROGRESSION AB Background: A common measure of rehabilitation effectiveness post-stroke is self-selected walking speed, yet individuals may achieve the same speed using different coordination strategies. Asymmetry in the propulsion generated by each leg can provide insight into paretic leg coordination due to its relatively strong correlation with hemiparetic severity. Subjects walking at the same speed can exhibit different propulsion asymmetries, with some subjects relying more on the paretic leg and others on the nonparetic leg. The goal of this study was to assess whether analyzing propulsion asymmetry can help distinguish between improved paretic leg coordination versus nonparetic leg compensation. Methods: Three-dimensional forward dynamics simulations were developed for two post-stroke hemiparetic subjects walking at identical speeds before/after rehabilitation with opposite changes in propulsion asymmetry. Changes in the individual muscle contributions to forward propulsion were examined. Findings: The major source of increased forward propulsion in both subjects was from the ankle plantarflexors. How they were utilized differed and appears related to changes in propulsion asymmetry. Subject A increased propulsion generated from the paretic plantarflexors, while Subject B increased propulsion generated from the nonparetic plantarflexors. Each subject's strategy to increase speed also included differences in other muscle groups (e.g., hamstrings) that did not appear to be related to propulsion asymmetry. Interpretation: The results of this study highlight how speed cannot be used to elucidate underlying muscle coordination changes following rehabilitation. In contrast, propulsion asymmetry appears to provide insight into changes in plantarflexor output affecting propulsion generation and may be useful in monitoring rehabilitation outcomes. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Allen, Jessica L.; Neptune, Richard R.] Univ Texas Austin, Dept Mech Engn, Austin, TX 78712 USA. [Kautz, Steven A.] Med Univ S Carolina, Dept Hlth Sci & Res, Charleston, SC 29425 USA. [Kautz, Steven A.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Neptune, RR (reprint author), Univ Texas Austin, Dept Mech Engn, 1 Univ Stn C2200, Austin, TX 78712 USA. EM rneptune@mail.utexas.edu FU NIH [R01 NS55380]; Rehabilitation Research & Development Service of the VA; NSF Graduate Research Fellowship Program FX The authors would like to thank Dr. Mark Bowden and the intervention research team for their contributions to the data collection and processing. This project was supported by NIH grant R01 NS55380, the Rehabilitation Research & Development Service of the VA, and the NSF Graduate Research Fellowship Program. The comments are solely the responsibility of the authors and do not necessarily represent the official views of the NIH, NICHD, VA or NSF. NR 42 TC 6 Z9 6 U1 3 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0268-0033 EI 1879-1271 J9 CLIN BIOMECH JI Clin. Biomech. PD AUG PY 2014 VL 29 IS 7 BP 780 EP 786 DI 10.1016/j.clinbiomech.2014.06.001 PG 7 WC Engineering, Biomedical; Orthopedics; Sport Sciences SC Engineering; Orthopedics; Sport Sciences GA AQ1GY UT WOS:000342531100010 PM 24973825 ER PT J AU Ho, JM Anekonda, VT Thompson, BW Zhu, MY Curry, RW Hwang, BH Morton, GJ Schwartz, MW Baskin, DG Appleyard, SM Blevins, JE AF Ho, Jacqueline M. Anekonda, Vishwanath T. Thompson, Benjamin W. Zhu, Mingyan Curry, Robert W. Hwang, Bang H. Morton, Gregory J. Schwartz, Michael W. Baskin, Denis G. Appleyard, Suzanne M. Blevins, James E. TI Hindbrain Oxytocin Receptors Contribute to the Effects of Circulating Oxytocin on Food Intake in Male Rats SO ENDOCRINOLOGY LA English DT Article ID BRAIN-STEM NUCLEI; C-FOS EXPRESSION; HUMAN GASTROINTESTINAL-TRACT; PROLACTIN-RELEASING PEPTIDE; DORSAL VAGAL COMPLEX; PARAVENTRICULAR NUCLEUS; MESSENGER-RNA; CATECHOLAMINERGIC NEURONS; ADMINISTERED OXYTOCIN; GASTRIC-MOTILITY AB Oxytocin (OT)-elicited hypophagia has been linked to neural activity in the nucleus of the solitary tract (NTS). Because plasma OT levels increase after a meal, we hypothesized that circulating OT acts at both peripheral and hindbrain OT receptors (OTRs) to limit food intake. To initially determine whether circulating OT inhibits food intake by acting at hindbrain OTRs, we pretreated rats with an OTR antagonist administered into the fourth ventricle (4V) followed by either central or systemic OT administration. Administration of the OTR antagonist into the 4V blocked anorexia induced by either 4V or ip injection of OT. However, blockade of peripheral OTRs also weakened the anorectic response to ip OT. Our data suggest a predominant role for hindbrain OTRs in the hypophagic response to peripheral OT administration. To elucidate central mechanisms of OT hypophagia, we tested whether OT activates NTS catecholaminergic neurons. OT (ip) increased the number of NTS cells expressing c-Fos, of which 10%-15% were catecholaminergic. Furthermore, electrophysiological studies in mice revealed that OT stimulated 47% (8 of 17) of NTS catecholamine neurons through a presynaptic mechanism. However, OT-elicited hypophagia did not appear to require activation of alpha(1)-adrenoceptors, and blockade of glucagon-like peptide-1 receptors similarly did not attenuate anorexia induced by OT. These findings demonstrate that OT elicits satiety through both central and peripheral OTRs and that although catecholamine neurons are a downstream target of OT signaling in the NTS, the hypophagic effect is mediated independently of alpha(1)-adrenoceptor signaling. C1 [Ho, Jacqueline M.; Anekonda, Vishwanath T.; Thompson, Benjamin W.; Curry, Robert W.; Hwang, Bang H.; Baskin, Denis G.; Blevins, James E.] Vet Affairs Puget Sound Hlth Care Syst, Res & Dev Serv, Seattle, WA 98108 USA. [Ho, Jacqueline M.; Morton, Gregory J.; Schwartz, Michael W.; Baskin, Denis G.; Blevins, James E.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Morton, Gregory J.; Schwartz, Michael W.] Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. [Morton, Gregory J.; Schwartz, Michael W.] Univ Washington, Dept Med, Diabet & Obes Ctr Excellence, Seattle, WA 98195 USA. [Zhu, Mingyan; Appleyard, Suzanne M.] Washington State Univ, Dept Integrat Physiol & Neurosci, Program Neurosci, Pullman, WA 99164 USA. RP Blevins, JE (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Res 151,1660 South Columbian Way, Seattle, WA 98108 USA. EM jeblevin@u.washington.edu FU Research and Development Service of the Department of Veterans Affairs; Cellular and Molecular Imaging Core of the Diabetes Research Center at the University of Washington; National Institutes of Health [P30DK017047, P30DK017047-31689, DK083452]; Department of Veterans Affairs Merit Review Research Program; Diabetes, Obesity, and Metabolism Training Grant [2T32DK007247]; Veterans Affairs Senior Research Career Scientist award FX This work was supported by the Research and Development Service of the Department of Veterans Affairs and the Cellular and Molecular Imaging Core of the Diabetes Research Center at the University of Washington and supported by National Institutes of Health Grant P30DK017047. The research in our laboratory has been supported by the Department of Veterans Affairs Merit Review Research Program as well as National Institutes of Health Grants P30DK017047-31689, DK083452 (to S.M.A.), and Diabetes, Obesity, and Metabolism Training Grant 2T32DK007247. D.G.B. is the recipient of a Veterans Affairs Senior Research Career Scientist award. NR 70 TC 10 Z9 10 U1 0 U2 8 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD AUG PY 2014 VL 155 IS 8 BP 2845 EP 2857 DI 10.1210/en.2014-1148 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AP8QL UT WOS:000342343800011 PM 24877632 ER PT J AU McMillan, KK Pugh, MJ Hamid, H Salinsky, M Pugh, J Noel, PH Finley, EP Leykum, LK Lanham, HJ LaFrance, WC AF McMillan, Katharine K. Pugh, Mary Jo Hamid, Hamada Salinsky, Martin Pugh, Jacqueline Noel, Polly H. Finley, Erin P. Leykum, Luci K. Lanham, Holly J. LaFrance, W. Curt, Jr. TI Providers' perspectives on treating psychogenic nonepileptic seizures: Frustration and hope SO EPILEPSY & BEHAVIOR LA English DT Article DE Nonepileptic seizures; Diagnosis; Treatment; Veterans; Practitioners; Cognitive behavioral therapy ID GROUP PSYCHOEDUCATION; EPILEPSY CENTER; CARE; DIAGNOSIS; VETERANS; PSYCHIATRISTS; PERCEPTIONS; MANAGEMENT; SYMPTOMS; OUTCOMES AB Recent diagnostic and treatment advances in psychogenic nonepileptic seizures (PNES) have the potential to improve care for patients, but little is known about the current state of PNES care delivery in the Veterans Health Administration (VA). We conducted semistructured interviews with 74 health-care clinicians and workers in the VA, eliciting provider perceptions of PNES care. Data were analyzed according to principles of Grounded Theory. The results revealed variation in care and two emergent domain themes of frustration and hope. Frustration was manifest in subthemes including Complexity, Patient Acceptance, Uncertainty About Treatment, Need for Evidence-based Treatment, and Failure of Cross-Disciplinary Collaboration between neurologists and mental health providers. Hope encompassed subthemes of Positive Attitudes, Developing Cross-Disciplinary Treatment, and Specific PNES Care. Increased resources for diagnosing, treating, and researching PNES have improved awareness of the disorder. More research is needed to understand patients' and caregivers' perceptions of PNES care. (C) 2014 Elsevier Inc. All rights reserved. C1 [McMillan, Katharine K.; Pugh, Mary Jo; Noel, Polly H.; Finley, Erin P.; Leykum, Luci K.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [McMillan, Katharine K.; Pugh, Mary Jo; Pugh, Jacqueline; Noel, Polly H.; Finley, Erin P.; Leykum, Luci K.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Pugh, Mary Jo; Hamid, Hamada] VA Epilepsy Ctr Excellence, San Antonio, TX USA. [Hamid, Hamada] VA Connecticut Healthcare Syst, West Haven, CT 06516 USA. [Hamid, Hamada] Yale Univ, New Haven, CT USA. [Salinsky, Martin] Portland VA Med Ctr, Portland, OR USA. [Salinsky, Martin] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Lanham, Holly J.] Univ Texas Austin, McCombs Sch Business, Austin, TX 78712 USA. [LaFrance, W. Curt, Jr.] Brown Univ, Rhode Isl Hosp, Alpert Med Sch, Providence Vet Affairs Med Ctr, Providence, RI 02903 USA. [LaFrance, W. Curt, Jr.] Brown Univ, Rhode Isl Hosp, Alpert Med Sch, Neuropsychiat & Behav Neurol Div, Providence, RI 02903 USA. [Finley, Erin P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Finley, Erin P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. RP McMillan, KK (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, MSC 7933, San Antonio, TX 78229 USA. EM mcmillank@uthscsa.edu OI LaFrance, Jr., W Curt/0000-0002-4901-3852; Pugh, Jacqueline/0000-0003-4933-141X; Pugh, Mary Jo/0000-0003-4196-7763; Finley, Erin/0000-0003-4497-7721 FU VA Health Services Research and Development [IIR-067-11-2]; Implementation Research Institute (IRI) at the George Warren Brown School of Social Work, Washington University in St. Louis, through an award from the National Institute of Mental Health [R25 MH080916-01A2] FX VA Health Services Research and Development (IIR-067-11-2; Dr. MJ Pugh PI) funded this study. Dr. Finley is an investigator with the Implementation Research Institute (IRI) at the George Warren Brown School of Social Work, Washington University in St. Louis, through an award from the National Institute of Mental Health (R25 MH080916-01A2) and the Department of Veterans Affairs, Health Services Research & Development Service, Quality Enhancement Research Initiative (QUERI). The content of this article is solely the responsibility of the authors and does not necessarily reflect the official views of the Veterans' Health Administration. The funding organizations had no role in the design and conduct of the study; the collection, management, analysis, and interpretation of the data; or the preparation, review, or approval of the manuscript. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense. NR 42 TC 13 Z9 13 U1 4 U2 10 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-5050 EI 1525-5069 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD AUG PY 2014 VL 37 BP 276 EP 281 DI 10.1016/j.yebeh.2014.07.001 PG 6 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA AP7MJ UT WOS:000342261100048 PM 25128685 ER PT J AU Swanson, CM Nielson, CM Shrestha, S Lee, CG Barrett-Connor, E Jans, I Cauley, JA Boonen, S Bouillon, R Vanderschueren, D Orwoll, ES AF Swanson, Christine M. Nielson, Carrie M. Shrestha, Smriti Lee, Christine G. Barrett-Connor, Elizabeth Jans, Ivo Cauley, Jane A. Boonen, Steven Bouillon, Roger Vanderschueren, Dirk Orwoll, Eric S. CA Osteoporotic Fractures Men MrOS St TI Higher 25(OH)D-2 Is Associated With Lower 25(OH)D-3 and 1,25(OH)(2)D-3 SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID VITAMIN-D DEFICIENCY; SERUM 25-HYDROXYVITAMIN D; OLDER MEN; OSTEOPOROTIC FRACTURES; D 25-HYDROXYLASE; D-2; SUPPLEMENTATION; CHOLECALCIFEROL; ERGOCALCIFEROL; CYP2R1 AB Context: Despite common use of supplemental vitamin D-2 in clinical practice, the associations of serum vitamin D-2 concentrations with other vitaminDmetabolites and total vitamin D are unclear. Objective: The aim of the study was to measure vitamin D-2 and D-3 levels and examine their associations with each other and with total vitamin D. Design: We performed a cross-sectional analysis of 679 randomly selected participants from the Osteoporotic Fractures in Men Study. 25-Hydroxyvitamin D-2 [ 25(OH)D-2], 25(OH)D-3, 1,25-dihydroxyvitamin D-2 [1,25(OH)(2)D-2], and 1,25(OH)(2)D-3 were measured using liquid chromatography-tandem mass spectrometry and were summed to obtain total 25(OH)D and 1,25(OH)(2)D. Associations between all metabolites (D-2, D-3, and total levels) were examined using Wilcoxon rank-sum tests and Spearman correlations. Results: 25(OH)D-2 and 1,25(OH)(2)D-2 were detectable in 189 (27.8%) and 178 (26.2%) of the men, respectively. Higher 25(OH)D-2 levels did not correlate with higher total 25(OH) D (r = 0.10; P = .17), although median total 25(OH)D was slightly higher in those with detectable vs undetectable 25(OH)D-2 (25.8 vs 24.3 ng/mL; P < .001). 25(OH)D-2 was not positively associated with total 1,25(OH)(2)D levels (r = -0.11; P = .13), and median 1,25(OH)(2)D level was not higher in those with detectable vs undetectable 25(OH)D-2. Higher 25(OH)D-2 was associated with lower 25(OH)D-3 (r = -0.35; P < .001) and 1,25(OH)(2)D-3 (r = -0.32; P < .001), with median levels of both D-3 metabolites 18-35% higher when D-2 metabolites were undetectable. Conclusions: In a cohort of older men, 25(OH)D-2 is associated with lower levels of 25(OH)D-3 and 1,25(OH)(2)D-3, suggesting that vitamin D-2 may decrease the availability of D-3 and may not increase calcitriol levels. C1 [Swanson, Christine M.; Lee, Christine G.; Orwoll, Eric S.] Oregon Hlth & Sci Univ, Div Endocrinol, Portland, OR 97239 USA. [Swanson, Christine M.; Nielson, Carrie M.; Shrestha, Smriti; Lee, Christine G.; Orwoll, Eric S.] Oregon Hlth & Sci Univ, Bone & Mineral Unit, Portland, OR 97239 USA. [Nielson, Carrie M.] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97239 USA. [Lee, Christine G.] Portland VA Med Ctr, Res Serv, Portland, OR 97239 USA. [Barrett-Connor, Elizabeth] Univ Calif San Diego, Dept Family & Prevent Med, Div Epidemiol, La Jolla, CA 92093 USA. [Jans, Ivo; Vanderschueren, Dirk] Univ Leuven, KU Leuven, Lab Diagnost Med, B-3000 Leuven, Belgium. [Cauley, Jane A.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Boonen, Steven] Univ Leuven, KU Leuven, Div Geriatr Med, B-3000 Leuven, Belgium. [Boonen, Steven] Univ Leuven, KU Leuven, Ctr Metab Bone Dis, B-3000 Leuven, Belgium. [Bouillon, Roger; Vanderschueren, Dirk] Univ Leuven, KU Leuven, Lab Clin & Expt Endocrinol, B-3000 Leuven, Belgium. RP Orwoll, ES (reprint author), 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM Orwoll@ohsu.edu RI Cauley, Jane/N-4836-2015 OI Cauley, Jane/0000-0003-0752-4408 FU National Institutes of Health; National Institute of Arthritis and Musculoskeletal and Skin Diseases; National Institute on Aging; National Center for Research Resources; NIH Roadmap for Medical Research [U01 AR45580, U01 AR45614, U01 AR45632, U01 AR45647, U01 AR45654, U01 AR45583, U01 AG18197, U01 AG027810, UL1 TR000128]; Merck Co, Inc. [SRA-12-009]; National Institute of Diabetes and Digestive and Kidney Diseases [T32DK007674-20]; University Hospital in Leuven FX The Osteoporotic Fractures in Men (MrOS) Study is supported by National Institutes of Health funding. The following institutes provide support: the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the National Institute on Aging, the National Center for Research Resources, and NIH Roadmap for Medical Research under the following grant numbers: U01 AR45580, U01 AR45614, U01 AR45632, U01 AR45647, U01 AR45654, U01 AR45583, U01 AG18197, U01 AG027810, and UL1 TR000128.; This work was supported in part by an independent investigator grant (SRA-12-009) (to E.S.O.) from Merck & Co, Inc. C.M.S. is supported by National Institute of Diabetes and Digestive and Kidney Diseases Grant T32DK007674-20. D.V. is a senior clinical investigator supported by the University Hospital in Leuven. NR 30 TC 9 Z9 9 U1 1 U2 7 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 2014 VL 99 IS 8 BP 2736 EP 2744 DI 10.1210/jc.2014-1069 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AP8PO UT WOS:000342341200046 PM 24828488 ER PT J AU Calvert, JK Holt, SK Mossanen, M James, AC Wright, JL Porter, MP Gore, JL AF Calvert, Joshua K. Holt, Sarah K. Mossanen, Matthew James, Andrew C. Wright, Jonathan L. Porter, Michael P. Gore, John L. TI Use and Outcomes of Extended Antibiotic Prophylaxis in Urological Cancer Surgery SO JOURNAL OF UROLOGY LA English DT Article DE prostatic neoplasms; kidney neoplasms; urinary bladder neoplasms; antibiotic prophylaxis; cross infection ID CLOSTRIDIUM-DIFFICILE INFECTION; PROSTATE-CANCER; ANTIMICROBIAL-PROPHYLAXIS; BLADDER-CANCER; KIDNEY CANCER; RISK; METAANALYSIS; CARE; CYSTECTOMY; THERAPY AB Purpose: Although perioperative antibiotic prophylaxis prevents postoperative infectious complications, national guidelines recommend cessation of antibiotics within 24 hours after the procedure. Extended antibiotic prophylaxis beyond 24 hours may contribute to hospital acquired infections such as Clostridium difficile colitis. We evaluated practice patterns of antibiotic prophylaxis in genitourinary cancer surgery and assessed the impact of antibiotic prophylaxis on hospital acquired C. difficile infections. Materials and Methods: We identified 59,184 patients treated with radical prostatectomy, 27,921 who underwent partial or radical nephrectomy, and 5,425 treated with radical cystectomy for prostate, kidney and bladder cancers, respectively, from the Premier Perspective Database (Premier Inc., Charlotte, North Carolina) from 2007 to 2012. We constructed hierarchical linear regression models to identify patient and hospital factors associated with extended antibiotic prophylaxis. We evaluated the association between extended antibiotic prophylaxis and C. difficile infections for patients who underwent partial or radical nephrectomy and radical cystectomy with multivariate logistic regression. Results: Surgery specific models demonstrated that hospital identity was associated with a substantial proportion of the variation in extended antibiotic prophylaxis (20% to 35% for radical prostatectomy, partial or radical nephrectomy, and radical cystectomy). Postoperative C. difficile colitis occurred in 0.02% of patients treated with radical prostatectomy, 0.23% of those treated with partial or radical nephrectomy and 1.7% of those treated with radical cystectomy. On multivariate analysis extended antibiotic prophylaxis was associated with higher odds of C. difficile infection after partial or radical nephrectomy (OR 3.79, 95% CI 2.46-5.84) and radical cystectomy (OR 1.64, 95% CI 1.12-2.39). Conclusions: Antibiotics may be overused after genitourinary cancer surgery and this overuse is associated with hospital acquired C. difficile colitis. Efforts are needed to encourage greater compliance with evidence-based approaches to postoperative care. C1 [Calvert, Joshua K.; Holt, Sarah K.; Mossanen, Matthew; James, Andrew C.; Wright, Jonathan L.; Porter, Michael P.; Gore, John L.] Univ Washington, Dept Urol, Seattle, WA 98195 USA. [Wright, Jonathan L.; Porter, Michael P.] VA Puget Sound Hlth Care Syst, Div Urol, Seattle, WA 98195 USA. RP Gore, JL (reprint author), 1959 NE Pacific St,Box 356510, Seattle, WA 98195 USA. EM jlgore@u.washington.edu NR 27 TC 17 Z9 18 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 EI 1527-3792 J9 J UROLOGY JI J. Urol. PD AUG PY 2014 VL 192 IS 2 BP 425 EP 429 DI 10.1016/j.juro.2014.02.096 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA AP5BT UT WOS:000342095400038 PM 24603103 ER PT J AU Ripley, D Wierman, M Gerber, D Weintraub, A Newman, J AF Ripley, David Wierman, Margaret Gerber, Don Weintraub, Alan Newman, Jody TI Comment on The Decision to Provide Testosterone Supplementation to Patients With Traumatic Brain Injury SO PM&R LA English DT Letter C1 [Ripley, David] Rehabil Inst Chicago, Chicago, IL 60611 USA. [Wierman, Margaret] Univ Colorado, Sch Med, Aurora, CO USA. [Wierman, Margaret] Denver VA Med Ctr, Denver, CO USA. [Gerber, Don] Craig Hosp, Brain Injury Program, Englewood, CO USA. [Weintraub, Alan; Newman, Jody] Craig Hosp, Englewood, CO USA. RP Ripley, D (reprint author), Rehabil Inst Chicago, Chicago, IL 60611 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-1482 EI 1934-1563 J9 PM&R JI PM&R PD AUG PY 2014 VL 6 IS 8 BP 761 EP 761 DI 10.1016/j.pmrj.2014.03.008 PG 1 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA AO8PN UT WOS:000341616800017 PM 25169710 ER PT J AU Ross, RJ AF Ross, Richard J. TI The Changing REM Sleep Signature of Posttraumatic Stress Disorder SO SLEEP LA English DT Editorial Material ID DEPENDENT PLASTICITY; COMBAT VETERANS; DISTURBANCE; PRAZOSIN; NIGHTMARES; MECHANISM; PTSD C1 [Ross, Richard J.] Philadelphia VA Med Ctr, Behav Hlth Serv, Philadelphia, PA 19104 USA. [Ross, Richard J.] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Ross, RJ (reprint author), Philadelphia VA Med Ctr, Behav Hlth Serv, 116 MHC,Univ & Woodland Ave, Philadelphia, PA 19104 USA. EM rossri@mail.med.upenn.edu FU NIMHD NIH HHS [1P20MD006899-01] NR 22 TC 4 Z9 4 U1 6 U2 12 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 EI 1550-9109 J9 SLEEP JI Sleep PD AUG 1 PY 2014 VL 37 IS 8 BP 1281 EP 1282 DI 10.5665/sleep.3912 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AO7DL UT WOS:000341512100004 PM 25083007 ER PT J AU Pellegrino, R Kavakli, IH Goel, N Cardinale, CJ Dinges, DF Kuna, ST Maislin, G Van Dongen, HPA Tufik, S Hogenesch, JB Hakonarson, H Pack, AI AF Pellegrino, Renata Kavakli, Ibrahim Halil Goel, Namni Cardinale, Christopher J. Dinges, David F. Kuna, Samuel T. Maislin, Greg Van Dongen, Hans P. A. Tufik, Sergio Hogenesch, John B. Hakonarson, Hakon Pack, Allan I. TI A Novel BHLHE41 Variant is Associated with Short Sleep and Resistance to Sleep Deprivation in Humans SO SLEEP LA English DT Article DE BHLHE41; delta power; genetics; sleep; sleep deprivation; sleep loss ID SLOW-WAVE ACTIVITY; VIGILANCE TEST PVT; E-BOX ELEMENTS; TRANSCRIPTION FACTOR; INTERINDIVIDUAL DIFFERENCES; GENE-EXPRESSION; 2-PROCESS MODEL; MOLECULAR CLOCK; LONG SLEEPERS; DEC2 AB Study Objectives: Earlier work described a mutation in DEC2 also known as BHLHE41 (basic helix-loop-helix family member e41) as causal in a family of short sleepers, who needed just 6 h sleep per night. We evaluated whether there were other variants of this gene in two well-phenotyped cohorts. Design: Sequencing of the BHLHE41 gene, electroencephalographic data, and delta power analysis and functional studies using cell-based luciferase. Results: We identified new variants of the BHLHE41 gene in two cohorts who had either acute sleep deprivation (n = 200) or chronic partial sleep deprivation (n = 217). One variant, Y362H, at another location in the same exon occurred in one twin in a dizygotic twin pair and was associated with reduced sleep duration, less recovery sleep following sleep deprivation, and fewer performance lapses during sleep deprivation than the homozygous twin. Both twins had almost identical amounts of non rapid eye movement (NREM) sleep. This variant reduced the ability of BHLHE41 to suppress CLOCK/BMAL1 and NPAS2/BMAL1 transactivation in vitro. Another variant in the same exome had no effect on sleep or response to sleep deprivation and no effect on CLOCK/BMAL1 transactivation. Random mutagenesis identified a number of other variants of BHLHE41 that affect its function. Conclusions: There are a number of mutations of BHLHE41. Mutations reduce total sleep while maintaining NREM sleep and provide resistance to the effects of sleep loss. Mutations that affect sleep also modify the normal inhibition of BHLHE41 of CLOCK/BMAL1 transactivation. Thus, clock mechanisms are likely involved in setting sleep length and the magnitude of sleep homeostasis. C1 [Pellegrino, Renata; Cardinale, Christopher J.; Hakonarson, Hakon] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA. [Pellegrino, Renata; Goel, Namni; Dinges, David F.; Kuna, Samuel T.; Maislin, Greg; Pack, Allan I.] Univ Penn, Perelman Sch Med, Ctr Sleep & Circadian Neurobiol, Philadelphia, PA 19104 USA. [Pellegrino, Renata; Tufik, Sergio] Univ Fed Sao Paulo, UNIFESP, Dept Psicobiol, Sao Paulo, Brazil. [Kavakli, Ibrahim Halil] Koc Univ, Dept Chem & Biol Engn, Sariyer, Turkey. [Kavakli, Ibrahim Halil] Koc Univ, Dept Mol Biol & Genet, Sariyer, Turkey. [Goel, Namni; Dinges, David F.] Univ Penn, Dept Psychiat, Perelman Sch Med, Div Sleep & Chronobiol, Philadelphia, PA 19104 USA. [Kuna, Samuel T.; Maislin, Greg; Pack, Allan I.] Univ Penn, Perelman Sch Med, Div Sleep Med, Philadelphia, PA 19104 USA. [Kuna, Samuel T.] Philadelphia Vet Affairs Med Ctr, Dept Med, Philadelphia, PA USA. [Van Dongen, Hans P. A.] Washington State Univ, Sleep & Performance Res Ctr, Pullman, WA 99164 USA. [Hakonarson, Hakon] Univ Penn, Dept Pharmacol, Perelman Sch Med, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA. RP Pellegrino, R (reprint author), Childrens Hosp Philadelphia, Ctr Appl Genom, Abramson Res Ctr, 3615 Civ Ctr Blvd,Suite 1014, Philadelphia, PA 19104 USA. EM renata.pellegrino@gmail.com RI Cardinale, Christopher/G-3351-2013 OI Cardinale, Christopher/0000-0001-7513-8977 FU NIH [P01 HL094307, NR004281]; Institutional Development Fund from the Center for Applied Genomics at The Children's Hospital of Philadelphia; National Space Biomedical Research Institute through NASA [NCC 9-58]; CTRC [UL1RR024134]; Department of the Navy, Office of Naval Research [N00014-11-1-0361]; Pulsar Informatics; Boeing Company; Battelle Center for Human Performance Safety; Institutes for Behavior Resources; FedEx Express FX This was not an industry supported study. This work was supported in part by NIH grant P01 HL094307 and Institutional Development Fund from the Center for Applied Genomics at The Children's Hospital of Philadelphia. Data analyzed from experiments on chronic partial sleep deprivation were supported by the National Space Biomedical Research Institute through NASA NCC 9-58, NIH NR004281, CTRC UL1RR024134 and the Department of the Navy, Office of Naval Research Award No. N00014-11-1-0361. Drs Pellegrino and Kavakli are co-first authors. Dr. Dinges is Editor-in-Chief of SLEEP. Dr. Van Dongen has received grant funding from Pulsar Informatics, Boeing Company, Battelle Center for Human Performance & Safety, and Institutes for Behavior Resources; has received consulting fees from Pulsar Informatics and FedEx Express; and has participated in a paid speaking engagement with the Ohio Sleep Medicine Institute. The other authors have indicated no financial conflicts of interest. NR 47 TC 13 Z9 13 U1 2 U2 26 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 EI 1550-9109 J9 SLEEP JI Sleep PD AUG 1 PY 2014 VL 37 IS 8 BP 1327 EP U127 DI 10.5665/sleep.3924 PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AO7DL UT WOS:000341512100010 PM 25083013 ER PT J AU Manzo, CE Merrigan, MM Johnson, S Gerding, DN Riley, TV Silva, J Brazier, JS AF Manzo, Carl E. Merrigan, Michelle M. Johnson, Stuart Gerding, Dale N. Riley, Thomas V. Silva, Joseph, Jr. Brazier, Jon S. CA Int Clostridium Difficile Study Gr TI International typing study of Clostridium difficile SO ANAEROBE LA English DT Article DE Clostridium difficile; Genotypic typing; Phenotypic typing; PCR ribotyping; REA typing ID SYSTEMS; SCHEME; STRAIN AB We report the results of an international Clostridium difficile typing study to cross reference strain designations for seven typing methodologies and facilitate inter-laboratory communication. Four genotypic and three phenotypic methods were used to type 100 isolates and compare the results to 39 PCR ribotypes identified among the collection. Published by Elsevier Ltd. C1 [Manzo, Carl E.; Johnson, Stuart; Gerding, Dale N.] Loyola Univ, Chicago Stritch Sch Med, Maywood, IL 60153 USA. [Merrigan, Michelle M.; Johnson, Stuart; Gerding, Dale N.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. [Riley, Thomas V.] Univ Western Australia, Perth, WA 6009, Australia. [Riley, Thomas V.] Queen Elizabeth II Med Ctr, Perth, WA, Australia. [Silva, Joseph, Jr.] Univ Calif Davis, Sacramento, CA 95817 USA. [Brazier, Jon S.] Univ Wales Hosp, Publ Hlth Lab, Anaerobe Reference Unit, Cardiff CF4 4XW, S Glam, Wales. RP Johnson, S (reprint author), Edward Hines Jr VA Hosp, Res Serv, 5000 S 5th St, Hines, IL 60141 USA. EM stuart.johnson2@va.gov; dale.gerding2@va.gov FU US Department of Veterans Affairs Research Service FX This work was supported in part by the US Department of Veterans Affairs Research Service Merit Review grants to DNG and SJ. NR 14 TC 3 Z9 3 U1 0 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1075-9964 EI 1095-8274 J9 ANAEROBE JI Anaerobe PD AUG PY 2014 VL 28 BP 4 EP 7 DI 10.1016/j.anaerobe.2014.04.005 PG 4 WC Microbiology SC Microbiology GA AO4YT UT WOS:000341348000002 PM 24768986 ER PT J AU Kowalkowski, MA Mims, MA Day, RS Du, XL Chan, W Chiao, EY AF Kowalkowski, M. A. Mims, M. A. Day, R. S. Du, X. L. Chan, W. Chiao, E. Y. TI Longer duration of combination antiretroviral therapy reduces the risk of Hodgkin lymphoma: A cohort study of HIV-infected male veterans SO CANCER EPIDEMIOLOGY LA English DT Article DE Hodgkin lymphoma; HIV; Non-AIDS defining cancer; Epidemiology; Combined antiretroviral therapy ID UNITED-STATES; IN-VITRO; IMMUNE RECONSTITUTION; PROTEASE INHIBITOR; CARCINOMA-CELLS; AIDS; CANCER; NELFINAVIR; DISEASE; VIVO AB Background: Hodgkin lymphoma (HL) incidence has increased since combined antiretroviral therapy (cART) introduction. It is unclear how different cART classes (e.g., protease inhibitors (PI), non-nucleoside reverse transcription inhibitors (NNRTI)) influence HL. This study aimed to determine the effects of cART duration on HL incidence among HIV-infected veterans. Methods: We performed a retrospective cohort study utilizing the Veterans Affairs HIV Clinical Case Registry (1985-2010). HL cases were identified using ICD-9 codes (201.4-9). cART, PI, and NNRTI duration was the aggregate number of treatment days delivered. Incidence rates (IR) and rate ratios (IRR) were calculated from Poisson regression models to examine the effects of cART duration on HL. Results: 31,576 cART users contributed 288,736 person-years (PY) and 211 HL cases (IR = 7.3/10,000 person-years). HL incidence decreased from 25.1/10,000 PY (95%CI = 18.9-33.4) within the first year of cART to 0.6/10,000 PY (95%CI = 0.3-1.6) after >= 10 years. In multivariable models, each additional year of cART was associated with decreased HL incidence (IRR = 0.80; 95%CI = 0.75-0.86); similar effects were observed in models assessing HL incidence by PI and NNRTI. Conclusion: Our findings indicate long-term cART of any class is associated with decreased HL risk. High HL incidence directly following cART initiation supports a potential immune reconstitution mechanism in HIV-related HL. Further research is needed to evaluate the interaction between early cART, immune reconstitution, and HL. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Kowalkowski, M. A.] Levine Canc Inst, Carolinas HealthCare Syst, Charlotte, NC 28204 USA. [Kowalkowski, M. A.; Mims, M. A.; Chiao, E. Y.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Kowalkowski, M. A.; Chiao, E. Y.] Houston Hlth Serv Res & Dev Ctr Excellence, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. [Day, R. S.; Du, X. L.] Univ Texas Houston, Sch Publ Hlth, Dept Epidemiol Human Genet & Environm Sci, Houston, TX USA. [Chan, W.] Univ Texas Houston, Sch Publ Hlth, Dept Biostat, Houston, TX USA. RP Kowalkowski, MA (reprint author), Levine Canc Inst, Carolinas HealthCare Syst, Charlotte, NC 28204 USA. EM marc.kowalkowski@carolinashealthcare.org FU Houston Health Services Research and Development Center of Innovation [HFP90-020]; Michael E. DeBakey Veterans Affairs Medical Center; Baylor College of Medicine Dan L. Duncan Cancer Center [P30CA125123-04S1]; Baylor-UTHouston Center for AIDS Research (CFAR); NIH [AI036211]; NCI [R01CA163103] FX This work was supported in part by resources and the use of facilities at the Houston Health Services Research and Development Center of Innovation (HFP90-020), Michael E. DeBakey Veterans Affairs Medical Center and the Baylor College of Medicine Dan L. Duncan Cancer Center (P30CA125123-04S1). This research was also supported by the Baylor-UTHouston Center for AIDS Research (CFAR), an NIH-funded program (AI036211). EYC (R01CA163103) also received support from the NCI. The funders had no role in study design, data collection and analysis, or preparation of this report. NR 33 TC 8 Z9 8 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1877-7821 EI 1877-783X J9 CANCER EPIDEMIOL JI Cancer Epidemiol. PD AUG PY 2014 VL 38 IS 4 BP 386 EP 392 DI 10.1016/j.canep.2014.05.009 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA AO5AI UT WOS:000341352100010 PM 24947588 ER PT J AU Liclican, EL Walser, TC Hazra, S Krysan, K Park, SJ Pagano, PC Gardner, BK Larsen, JE Minna, JD Dubinett, SM AF Liclican, Elvira L. Walser, Tonya C. Hazra, Saswati Krysan, Kostyantyn Park, Stacy J. Pagano, Paul C. Gardner, Brian K. Larsen, Jill E. Minna, John D. Dubinett, Steven M. TI Loss of miR125a Expression in a Model of K-ras-Dependent Pulmonary Premalignancy SO CANCER PREVENTION RESEARCH LA English DT Article ID CELL LUNG-CANCER; ACTIVATED RECEPTOR-GAMMA; MICRORNA EXPRESSION; EPITHELIAL-CELLS; CIGARETTE-SMOKE; DOWN-REGULATION; CHEMOPREVENTION; PIOGLITAZONE; ROSIGLITAZONE; ANGIOGENESIS AB Understanding the molecular pathogenesis of lung cancer is necessary to identify biomarkers/targets specific to individual airway molecular profiles and to identify options for targeted chemoprevention. Herein, we identify mechanisms by which loss of microRNA (miRNA) 125a-3p (miR125a) contributes to the malignant potential of human bronchial epithelial cells (HBEC) harboring an activating point mutation of the K-ras proto-oncogene (HBEC K-ras). Among other miRNAs, we identified significant miR125a loss in HBEC K-ras lines and determined that miR125a is regulated by the PEA3 transcription factor. PEA3 is upregulated in HBEC K-ras cells, and genetic knockdown of PEA3 restores miR125a expression. From a panel of inflammatory/angiogenic factors, we identified increased CXCL1 and vascular endothelial growth factor (VEGF) production by HBEC K-ras cells and determined that miR125a overexpression significantly reduces K-ras-mediated production of these tumorigenic factors. miR125a overexpression also abrogates increased proliferation of HBEC K-ras cells and suppresses anchorage-independent growth (AIG) of HBEC K-ras/P53 cells, the latter of which is CXCL1-dependent. Finally, pioglitazone increases levels of miR125a in HBEC K-ras cells via PEA3 downregulation. In addition, pioglitazone and miR125a overexpression elicit similar phenotypic responses, including suppression of both proliferation and VEGF production. Our findings implicate miR125a loss in lung carcinogenesis and lay the groundwork for future studies to determine whether miR125a is a possible biomarker for lung carcinogenesis and/or a chemoprevention target. Moreover, our studies illustrate that pharmacologic augmentation of miR125a in K-ras-mutated pulmonary epithelium effectively abrogates several deleterious downstream events associated with the mutation. (C)2014 AACR. C1 [Liclican, Elvira L.; Walser, Tonya C.; Hazra, Saswati; Krysan, Kostyantyn; Park, Stacy J.; Gardner, Brian K.; Dubinett, Steven M.] Univ Calif Los Angeles, David Geffen Sch Med, Div Pulm & Crit Care Med, Dept Med, Los Angeles, CA 90095 USA. [Dubinett, Steven M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Pagano, Paul C.; Dubinett, Steven M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. [Liclican, Elvira L.; Walser, Tonya C.; Hazra, Saswati; Krysan, Kostyantyn; Park, Stacy J.; Gardner, Brian K.; Dubinett, Steven M.] Jonsson Comprehens Canc Ctr, Los Angeles, CA 90034 USA. [Dubinett, Steven M.] VA Greater Los Angeles Hlth Care Ctr, Los Angeles, CA USA. [Larsen, Jill E.; Minna, John D.] Univ Texas SW Med Ctr Dallas, Dept Med, Dallas, TX 75390 USA. [Larsen, Jill E.; Minna, John D.] Univ Texas SW Med Ctr Dallas, Dept Pharmacol, Dallas, TX 75390 USA. RP Dubinett, SM (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Pulm & Crit Care Med, Ctr Hlth Sci 37 131, 10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM sdubinett@mednet.ucla.edu RI Larsen, Jill/G-3787-2010 OI Larsen, Jill/0000-0001-7806-3931 FU NIH/NHLBI [T32HL072752]; NCI [U01CA152751]; NIH/NCATS UCLA CTSI [UL1TR000124]; Department of Veteran Affairs [5I01BX000359]; NCI Lung Cancer SPORE [P50CA70907]; Cancer Prevention & Research Institute of Texas [RP120732] FX These studies were supported by funding from the following sources: NIH/NHLBI #T32HL072752 (to S.M. Dubinett, E.L. Liclican, T.C. Walser, S.J. Park), NCI #U01CA152751 (to S.M. Dubinett, T.C. Walser, K. Krysan, B.K. Gardner), NIH/NCATS UCLA CTSI #UL1TR000124 (to S.M. Dubinett), Department of Veteran Affairs #5I01BX000359 (S. M. Dubinett), NCI Lung Cancer SPORE #P50CA70907 (to J.D. Minna, J.E. Larsen), and Cancer Prevention & Research Institute of Texas #RP120732 (to J.D. Minna). NR 47 TC 1 Z9 1 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 EI 1940-6215 J9 CANCER PREV RES JI Cancer Prev. Res. PD AUG PY 2014 VL 7 IS 8 BP 845 EP 855 DI 10.1158/1940-6207.CAPR-14-0063 PG 11 WC Oncology SC Oncology GA AO9TU UT WOS:000341701200009 PM 24913817 ER PT J AU Bekelman, JE Epstein, AJ Emanuel, EJ AF Bekelman, Justin E. Epstein, Andrew J. Emanuel, Ezekiel J. TI Getting the Next Version of Payment Policy "Right" on the Road Toward Accountable Cancer Care SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Editorial Material ID CLUSTER RANDOMIZED-TRIALS; HEALTH-CARE; QUALITY; PROVIDERS; BEHAVIOR C1 [Bekelman, Justin E.] Univ Penn, Abramson Canc Ctr, Perelman Sch Med, Dept Radiat Oncol, Philadelphia, PA 19104 USA. [Bekelman, Justin E.] Univ Penn, Leonard Davis Inst Hlth Econ, Ctr Hlth Incent & Behav Econ, Philadelphia, PA 19104 USA. [Bekelman, Justin E.; Emanuel, Ezekiel J.] Univ Penn, Perelman Sch Med, Dept Med Eth & Hlth Policy, Philadelphia, PA 19104 USA. [Epstein, Andrew J.] Univ Penn, Perelman Sch Med, Dept Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. [Emanuel, Ezekiel J.] Univ Penn, Wharton Sch Business, Dept Hlth Care Management, Philadelphia, PA 19104 USA. [Epstein, Andrew J.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equity Res & Promot, Dept Vet Affairs, Philadelphia, PA USA. RP Bekelman, JE (reprint author), Univ Penn, Abramson Canc Ctr, Perelman Ctr Adv Med, Perelman Sch Med, 4 West,3400 Civic Ctr Blvd, Philadelphia, PA 19104 USA. EM bekelman@uphs.upenn.edu FU NCI NIH HHS [K07-CA163616, K07 CA163616] NR 19 TC 1 Z9 1 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD AUG 1 PY 2014 VL 89 IS 5 BP 954 EP 957 DI 10.1016/j.ijrobp.2014.04.022 PG 4 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA AO6IK UT WOS:000341453600005 PM 25035198 ER PT J AU Kerlikowske, K Hubbard, R Tosteson, ANA AF Kerlikowske, Karla Hubbard, Rebecca Tosteson, Anna N. A. TI Higher Mammography Screening Costs Without Appreciable Clinical Benefit: The Case of Digital Mammography SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID BREAST-CANCER; COMMUNITY PRACTICE; STAGE; WOMEN; RISK; AGE C1 [Kerlikowske, Karla] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Kerlikowske, Karla] Univ Calif San Francisco, Dept Vet Affairs, Gen Internal Med Sect, San Francisco, CA 94143 USA. [Hubbard, Rebecca] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Tosteson, Anna N. A.] Dartmouth Inst Hlth Policy & Clin Practice, Lebanon, NH USA. [Tosteson, Anna N. A.] Geisel Sch Med Dartmouth, Norris Cotton Canc Ctr, Lebanon, NH USA. RP Kerlikowske, K (reprint author), San Francisco VA Med Ctr, Gen Internal Med Sect, 111A1,4150 Clement St, San Francisco, CA 94121 USA. EM Karla.Kerlikowske@ucsf.edu NR 19 TC 2 Z9 2 U1 1 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD AUG PY 2014 VL 106 IS 8 AR dju191 DI 10.1093/jnci/dju191 PG 2 WC Oncology SC Oncology GA AO8XB UT WOS:000341637800025 ER PT J AU Mulligan, JK Nagel, W O'Connell, BP Wentzel, J Atkinson, C Schlosser, RJ AF Mulligan, Jennifer K. Nagel, Whitney O'Connell, Brendan P. Wentzel, Jennifer Atkinson, Carl Schlosser, Rodney J. TI Cigarette smoke exposure is associated with vitamin D3 deficiencies in patients with chronic rhinosinusitis SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Vitamin D; secondhand smoke; sinusitis; epithelial cell ID ALLERGIC FUNGAL RHINOSINUSITIS; PRO-INFLAMMATORY CYTOKINE; REGULATORY T-CELLS; DENDRITIC CELLS; EPITHELIAL-CELLS; 2ND-HAND SMOKE; NASAL POLYPS; LIQUID-CHROMATOGRAPHY; 25-HYDROXYVITAMIN D; CHILDHOOD ASTHMA AB Background: Cigarette smoke (CS) plays a role in the exacerbation of chronic rhinosinusitis (CRS); however, the mechanism for this is unknown. We hypothesize that CS impairs human sinonasal epithelial cell (HSNEC) conversion of 25(OH) D3 (25VD3) to 1,25-dihydroxyvitamin D3 (1,25VD3) and, furthermore, that supplementation with 1,25VD3 will reverse smoke-induced inflammatory responses by HSNECs. Objective: We sought to determine the effect of CS on vitamin D3 (VD3) levels, conversion, and regulation of CS-induced inflammation in control subjects and patients with CRS. Methods: Blood and sinus tissue explants were collected at the time of surgery from control subjects, patients with chronic rhinosinusitis without nasal polyps, and patients with chronic sinusitis with nasal polyps (CRSwNP). Expression of VD3 metabolizing enzymes were measured by using RT-PCR. Primary HSNECs were cultured from tissue explants. 25VD3 with and without cigarette smoke extract (CSE) was used to examine conversion of 25VD3 to 1,25VD3, as well as HSNEC production of proinflammatory cytokines. Results: CS exposure was associated with reduced circulating and sinonasal 25VD3 levels in all groups compared with those seen in CS-naive, disease-matched counterparts. CS exposure decreased expression of CYP27B1 and was especially pronounced in patients with CRSwNP. CSE impairs control HSNEC conversion of 25VD3. HSNECs from patients with CRSwNP also demonstrate an intrinsic reduction in conversion of 25VD3 to 1,25VD3. Exogenous 1,25VD3 reduces CSE-induced cytokine production by HSNECs. Conclusions: Exposure to CS is associated with reduced 25VD3 levels and an impaired ability of HSNECs to convert 25VD3 to 1,25VD3. Addition of 1,25VD3 reduces the proinflammatory effects of CS on HSNECs. Impaired VD3 conversion by CS exposure represents a novel mechanism through which CS induces its proinflammatory effects. C1 [Mulligan, Jennifer K.; Nagel, Whitney; O'Connell, Brendan P.; Wentzel, Jennifer; Schlosser, Rodney J.] Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, Charleston, SC USA. [Mulligan, Jennifer K.] Med Univ S Carolina, Dept Pediat, Charleston, SC USA. [Atkinson, Carl] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC USA. [Mulligan, Jennifer K.; Schlosser, Rodney J.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Mulligan, JK (reprint author), 135 Rutledge Ave,MSC 550, Charleston, SC 29425 USA. EM konopa@musc.edu FU Flight Attendant Medical Research Institute [092401, 113039]; National Institutes of Health [R01HL091944]; Department of Veterans Affairs FX Supported by grants from the Flight Attendant Medical Research Institute (092401 to J.K.M. and 113039 to R.J.S.), the National Institutes of Health (R01HL091944 to C. A.), and a grant from the Department of Veterans Affairs. NR 55 TC 18 Z9 18 U1 1 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD AUG PY 2014 VL 134 IS 2 BP 342 EP + DI 10.1016/j.jaci.2014.01.039 PG 9 WC Allergy; Immunology SC Allergy; Immunology GA AO5GB UT WOS:000341370800013 PM 24698317 ER PT J AU Harrell, KM Wilkins, SS Connor, MK Chodosh, J AF Harrell, Kathryn M. Wilkins, Stacy S. Connor, Megan K. Chodosh, Joshua TI Telemedicine and the Evaluation of Cognitive Impairment: The Additive Value of Neuropsychological Assessment SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION LA English DT Article DE Telemedicine; telehealth; neuropsychology; dementia; cognitive assessment ID TELEMENTAL HEALTH-SERVICES; MINI-MENTAL-STATE; ALZHEIMERS-DISEASE; SCREENING TOOL; PRIMARY-CARE; IN-PERSON; DEMENTIA; TELEHEALTH; RELIABILITY; DIAGNOSIS AB Introduction: The number of people in the United States living with dementia is projected to rise to over 7.1 million in the next 12 years, representing a 40% increase from current levels. This anticipated "dementia tsunami" has led to a recent state and national policy emphasis on early detection, improved care quality, reduced caregiver burden, and increased access to care. The ability to achieve these objectives is limited by few dementia specialists in rural and small communities and the challenges of travel to and within congested urban regions for dementia patients and their caregivers. Telemedicine is one such means for responding to this lack of access to subspecialty assessment and care. We describe our early experiences with this technology applied to neuropsychological assessments, with data from 31 patients. Methods: As part of an interdisciplinary dementia care demonstration project, clinical video teleconferencing provides real-time high resolution video interactions between dementia subspecialists in a major metropolitan medical center and patients in 3 outlying clinics located 180, 150, and 100 miles away. Comprehensive neuropsychological assessments, designed to address referral questions related to neurocognitive disorders via clinical video teleconferencing, are conducted as one component of interdisciplinary care. Outcomes: Eighty-seven percent of patients referred for neuropsychological assessment had an inaccurate neurocognitive diagnosis at the time of referral. Unmet and unrecognized mental health treatment needs were identified in over 77% of patients. In addition, acceptance was good for patients, caregivers, and clinicians. Discussion: Teleneuropsychology is proving to be an excellent resource for clarifying cognitive and psychiatric diagnoses, and integrating individual strengths, weaknesses, and preferences into treatment and care plans used by other health care providers, patients, and caregivers. Published by Elsevier Inc. on behalf of AMDA - The Society for Post-Acute and Long-Term Care Medicine. C1 [Harrell, Kathryn M.; Wilkins, Stacy S.; Connor, Megan K.; Chodosh, Joshua] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Wilkins, Stacy S.; Chodosh, Joshua] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Harrell, KM (reprint author), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd 11G, Los Angeles, CA 90073 USA. EM kathryn.harrell@va.gov OI Chodosh, Joshua/0000-0001-7784-4306 FU US Department of Veterans Affairs, Office of Rural Health (ORH) [N22-FY13Q1-S1-P00555] FX Funding for this clinical demonstration project was provided by the US Department of Veterans Affairs, Office of Rural Health (ORH Project ID Number: N22-FY13Q1-S1-P00555). NR 51 TC 11 Z9 11 U1 2 U2 18 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-8610 EI 1538-9375 J9 J AM MED DIR ASSOC JI J. Am. Med. Dir. Assoc. PD AUG PY 2014 VL 15 IS 8 BP 600 EP 606 DI 10.1016/j.jamda.2014.04.015 PG 7 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA AO2PL UT WOS:000341167400014 PM 24913209 ER PT J AU Dransfield, MT Feldman, G Korenblat, P LaForce, CF Locantore, N Pistolesi, M Watkins, ML Crim, C Martinez, FJ AF Dransfield, Mark T. Feldman, Gregory Korenblat, Phillip LaForce, Craig F. Locantore, Nicholas Pistolesi, Massimo Watkins, Michael L. Crim, Courtney Martinez, Fernando J. TI Efficacy and safety of once-daily fluticasone furoate/vilanterol (100/25 mcg) versus twice-daily fluticasone propionate/salmeterol (250/50 mcg) in COPD patients SO RESPIRATORY MEDICINE LA English DT Article DE Chronic obstructive pulmonary disease; Head-to-head; Inhaled corticosteroid; Long-acting beta(2)-agonist; Lung function ID MU-G; RANDOMIZED-TRIAL; PERSISTENT ASTHMA; LUNG-FUNCTION; FUROATE; EXACERBATIONS; SALMETEROL; VILANTEROL; AGONIST AB Background: Fluticasone furoate/vilanterol (FF/VI) is an inhaled corticosteroid/long-acting beta2-agonist (ICS/LABA), recently approved as once-daily maintenance therapy for COPD. We compared the lung function effects of FF/VI with those of twice-daily fluticasone propionate/salmeterol (FP/SAL). Methods: Three 12 week studies comparing FF/VI and FP/SAL were conducted. Patients aged >= 40 years with moderate-to-very severe COPD were randomized to receive double-blind, double-dummy FF/VI 100/25 mcg once-daily, or FP/SAL 250/50 nncg twice-daily for 12 weeks following a 2 week placebo run-in period. The primary endpoint of each study was change from baseline trough in 0-24 h weighted mean FEV1 (wmFEV(1)) on Day 84. Safety was also assessed. Results: In Study 1 (HZC113109) (intent-to-treat n: FF/VI = 260; FP/SAL = 259), the increase from baseline in 0-24 h wmFEVi was significantly greater with FF/VI than FP/SAL (A80 mL, P < 0.001). In Study 2 (HZC112352) (intent-to-treat n: FF/VI = 259; FP/SAL = 252) and Study 3 (RLV116974) (intent-to-treat n: FF/VI = 412; FP/SAL = 416), the increase from baseline in 0 24 h wmFEVi was not significantly greater with FF/VI than FP/SAL (A29 mL, P = 0.267; A25 mL, P = 0.137). The treatment difference was statistically but not clinically significant in a pooled analysis (6,41 mL, P < 0.001). Pooled adverse events (FF/VI 27%; FP/SAL 28%) and serious adverse events (FF/VI 2%; FP/SAL 3%) were similar between treatments. Conclusions: Our data suggest that once-daily FF/VI 100/25 mcg provides FEV, improvement in COPD that is at least comparable with that conferred by twice-daily FP/SAL 250/50 mcg, although interpretation is limited by differences in individual study outcomes. The safety profiles of FF/VI 100/25 mcg and FP/SAL 250/50 mcg are similar. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Dransfield, Mark T.] Univ Alabama Birmingham, UAB Lung Hlth Ctr, Birmingham, AL 35294 USA. [Dransfield, Mark T.] Birmingham VA Med Ctr, Birmingham, AL 35233 USA. [Feldman, Gregory] S Carolina Pharmaceut Res, Spartanburg, SC 29303 USA. [Korenblat, Phillip] Clin Res Ctr LLB, St Louis, MO 63141 USA. [LaForce, Craig F.] North Carolina Clin Res, Raleigh, NC 27607 USA. [Locantore, Nicholas; Watkins, Michael L.; Crim, Courtney] GlaxoSmithKline, Res Triangle Pk, NC 27709 USA. [Pistolesi, Massimo] Univ Florence, I-50121 Florence, Italy. [Martinez, Fernando J.] Univ Michigan, Ann Arbor, MI 48109 USA. RP Dransfield, MT (reprint author), Univ Alabama Birmingham, UAB Lung Hlth Ctr, Div Pulm Allergy & Crit Care Med, 1900 Univ Blvd,THT-422, Birmingham, AL 35294 USA. EM mdrans99@uab.edu FU GlaxoSmithKline (GSK) [HZC113109, HZC112352, RLV116974]; GlaxoSmithKline FX This study was funded by GlaxoSmithKline (GSK study numbers HZC113109, HZC112352, RLV116974). NL, an employee of the sponsor (GlaxoSmithKline), performed the statistical analysis; all authors (MTD, GE, PK, CFL, NL, MP, MLW, CC, FJM) contributed to the study design, interpreted the data and developed the manuscript. All authors had full access to the data and were responsible for the decision to publish the paper. The authors acknowledge the contribution of Anna Ellsworth, who performed the statistical analysis of Study 3 and of the pooled analysis, and thank all patients and investigators involved in the study. Editorial support, in the form of development of a draft outline in consultation with the authors, development of a manuscript first draft in consultation with the authors, editorial suggestions to draft versions of this paper, assembling tables and figures, collating author comments, copyediting, fact checking, referencing and graphic services, was provided by Geoff Weller, PhD, and Ian Grieve, PhD, at Gardiner-Caldwell Communications (Macclesfield, UK) and was funded by GlaxoSmithKline. NR 25 TC 18 Z9 19 U1 2 U2 9 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0954-6111 EI 1532-3064 J9 RESP MED JI Respir. Med. PD AUG PY 2014 VL 108 IS 8 BP 1171 EP 1179 DI 10.1016/j.rmed.2014.05.008 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System SC Cardiovascular System & Cardiology; Respiratory System GA AO4YU UT WOS:000341348100012 PM 24998880 ER PT J AU Minzenberg, MJ Lesh, TA Niendam, TA Yoon, JH Rhoades, RN Carter, CS AF Minzenberg, Michael J. Lesh, Tyler A. Niendam, Tara A. Yoon, Jong H. Rhoades, Remy N. Carter, Cameron S. TI Frontal cortex control dysfunction related to long-term suicide risk in recent-onset schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; Suicide; Cognitive control; fMRI; Frontal cortex ID COGNITIVE CONTROL; PREFRONTAL CORTEX; 1ST EPISODE; PREMOTOR AREAS; WORST-POINT; BEHAVIOR; PSYCHOSIS; MOTOR; PREVENTION; VOLUME AB Objective: Suicide is highly-prevalent and the most serious outcome in schizophrenia, yet the disturbances in neural system functions that confer suicide risk remain obscure. Circuits operated by the prefrontal cortex (PFC) are altered in psychotic disorders, and various PFC changes are observed in post-mortem studies of completed suicide. We tested whether PFC activity during goal-representation (an important component of cognitive control) relates to long-term suicide risk in recent-onset schizophrenia. Method: 35 patients with recent-onset of DSM-IV-TR-defined schizophrenia (SZ) were evaluated for long-term suicide risk (using the Columbia Suicide Severity Rating Scale) and functional MRI during cognitive control task performance. Group-level regression models associating control-related brain activation with suicide risk controlled for depression, psychosis and impulsivity. Results: Within this group, past suicidal ideation was associated with lower activation with goal-representation demands in multiple PFC sectors. Among those with past suicidal ideation (n = 18), reported suicidal behavior was associated with lower control-related activation in premotor cortex ipsilateral to the active primary motor cortex. Conclusions: This study provides unique evidence that suicide risk directly relates to PFC-based circuit dysfunction during goal-representation, in a major mental illness with significant suicide rates. Among those with suicidal ideation, the overt expression in suicidal behavior may stem from impairments in premotor cortex support of action-planning as an expression of control. Furtherwork should address how PFC-based control function changes with risk over time, whether this brain-behavior relationship is specific to schizophrenia, and address its potential utility as a biomarker for interventions to mitigate suicide risk. Published by Elsevier B.V. C1 [Minzenberg, Michael J.; Rhoades, Remy N.] Univ Calif San Francisco, Sch Med, Dept Psychiat, San Francisco, CA 94143 USA. [Minzenberg, Michael J.; Rhoades, Remy N.] Vet Affairs Med Ctr, San Francisco, CA 94121 USA. [Lesh, Tyler A.; Niendam, Tara A.; Carter, Cameron S.] Univ Calif Davis, Sch Med, Dept Psychiat, Sacramento, CA 95817 USA. [Carter, Cameron S.] Univ Calif Davis, Ctr Neurosci, Davis, CA 95616 USA. [Yoon, Jong H.] Stanford Sch Med, Dept Psychiat & Behav Sci, Palo Alto, CA USA. [Yoon, Jong H.] VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. RP Minzenberg, MJ (reprint author), San Francisco VA Med Ctr, 116C,4150 Clement St, San Francisco, CA 94121 USA. EM Michael.minzenberg@ucsf.edu RI Niendam, Tara/K-8475-2015 OI Niendam, Tara/0000-0003-2285-5002 FU American Foundation for Suicide Prevention Young Investigator Award; Doris Duke Charitable Foundation Grant [2009045, MH059883] FX This work was supported by an American Foundation for Suicide Prevention Young Investigator Award, and the Doris Duke Charitable Foundation Grant # 2009045, both to MJM, and MH059883 to CSC. NR 41 TC 10 Z9 12 U1 1 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD AUG PY 2014 VL 157 IS 1-3 BP 19 EP 25 DI 10.1016/j.schres.2014.05.039 PG 7 WC Psychiatry SC Psychiatry GA AO4MR UT WOS:000341314100004 PM 24972755 ER PT J AU McCleery, A Ventura, J Kern, RS Subotnik, KL Gretchen-Doorly, D Green, MF Hellemann, GS Nuechterlein, KH AF McCleery, A. Ventura, J. Kern, R. S. Subotnik, K. L. Gretchen-Doorly, D. Green, M. F. Hellemann, G. S. Nuechterlein, K. H. TI Cognitive functioning in first-episode schizophrenia: MATRICS Consensus Cognitive Battery (MCCB) Profile of Impairment SO SCHIZOPHRENIA RESEARCH LA English DT Article DE MCCB; First-episode schizophrenia; Cognition; Profile analysis; First episode schizophrenia ID FIRST-EPISODE SCHIZOPHRENIA; FACIAL AFFECT RECOGNITION; 1ST EPISODE; ONSET SCHIZOPHRENIA; WORKING-MEMORY; PSYCHOSIS; DEFICITS; DISORDERS; DETERIORATION; RELIABILITY AB Background: Although many studies have assessed cognitive functioning in first-episode schizophrenia (FESz), the pattern and severity of impairment across cognitive domains remain unclear. Moreover, few studies have directly compared the pattern of cognitive performance between FESz and chronic schizophrenia (CSz). In this study we examined the cognitive impairment profile in FESz using a standardized neurocognitive battery (MATRICS Consensus Cognitive Battery; MCCB). Methods: MCCB data were compared from 105 FESz patients, 176 CSz patients and 300 non-psychiatric (NP) participants. Mixed model analysis evaluated group differences in MCCB profiles and relative strengths and weaknesses in the MCCB profiles of patients. Clinical implications of MCCB performance were also examined; we compared the proportion of participants from each group who exhibited clinically-significant global cognitive impairment based on the MCCB Overall Composite score. Results: FESz and CSz showed impaired performance across all MCCB domains relative to NP. With the exception of relative preservation of working memory and social cognition in FESz, the MCCB domain scores were similar in FESz and CSz. The distribution of impairment on the Overall Composite score did not significantly differ between FESz and CSz; compared to NP, both patient groups were over represented in moderate and severe impairment categories. Conclusion: The pattern, magnitude, and distribution of severity of impairment in FESz were similar to that observed in CSz. However, early in the illness, there may be relative sparing of working memory and social cognition. (C) 2014 Elsevier B.V. All rights reserved. C1 [McCleery, A.; Ventura, J.; Kern, R. S.; Subotnik, K. L.; Gretchen-Doorly, D.; Green, M. F.; Hellemann, G. S.; Nuechterlein, K. H.] Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst Neurosci & Human Behav, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Kern, R. S.; Green, M. F.] Greater Los Angeles VA Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr MIRECC 22, Los Angeles, CA USA. [Nuechterlein, K. H.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. RP McCleery, A (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst Neurosci & Human Behav, Dept Psychiat, 300 Med Plaza,Room 2213, Los Angeles, CA 90095 USA. EM amccleery@mednet.ucla.edu RI McCleery, Amanda/D-5471-2016 OI McCleery, Amanda/0000-0003-2714-6897 FU MATRICS Assessment, Inc.; Janssen Scientific Affairs [R092670SCH4005, RIS-NAP-4009]; Genentech [ML28264]; Posit Science [BPI-1000-11]; Genentech, Inc. [C4-150335]; Janssen Scientific Affairs, LLC; Genentech, Inc.; Amgen Foundation [20130132] FX M.F. Green and K.H. Nuechterlein are officers within MATRICS Assessment, Inc., the publisher of the MCCB, but do not receive any financial remuneration for their respective roles. R.S. Kern is an officer for MATRICS Assessment, Inc. and receives financial compensation for his role within the non-profit organization. K. H. Nuechterlein has received unrelated research grants from Janssen Scientific Affairs (R092670SCH4005; RIS-NAP-4009), Genentech (ML28264), and Posit Science (BPI-1000-11) and has been a consultant to Otsuka and Genentech. J. Ventura has received funding from Genentech, Inc. (C4-150335). He has served as a consultant to Brain Plasticity, Inc., and Boehringer-Ingelheim GmbH. K.L. Subotnik and D. Gretchen-Doorly have received research funding from Janssen Scientific Affairs, LLC, and Genentech, Inc., through grants to K. H. Nuechterlein and J. Ventura. K. L. Subotnik is a consultant to Otsuka America Pharmaceutical, Inc. M. F. Green has been a consultant to AbbVie, Biogen, DSP, FORUM Pharmaceuticals, and Roche, and he is on the scientific advisory board of Mnemosyne. He has received research funds from Amgen Foundation (20130132). All other authors declare they have no conflicts of interest. NR 60 TC 14 Z9 15 U1 7 U2 22 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD AUG PY 2014 VL 157 IS 1-3 BP 33 EP 39 DI 10.1016/j.schres.2014.04.039 PG 7 WC Psychiatry SC Psychiatry GA AO4MR UT WOS:000341314100006 PM 24888526 ER PT J AU Walsh-Messinger, J Ramirez, PM Wong, P Antonius, D Aujero, N McMahon, K Opler, LA Malaspina, D AF Walsh-Messinger, Julie Ramirez, Paul Michael Wong, Philip Antonius, Daniel Aujero, Nicole McMahon, Kevin Opler, Lewis A. Malaspina, Dolores TI Impairment in emotional modulation of attention and memory in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; Emotion; Cognition; Negative symptoms ID SERIAL VISUAL PRESENTATION; AFFECTIVE-PICTURE-SYSTEM; HUMAN AMYGDALA; BLINK; WORDS; PERCEPTION; BEHAVIOR; STIMULI; AROUSAL; INFORMATION AB Emotion plays a critical role in cognition and goal-directed behavior via complex interconnections between the emotional and motivational systems. It has been hypothesized that the impairment in goal-directed behavior widely noted in schizophrenia may result from defects in the interaction between the neural (ventral) emotional system and (rostral) cortical processes. The present study examined the impact of emotion on attention and memory in schizophrenia. Twenty-five individuals with schizophrenia related psychosis and 25 healthy control subjects were administered a computerized task in which they were asked to search for target images during a Rapid Serial Visual Presentation of pictures. Target stimuli were either positive or negative, or neutral images presented at either 200 ms or 700 ms lag. Additionally, a visual hedonic task was used to assess differences between the schizophrenia group and controls on ratings of valence and arousal from the picture stimuli. Compared to controls, individuals with schizophrenia detected fewer emotional images under both the 200 ms and 700 ms lag conditions. Multivariate analyses showed that the schizophrenia group also detected fewer positive images under the 700 ms lag condition and fewer negative images under the 200 ms lag condition. Individuals with schizophrenia reported higher pleasantness and unpleasantness ratings than controls in response to neutral stimuli, while controls reported higher arousal ratings for neutral and positive stimuli compared to the schizophrenia group. These results highlight dysfunction in the neural modulation of emotion, attention, and cortical processing in schizophrenia, adding to the growing but mixed body of literature on emotion processing in the disorder. Published by Elsevier B.V. C1 [Walsh-Messinger, Julie; Ramirez, Paul Michael; Wong, Philip] Long Isl Univ, Dept Psychol, Brooklyn, NY USA. [Walsh-Messinger, Julie; Antonius, Daniel; Aujero, Nicole; McMahon, Kevin; Malaspina, Dolores] NYU, Sch Med, Dept Psychiat, InSPIRES, New York, NY USA. [Antonius, Daniel] SUNY Buffalo, Buffalo, NY 14260 USA. [Antonius, Daniel] Erie Cty Forens Mental Hlth Serv, Buffalo, NY USA. [Opler, Lewis A.] Columbia Univ, Dept Psychiat, New York, NY USA. [Malaspina, Dolores] NY State Off Mental Hlth, Creedmoor Psychiat Ctr, Queens, NY USA. RP Walsh-Messinger, J (reprint author), James J Peters VA Med Ctr, Mental Illness Res Educ & Clin Ctr MIRECC, 130 West Kingsbridge Rd,6th Floor,Suite 6A-41C, Bronx, NY 10468 USA. EM julie.walshmessinger@mssm.edu FU National Institute of Mental Health [RC1MH088843, 2K24MH00169] FX This work was supported by the National Institute of Mental Health grants RC1MH088843 (DM) and 2K24MH00169 (DM). NR 58 TC 4 Z9 4 U1 3 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD AUG PY 2014 VL 157 IS 1-3 BP 63 EP 69 DI 10.1016/j.schres.2014.05.014 PG 7 WC Psychiatry SC Psychiatry GA AO4MR UT WOS:000341314100011 PM 24910446 ER PT J AU Tabak, NT Granholm, E AF Tabak, Naomi T. Granholm, Eric TI Mindful cognitive enhancement training for psychosis: A pilot study SO SCHIZOPHRENIA RESEARCH LA English DT Letter ID MEDITATION; ATTENTION C1 [Tabak, Naomi T.; Granholm, Eric] Vet Affairs San Diego Healthcare Syst, San Diego, CA USA. [Granholm, Eric] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. RP Tabak, NT (reprint author), Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, MIRECC, Bldg 210,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM ntabak@ucla.edu RI Granholm, Eric/P-7680-2014 FU NIMH NIH HHS [T32 MH096682, T32MH09668] NR 10 TC 2 Z9 2 U1 1 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD AUG PY 2014 VL 157 IS 1-3 BP 312 EP 313 DI 10.1016/j.schres.2014.06.002 PG 2 WC Psychiatry SC Psychiatry GA AO4MR UT WOS:000341314100049 PM 24968738 ER PT J AU Deyo, RA Dworkin, SF Amtmann, D Andersson, G Borenstein, D Carragee, E Carrino, J Chou, R Cook, K DeLitto, A Goertz, C Khalsa, P Loeser, J Mackey, S Panagis, J Rainville, J Tosteson, T Turk, D Von Korff, M Weiner, DK AF Deyo, Richard A. Dworkin, Samuel F. Amtmann, Dagmar Andersson, Gunnar Borenstein, David Carragee, Eugene Carrino, John Chou, Roger Cook, Karon DeLitto, Anthony Goertz, Christine Khalsa, Partap Loeser, John Mackey, Sean Panagis, James Rainville, James Tosteson, Tor Turk, Dennis Von Korff, Michael Weiner, Debra K. TI Report of the NIH Task Force on Research Standards for Chronic Low Back Pain SO SPINE JOURNAL LA English DT Article DE Low back pain; chronic low back pain; research standards; minimum dataset; NIH Task Force ID CLINICAL-PRACTICE GUIDELINE; DEFINING CHRONIC PAIN; INFORMATION-SYSTEM PROMIS; FUNCTION ITEM BANK; QUALITY-OF-LIFE; PRIMARY-CARE; PROGNOSTIC APPROACH; SCREENING TOOL; START BACK; OUTCOME MEASURES AB Despite rapidly increasing intervention, functional disability due to chronic low back pain (cLBP) has increased in recent decades. We often cannot identify mechanisms to explain the major negative impact cLBP has on patients' lives. Such cLBP is often termed non-specific and may be due to multiple biologic and behavioral etiologies. Researchers use varied inclusion criteria, definitions, baseline assessments, and outcome measures, which impede comparisons and consensus. Therefore, NIH Pain Consortium charged a Research Task Force (RTF) to draft standards for research on cLBP. The resulting multidisciplinary panel recommended using 2 questions to define cLBP; classifying cLBP by its impact (defined by pain intensity, pain interference, and physical function); use of a minimum dataset to describe research participants (drawing heavily on the PROMIS methodology); reporting "responder analyses'' in addition to mean outcome scores; and suggestions for future research and dissemination. The Pain Consortium has approved the recommendations, which investigators should incorporate into NIH grant proposals. The RTF believes that these recommendations will advance the field, help to resolve controversies, and facilitate future research addressing the genomic, neurologic, and other mechanistic substrates of chronic low back pain. We expect that the RTF recommendations will become a dynamic document and undergo continual improvement. PERSPECTIVE: A task force was convened by the NIH Pain Consortium with the goal of developing research standards for chronic low back pain. The results included recommendations for definitions, a minimum dataset, reporting outcomes, and future research. Greater consistency in reporting should facilitate comparisons among studies and the development of phenotypes. This guideline article was first reported in the The Journal of Pain. (C) 2014 by the American Pain Society. C1 [Deyo, Richard A.; Chou, Roger] Oregon Hlth & Sci Univ, Portland, OR 97239 USA. [Dworkin, Samuel F.; Amtmann, Dagmar; Loeser, John; Turk, Dennis] Univ Washington, Seattle, WA 98195 USA. [Andersson, Gunnar] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Borenstein, David] George Washington Univ, Washington, DC USA. [Carragee, Eugene; Mackey, Sean] Stanford Univ, Stanford, CA 94305 USA. [Carrino, John; Weiner, Debra K.] Johns Hopkins Univ, Baltimore, MD USA. [Cook, Karon] Northwestern Univ, Evanston, IL USA. [DeLitto, Anthony] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [DeLitto, Anthony] Univ Pittsburgh, Pittsburgh, PA USA. [Goertz, Christine] Palmer Coll Chiropract, Davenport, IA USA. [Khalsa, Partap] Natl Ctr Complementary & Alternat Med, Bethesda, MD USA. [Panagis, James] Natl Inst Arthritis Musculoskeletal & Skin Dis, Bethesda, MD USA. [Rainville, James] New England Baptist Hosp, Roxbury Crossing, MA USA. [Tosteson, Tor] Dartmouth Coll, Hanover, NH USA. [Von Korff, Michael] Grp Hlth Res Inst, Seattle, WA USA. RP Deyo, RA (reprint author), Oregon Hlth & Sci Univ, 3181 SW Sam Jackson Pk Rd,Mail Code FM, Portland, OR 97239 USA. EM deyor@ohsu.edu FU National Center for Complementary and Alternative Medicine; National Institute for Arthritis, Musculoskeletal, and Skin Diseases FX This study was supported by the National Center for Complementary and Alternative Medicine and the National Institute for Arthritis, Musculoskeletal, and Skin Diseases. NR 124 TC 6 Z9 6 U1 8 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1529-9430 EI 1878-1632 J9 SPINE J JI Spine Journal PD AUG PY 2014 VL 14 IS 8 BP 1375 EP 1391 DI 10.1016/j.spinee.2014.05.002 PG 17 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA AO4JT UT WOS:000341304300002 PM 24950669 ER PT J AU Yokoe, DS Anderson, DJ Berenholtz, SM Calfee, DP Dubberke, ER Ellingson, KD Gerding, DN Haas, JP Kaye, KS Klompas, M Lo, E Marschall, J Mermel, LA Nicolle, LE Salgado, CD Bryant, K Classen, D Crist, K Deloney, VM Fishman, NO Foster, N Goldmann, DA Humphreys, E Jernigan, JA Padberg, J Perl, TM Podgorny, K Septimus, EJ VanAmringe, M Weaver, T Weinstein, RA Wise, R Maragakis, LL AF Yokoe, Deborah S. Anderson, Deverick J. Berenholtz, Sean M. Calfee, David P. Dubberke, Erik R. Ellingson, Katherine D. Gerding, Dale N. Haas, Janet P. Kaye, Keith S. Klompas, Michael Lo, Evelyn Marschall, Jonas Mermel, Leonard A. Nicolle, Lindsay E. Salgado, Cassandra D. Bryant, Kristina Classen, David Crist, Katrina Deloney, Valerie M. Fishman, Neil O. Foster, Nancy Goldmann, Donald A. Humphreys, Eve Jernigan, John A. Padberg, Jennifer Perl, Trish M. Podgorny, Kelly Septimus, Edward J. VanAmringe, Margaret Weaver, Tom Weinstein, Robert A. Wise, Robert Maragakis, Lisa L. TI A Compendium of Strategies to Prevent Healthcare-Associated Infections in Acute Care Hospitals: 2014 Updates SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID CLOSTRIDIUM-DIFFICILE INFECTIONS; RESISTANT STAPHYLOCOCCUS-AUREUS; SURGICAL SITE INFECTIONS; BLOOD-STREAM INFECTIONS; TRANSMISSION AB Since the publication of "A Compendium of Strategies to Prevent Healthcare-Associated Infections in Acute Care Hospitals" in 2008, prevention of healthcare-associated infections (HAIs) has become a national priority. Despite improvements, preventable HAIs continue to occur. The 2014 updates to the Compendium were created to provide acute care hospitals with up-to-date, practical, expert guidance to assist in prioritizing and implementing their HAI prevention efforts. They are the product of a highly collaborative effort led by the Society for Healthcare Epidemiology of America (SHEA), the Infectious Diseases Society of America (IDSA), the American Hospital Association (AHA), the Association for Professionals in Infection Control and Epidemiology (APIC), and The Joint Commission, with major contributions from representatives of a number of organizations and societies with content expertise, including the Centers for Disease Control and Prevention (CDC), the Institute for Healthcare Improvement (IHI), the Pediatric Infectious Diseases Society (PIDS), the Society for Critical Care Medicine (SCCM), the Society for Hospital Medicine (SHM), and the Surgical Infection Society (SIS). C1 [Yokoe, Deborah S.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Yokoe, Deborah S.; Goldmann, Donald A.] Harvard Univ, Sch Med, Boston, MA USA. [Anderson, Deverick J.] Duke Univ, Med Ctr, Durham, NC USA. [Berenholtz, Sean M.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Berenholtz, Sean M.; Perl, Trish M.; Maragakis, Lisa L.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Calfee, David P.] Weill Cornell Med Coll, New York, NY USA. [Dubberke, Erik R.] Washington Univ, Sch Med, St Louis, MO USA. [Ellingson, Katherine D.; Jernigan, John A.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Gerding, Dale N.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. [Gerding, Dale N.] Loyola Univ Chicago, Stritch Sch Med, Chicago, IL USA. [Haas, Janet P.] Westchester Med Ctr, Valhalla, NY USA. [Haas, Janet P.] New York Med Coll, Valhalla, NY 10595 USA. [Kaye, Keith S.] Detroit Med Ctr, Detroit, MI USA. [Kaye, Keith S.] Wayne State Univ, Detroit, MI USA. [Klompas, Michael] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Lo, Evelyn] St Boniface Gen Hosp, Winnipeg, MB R2H 2A6, Canada. [Lo, Evelyn; Nicolle, Lindsay E.] Univ Manitoba, Winnipeg, MB, Canada. [Marschall, Jonas] Univ Hosp Bern, CH-3010 Bern, Switzerland. [Marschall, Jonas] Univ Bern, Bern, Switzerland. [Mermel, Leonard A.] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA. [Mermel, Leonard A.] Rhode Isl Hosp, Providence, RI USA. [Nicolle, Lindsay E.] Hlth Sci Ctr, Winnipeg, MB, Canada. [Salgado, Cassandra D.] Med Univ S Carolina, Charleston, SC 29425 USA. [Bryant, Kristina] Univ Louisville, Louisville, KY 40292 USA. [Classen, David] Univ Utah, Sch Med, Salt Lake City, UT USA. [Crist, Katrina; Weaver, Tom] Assoc Profess Infect Control & Epidemiol, Washington, DC USA. [Deloney, Valerie M.; Humphreys, Eve] Soc Healthcare Epidemiol Amer, Arlington, VA USA. [Fishman, Neil O.] Univ Penn Hlth Syst, Philadelphia, PA USA. [Foster, Nancy] Amer Hosp Assoc, Washington, DC USA. [Goldmann, Donald A.] Inst Healthcare Improvement, Cambridge, MA USA. [Goldmann, Donald A.] Boston Childrens Hosp, Boston, MA USA. [Jernigan, John A.] Emory Univ, Sch Med, Atlanta, GA USA. [Padberg, Jennifer] Infect Dis Soc Amer, Arlington, VA USA. [Podgorny, Kelly; VanAmringe, Margaret; Wise, Robert] Joint Commiss, Oak Brook Terrace, IL USA. [Septimus, Edward J.] Texas A&M Hlth Sci Ctr, Coll Med, Houston, TX USA. [Septimus, Edward J.] Hosp Corp Amer, Nashville, TN USA. [Weinstein, Robert A.] Stroger Hosp, Chicago, IL USA. [Weinstein, Robert A.] Rush Univ, Med Ctr, Chicago, IL 60612 USA. RP Yokoe, DS (reprint author), 181 Longwood Ave, Boston, MA 02115 USA. EM dyokoe@partners.org FU Society for Healthcare Epidemiology of America FX Support for this Compendium was provided by the Society for Healthcare Epidemiology of America. NR 21 TC 0 Z9 0 U1 1 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X EI 1559-6834 J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD AUG PY 2014 VL 35 IS 8 BP 967 EP 977 DI 10.1086/677216 PG 11 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA AL3RQ UT WOS:000339046900005 ER PT J AU Batki, SL Pennington, DL Lasher, B Neylan, TC Metzler, T Waldrop, A Delucchi, K Herbst, E AF Batki, Steven L. Pennington, David L. Lasher, Brooke Neylan, Thomas C. Metzler, Thomas Waldrop, Angela Delucchi, Kevin Herbst, Ellen TI Topiramate Treatment of Alcohol Use Disorder in Veterans with Posttraumatic Stress Disorder: A Randomized Controlled Pilot Trial SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Topiramate; Clinical Trial; Alcohol Use Disorder; Posttraumatic Stress Disorder; Cognition ID PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; COGNITIVE FUNCTION; DEPENDENT PATIENTS; OPEN-LABEL; ADD-ON; EFFICACY; PTSD; NALTREXONE; THERAPY AB Background: The course of posttraumatic stress disorder (PTSD) is frequently and severely complicated by co-occurring alcohol use disorder (AUD), yet there are few reports of pharmacologic treatments for these comorbid conditions. The objective of this pilot study was to obtain a preliminary assessment of the efficacy and safety of topiramate in reducing alcohol use and PTSD symptoms in veterans with both disorders. Methods: This was a prospective 12-week, randomized, double-blind, placebo-controlled pilot trial of flexible-dose topiramate up to 300 mg/d in 30 veterans with PTSD and AUD. The primary outcome measure was frequency of drinking. Secondary outcomes consisted of other measures of alcohol use and PTSD symptom severity. Results: Within-group analyses showed that topiramate treatment was associated with significant reductions in frequency and amount of alcohol use and alcohol craving from baseline through week 12. Between-group analyses showed that topiramate reduced frequency of alcohol use and alcohol craving significantly more than placebo and tended to reduce drinking amount. Topiramate treatment was also associated with decreased PTSD symptom severity and tended to reduce hyperarousal symptoms compared with placebo. Topiramate transiently impaired learning and memory, with significant recovery by the end of treatment. Conclusions: These preliminary results indicate that in veterans with co-occurring PTSD and AUD, topiramate may be effective in reducing alcohol consumption, alcohol craving, and PTSD symptom severity-particularly hyperarousal symptoms. Topiramate was associated with transient cognitive impairment but was otherwise well tolerated. C1 [Batki, Steven L.; Pennington, David L.; Lasher, Brooke; Neylan, Thomas C.; Metzler, Thomas; Waldrop, Angela; Herbst, Ellen] San Francisco VA Med Ctr, San Francisco, CA USA. [Batki, Steven L.; Pennington, David L.; Lasher, Brooke; Neylan, Thomas C.; Metzler, Thomas; Waldrop, Angela; Herbst, Ellen] NCIRE, Addict Res Program, San Francisco, CA USA. [Batki, Steven L.; Neylan, Thomas C.; Metzler, Thomas; Waldrop, Angela; Delucchi, Kevin; Herbst, Ellen] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. RP Batki, SL (reprint author), San Francisco VA Med Ctr 116E, Dept Psychiat, Subst Abuse Programs, 4150 Clement St, San Francisco, CA 94121 USA. EM steven.batki@ucsf.edu FU Department of Defense [W81XWH-05-2-0094, W81XWH-12-2-0137, W81XWH-11-2-0245]; National Center for Research Resources; National Center for Advancing Translational Sciences, National Institutes of Health UCSF-CTSI [UL1 RR024131] FX This work was supported by grants from the Department of Defense W81XWH-05-2-0094, W81XWH-12-2-0137, and W81XWH-11-2-0245 (SLB), National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health UCSF-CTSI UL1 RR024131, which were administered by the Northern California Institute for Research and Education, and with resources of the Veterans Affairs Medical Center, San Francisco, California. NR 43 TC 15 Z9 16 U1 9 U2 18 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD AUG PY 2014 VL 38 IS 8 BP 2169 EP 2177 DI 10.1111/acer.12496 PG 9 WC Substance Abuse SC Substance Abuse GA AO2UQ UT WOS:000341181900005 PM 25092377 ER PT J AU Hill, JN Hogan, TP Cameron, KA Guihan, M Goldstein, B Evans, ME Evans, CT AF Hill, Jennifer N. Hogan, Timothy P. Cameron, Kenzie A. Guihan, Marylou Goldstein, Barry Evans, Martin E. Evans, Charlesnika T. TI Perceptions of methicillin-resistant Staphylococcus aureus and hand hygiene provider training and patient education: Results of a mixed method study of health care providers in Department of Veterans Affairs spinal cord injury and disorder units SO AMERICAN JOURNAL OF INFECTION CONTROL LA English DT Article DE Provider training; Patient education; Methicillin-resistant Staphylococcus aureus; Spinal cord injury and disorders ID INFECTIONS; KNOWLEDGE; PREVENTION; BELIEFS; ATTITUDES; AWARENESS; STAFF; MRSA AB Background: The goal of this study was to assess current practices for training of spinal cord injury and disorder (SCI/D) health care workers and education of veterans with SCI/D in Department of Veterans Affairs (VA) spinal cord injury (SCI) centers on methicillin-resistant Staphylococcus aureus (MRSA) prevention. Methods: Mixed methods. A Web-based survey was distributed to 673 VA SCI/D providers across 24 SCI centers; 21 acute care and 1 long-term care facility participated. There were 295 that responded, 228 had complete data and were included in this analysis. Semistructured interviews were conducted with 30 SCI/D providers across 9 SCI centers. Results: Nurses, physicians, and therapists represent most respondents (92.1%, n = 210); over half (56.6%, n = 129) were nurses. Of providers, 75.9% (n = 173) reported receiving excellent or good training on how to educate patients about MRSA. However, nurses were more likely to report having excellent or good training for how to educate patients about MRSA (P = .005). Despite this, only 63.6% (n = 82) of nurses perceived the education they provide patients on how MRSA is transmitted as excellent or good. Conclusion: Despite health care workers reporting receiving excellent or good training on MRSA-related topics, this did not translate to excellent or good education for patients, suggesting that health care workers need additional training for educating patients. Population-specific MRSA prevention educational materials may also assist providers in educating patients about MRSA prevention for individuals with SCI/D. Published by Elsevier Inc. on behalf of the Association for Professionals in Infection Control and Epidemiology, Inc. C1 [Hill, Jennifer N.; Guihan, Marylou; Evans, Charlesnika T.] Edward Hines Jr VA Hosp, Vet Hlth Adm, Dept Vet Affairs, Spinal Cord Injury Qual Enhancement Res Initiat, Hines, IL 60141 USA. [Hill, Jennifer N.; Guihan, Marylou; Evans, Charlesnika T.] Edward Hines Jr VA Hosp, Ctr Innovat Complex Chron Healthcare, Hines, IL 60141 USA. [Hogan, Timothy P.] Edith Nourse Rogers Mem Vet Hosp, US Dept Vet Affairs, Ctr Healthcare Org & Implementat Res, Bedford, MA USA. [Hogan, Timothy P.] Edith Nourse Rogers Mem Vet Hosp, US Dept Vet Affairs, Natl EHlth Qual Enhancement Res Initiat Coordinat, EHlth Qual Enhancement Res Initiat, Bedford, MA USA. [Hogan, Timothy P.] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Div Hlth Informat & Implementat Sci, Worcester, MA USA. [Hogan, Timothy P.] Northwestern Univ, Dept Med, Feinberg Sch Med, Div Gen Internal Med & Geriatr, Chicago, IL 60611 USA. [Cameron, Kenzie A.; Evans, Charlesnika T.] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL USA. [Cameron, Kenzie A.; Evans, Charlesnika T.] Northwestern Univ, Feinberg Sch Med, Ctr Healthcare Studies, Chicago, IL USA. [Goldstein, Barry] Dept Vet Affairs, Patient Care Serv, Spinal Cord Injury Disorders Serv, Seattle, WA USA. [Goldstein, Barry] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Evans, Martin E.] Dept Vet Affairs, Vet Hlth Adm Methicillin Resistant Staphylococcus, Natl Infect Dis Serv, Cent Off, Lexington, KY USA. [Evans, Martin E.] Lexington VA Med Ctr, Lexington, KY USA. [Evans, Martin E.] Univ Kentucky, Sch Med, Dept Internal Med, Div Infect Dis, Lexington, KY 40536 USA. RP Hill, JN (reprint author), Edward Hines Jr VA Hosp, Vet Hlth Adm, Dept Vet Affairs, 5000 S 5th Ave 151H, Hines, IL 60141 USA. EM jennifer.hill3@va.gov OI Cameron, Kenzie/0000-0002-3535-6459 FU United States Department of Veterans Affairs, Office of Research and Development, Health Services Research and Development Service, and Quality Enhancement Research Initiative [RRP09-163] FX This study was supported by the United States Department of Veterans Affairs, Office of Research and Development, Health Services Research and Development Service, and Quality Enhancement Research Initiative (Grant: RRP09-163). The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs. NR 25 TC 2 Z9 2 U1 2 U2 12 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-6553 EI 1527-3296 J9 AM J INFECT CONTROL JI Am. J. Infect. Control PD AUG PY 2014 VL 42 IS 8 BP 834 EP 840 DI 10.1016/j.ajic.2014.04.026 PG 7 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA AO4KN UT WOS:000341306700004 PM 24950922 ER PT J AU Pang, CE Shah, VP Sarraf, D Freund, KB AF Pang, Claudine E. Shah, Vinnie P. Sarraf, David Freund, K. Bailey TI Ultra-Widefield Imaging With Autofluorescence and Indocyanine Green Angiography in Central Serous Chorioretinopathy SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID UVEAL EFFUSION SYNDROME; FUNDUS AUTOFLUORESCENCE; SURGICAL-TREATMENT; CLINICAL-FEATURES; PATHOGENESIS; HYPOTHESIS AB PURPOSE: To describe the spectrum of ultra-widefield autofluorescence (AF) and indocyanine green (ICG) angiographic findings in central serous chorioretinopathy (CSC). DESIGN: Retrospective observational case series. METHODS: In 37 patients, 65 eyes with CSC from 2 vitreoretinal clinical practices were imaged using ultra-widefield AF and 24 of these eyes with ultra-widefield ICG angiography. Images were correlated with clinical findings and spectral-domain optical coherence tomography (OCT). RESULTS: In 37 (57%) eyes, a variety of altered AF patterns, including gravitational tracts, extended beyond the posterior 50 degrees of retina. Hyper-AF corresponded to areas of subretinal fluid (SRF) on spectral-domain OCT and was found to persist in 44 (70%) eyes for up to 8 years despite resolution of SRF. These areas corresponded to outer retinal atrophy with viable retinal pigment epithelium (RPE) on spectral-domain OCT and may be explained by the unmasking of normal background RPE AF. Ultra-widefield ICG angiography revealed dilated choroidal vessels and choroidal hyperpermeability in areas corresponding to altered AF on ultra-widefield AF in all 24 eyes. In 20 (83.3%) eyes, dilated vessels were observed in association with 1 or more congested vortex veins ampullas, suggesting that outflow congestion may be a contributing factor to the pathogenesis of CSC. CONCLUSIONS: Ultra-widefield AF and ICG angiography in CSC revealed more widespread disease in a single image than with standard field imaging and may be useful for identifying peripheral areas of previous or ongoing SRF and choroidal hyperpermeability that can assist in the diagnosis of CSC, surveillance of recurrent disease and treatment of active disease. (C) 2014 by Elsevier Inc. All rights reserved. C1 [Pang, Claudine E.; Shah, Vinnie P.; Freund, K. Bailey] Vitreous Retina Macula Consultants New York, New York, NY 10022 USA. [Pang, Claudine E.; Freund, K. Bailey] Manhattan Eye Ear & Throat Hosp, LuEsther T Mertz Retinal Res Ctr, New York, NY 10021 USA. [Shah, Vinnie P.; Freund, K. Bailey] NYU, Sch Med, Dept Ophthalmol, New York, NY 10003 USA. [Sarraf, David] Univ Calif Los Angeles, Jules Stein Eye Inst, Retinal Disorders & Ophthalm Genet Div, Los Angeles, CA 90024 USA. [Sarraf, David] Greater Los Angeles VA Healthcare Ctr, Los Angeles, CA USA. RP Freund, KB (reprint author), Vitreous Retina Macula Consultants New York, 460 Pk Ave,Fifth Floor, New York, NY 10022 USA. EM kbfnyf@aol.com OI Shah, Vinnie/0000-0003-1325-7019; Freund, K. Bailey/0000-0002-7888-9773 FU Macula Foundation, Inc., New York, NY, USA; Regeneron; Heidelberg FX ALL AUTHORS HAVE COMPLETED AND SUBMITTED THE ICMJE FORM FOR DISCLOSURE OF POTENTIAL CONFLICTS OF INTEREST, and the following were reported. Financial support was received from the Macula Foundation, Inc., New York, NY, USA. The funding organization had no role in the design or conduct of this research. Dr Freund is a consultant to Genentech, Regeneron, Optos, Heidelberg Engineering, and Bayer. Dr Sarraf received research support from Regeneron and financial support from Heidelberg. Dr Pang and Dr Shah have no financial disclosures. Design and conduct of study (C.E.P., V.P.S., K.B.F., D.S.); Collection, management, analysis, and interpretation of data (C.E.P., V.P.S., K.B.F., D.S.); and Preparation, review, or approval of the manuscript (C.E.P., V.P.S., K.B.F., D.S.). NR 36 TC 13 Z9 14 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 EI 1879-1891 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD AUG PY 2014 VL 158 IS 2 BP 362 EP 371 DI 10.1016/j.ajo.2014.04.021 PG 10 WC Ophthalmology SC Ophthalmology GA AN6EB UT WOS:000340686600021 PM 24794091 ER PT J AU Ioannou, GN Beste, LA Green, PK AF Ioannou, George N. Beste, Lauren A. Green, Pamela K. TI Similar Effectiveness of Boceprevir and Telaprevir Treatment Regimens for Hepatitis C Virus Infection on the Basis of a Nationwide Study of Veterans SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE DAA; Antiviral Therapy; Population; APRI; Outcome; LDL ID HEPATOCELLULAR-CARCINOMA; CIRRHOSIS; PREDICTORS; PREVALENCE; FIBROSIS AB BACKGROUND & AIMS: We investigated the real-world effectiveness of triple therapy regimens against hepatitis C virus (HCV) and compared rates of sustained virologic response (SVR) between telaprevir-based and boceprevir-based regimens in a population-based study. METHODS: We analyzed data on all patients in the Veterans Administration healthcare system who were infected with HCV genotype 1 and began treatment with pegylated interferon, ribavirin, and either boceprevir (n = 3696,83%) or telaprevir (n = 759,17%) from June 2011 to February 2013. RESULTS: Patients treated with telaprevir were more likely to have baseline characteristics associated with not achieving SVR than patients treated with boceprevir. Fewer than half of patients eligible for short-duration regimens (28 weeks for boceprevir, 24 weeks for telaprevir) successfully completed treatment (37% for boceprevir, 27.5% for telaprevir); similar to 25% discontinued early, and the remaining patients were treated for longer durations. Of the patients who were supposed to complete 48-week regimens, only 35% of boceprevir-treated and 34% of telaprevir-treated patients completed >44 weeks. The rate of SVR was 51.5% overall, 42.7% among patients with cirrhosis, 56.8% among treatment-naive patients, 64.2% among prior relapsers, 31.7% among prior partial responders, and 29.8% among prior null responders. There were no significant differences in rate of SVR between patients given boceprevir or telaprevir in the entire population or among subgroups. The most important predictors of failure to achieve SVR were IL28B genotype, high viral load, black race, diabetes, high aspartate aminotransferase to platelet ratio index or FIB-4 scores, low platelet counts, or low levels of low-density lipoprotein cholesterol. Erythropoietin use was not associated with SVR. CONCLUSIONS: In a nationwide analysis of veterans with HCV genotype 1 infection, rates of SVR were similar for those treated with boceprevir vs telaprevir. However, rates of treatment completion and SVR in real clinical practice were substantially lower than those in clinical trials. C1 [Ioannou, George N.] Vet Affairs Puget Sound Hlth Care Syst, Div Gastroenterol, Seattle, WA 98108 USA. [Ioannou, George N.; Green, Pamela K.] Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA 98108 USA. [Beste, Lauren A.] Vet Affairs Puget Sound Hlth Care Syst, Div Internal Med, Seattle, WA 98108 USA. [Ioannou, George N.] Univ Washington, Div Gastroenterol, Seattle, WA 98195 USA. [Beste, Lauren A.] Univ Washington, Div Internal Med, Seattle, WA 98195 USA. RP Ioannou, GN (reprint author), Vet Affairs Puget Sound Hlth Care Syst, S 111 Gastro,1660 S Columbian Way, Seattle, WA 98108 USA. EM georgei@medicine.washington.edu FU Merit Review grant, Clinical Science Research and Development, Office of Research and Development, Veterans Affairs [I01CX000320] FX Supported by a Merit Review grant (I01CX000320), Clinical Science Research and Development, Office of Research and Development, Veterans Affairs (G.N.I.). NR 15 TC 25 Z9 25 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 EI 1542-7714 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD AUG PY 2014 VL 12 IS 8 BP 1371 EP 1380 DI 10.1016/j.cgh.2013.12.011 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AO2BG UT WOS:000341119700027 PM 24361415 ER PT J AU May, FP Bromley, EG Reid, MW Baek, M Yoon, J Cohen, E Lee, A van Oijen, MGH Spiegel, BMR AF May, Folasade P. Bromley, Erica G. Reid, Mark W. Baek, Michael Yoon, Jessica Cohen, Erica Lee, Aaron van Oijen, Martijn G. H. Spiegel, Brennan M. R. TI Low uptake of colorectal cancer screening among African Americans in an integrated Veterans Affairs health care network SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID COLON-CANCER; MEDICARE BENEFICIARIES; DISPARITIES; POPULATION; PREDICTORS; PATTERNS; COVERAGE; WOMEN AB Background: African Americans have the highest incidence and mortality from colorectal cancer (CRC). Despite guidelines to initiate screening with colonoscopy at age 45 in African Americans, the CRC incidence remains high in this group. Objective: To examine the rates and predictors of CRC screening uptake as well as time to screening in a population of African Americans and non-African Americans in a health care system that minimizes variations in insurance and access. Design: Retrospective cohort study. Setting: Greater Los Angeles Veterans Affairs (VA) Healthcare System. Patients: Random sample (N = 357) of patients eligible for initial CRC screening. Main Outcome Measurements: Uptake of any screening method; uptake of colonoscopy, in particular; predictors of screening; and time to screening in African Americans and non-African Americans. Results: The overall screening rate by any method was 50%. Adjusted rates for any screening were lower among African Americans than non-African Americans (42% vs 58%; odds ratio [OR] 0.49; 95% confidence interval [CI], 0.31-0.77). Colonoscopic screening was also lower in African Americans (11% vs 23%; adjusted OR 0.43; 95% CI, 0.24-0.77). In addition to race, homelessness, lower service connectedness, taking more prescription drugs, and not seeing a primary care provider within 2 years of screening eligibility predicted lower uptake of screening. Time to screening colonoscopy was longer in African Americans (adjusted hazard ratio 0.43; 95% CI, 0.25-0.75). Limitations: The sample may not be generalizable. Conclusions: We found marked disparities in CRC screening despite similar access to care across races. Despite current guidelines aimed at increasing CRC screening in African Americans, participation in screening remained low, and use of colonoscopy was infrequent. C1 [May, Folasade P.; Bromley, Erica G.; Baek, Michael; Yoon, Jessica; Cohen, Erica; Lee, Aaron; Spiegel, Brennan M. R.] VA Greater Los Angeles Healthcare Syst, Dept Med, Div Gastroenterol, Los Angeles, CA USA. [May, Folasade P.; van Oijen, Martijn G. H.; Spiegel, Brennan M. R.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Digest Dis, Los Angeles, CA 90073 USA. [May, Folasade P.; Spiegel, Brennan M. R.] UCLA Fielding Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA USA. [May, Folasade P.; Reid, Mark W.; Spiegel, Brennan M. R.] UCLA VA Ctr Outcomes Res & Educ CORE, Los Angeles, CA USA. RP Spiegel, BMR (reprint author), Univ Calif Los Angeles, UCLA VA Ctr Outcomes Res & Educ CORE, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd,Bldg 115,Room 215, Los Angeles, CA 90073 USA. FU NIH [T32DK07180-34] FX All authors disclosed no financial relationships relevant to this publication. This research was supported by NIH training grant T32DK07180-34 to Dr May. NR 26 TC 9 Z9 9 U1 2 U2 7 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 EI 1097-6779 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD AUG PY 2014 VL 80 IS 2 BP 291 EP 298 DI 10.1016/j.gie.2014.01.045 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AO2KX UT WOS:000341151700012 PM 24674351 ER PT J AU Yaghoobi, M AF Yaghoobi, Mohammad TI Treatment of patients with new diagnosis of achalasia: laparoscopic Heller's myotomy may be more effective than pneumatic dilation SO GASTROINTESTINAL ENDOSCOPY LA English DT Letter C1 Med Univ S Carolina, Div Gastroenterol & Hepatol, Ralph H Johnson VA Med Ctr, Charleston, SC 29425 USA. RP Yaghoobi, M (reprint author), Med Univ S Carolina, Div Gastroenterol & Hepatol, Ralph H Johnson VA Med Ctr, Charleston, SC 29425 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 EI 1097-6779 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD AUG PY 2014 VL 80 IS 2 BP 360 EP 360 DI 10.1016/j.gie.2014.02.029 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AO2KX UT WOS:000341151700035 PM 25034845 ER PT J AU Nelson, KM Helfrich, C Sun, HL Hebert, PL Liu, CF Dolan, E Taylor, L Wong, E Maynard, C Hernandez, SE Sanders, W Randall, I Curtis, I Schectman, G Stark, R Fihn, SD AF Nelson, Karin M. Helfrich, Christian Sun, Haili Hebert, Paul L. Liu, Chuan-Fen Dolan, Emily Taylor, Leslie Wong, Edwin Maynard, Charles Hernandez, Susan E. Sanders, William Randall, Ian Curtis, Idamay Schectman, Gordon Stark, Richard Fihn, Stephan D. TI Implementation of the Patient-Centered Medical Home in the Veterans Health Administration Associations With Patient Satisfaction, Quality of Care, Staff Burnout, and Hospital and Emergency Department Use SO JAMA INTERNAL MEDICINE LA English DT Article ID RECEIVING PRIMARY-CARE; CLINICS; TRANSFORMATION; PHYSICIANS; INVENTORY; SYSTEM AB IMPORTANCE In 2010, the Veterans Health Administration (VHA) began implementing the patient-centered medical home (PCMH) model. The Patient Aligned Care Team (PACT) initiative aims to improve health outcomes through team-based care, improved access, and care management. To track progress and evaluate outcomes at all VHA primary care clinics, we developed and validated a method to assess PCMH implementation. OBJECTIVES To create an index that measures the extent of PCMH implementation, describe variation in implementation, and examine the association between the implementation index and key outcomes. DESIGN, SETTING, AND PARTICIPANTS We conducted an observational study using data on more than 5.6 million veterans who received care at 913 VHA hospital-based and community-based primary care clinics and 5404 primary care staff from (1) VHA clinical and administrative databases, (2) a national patient survey administered to a weighted random sample of veterans who received outpatient care from June 1 to December 31, 2012, and (3) a survey of all VHA primary care staff in June 2012. Composite scores were constructed for 8 core domains of PACT: access, continuity, care coordination, comprehensiveness, self-management support, patient-centered care and communication, shared decision making, and team-based care. MAIN OUTCOMES AND MEASURES Patient satisfaction, rates of hospitalization and emergency department use, quality of care, and staff burnout. RESULTS Fifty-three items were included in the PACT Implementation Progress Index (Pi(2)). Compared with the 87 clinics in the lowest decile of the Pi(2), the 77 sites in the top decile exhibited significantly higher patient satisfaction (9.33 vs 7.53; P < .001), higher performance on 41 of 48 measures of clinical quality, lower staff burnout (Maslach Burnout Inventory emotional exhaustion subscale, 2.29 vs 2.80; P = .02), lower hospitalization rates for ambulatory care-sensitive conditions (4.42 vs 3.68 quarterly admissions for veterans 65 years or older per 1000 patients; P < .001), and lower emergency department use (188 vs 245 visits per 1000 patients; P < .001). CONCLUSIONS AND RELEVANCE The extent of PCMH implementation, as measured by the Pi2, was highly associated with important outcomes for both patients and providers. This measure will be used to track the effectiveness of implementing PACT over time and to elucidate the correlates of desired health outcomes. C1 [Nelson, Karin M.; Helfrich, Christian; Sun, Haili; Hebert, Paul L.; Liu, Chuan-Fen; Dolan, Emily; Taylor, Leslie; Maynard, Charles; Hernandez, Susan E.; Randall, Ian] VA Puget Sound Hlth Care Syst, Seattle Ctr Innovat Vet Ctr & Value Driven Care, Seattle, WA 98108 USA. [Nelson, Karin M.; Fihn, Stephan D.] VA Puget Sound Hlth Care Syst, Gen Internal Med Serv, Seattle, WA 98108 USA. [Nelson, Karin M.; Fihn, Stephan D.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Helfrich, Christian; Sun, Haili; Hebert, Paul L.; Liu, Chuan-Fen; Wong, Edwin; Maynard, Charles; Hernandez, Susan E.; Randall, Ian] Univ Washington, Sch Publ Hlth, Dept Hlth Serv, Seattle, WA 98195 USA. [Sanders, William; Curtis, Idamay; Fihn, Stephan D.] Vet Hlth Adm, Off Analyt & Business Intelligence, Washington, DC USA. [Schectman, Gordon] US Dept Vet Affairs, Off Patient Care Serv, Washington, DC USA. [Stark, Richard] US Dept Vet Affairs, Off Clin Operat, Washington, DC USA. RP Nelson, KM (reprint author), VA Puget Sound Hlth Care Syst, Seattle Ctr Innovat Vet Ctr & Value Driven Care, 1100 Olive Way,Ste 1400, Seattle, WA 98108 USA. EM karin.nelson@va.gov RI Maynard, Charles/N-3906-2015 OI Maynard, Charles/0000-0002-1644-7814 FU VHA Office of Patient Care Service FX This work was supported by the VHA Office of Patient Care Service. NR 43 TC 40 Z9 40 U1 11 U2 39 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD AUG PY 2014 VL 174 IS 8 BP 1350 EP 1358 DI 10.1001/jamainternmed.2014.2488 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA AN2WP UT WOS:000340447000031 PM 25055197 ER PT J AU Wiener, RS Slatore, CG AF Wiener, Renda Soylemez Slatore, Christopher G. TI Real-World Evidence About Potential Psychosocial Harms of Lung Cancer Screening SO JAMA INTERNAL MEDICINE LA English DT Letter ID PULMONARY NODULES C1 [Wiener, Renda Soylemez] Boston Univ, Sch Med, Ctr Pulm, Boston, MA 02118 USA. [Wiener, Renda Soylemez] Edith Nourse Rogers Mem Vet Hosp, Ctr Healthcare Org & Implementat Res, Bedford, MA USA. [Slatore, Christopher G.] Portland VA Med Ctr, Hlth Serv Res & Dev, Portland, OR USA. [Slatore, Christopher G.] Oregon Hlth & Sci Univ, Div Pulm & Crit Care Med, Portland, OR 97201 USA. RP Wiener, RS (reprint author), Boston Univ, Sch Med, Ctr Pulm, 72 E Concord St,R-304, Boston, MA 02118 USA. EM rwiener@bu.edu OI Wiener, Renda/0000-0001-7712-2135 NR 4 TC 0 Z9 0 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD AUG PY 2014 VL 174 IS 8 BP 1416 EP 1416 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA AN2WP UT WOS:000340447000055 PM 25090181 ER PT J AU Sacks, GD Dawes, AJ Russell, MM Lin, AY Maggard-Gibbons, M Winograd, D Chung, HR Tomlinson, J Tillou, A Shew, SB Hiyama, DT Cryer, HG Brunicardi, FC Hiatt, JR Ko, C AF Sacks, Greg D. Dawes, Aaron J. Russell, Marcia M. Lin, Anne Y. Maggard-Gibbons, Melinda Winograd, Deborah Chung, Hallie R. Tomlinson, James Tillou, Areti Shew, Stephen B. Hiyama, Darryl T. Cryer, H. Gill Brunicardi, F. Charles Hiatt, Jonathan R. Ko, Clifford TI Evaluation of Hospital Readmissions in Surgical Patients Do Administrative Data Tell the Real Story? SO JAMA SURGERY LA English DT Article ID QUALITY IMPROVEMENT PROGRAM; POSTOPERATIVE ADVERSE EVENTS; DATA SETS; COMPLICATIONS; RATES AB IMPORTANCE The Centers for Medicare & Medicaid Services has developed an all-cause readmission measure that uses administrative data to measure readmission rates and financially penalize hospitals with higher-than-expected readmission rates. OBJECTIVES To examine the accuracy of administrative codes in determining the cause of readmission as determined by medical record review, to evaluate the readmission measure's ability to accurately identify a readmission as planned, and to document the frequency of readmissions for reasons clinically unrelated to the original hospital stay. DESIGN, SETTING, AND PARTICIPANTS Retrospective review of all consecutive patients discharged from general surgery services at a tertiary care, university-affiliated teaching hospital during 8 consecutive quarters (quarter 4 [October through December] of 2009 through quarter 3 [July through September] of 2011). Clinical readmission diagnosis determined from direct medical record review was compared with the administrative diagnosis recorded in a claims database. The number of planned hospital readmissions defined by the readmission measure was compared with the number identified using clinical data. Readmissions unrelated to the original hospital stay were identified using clinical data. MAIN OUTCOMES AND MEASURES Discordance rate between administrative and clinical diagnoses for all hospital readmissions, discrepancy between planned readmissions defined by the readmission measure and identified by clinical medical record review, and fraction of hospital readmissions unrelated to the original hospital stay. RESULTS Of the 315 hospital readmissions, the readmission diagnosis listed in the administrative claims data differed from the clinical diagnosis in 97 readmissions (30.8%). The readmission measure identified 15 readmissions (4.8%) as planned, whereas clinical data identified 43 readmissions (13.7%) as planned. Unrelated readmissions comprised 70 of the 258 unplanned readmissions (27.1%). CONCLUSIONS AND RELEVANCE Administrative billing data, as used by the readmission measure, do not reliably describe the reason for readmission. The readmission measure accounts for less than half of the planned readmissions and does not account for the nearly one-third of readmissions unrelated to the original hospital stay. Implementation of this readmission measure may result in unwarranted financial penalties for hospitals. C1 [Sacks, Greg D.; Dawes, Aaron J.; Russell, Marcia M.; Lin, Anne Y.; Maggard-Gibbons, Melinda; Winograd, Deborah; Chung, Hallie R.; Tomlinson, James; Tillou, Areti; Shew, Stephen B.; Hiyama, Darryl T.; Cryer, H. Gill; Brunicardi, F. Charles; Hiatt, Jonathan R.; Ko, Clifford] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. [Russell, Marcia M.; Maggard-Gibbons, Melinda; Tomlinson, James; Ko, Clifford] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Sacks, GD (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, 10833 Le Conte Ave,72-215 CHS, Los Angeles, CA 90095 USA. EM gsacks@mednet.ucla.edu OI Dawes, Aaron/0000-0003-4574-6765 NR 20 TC 33 Z9 33 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6254 EI 2168-6262 J9 JAMA SURG JI JAMA Surg. PD AUG PY 2014 VL 149 IS 8 BP 759 EP 764 DI 10.1001/jamasurg.2014.18 PG 6 WC Surgery SC Surgery GA AN8DZ UT WOS:000340834300002 PM 24920156 ER PT J AU McCann, RA Armstrong, CM Skopp, NA Edwards-Stewart, A Smolenski, DJ June, JD Metzger-Abamukong, M Reger, GM AF McCann, Russell A. Armstrong, Christina M. Skopp, Nancy A. Edwards-Stewart, Amanda Smolenski, Derek J. June, Jennifer D. Metzger-Abamukong, Melinda Reger, Greg M. TI Virtual reality exposure therapy for the treatment of anxiety disorders: An evaluation of research quality SO JOURNAL OF ANXIETY DISORDERS LA English DT Review DE Randomized controlled trials; Effectiveness; Adherence ID POSTTRAUMATIC-STRESS-DISORDER; COGNITIVE-BEHAVIORAL THERAPY; RANDOMIZED CONTROLLED-TRIALS; PUBLIC SPEAKING ANXIETY; IN-VIVO EXPOSURE; CLINICAL-TRIAL; PANIC DISORDER; CONSORT STATEMENT; GRADED EXPOSURE; SPIDER PHOBIA AB Randomized controlled trials (RCTs) support the effectiveness of virtual reality exposure therapy (VRET) for anxiety disorders; however, the overall quality of the VRET RCT literature base has yet to be evaluated. This study reviewed 27 VRET RCTs and the degree of adherence to 8 RCT research design criteria derived from existing standards. Adherence to the study quality criteria was generally low as the articles met an average 2.85 criteria (SD = 1.56). None of the studies met more than six quality criteria. Study quality did not predict effect size; however, a reduction in effect size magnitude was observed for studies with larger sample sizes when comparing VRET to non-active control groups. VRET may be an effective method of treatment but caution should be exercised in interpreting the existing body of literature supporting VRET relative to existing standards of care. The need for well-designed VRET research is discussed. (C) 2014 Published by Elsevier Ltd. C1 [McCann, Russell A.; Armstrong, Christina M.; Skopp, Nancy A.; Edwards-Stewart, Amanda; Smolenski, Derek J.; June, Jennifer D.; Metzger-Abamukong, Melinda; Reger, Greg M.] Madigan Army Med Ctr, Natl Ctr Telehlth & Technol, Tacoma, WA 98431 USA. RP Reger, GM (reprint author), VA Puget Sound, 9600 Vet Dr, Tacoma, WA 98493 USA. EM Greg.reger2@gmail.com NR 58 TC 13 Z9 13 U1 8 U2 47 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6185 EI 1873-7897 J9 J ANXIETY DISORD JI J. Anxiety Disord. PD AUG PY 2014 VL 28 IS 6 BP 625 EP 631 DI 10.1016/j.janxdis.2014.05.010 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AN8OW UT WOS:000340864500015 PM 25093964 ER PT J AU Vagin, O Tokhtaeva, E Garay, PE Souda, P Bassilian, S Whitelegge, JP Lewis, R Sachs, G Wheeler, L Aoki, R Fernandez-Salas, E AF Vagin, Olga Tokhtaeva, Elmira Garay, Patton E. Souda, Puneet Bassilian, Sara Whitelegge, Julian P. Lewis, Ramilla Sachs, George Wheeler, Larry Aoki, Roger Fernandez-Salas, Ester TI Recruitment of septin cytoskeletal proteins by botulinum toxin A protease determines its remarkable stability SO JOURNAL OF CELL SCIENCE LA English DT Article DE Septin; Botulinum toxin A protease; Protein stability; Degradation; Ubiquitylation ID NEUROTRANSMITTER RELEASE; MAMMALIAN SEPTINS; BETA(1) SUBUNITS; NEUROTOXIN; FORCHLORFENURON; RECOGNITION; SIGNALS; COMPLEX; AP-3; LOCALIZATION AB Proteolytic cleavage of synaptosomal-associated protein 25 by the light chain of botulinum neurotoxin type A (LCA) results in a blockade of neurotransmitter release that persists for several months in motor neurons. The L428A/L429A mutation in LCA is known to significantly shorten both the proteolytic and neuroparalytic effects of the neurotoxin in mice. To elucidate the cellular mechanism for LCA longevity, we studied the effects of L428A/L429A mutation on the interactome, localization and stability of LCA expressed in cultured neuronal cells. Mass spectrometry analysis of the LCA interactome showed that the mutation prevented the interaction of LCA with septins. The wild-type LCA was concentrated in plasma-membrane-associated clusters, colocalizing with septins-2 and septin-7, which accumulated in these clusters only in the presence of LCA. The L428A/L429A mutation decreased co-clustering of LCA and septins and accelerated proteasomal and non-proteasomal degradation of LCA. Similarly, the impairment of septin oligomerization by forchlorfenuron or silencing of septin-2 prevented LCA interaction and clustering with septins and increased LCA degradation. Therefore, the dileucine-mediated LCA-septin co-clustering is crucial for the long-lasting stabilization of LCA-related proteolytic and presumably neuroparalytic activity. C1 [Vagin, Olga; Tokhtaeva, Elmira; Bassilian, Sara; Sachs, George] UCLA, Sch Med, Dept Physiol, Los Angeles, CA 91343 USA. [Vagin, Olga; Tokhtaeva, Elmira; Bassilian, Sara; Sachs, George] Vet Adm Greater Los Angeles Hlth Care Syst, Los Angeles, CA 91343 USA. [Garay, Patton E.; Lewis, Ramilla; Wheeler, Larry; Aoki, Roger; Fernandez-Salas, Ester] Allergan Pharmaceut Inc, Dept Biol Sci, Irvine, CA 92612 USA. [Souda, Puneet; Whitelegge, Julian P.] Univ Calif Los Angeles, Semel Inst, NPI, Pasarow Mass Spectrometry Lab, Los Angeles, CA 90095 USA. RP Vagin, O (reprint author), UCLA, Sch Med, Dept Physiol, Los Angeles, CA 91343 USA. EM olgav@ucla.edu FU Allergan, Inc. FX This work was supported by a grant from Allergan, Inc. to O.V. NR 56 TC 6 Z9 6 U1 0 U2 6 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 EI 1477-9137 J9 J CELL SCI JI J. Cell Sci. PD AUG 1 PY 2014 VL 127 IS 15 BP 3294 EP 3308 DI 10.1242/jcs.146324 PG 15 WC Cell Biology SC Cell Biology GA AO2SS UT WOS:000341176800010 PM 24928902 ER PT J AU Pierre, JF Barlow-Anacker, AJ Erickson, CS Heneghan, AF Leverson, GE Dowd, SE Epstein, ML Kudsk, KA Gosain, A AF Pierre, Joseph F. Barlow-Anacker, Amanda J. Erickson, Christopher S. Heneghan, Aaron F. Leverson, Glen E. Dowd, Scot E. Epstein, Miles L. Kudsk, Kenneth A. Gosain, Ankush TI Intestinal dysbiosis and bacterial enteroinvasion in a murine model of Hirschsprung's disease SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article DE Hirschsprung's disease; Hirschsprung's-associated enterocolitis; Microbiome; Secretory phospholipase A2; Dysbiosis; Mucosal immunity ID AMPLICON PYROSEQUENCING BTEFAP; INFLAMMATORY-BOWEL-DISEASE; ALPHA-DEFENSIN EXPRESSION; ENTERIC NERVOUS-SYSTEM; ILEAL CROHNS-DISEASE; KINASE RECEPTOR RET; NECROTIZING ENTEROCOLITIS; PHOSPHOLIPASE A(2); ESCHERICHIA-COLI; NEURAL CREST AB Background/purpose: Hirschsprung's disease (HSCR), characterized by the absence of ganglia in the distal colon, results in functional obstruction. Despite surgical resection of the aganglionic segment, around 40% of patients suffer recurrent life threatening Hirschsprung's-associated enterocolitis (HAEC). The aim of this study was to investigate whether gut microbiota and intestinal immunity changes contribute to the HAEC risk in an HSCR model. Methods: Mice with neural crest conditional deletion of Endothelin receptor B (EdnrB) and their littermate controls were used (EdnrB-null and EdnrB-het). Bacterial DNA was prepared from cecal contents of P16-18 and P21-24 animals and pyrosequencing employed for microbiome analysis. Ileal tissue was isolated and secretory phospholipase A(2) (sPLA(2)) expression and activity determined. Enteroinvasion of Escherichia coli into ileal explants was measured using an ex vivo organ culture system. Results: EdnrB-het and EdnrB-nulls displayed similar flora, sPLA(2) expression and activity at P16-18. However, by P21-24, EdnrB-hets demonstrated increased Lactobacillus and decreased Bacteroides and Clostridium, while EdnrB-nulls exhibited reciprocal changes. EdnrB-nulls also showed reduced sPLA(2) expression and luminal activity at this stage. Functionally, EdnrB-nulls were more susceptible to enteroinvasion with E. coli ex vivo and released less sPLA(2) than EdnrB-hets. Conclusions: Initially, EdnrB-het and EdnrB-nulls contain similar cecal flora but then undergo reciprocal changes. EdnrB-nulls display dysbiosis, demonstrate impaired mucosal defense, decreased luminal sPLA(2) and increased enteroinvasion of E. coli just prior to robust colonic inflammation and death. These findings suggest a role for the intestinal microbiome in the development of HAEC. (C) 2014 Elsevier Inc. All rights reserved. C1 [Pierre, Joseph F.; Barlow-Anacker, Amanda J.; Erickson, Christopher S.; Heneghan, Aaron F.; Leverson, Glen E.; Kudsk, Kenneth A.; Gosain, Ankush] Univ Wisconsin, Dept Surg, Sch Med & Publ Hlth, Madison, WI 53792 USA. [Epstein, Miles L.; Gosain, Ankush] Univ Wisconsin, Dept Neurosci, Sch Med & Publ Hlth, Madison, WI 53792 USA. [Dowd, Scot E.] Res & Testing Lab, Lubbock, TX USA. [Kudsk, Kenneth A.] William S Middleton Mem Vet Adm Med Ctr, Vet Adm Surg Serv, Madison, WI USA. RP Gosain, A (reprint author), Univ Wisconsin, Dept Surg, Clin Sci Ctr H4 750, 600 Highland Ave, Madison, WI 53792 USA. EM gosain@surgery.wisc.edu OI Gosain, Ankush/0000-0002-0428-1503 FU National Institutes of Health [NIDDK RO1DK081634]; Veteran's Affairs Office of Research and Development (Biomedical Laboratory Research & Development Award) [I01BX001672]; Central Surgical Association Foundation Turcotte Award; American Pediatric Surgery Association Foundation Award FX This work was supported by the National Institutes of Health (NIDDK RO1DK081634) to MLE, the Veteran's Affairs Office of Research and Development (Biomedical Laboratory Research & Development Award I01BX001672) to KAK, the Central Surgical Association Foundation Turcotte Award to AG, and the American Pediatric Surgery Association Foundation Award to AG. The contents of this article do not represent the views of the Veterans Affairs or the United States Government (KAK). NR 60 TC 12 Z9 14 U1 1 U2 9 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0022-3468 EI 1531-5037 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD AUG PY 2014 VL 49 IS 8 BP 1242 EP 1251 DI 10.1016/j.jpedsurg.2014.01.060 PG 10 WC Pediatrics; Surgery SC Pediatrics; Surgery GA AN0EM UT WOS:000340256200011 PM 25092084 ER PT J AU Mishra, RK Beatty, AL Jaganath, R Regan, M Wu, AHB Whooley, MA AF Mishra, Rakesh K. Beatty, Alexis L. Jaganath, Rajesh Regan, Mathilda Wu, Alan H. B. Whooley, Mary A. TI B-type Natriuretic Peptides for the Prediction of Cardiovascular Events in Patients With Stable Coronary Heart Disease: The Heart and Soul Study SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE adverse cardiovascular outcomes; BNP; NT-proBNP; risk assessment; stable coronary heart disease ID TERMINAL PRO-BNP; ARTERY-DISEASE; PROGNOSTIC VALUE; NT-PROBNP; BIOMARKERS; FAILURE; MORTALITY; PREVENTION; SECRETION; TRIAL AB Background-Brain-type natriuretic peptide (BNP) and the amino-terminal fragment of its prohormone (NT-proBNP) are known predictors of cardiovascular outcomes in patients with coronary heart disease; however, the relative prognostic value of these 2 biomarkers for secondary events remains unclear. Methods and Results-In 983 participants with stable coronary heart disease, we evaluated the association of BNP and NT-proBNP with time to hospitalization for heart failure, nonfatal myocardial infarction, stroke or transient ischemic attack, cardiovascular death, and combined major adverse cardiovascular events (MACE). During an average follow-up of 6.5 +/- 3.3 years, both BNP and NT-proBNP were associated with increased risk of MACE in a multivariable-adjusted model (hazard ratio per standard deviation of log BNP: 1.58; 95% Cl: 1.32 to 1.89; hazard ratio per standard deviation of log NT-proBNP: 1.84; 95% Cl: 1.52 to 2.24). When added to traditional risk factors, NT-proBNP predicted MACE better than BNP (C statistic: 0.76 versus 0.72, P<0.001). Similarly, the addition of NT-proBNP resulted in a greater net reclassification improvement for predicting MACE than the addition of BNP (65% for NT-proBNP, 56% for BNP). Conclusions-Both BNP and NT-proBNP were significant predictors of MACE in stable coronary heart disease; however, NT-proBNP was superior to BNP for net risk reclassification for MACE. C1 [Mishra, Rakesh K.; Beatty, Alexis L.; Jaganath, Rajesh; Whooley, Mary A.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94121 USA. [Wu, Alan H. B.] Univ Calif San Francisco, Dept Pathol & Lab Med, San Francisco, CA 94121 USA. [Mishra, Rakesh K.; Regan, Mathilda; Whooley, Mary A.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Mishra, RK (reprint author), Univ Calif San Francisco, Dept Med, San Francisco, CA 94121 USA. EM rakesh.mishra@ucsf.edu FU Department of Veterans Affairs (Washington, DC); National Heart, Lung, and Blood Institute [R01 HL079235]; American Federation for Aging Research; Robert Wood Johnson Foundation; Nancy Kirwan Heart Research Fund, San Francisco, California; Ischemia Research and Education Foundation; Roche Diagnostics Corporation; Alere Inc. FX The Heart and Soul Study was funded by the Department of Veterans Affairs (Washington, DC); the National Heart, Lung, and Blood Institute (grant R01 HL079235); the American Federation for Aging Research (Paul Beeson Scholars Program); the Robert Wood Johnson Foundation (Faculty Scholars Program); the Nancy Kirwan Heart Research Fund, San Francisco, California; and the Ischemia Research and Education Foundation. The NT-proBNP assays were funded by Roche Diagnostics Corporation. The BNP assays were funded by Alere Inc. NR 32 TC 8 Z9 8 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD AUG PY 2014 VL 3 IS 4 AR e000907 DI 10.1161/JAHA.114.000907 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AO4HD UT WOS:000341296600024 ER PT J AU Alosco, ML Gunstad, J Xu, X Clark, US Labbe, DR Riskin-Jones, HH Terrero, G Schwarz, NF Walsh, EG Poppas, A Cohen, RA Sweet, LH AF Alosco, Michael L. Gunstad, John Xu, Xiaomeng Clark, Uraina S. Labbe, Donald R. Riskin-Jones, Hannah H. Terrero, Gretel Schwarz, Nicolette F. Walsh, Edward G. Poppas, Athena Cohen, Ronald A. Sweet, Lawrence H. TI The impact of hypertension on cerebral perfusion and cortical thickness in older adults SO JOURNAL OF THE AMERICAN SOCIETY OF HYPERTENSION LA English DT Article DE Arterial spin labeling; Blood pressure; brain structure; cerebral blood flow ID SURFACE-BASED ANALYSIS; BLOOD-PRESSURE LEVELS; ALZHEIMERS-DISEASE; COGNITIVE FUNCTION; ANTIHYPERTENSIVE THERAPY; CEREBROVASCULAR-DISEASE; LONGITUDINAL CHANGES; BRAIN MORPHOLOGY; APOLIPOPROTEIN-E; FLOW-VELOCITY AB Hypertension may increase risk for dementia possibly because of its association with decreased cortical thickness. Disturbed cerebral autoregulation is one plausible mechanism by which hypertension impacts the cerebral structure, but the associations among hypertension, brain perfusion, and cortical thickness are poorly understood. The current sample consisted of 58 older adults with varying levels of vascular disease. Diagnostic history of hypertension and antihypertensive medication status was ascertained through self-report, and when available, confirmed by medical record review. All participants underwent arterial spin labeling and T1-weighted magnetic resonance imaging to quantify total and regional cortical perfusion and thickness. Analysis of covariance adjusting for medical variables showed that participants with hypertension exhibited reduced temporal and occipital brain perfusion and total and regional cortical thickness relative to those without hypertension. The effects of hypertension on total brain perfusion remained unchanged even after adjustment for age, although no such pattern emerged for cortical thickness. Decreased total brain perfusion predicted reduced thickness of the total brain and of the frontal, temporal, and parietal lobe cortices. Antihypertensive treatment was not associated with total cerebral perfusion or cortical thickness. This study provides initial evidence for the adverse effects of a diagnostic history of hypertension on brain hypoperfusion and reduced cortical thickness. Longitudinal studies are needed to investigate the role of hypertension and its interaction with other contributing factors (eg, age) in the manifestation of cerebral hypoperfusion and reduced cortical thickness. (C) 2014 American Society of Hypertension. All rights reserved. C1 [Alosco, Michael L.; Gunstad, John] Kent State Univ, Dept Psychol, Kent, OH 44242 USA. [Xu, Xiaomeng] Idaho State Univ, Dept Psychol, Pocatello, ID 83209 USA. [Clark, Uraina S.] Icahn Sch Med Mt Sinai, Dept Neurol, New York, NY 10029 USA. [Labbe, Donald R.] Brown Univ, Alpert Med Sch, Dept Psychiat & Human Behav, Providence, RI 02912 USA. [Riskin-Jones, Hannah H.] VA Greater Los Angeles Healthcare Syst, Brain Behav & Aging Res Ctr, Los Angeles, CA USA. [Terrero, Gretel] Brown Univ, Alpert Med Sch, Providence, RI 02912 USA. [Schwarz, Nicolette F.; Sweet, Lawrence H.] Univ Georgia, Dept Psychol, Athens, GA 30602 USA. [Walsh, Edward G.] Brown Univ, Dept Neurosci, Providence, RI 02912 USA. [Walsh, Edward G.] Brown Univ, Dept Diagnost Imaging, Providence, RI 02912 USA. [Poppas, Athena] Brown Univ, Dept Med, Alpert Med Sch, Providence, RI 02912 USA. [Cohen, Ronald A.] Univ Florida, Inst Aging, Clin Translat Res Program, Cognit Aging & Memory Program, Gainesville, FL USA. RP Alosco, ML (reprint author), Kent State Univ, Dept Psychol, Kent, OH 44242 USA. EM Malosco@kent.edu OI Clark, Uraina/0000-0002-2683-6696 FU National Institutes of Health Grant [R01HL084178] FX Support for this work was provided by National Institutes of Health Grant R01HL084178. NR 69 TC 11 Z9 11 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1933-1711 EI 1878-7436 J9 J AM SOC HYPERTENS JI J. Am. Soc. Hypertens. PD AUG PY 2014 VL 8 IS 8 BP 561 EP 570 DI 10.1016/j.jash.2014.04.002 PG 10 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AO3JT UT WOS:000341226200006 PM 25151318 ER PT J AU Tipps, ME Raybuck, JD Buck, KJ Lattal, KM AF Tipps, Megan E. Raybuck, Jonathan D. Buck, Kari J. Lattal, K. Matthew TI Delay and trace fear conditioning in C57BL/6 and DBA/2 mice: issues of measurement and performance SO LEARNING & MEMORY LA English DT Article ID INBRED MOUSE STRAINS; PROTEIN-KINASE-C; HIPPOCAMPUS-DEPENDENT MEMORY; F-1 HYBRIDS IMPLICATIONS; TRAIT LOCUS ANALYSIS; CONTEXTUAL FEAR; PREPULSE INHIBITION; GENETIC-DIFFERENCES; DORSAL HIPPOCAMPUS; SINGLE-GENE AB Strain comparison studies have been critical to the identification of novel genetic and molecular mechanisms in learning and memory. However, even within a single learning paradigm, the behavioral data for the same strain can vary greatly, making it difficult to form meaningful conclusions at both the behavioral and cellular level. In fear conditioning, there is a high level of variability across reports, especially regarding responses to the conditioned stimulus ( CS). Here, we compare C57BL/6 and DBA/2 mice using delay fear conditioning, trace fear conditioning, and a nonassociative condition. Our data highlight both the significant strain differences apparent in these fear conditioning paradigms and the significant differences in conditioning type within each strain. We then compare our data to an extensive literature review of delay and trace fear conditioning in these two strains. Finally, we apply a number of commonly used baseline normalization approaches to compare how they alter the reported differences. Our findings highlight three major sources of variability in the fear conditioning literature: CS duration, number of CS presentations, and data normalization to baseline measures. C1 [Tipps, Megan E.; Raybuck, Jonathan D.; Buck, Kari J.; Lattal, K. Matthew] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA. [Buck, Kari J.] Portland VA Med Ctr, Portland Alcohol Res Ctr, Portland, OR 97239 USA. RP Tipps, ME (reprint author), Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA. EM metipps@gmail.com FU National Institutes of Health [1F32 AA022011, F32DA031537, R01 DA005228, P60 AA10760, R01 AA011114, R24 AA020245, DA02592, T32 DA07262, T32 AA07468]; US Department of the Army/DOD-TATRC [W81XWH-12-2-0048]; Portland VA Medical Center FX This work was funded by National Institutes of Health 1F32 AA022011 (to M.E.T.); National Institutes of Health F32DA031537 (to J.D.R.); National Institutes of Health R01 DA005228, P60 AA10760, R01 AA011114, and R24 AA020245 (to K.J.B.); National Institutes of Health DA02592 and US Department of the Army/DOD-TATRC:W81XWH-12-2-0048 (to K.M.L.); and National Institutes of Health T32 DA07262 and T32 AA07468 and the Portland VA Medical Center. NR 76 TC 4 Z9 5 U1 0 U2 2 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1072-0502 EI 1549-5485 J9 LEARN MEMORY JI Learn. Mem. PD AUG PY 2014 VL 21 IS 8 BP 380 EP 393 DI 10.1101/lm.035261.114 PG 14 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA AO4IO UT WOS:000341300900003 PM 25031364 ER PT J AU Goldman, SM Kamel, F Ross, GW Jewell, SA Marras, C Hoppin, JA Umbach, DM Bhudhikanok, GS Meng, C Korell, M Comyns, K Hauser, RA Jankovic, J Factor, SA Bressman, S Lyons, KE Sandler, DP Langston, JW Tanner, CM AF Goldman, Samuel M. Kamel, Freya Ross, G. Webster Jewell, Sarah A. Marras, Connie Hoppin, Jane A. Umbach, David M. Bhudhikanok, Grace S. Meng, Cheryl Korell, Monica Comyns, Kathleen Hauser, Robert A. Jankovic, Joseph Factor, Stewart A. Bressman, Susan Lyons, Kelly E. Sandler, Dale P. Langston, J. William Tanner, Caroline M. TI Peptidoglycan Recognition Protein Genes and Risk of Parkinson's Disease SO MOVEMENT DISORDERS LA English DT Article DE Parkinson's disease; peptidoglycan; PGLYRP; microbiome; gut ID ALPHA-SYNUCLEIN; IMMUNE-RESPONSES; GUT MICROBIOTA; ASSOCIATION; INFLAMMATION; PATHOLOGY; SYSTEM; BRAIN; NEUROINFLAMMATION; NEURODEGENERATION AB Increased gut permeability, inflammation, and colonic alpha-synuclein pathology are present in early Parkinson's disease (PD) and have been proposed to contribute to PD pathogenesis. Peptidoglycan is a structural component of the bacterial cell wall. Peptidoglycan recognition proteins (PGRPs) maintain healthy gut microbial flora by regulating the immune response to both commensal and harmful bacteria. We tested the hypothesis that variants in genes that encode PGRPs are associated with PD risk. Participants in two independent case-control studies were genotyped for 30 single-nucleotide polymorphisms (SNPs) in the four PGLYRP genes. Using logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) adjusted for potential confounding variables, we conducted analyses in each study, separately and pooled. One SNP failed the assay, and three had little to no variation. The ORs were similar in both study populations. In pooled analyses, three of seven PGLYRP2 SNPs (rs3813135, rs733731, rs892145), one of five PGLYRP3 SNPs (rs2987763), and six of nine PGLYRP4 SNPs (rs10888557, rs12063091, rs3006440, rs3006448, rs3006458, and rs3014864) were significantly associated with PD risk. Association was strongest for PGLYRP4 5' untranslated region (UTR) SNP rs10888557 (GG reference, CG OR 0.6 [95% CI 0.4-0.9], CC OR 0.15 [95% CI 0.04-0.6]; log-additive P-trend, 0.0004). Common variants in PGLYRP genes are associated with PD risk in two independent studies. These results require replication, but they are consistent with hypotheses of a causative role for the gut microbiota and gastrointestinal immune response in PD. (C) 2014 International Parkinson and Movement Disorder Society C1 [Goldman, Samuel M.; Tanner, Caroline M.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Goldman, Samuel M.; Tanner, Caroline M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Goldman, Samuel M.; Bhudhikanok, Grace S.; Meng, Cheryl; Korell, Monica; Comyns, Kathleen; Langston, J. William] Parkinsons Inst, Sunnyvale, CA USA. [Kamel, Freya; Sandler, Dale P.] NIEHS, Epidemiol Branch, NIH, DHHS, Res Triangle Pk, NC 27709 USA. [Ross, G. Webster] Vet Affairs Pacific Isl Hlth Care Syst, Honolulu, HI USA. [Jewell, Sarah A.] German Ctr Neurodegenerat Dis, DZNE, Bonn, Germany. [Marras, Connie] Univ Toronto, Toronto Western Hosp, Toronto, ON M5T 2S8, Canada. [Hoppin, Jane A.] N Carolina State Univ, Raleigh, NC 27695 USA. [Umbach, David M.] NIEHS, Biostat Branch, NIH, DHHS, Res Triangle Pk, NC 27709 USA. [Hauser, Robert A.] Univ S Florida, Tampa, FL USA. [Jankovic, Joseph] Baylor Coll Med, Houston, TX 77030 USA. [Factor, Stewart A.] Emory Univ, Sch Med, Atlanta, GA USA. [Bressman, Susan] Beth Israel Deaconess Med Ctr, New York, NY 10003 USA. [Lyons, Kelly E.] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. RP Goldman, SM (reprint author), San Francisco VA Med Ctr, 4150 Clement St,PADRECC 127P, San Francisco, CA 94121 USA. EM samuel.goldman@ucsf.edu OI Jewell, Sarah/0000-0002-9877-2599; Kamel, Freya/0000-0001-5052-6615; Sandler, Dale/0000-0002-6776-0018 FU NIH; National Institute of Environmental Health Sciences; NIEHS [Z01-ES044007, Z01-ES049030, R01-ES10803, U54 ES012077]; NCI [Z01-CP010119]; Michael J. Fox Foundation; Parkinson's Unity Walk FX This study was supported in part by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences, NIEHS (grants Z01-ES044007 and Z01-ES049030), NCI (grant Z01-CP010119), NIEHS grants R01-ES10803 and U54 ES012077, the Michael J. Fox Foundation, Parkinson's Unity Walk, and James and Sharron Clark. SEARCH was supported by an unrestricted grant from a group of current and former manufacturers of welding consumables awarded to The Parkinson's Institute. NR 59 TC 8 Z9 9 U1 2 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 EI 1531-8257 J9 MOVEMENT DISORD JI Mov. Disord. PD AUG PY 2014 VL 29 IS 9 BP 1171 EP 1180 DI 10.1002/mds.25895 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA AN4BJ UT WOS:000340532300015 PM 24838182 ER PT J AU Rodriguez-Violante, M Gonzalez-Latapi, P Cervantes-Arriaga, A Camacho-Ordonez, A Weintraub, D AF Rodriguez-Violante, Mayela Gonzalez-Latapi, Paulina Cervantes-Arriaga, Amin Camacho-Ordonez, Azyadeh Weintraub, Daniel TI Impulse control and related disorders in Mexican Parkinson's disease patients SO PARKINSONISM & RELATED DISORDERS LA English DT Article DE Impulse control disorder; Parkinson's disease; Mexico; QUIP-RS ID COMPULSIVE DISORDERS; DOPAMINE AGONIST; RATING-SCALE; PREVALENCE; BEHAVIORS; QUESTIONNAIRE; VALIDATION; SYMPTOMS; DRUGS AB Background: Impulse control disorders (ICDs) are a relatively recent addition to the behavioral spectrum of PD-related non-motor symptoms. Social and economic factors may play a role on the ICD phenotype of PD patients. Objective: The aim of this study is to determine the prevalence and characterize the clinical profile of ICDs in a sample of low-income, low-education PD patients with no social security benefits from a Latin American country. Methods: We included 300 consecutive PD patients and 150 control subjects. The presence of ICD and related disorders was assessed using a structured interview. After the interview and neurological evaluation were concluded, all subjects completed the Questionnaire for Impulsive-compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS). Results: Regarding ICDs and related disorders (hobbyism-punding), 25.6% (n = 77) of patients in the PD group and 16.6% (n = 25) in the control group fulfilled criteria for at least one ICD or related disorder (p = 0.032). There was a statistically significant difference in the QUIP-RS mean score between PD and control subjects (5.6 +/- 9.7 and 2.7 +/- 4.21, p = 0.001). The most common ICD was compulsive eating for both PD (8.6%) and control (2.6%) groups. Conclusions: The results of this study confirm that for this population, symptoms of an ICD are significantly more frequent in PD subjects than in control subjects. Nevertheless, socioeconomic differences may contribute to a lower overall frequency and distinct pattern of ICDs in PD patients compared with what has been reported in other countries. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Rodriguez-Violante, Mayela; Gonzalez-Latapi, Paulina; Cervantes-Arriaga, Amin; Camacho-Ordonez, Azyadeh] Natl Inst Neurol & Neurosurg, Clin Lab Neurodegenerat Dis, Mexico City 14269, DF, Mexico. [Rodriguez-Violante, Mayela] Natl Inst Neurol & Neurosurg, Movement Disorders Clin, Mexico City 14269, DF, Mexico. [Weintraub, Daniel] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Univ Penn, Dept Neurol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Philadelphia Vet Affairs Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA USA. RP Rodriguez-Violante, M (reprint author), Natl Inst Neurol & Neurosurg, Clin Lab Neurodegenerat Dis, Insurgentes 3877, Mexico City 14269, DF, Mexico. EM mrodriguez@innn.edu.mx RI Rodriguez-Violante, Mayela/G-7056-2015 OI Rodriguez-Violante, Mayela/0000-0002-6041-9941; Cervantes-Arriaga, Amin/0000-0002-3935-9278 NR 28 TC 9 Z9 10 U1 1 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1353-8020 EI 1873-5126 J9 PARKINSONISM RELAT D JI Parkinsonism Relat. Disord. PD AUG PY 2014 VL 20 IS 8 BP 907 EP 910 DI 10.1016/j.parkreldis.2014.05.014 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA AO0DF UT WOS:000340978600021 PM 24935236 ER PT J AU Hu, XM Liou, AKF Leak, RK Xu, MY An, CR Suenaga, J Shi, YJ Gao, YQ Zheng, P Chen, J AF Hu, Xiaoming Liou, Anthony K. F. Leak, Rehana K. Xu, Mingyue An, Chengrui Suenaga, Jun Shi, Yejie Gao, Yanqin Zheng, Ping Chen, Jun TI Neurobiology of microglial action in CNS injuries: Receptor-mediated signaling mechanisms and functional roles SO PROGRESS IN NEUROBIOLOGY LA English DT Review DE Microglia; Receptor; Central nervous system injuries ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; FC-GAMMA-RECEPTOR; FOCAL CEREBRAL-ISCHEMIA; CENTRAL-NERVOUS-SYSTEM; ADVANCED GLYCATION ENDPRODUCTS; TOLL-LIKE RECEPTORS; NF-KAPPA-B; AMYLOID-BETA-PEPTIDE; MAST-CELL ACTIVATION; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS AB Microglia are the first line of immune defense against central nervous system (CNS) injuries and disorders. These highly plastic cells play dualistic roles in neuronal injury and recovery and are known for their ability to assume diverse phenotypes. A broad range of surface receptors are expressed on microglia and mediate microglial 'On' or 'Off' responses to signals from other host cells as well as invading microorganisms. The integrated actions of these receptors result in tightly regulated biological functions, including cell mobility, phagocytosis, the induction of acquired immunity, and trophic factor/inflammatory mediator release. Over the last few years, significant advances have been made toward deciphering the signaling mechanisms related to these receptors and their specific cellular functions. In this review, we describe the current state of knowledge of the surface receptors involved in microglial activation, with an emphasis on their engagement of distinct functional programs and their roles in CNS injuries. It will become evident from this review that microglial homeostasis is carefully maintained by multiple counterbalanced strategies, including, but not limited to, 'On' and 'Off' receptor signaling. Specific regulation of theses microglial receptors may be a promising therapeutic strategy against CNS injuries. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Hu, Xiaoming; Liou, Anthony K. F.; Suenaga, Jun; Shi, Yejie; Chen, Jun] Univ Pittsburgh, Sch Med, Ctr Cerebrovasc Dis Res, Pittsburgh, PA 15213 USA. [Hu, Xiaoming; Xu, Mingyue; An, Chengrui; Gao, Yanqin; Zheng, Ping; Chen, Jun] Fudan Univ, State Key Lab Med Neurobiol, Shanghai 200433, Peoples R China. [Hu, Xiaoming; Xu, Mingyue; An, Chengrui; Gao, Yanqin; Zheng, Ping; Chen, Jun] Fudan Univ, Inst Brain Sci, Shanghai 200433, Peoples R China. [Hu, Xiaoming; Chen, Jun] Vet Affairs Pittsburgh Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA 15240 USA. [Leak, Rehana K.] Duquesne Univ, Div Pharmaceut Sci, Pittsburgh, PA 15282 USA. RP Hu, XM (reprint author), Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA. EM hux2@upmc.edu; chenj2@upmc.edu RI Gao, Yanqin/I-6790-2016 OI Gao, Yanqin/0000-0002-4915-9819; Leak, Rehana/0000-0003-2817-7417; Shi, Yejie/0000-0001-7502-9201 FU American Heart Association [13SDG14570025]; Ethyl Vincent pilot grant in multiple sclerosis from Department of Neurology, University of Pittsburgh; Commonwealth Universal Research Enhancement (C.U.R.E.) Award from the Department of Health; Michael J. Fox Foundation Innovation Award; Chinese Natural Science Foundation grants [81171149, 81371306]; National Institutes of Health Grants [NS45048, NS62157, NS59806, NS36736]; Chinese Natural Science Foundation [81228008]; VA Merit Review FX Dr. Xiaoming Hu is supported by the American Heart Association (13SDG14570025) and the Ethyl Vincent pilot grant in multiple sclerosis from Department of Neurology, University of Pittsburgh. Dr. Rehana K. Leak is supported by a Commonwealth Universal Research Enhancement (C.U.R.E.) Award from the Department of Health and a Michael J. Fox Foundation Innovation Award. Dr. Yanqin Gao is supported by the Chinese Natural Science Foundation grants (81171149 and 81371306). Dr. Jun Chen is supported by the National Institutes of Health Grants (NS45048, NS62157, NS59806, and NS36736), Chinese Natural Science Foundation grants (81228008) and a VA Merit Review. NR 353 TC 28 Z9 29 U1 2 U2 25 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0301-0082 J9 PROG NEUROBIOL JI Prog. Neurobiol. PD AUG-SEP PY 2014 VL 119 BP 60 EP 84 DI 10.1016/j.pneurobio.2014.06.002 PG 25 WC Neurosciences SC Neurosciences & Neurology GA AO0GI UT WOS:000340986700004 PM 24923657 ER PT J AU Costa, DK Barg, FK Asch, DA Kahn, JM AF Costa, Deena Kelly Barg, Frances K. Asch, David A. Kahn, Jeremy M. TI Facilitators of an Interprofessional Approach to Care in Medical and Mixed Medical/Surgical ICUs: A Multicenter Qualitative Study SO RESEARCH IN NURSING & HEALTH LA English DT Article DE critical care; collaboration; communication; hospital/institutional environment; interprofessional care; health care delivery ID INTENSIVE-CARE; HEALTH-CARE; MECHANICAL VENTILATION; UNIT; COLLABORATION; MULTIDISCIPLINARY; MORTALITY; TEAMWORK; OUTCOMES; ASSOCIATION AB The purpose of this study was to describe clinicians' perceptions of interprofessional collaboration in the intensive care unit and identify factors associated with interprofessional collaboration. We performed 64 semi-structured interviews in seven hospitals with ICU nurses, physicians, respiratory therapists, nurse managers, clinical pharmacists, and dieticians. ICU clinicians perceived two distinct types of facilitators to interprofessional collaboration in critical care: cultural and structural. In the critical care setting, cultural and structural facilitators worked independently as well as in concert to create effective interprofessional collaboration. Initiatives aimed at creating and facilitating interprofessional collaboration should focus attention on cultural and structural facilitators to improve patient care and team effectiveness. (C) 2014 Wiley Periodicals, Inc. C1 [Costa, Deena Kelly] Univ Pittsburgh, Dept Crit Care Med, Pittsburgh, PA 15221 USA. [Barg, Frances K.] Univ Penn, Dept Family Med & Community Hlth, Perelman Sch Med, Philadelphia, PA 19104 USA. [Asch, David A.] Univ Penn, Perelman Sch Med, Ctr Hlth Equ Res & Promot, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. [Asch, David A.] Univ Penn, Wharton Sch, Ctr Hlth Equ Res & Promot, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. [Asch, David A.] Univ Penn, Ctr Hlth Care Innovat, Ctr Hlth Equ Res & Promot, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. [Kahn, Jeremy M.] Univ Pittsburgh, Dept Crit Care Med, Grad Sch Publ Hlth, Pittsburgh, PA 15221 USA. RP Costa, DK (reprint author), Univ Pittsburgh, Dept Crit Care Med, Scaife Hall Room 607 3550 Terrace Sreet, Pittsburgh, PA 15221 USA. EM kellydm2@upmc.edu FU National Institutes of Health [K23HL082650, T32HL007820] FX This work was supported by a career development award (K23HL082650) and an institutional training grant (T32HL007820) from the National Institutes of Health. We would like to acknowledge Eve Weiss at the University of Pennsylvania for thoughtful input and feedback on the manuscript. NR 45 TC 5 Z9 5 U1 2 U2 16 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0160-6891 EI 1098-240X J9 RES NURS HEALTH JI Res. Nurs. Health PD AUG PY 2014 VL 37 IS 4 BP 326 EP 335 DI 10.1002/nur.21607 PG 10 WC Nursing SC Nursing GA AN5XL UT WOS:000340665400008 PM 24995554 ER PT J AU Mehta, NN Miyasaki, SH Hirsch, J Fidler, RL AF Mehta, Niyati N. Miyasaki, Shelley H. Hirsch, Jan Fidler, Richard L. TI Easy-to-Implement Oral Cavity Modification to Expand Simulation-based Training in Airway Management SO SIMULATION IN HEALTHCARE-JOURNAL OF THE SOCIETY FOR SIMULATION IN HEALTHCARE LA English DT Article DE Emergency airway management; Dental trauma ID DENTAL INJURIES; INTUBATION AB Introduction: Injuries to the oral cavity and teeth can occur during routine intubation and general anesthesia but often occur in emergency situations when the priority of securing the airway supersedes preanesthetic evaluation. This study demonstrates the feasibility of modifying the oral cavity to increase the dental fidelity during emergency airway management. Methods: A Laerdal Manikin was used to manipulate the preexisting Polyester (hard) and the Vinyl (flexible) dentition sets that are interchangeable among the Laerdal family of manikins. Items easily available in a dental laboratory such as dental acrylic and dental impression material were used to create modifications. Results: Laerdal dentition sets were altered to simulate common dental (tooth-related) trauma encountered during intubation such as a fracture, luxation, or avulsion injuries. Anatomic variations such as carious (decayed) teeth, loose teeth, and class II malocclusion (overbite) were also fabricated. Tooth luxation was engineered to occur with pressure by a laryngoscope, and bleeding teeth were also created to demonstrate excessive pressure applied during direct laryngoscopy. It is feasible to improve the realism of the Laerdal family of manikins with simple modifications. Conclusions: This project proves the concept of feasibly fabricating anatomic variations to increase the fidelity of existing simulation manikins. Other anatomic variations present challenges to airway management, and future research will aim at creating additional modifications. In addition, future research will seek to quantify the improvement in airway management skills by anesthesia and emergency medicine providers by training on manikins with variable oral cavity anatomy. C1 [Mehta, Niyati N.; Miyasaki, Shelley H.; Hirsch, Jan; Fidler, Richard L.] Univ Calif San Francisco, San Francisco VA Med Ctr, Dept Clin Simulat Program, San Francisco, CA 94143 USA. RP Mehta, NN (reprint author), San Francisco VA Med Ctr, 4150 Clement St, San Francisco, CA 94121 USA. EM niyati.n.mehta@gmail.com NR 6 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1559-2332 EI 1559-713X J9 SIMUL HEALTHC JI Simul. Healthc. PD AUG PY 2014 VL 9 IS 4 BP 260 EP 263 DI 10.1097/SIH.0000000000000028 PG 4 WC Health Care Sciences & Services SC Health Care Sciences & Services GA AN7XG UT WOS:000340813700007 PM 24787560 ER PT J AU De Waele, JJ Rello, J Anzueto, A Moreno, R Lipman, J Sakr, Y Pickkers, P Leone, M Ferguson, A Oud, L Vincent, JL AF De Waele, Jan J. Rello, Jordi Anzueto, Antonio Moreno, Rui Lipman, Jeffrey Sakr, Yasser Pickkers, Peter Leone, Marc Ferguson, Andrew Oud, Lavi Vincent, Jean-Louis CA EPIC II Investigators TI Infections and Use of Antibiotics in Patients Admitted for Severe Acute Pancreatitis: Data from the EPIC II Study SO SURGICAL INFECTIONS LA English DT Article ID ACUTE NECROTIZING PANCREATITIS; DOUBLE-BLIND; FUNGAL-INFECTION; PREVALENCE; MANAGEMENT; TRIAL AB Background: Infectious complications are frequent in severe acute pancreatitis (SAP) but multinational epidemiologic data are lacking. The aim of the study was to analyze the characteristics of the infectious complications and antimicrobial use in this setting. Methods: One-day point prevalence study of infection in critically ill patients (Extended Prevalence of Infection in the ICU-II study), performed in 1,265 ICUs in 75 countries. Results: Of the 13,796 patients in the study, 159 were admitted with SAP. One-hundred sixteen (73%) had infections: 31% intra-abdominal, 16% extra-abdominal, and 26% both. Gram-negative bacteria were more prevalent than gram-positive organisms, anaerobes, or fungi. Therapeutically, penicillins and other beta-lactams were used most frequently. Prophylactic antibiotics were administered to 24% of the patients with SAP. Conclusions: Infections are frequent in patients admitted with SAP; most are intra-abdominal infections. Microbiology is diverse with gram-negative micro-organisms most frequently isolated. Most patients admitted to the ICU for SAP receive antibiotics at some point. C1 [De Waele, Jan J.] Ghent Med Sch & Univ Hosp, Dept Crit Care Med, Ghent, Belgium. [Rello, Jordi] Univ Autonoma Barcelona, Hosp Vall dHebron, Crit Care Dept, CIBERES, E-08193 Barcelona, Spain. [Anzueto, Antonio] Univ Texas Hlth Sci, Dept Pulm Crit Care, San Antonio, TX USA. [Anzueto, Antonio] Univ Texas Hlth Sci, Dept Internal Med, San Antonio, TX USA. [Anzueto, Antonio] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Moreno, Rui] Hosp Sao Jose, Ctr Hosp Lisboa Cent, UCINC, Lisbon, Portugal. [Lipman, Jeffrey] Univ Queensland, Sch Med, Discipline Anesthesiol & Crit Care, Herston, Qld, Australia. [Lipman, Jeffrey] Royal Brisbane & Womens Hosp, Dept Intens Care Med, Herston, Qld, Australia. [Sakr, Yasser] Univ Jena, Dept Anesthesiol & Intens Care, Jena, Germany. [Pickkers, Peter] Radboud Univ Nijmegen, Med Ctr, Dept Intens Care, NL-6525 ED Nijmegen, Netherlands. [Leone, Marc] Aix Marseille Univ, Hop Nord, AP HM,Dept Intens Care & Anesthesiol, Unite Rech Malad Infect & Transmissibles URMITE, Marseilles, France. [Ferguson, Andrew] Craigavon Area Hosp, Dept Intens Care Med, Portadown, North Ireland. [Oud, Lavi] Texas Tech Univ HSC, Div Pulm & Crit Care Med, Odessa, TX USA. [Vincent, Jean-Louis] Univ Libre Brussels, Erasme Hosp, Dept Intens Care, Brussels, Belgium. RP De Waele, JJ (reprint author), Ghent Univ Hosp, Dept Crit Care Med, De Pintelaan 185, B-9000 Ghent, Belgium. EM jan.dewaele@UGent.be RI Pickkers, R.P./H-8080-2014; Sakr, Yasser/D-9802-2013; Leone, Marc/P-4835-2016 OI Leone, Marc/0000-0002-3097-758X; Rello, Jordi/0000-0003-0676-6210 NR 21 TC 4 Z9 4 U1 0 U2 4 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-2964 EI 1557-8674 J9 SURG INFECT JI Surg. Infect. PD AUG PY 2014 VL 15 IS 4 BP 394 EP 398 DI 10.1089/sur.2012.228 PG 5 WC Infectious Diseases; Surgery SC Infectious Diseases; Surgery GA AO0PY UT WOS:000341014100007 PM 24819027 ER PT J AU Subak, LL Goode, PS Brubaker, L Kusek, JW Schembri, M Lukacz, ES Kraus, SR Chai, TC Norton, P Tennstedt, SL AF Subak, Leslee L. Goode, Patricia S. Brubaker, Linda Kusek, John W. Schembri, Michael Lukacz, Emily S. Kraus, Stephen R. Chai, Toby C. Norton, Peggy Tennstedt, Sharon L. CA Urinary Incontinence Treatment Net TI Urinary incontinence management costs are reduced following Burch or sling surgery for stress incontinence SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE costs; cost analysis; urinary incontinence; urinary incontinence costs ID QUALITY-OF-LIFE; WOMEN; TRIAL AB OBJECTIVE: The objective of the study was to estimate the effect of Burch and fascial sling surgery on out-of-pocket urinary incontinence (UI) management costs at 24 months postoperatively and identify predictors of change in cost among women enrolled in a randomized trial comparing these procedures. STUDY DESIGN: Resources used for UI management (supplies, laundry, dry cleaning) were self-reported by 491 women at baseline and 24 months after surgery, and total out-of-pocket costs for UI management (in 2012 US dollars) were estimated. Data from the 2 surgical groups were combined to examine the change in cost for UI management over 24 months. Univariate and bivariate changes in cost were analyzed using the Wilcoxon signed rank test. Predictors of change in cost were examined using multivariate mixed models. RESULTS: At baseline mean (+/- SD) age of participants was 53 +/- 10 years, and the frequency of weekly UI episodes was 23 +/- 21. Weekly UI episodes decreased by 86% at 24 months (P < .001). The mean weekly cost was $16.60 +/- $27.00 (median $9.39) at baseline and $4.57 +/- $15.00 (median $0.10) at 24 months (P < .001), a decrease of 72%. In multivariate analyses, cost decreased by $3.38 +/- $0.77 per week for each decrease of 1 UI episode per day (P < .001) and was strongly associated with greater improvement in Urogenital Distress Inventory and Incontinence Impact Questionnaire scores (P < .001) and decreased 24-hour pad weight (P < .02). CONCLUSION: Following Burch or fascial sling surgery, the UI management cost at 24 months decreased by 72% ($625 per woman per year) and was strongly associated with decreasing UI frequency. Reduced out-of-pocket expenses may be a benefit of these established urinary incontinence procedures. C1 [Subak, Leslee L.; Schembri, Michael] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94115 USA. [Subak, Leslee L.; Schembri, Michael] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94115 USA. [Subak, Leslee L.; Schembri, Michael] Univ Calif San Francisco, Dept Urol, San Francisco, CA 94115 USA. [Subak, Leslee L.] San Francisco VA Med Ctr, San Francisco, CA USA. [Lukacz, Emily S.] Univ Calif San Diego, Sch Med, Dept Reprod Med, San Diego, CA 92103 USA. [Goode, Patricia S.] Birmingham Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Birmingham, AL USA. [Goode, Patricia S.] Univ Alabama Birmingham, Birmingham, AL USA. [Brubaker, Linda] Loyola Univ, Chicago Sch Med, Dept Obstet & Gynecol, Chicago, IL 60611 USA. [Brubaker, Linda] Loyola Univ, Chicago Sch Med, Dept Urol, Chicago, IL 60611 USA. [Kusek, John W.] Natl Inst Diabet & Digest & Kidney Dis, Bethesda, MD USA. [Chai, Toby C.] Univ Maryland, Sch Med, Dept Urol, Baltimore, MD 21201 USA. [Kraus, Stephen R.] Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, San Antonio, TX 78229 USA. [Norton, Peggy] Univ Utah, Sch Med, Dept Obstet & Gynecol, Salt Lake City, UT 84132 USA. [Tennstedt, Sharon L.] New England Res Inst, Watertown, MA 02172 USA. RP Subak, LL (reprint author), Univ Calif San Francisco, Mt Zion Womens Hlth Clin Res Ctr, 1635 Divisadero St,Suite 600, San Francisco, CA 94115 USA. EM subakl@obgyn.ucsf.edu OI Wadie, Bassem/0000-0002-6977-6849 FU National Institute of Diabetes and Digestive and Kidney Diseases [U01 DK58225, U01 DK58229, U01 DK58234, U01 DK58231, U01 DK60379, U01 DK60380, U01 DK60393, U01 DK60395, U01 DK60397, U01 DK60401]; Eunice Kennedy Shriver National Institute of Child Health and Human Development; Office of Research in Women's Health, National Institutes of Health FX This study was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (U01 DK58225, U01 DK58229, U01 DK58234, U01 DK58231, U01 DK60379, U01 DK60380, U01 DK60393, U01 DK60395, U01 DK60397, and U01 DK60401) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Office of Research in Women's Health, National Institutes of Health. NR 21 TC 3 Z9 3 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD AUG PY 2014 VL 211 IS 2 AR 171.e1 DI 10.1016/j.ajog.2014.03.012 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AN0FM UT WOS:000340259300025 PM 24631433 ER PT J AU Buie, JNJ Oates, JC AF Buie, Joy N. Jones Oates, Jim C. TI Role of Interferon Alpha in Endothelial Dysfunction: Insights Into Endothelial Nitric Oxide Synthase-Related Mechanisms SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Review DE Autoimmune disease; SLE: Systemic Lupus Erythematosus; Endothelial dysfunction; Type I interferons; Endothelial nitric oxide synthase; Lupus ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; CHRONIC HEPATITIS-C; ENOS-KNOCKOUT MICE; DEPENDENT PROTEIN-KINASE; NF-KAPPA-B; PROGENITOR CELLS; GROWTH-FACTOR; INSULIN-RESISTANCE; PROMOTER ACTIVITY; AP-1 ACTIVITY AB Systemic lupus erythematosus (SLE) is an autoimmune disease that is characterized by the production of autoantibodies against nuclear antigens such as double-stranded DNA. Lupus predominantly affects women (ratio, 9:1). Moreover, premenopausal women with SLE are 50 times more likely to have a myocardial infarction. Although specific risk factors for advanced cardiovascular complications have not been identified in this patient population, endothelial dysfunction is highly prevalent. Recent studies show that the type I interferon signature gene expression coincides with impaired brachial artery flow-mediated dilation and diminished endothelial progenitor cell circulation, both markers of impaired endothelial function. Although many factors promote the development of vascular endothelial dysfunction, all pathways converge on the diminished activity of endothelial nitric oxide synthase (eNOS) and loss of nitric oxide (NO) bioavailability. Studies examining the effects of type I interferons on eNOS and NO in SLE are missing. This literature review examines the current literature regarding the role of type I interferons in cardiovascular disease and its known effects on regulators of eNOS and NO bioavailability that are important for proper endothelial cell function. C1 [Buie, Joy N. Jones; Oates, Jim C.] Med Univ S Carolina, Dept Med, Div Rheumatol & Immunol, Charleston, SC 29425 USA. [Buie, Joy N. Jones; Oates, Jim C.] Med Univ S Carolina, Ralph H Johnson VAMC, Med Res Serv, Dept Microbiol & Immunol, Charleston, SC 29425 USA. RP Buie, JNJ (reprint author), Med Univ S Carolina, Div Rheumatol & Immunol, Dept Microbiol & Immunol, 96 Jonathan Lucas St,Clin Sci Bldg Suite 816, Charleston, SC 29425 USA. EM jonejn@musc.edu FU Ralph H. Johnson VA Medical Center [5I01CX00021804]; National Institute of Arthritis and Musculoskeletal and Skin Diseases Veterans Affairs Research Enhancement Awards Program [5RO1AR04547613]; Initiative for Maximizing Student Diversity (IMSD); National Institute of General Medical Sciences National Arthritis Foundation [5R25GM07264308] FX Supported by Ralph H. Johnson VA Medical Center (5I01CX00021804), National Institute of Arthritis and Musculoskeletal and Skin Diseases Veterans Affairs Research Enhancement Awards Program (5RO1AR04547613), Initiative for Maximizing Student Diversity (IMSD), National Institute of General Medical Sciences National Arthritis Foundation (5R25GM07264308). NR 90 TC 5 Z9 5 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-9629 EI 1538-2990 J9 AM J MED SCI JI Am. J. Med. Sci. PD AUG PY 2014 VL 348 IS 2 BP 168 EP 175 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA AN4LK UT WOS:000340559100015 ER PT J AU Allen, KD Golightly, YM Callahan, LF Helmick, CG Ibrahim, SA Kwoh, CK Renner, JB Jordan, JM AF Allen, Kelli D. Golightly, Yvonne M. Callahan, Leigh F. Helmick, Charles G. Ibrahim, Said A. Kwoh, C. Kent Renner, Jordan B. Jordan, Joanne M. TI Race and Sex Differences in Willingness to Undergo Total Joint Replacement: The Johnston County Osteoarthritis Project SO ARTHRITIS CARE & RESEARCH LA English DT Article ID TOTAL KNEE REPLACEMENT; TOTAL HIP-ARTHROPLASTY; PATIENT EXPECTATIONS; AFRICAN-AMERICANS; SOCIAL SUPPORT; UNITED-STATES; SURGERY; OUTCOMES; DISPARITIES; PREFERENCES AB Objective. Using data from the community-based Johnston County Osteoarthritis Project, we examined race and sex variations in willingness to undergo, and perceptions regarding, total joint replacement (TJR). Methods. Analyses were conducted for the total sample who participated in a followup measurement period from 2006-2010 (n = 1,522) and a subsample with symptomatic hip and/or knee osteoarthritis (sOA; n = 445). Participants indicated how willing they would be to have TJR (hip or knee) if their doctor recommended it; responses were categorized as "definitely" or "probably" willing versus "unsure," "probably not," or "definitely not" willing, or "don't know." Participants answered 7 questions regarding perceptions of TJR outcomes. Multivariable logistic regression models of willingness included participant characteristics (including socioeconomic status) and TJR perception variables that were associated with willingness at the P < 0.1 level in bivariate analyses. Results. African Americans had lower odds of willingness to undergo TJR than whites in the total sample (adjusted odds ratio [OR] 0.47 [95% confidence interval (95% CI) 0.31-0.72]) and the sOA subsample (adjusted OR 0.42 [95% CI 0.25-0.69]). There were no sex differences in willingness. African Americans expected poorer TJR outcomes than whites, but sex differences were minimal; perceptions of TJR outcomes were not significantly associated with willingness. Conclusion. In this community sample, race differences in TJR willingness and perceptions were substantial, but sex differences were small. Perceptions of TJR did not appear to affect willingness or explain race differences in willingness. C1 [Allen, Kelli D.] Durham VA Med Ctr, Durham, NC 27705 USA. [Allen, Kelli D.] Duke Univ, Med Ctr, Durham, NC USA. [Golightly, Yvonne M.; Callahan, Leigh F.; Renner, Jordan B.; Jordan, Joanne M.] Univ N Carolina, Thurston Arthrit Res Ctr, Chapel Hill, NC USA. [Helmick, Charles G.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Ibrahim, Said A.] Vet Affairs Med Ctr, Philadelphia, PA USA. [Ibrahim, Said A.] Perelman Univ Penn, Sch Med, Philadelphia, PA USA. [Kwoh, C. Kent] Univ Arizona, Tucson, AZ USA. RP Allen, KD (reprint author), Durham VA Med Ctr, Hlth Serv Res & Dev Serv 152, 508 Fulton St, Durham, NC 27705 USA. EM kelli.allen@duke.edu FU CDC/Association of Schools of Public Health [S1734, S3486]; National Institute of Arthritis and Musculoskeletal and Skin Diseases Multipurpose Arthritis and Musculoskeletal Disease Center [5-P60-AR30701]; National Institute of Arthritis and Musculoskeletal and Skin Diseases Multidisciplinary Clinical Research Center [5-P60-AR49465-03]; Arthritis Foundation Postdoctoral Fellowship Award; K24 Award from the National Institute of Arthritis and Musculoskeletal and Skin Diseases [1-K24-AR-055259-01]; Sci Metrika, LLC.; Pfizer FX Supported in part by the CDC/Association of Schools of Public Health (cooperative agreements S1734 and S3486), the National Institute of Arthritis and Musculoskeletal and Skin Diseases Multipurpose Arthritis and Musculoskeletal Disease Center (grant 5-P60-AR30701), the National Institute of Arthritis and Musculoskeletal and Skin Diseases Multidisciplinary Clinical Research Center (grant 5-P60-AR49465-03), and an Arthritis Foundation Postdoctoral Fellowship Award to Dr. Golightly. Dr. Ibrahim's work was supported by a K24 Award from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (grant 1-K24-AR-055259-01).; Dr. Callahan has received consultancy fees, speaking fees, and/or honoraria (less than $10,000 each) from Sci Metrika, LLC. Dr. Kwoh has received consultancy fees, speaking fees, and/or honoraria (less than $10,000) from Pfizer. NR 39 TC 15 Z9 15 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2151-464X EI 2151-4658 J9 ARTHRIT CARE RES JI Arthritis Care Res. PD AUG PY 2014 VL 66 IS 8 BP 1193 EP 1202 DI 10.1002/acr.22295 PG 10 WC Rheumatology SC Rheumatology GA AN1PR UT WOS:000340356600008 PM 24470235 ER PT J AU George, M Pullman-Mooar, S Hussain, F Schumacher, HR AF George, Michael Pullman-Mooar, Sally Hussain, Fauzia Schumacher, H. Ralph TI Evaluating Appropriate Use of Prophylactic Colchicine for Gout Flare Prevention SO ARTHRITIS CARE & RESEARCH LA English DT Article ID SERUM URATE; ARTHRITIS; THERAPY; HYPERURICEMIA; ALLOPURINOL; FEBUXOSTAT; MANAGEMENT; PLACEBO; ATTACKS; TRIAL AB Objective. American College of Rheumatology and European League Against Rheumatism guidelines recommend colchicine to prevent gout flares in patients initiating and increasing uric acid-lowering therapy until serum uric acid is maintained at <= 6 mg/dl. We aimed to evaluate how well colchicine prescribing practices adhere to these guidelines and to examine factors associated with improved prescribing. Methods. Electronic medical records were reviewed for 126 patients with active colchicine prescriptions for prophylaxis of gout flares. Colchicine prescribing was defined as inappropriate if 1) no concurrent urate-lowering therapy was prescribed, 2) uric acid was not at goal and urate-lowering therapy had not been increased in the past 3 months, or 3) uric acid goals were met for >1 year and flares had resolved in the absence of tophi. Results. Colchicine use was considered inappropriate in 93 patients (73.8%). Thirty-four were prescribed no urate-lowering therapy, 50 were above the uric acid goal without urate-lowering therapy increase in the prior 3 months, and 9 were at the uric acid goal for >1 year without flares or tophi. Patients appropriately prescribed colchicine were younger and were more likely to have been seen by a rheumatologist. Allopurinol dose and allergy, uric acid level, and renal function were similar in the 2 groups. Conclusion. We found a high prevalence of what we considered inappropriate prophylactic colchicine use, driven largely by failure to prescribe concurrent urate-lowering therapies or adequately increase these medications. Rheumatology consultation was associated with improved colchicine prescribing. C1 [George, Michael] Hosp Univ Penn, Philadelphia, PA 19104 USA. [Pullman-Mooar, Sally; Schumacher, H. Ralph] VA Med Ctr, Philadelphia, PA USA. [Pullman-Mooar, Sally; Schumacher, H. Ralph] Univ Penn, Philadelphia, PA 19104 USA. [Hussain, Fauzia] Philadelphia VA Med Ctr, Philadelphia, PA USA. RP George, M (reprint author), Univ Penn, Div Rheumatol, 8th Floor,Penn Tower,3400 Spruce St, Philadelphia, PA 19104 USA. EM michael.george@uphs.upenn.edu FU American College of Rheumatology Ephraim P. Engelman Endowed Resident Research Preceptorship Award; Ardea; Metabolex; Novartis; Pfizer; Regeneron; Takeda FX Supported by the American College of Rheumatology Ephraim P. Engelman Endowed Resident Research Preceptorship Award.; Dr. Schumacher has received consulting fees (less than $10,000 each) from Ardea, Metabolex, Novartis, Pfizer, Regeneron, and Takeda. NR 16 TC 3 Z9 3 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2151-464X EI 2151-4658 J9 ARTHRIT CARE RES JI Arthritis Care Res. PD AUG PY 2014 VL 66 IS 8 BP 1258 EP 1262 DI 10.1002/acr.22275 PG 5 WC Rheumatology SC Rheumatology GA AN1PR UT WOS:000340356600017 PM 24376081 ER PT J AU Halter, JB Musi, N Horne, FM Crandall, JP Goldberg, A Harkless, L Hazzard, WR Huang, ES Kirkman, MS Plutzky, J Schmader, KE Zieman, S High, KP AF Halter, Jeffrey B. Musi, Nicolas Horne, Frances McFarland Crandall, Jill P. Goldberg, Andrew Harkless, Lawrence Hazzard, William R. Huang, Elbert S. Kirkman, M. Sue Plutzky, Jorge Schmader, Kenneth E. Zieman, Susan High, Kevin P. TI Diabetes and Cardiovascular Disease in Older Adults: Current Status and Future Directions SO DIABETES LA English DT Article ID 10-YEAR FOLLOW-UP; A-BETA OLIGOMERS; WEIGHT-LOSS; INSULIN-RESISTANCE; RISK-FACTORS; SEVERE HYPOGLYCEMIA; ALZHEIMER-DISEASE; KIDNEY-DISEASE; HEART-FAILURE; UNITED-STATES AB The prevalence of diabetes increases with age, driven in part by an absolute increase in incidence among adults aged 65 years and older. Individuals with diabetes are at higher risk for cardiovascular disease, and age strongly predicts cardiovascular complications. Inflammation and oxidative stress appear to play some role in the mechanisms underlying aging, diabetes, cardiovascular disease, and other complications of diabetes. However, the mechanisms underlying the age-associated increase in risk for diabetes and diabetes-related cardiovascular disease remain poorly understood. Moreover, because of the heterogeneity of the older population, a lack of understanding of the biology of aging, and inadequate study of the effects of treatments on traditional complications and geriatric conditions associated with diabetes, no consensus exists on the optimal interventions for older diabetic adults. The Association of Specialty Professors, along with the National Institute on Aging, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Heart, Lung, and Blood Institute, and the American Diabetes Association, held a workshop, summarized in this Perspective, to discuss current knowledge regarding diabetes and cardiovascular disease in older adults, identify gaps, and propose questions to guide future research. C1 [Halter, Jeffrey B.] Univ Michigan, Sch Med, Dept Internal Med, Div Geriatr & Palliat Med, Ann Arbor, MI 48109 USA. [Musi, Nicolas] Univ Texas Hlth Sci Ctr San Antonio, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78229 USA. [Musi, Nicolas] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Horne, Frances McFarland] Assoc Specialty Prof, Alexandria, VA USA. [Crandall, Jill P.] Albert Einstein Coll Med, Div Endocrinol, Dept Med, Bronx, NY 10467 USA. [Goldberg, Andrew] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Goldberg, Andrew] Baltimore VA Med Ctr, Geriatr Res Educ & Clin Ctr, Baltimore, MD USA. [Harkless, Lawrence] Western Univ Hlth Sci, Pomona, CA USA. [Hazzard, William R.] Univ Washington, Dept Med, Puget Sound VA Hlth Care Syst, Seattle, WA USA. [Huang, Elbert S.] Univ Chicago, Dept Med, Div Gen Internal Med, Chicago, IL 60637 USA. [Kirkman, M. Sue] Univ N Carolina, Dept Med, Div Endocrinol & Metab, Chapel Hill, NC USA. [Plutzky, Jorge] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Schmader, Kenneth E.] Duke Univ, Sch Med, Geriatr Res Educ & Clin Ctr, Durham, NC USA. [Schmader, Kenneth E.] Durham VA Med Ctr, Durham, NC USA. [Zieman, Susan] NIA, Bethesda, MD 20892 USA. [High, Kevin P.] Wake Forest Sch Med, Dept Internal Med, Infect Dis Sect, Winston Salem, NC USA. RP Halter, JB (reprint author), Univ Michigan, Sch Med, Dept Internal Med, Div Geriatr & Palliat Med, Ann Arbor, MI 48109 USA. EM jhalter@umich.edu; musi@uthscsa.edu FU National Institute on Aging [1-U13-AG-040938 01]; John A. Hartford Foundation; National Institutes of Health's National Institute on Aging; Alliance for Academic Internal Medicine; American Diabetes Association FX Funding. This workshop was supported by generous grants to Association of Specialty Professors from the National Institute on Aging (1-U13-AG-040938 01) and the John A. Hartford Foundation (J.B.H., K.E.S., K.P.H.). J.B.H. reports grants from the John A. Hartford Foundation, National Institutes of Health's National Institute on Aging, and Alliance for Academic Internal Medicine during the conduct of the project, and from the American Diabetes Association outside the submitted work. F.M.H. reports grants from the John A. Hartford Foundation during the conduct of the project. NR 54 TC 29 Z9 29 U1 2 U2 12 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD AUG PY 2014 VL 63 IS 8 BP 2578 EP 2589 DI 10.2337/db14-0020 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AN0GK UT WOS:000340262100004 PM 25060886 ER PT J AU Long, JA Wang, A Medvedeva, EL Eisen, SV Gordon, AJ Kreyenbuhl, J Marcus, SC AF Long, Judith A. Wang, Andrew Medvedeva, Elina L. Eisen, Susan V. Gordon, Adam J. Kreyenbuhl, Julie Marcus, Steven C. TI Glucose Control and Medication Adherence Among Veterans With Diabetes and Serious Mental Illness: Does Collocation of Primary Care and Mental Health Care Matter? SO DIABETES CARE LA English DT Article ID NEUROPSYCHOLOGICAL STATUS; REPEATABLE BATTERY; SCREENING-TEST; SCHIZOPHRENIA; DISORDERS; VALIDITY; RELIABILITY; PREVALENCE; MORTALITY; MELLITUS AB OBJECTIVE Persons with serious mental illness (SMI) may benefit from collocation of medical and mental health healthcare professionals and services in attending to their chronic comorbid medical conditions. We evaluated and compared glucose control and diabetes medication adherence among patients with SMI who received collocated care to those not receiving collocated care (which we call usual care). RESEARCH DESIGN AND METHODS We performed a cross-sectional, observational cohort study of 363 veteran patients with type 2 diabetes and SMI who received care from one of three Veterans Affairs medical facilities: two sites that provided both collocated and usual care and one site that provided only usual care. Through a survey, laboratory tests, and medical records, we assessed patient characteristics, glucose control as measured by a current HbA(1c), and adherence to diabetes medication as measured by the medication possession ration (MPR) and self-report. RESULTS In the sample, the mean HbA(1c) was 7.4% (57 mmol/mol), the mean MPR was 80%, and 51% reported perfect adherence to their diabetes medications. In both unadjusted and adjusted analyses, there were no differences in glucose control and medication adherence by collocation of care. Patients seen in collocated care tended to have better HbA(1c) levels (beta = 20.149; P = 0.393) and MPR values (beta = 0.34; P = 0.132) and worse self-reported adherence (odds ratio 0.71; P = 0.143), but these were not statistically significant. CONCLUSIONS In a population of veterans with comorbid diabetes and SMI, patients on average had good glucose control and medication adherence regardless of where they received primary care. C1 [Long, Judith A.; Wang, Andrew; Medvedeva, Elina L.; Marcus, Steven C.] Philadelphia VA Med Ctr, Ctr Hlth Equity Res & Promot, Philadelphia, PA 19104 USA. [Long, Judith A.] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Eisen, Susan V.] Edith Nourse Rogers Mem Vet Adm Hosp, Ctr Healthcare Org & Implementat Res, Bedford, MA 01730 USA. [Eisen, Susan V.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Gordon, Adam J.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. [Gordon, Adam J.] VA Pittsburgh Healthcare Syst, Mental Illness Res Educ & Clin Ctr, Pittsburgh, PA USA. [Gordon, Adam J.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Kreyenbuhl, Julie] VA Capitol Hlth Care Network, Mental Illness Res Educ & Clin Ctr, Baltimore, MD USA. [Kreyenbuhl, Julie] Univ Maryland, Sch Med, Dept Psychiat, Div Res Serv, Baltimore, MD 21201 USA. [Marcus, Steven C.] Univ Penn, Penn Sch Social Policy & Practice, Philadelphia, PA 19104 USA. RP Long, JA (reprint author), Philadelphia VA Med Ctr, Ctr Hlth Equity Res & Promot, Philadelphia, PA 19104 USA. EM jalong@mail.med.upenn.edu FU VA Health Services Research Development [IIR-07-124-3] FX This work was supported by VA Health Services Research & Development IIR-07-124-3. NR 30 TC 6 Z9 6 U1 1 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD AUG PY 2014 VL 37 IS 8 BP 2261 EP 2267 DI 10.2337/dc13-0051 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AN3MI UT WOS:000340491800041 PM 24879839 ER PT J AU Dominitz, JA Robertson, DJ AF Dominitz, Jason A. Robertson, Douglas J. TI Tailoring Colonoscopic Screening to Individual Risk SO GASTROENTEROLOGY LA English DT Editorial Material ID SOCIETY-TASK-FORCE; COLORECTAL-CANCER; AMERICAN-COLLEGE; ADVANCED NEOPLASIA; GREATER-THAN-9 MM; SURVEILLANCE; POLYPS; SEX; COLONOGRAPHY; PREVALENCE C1 [Dominitz, Jason A.] Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Robertson, Douglas J.] Geisel Sch Med Dartmouth, White River Junct VA Med Ctr, Gastroenterol Sect, White River Jct, VT USA. RP Dominitz, JA (reprint author), Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, 1660 S Columbian Way 111 Gastro, Seattle, WA 98108 USA. EM jason.dominitz@va.gov OI Dominitz, Jason/0000-0002-8070-7086 NR 24 TC 3 Z9 3 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD AUG PY 2014 VL 147 IS 2 BP 264 EP 266 DI 10.1053/j.gastro.2014.06.018 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AN2WX UT WOS:000340447800008 PM 24976032 ER PT J AU Luo, YX Wong, CJ Kaz, AM Dzieciatkowski, S Carter, KT Morris, SM Wang, JP Willis, JE Makar, KW Ulrich, CM Lutterbaugh, JD Shrubsole, MJ Zheng, W Markowitz, SD Grady, WM AF Luo, Yanxin Wong, Chao-Jen Kaz, Andrew M. Dzieciatkowski, Slavomir Carter, Kelly T. Morris, Shelli M. Wang, Jianping Willis, Joseph E. Makar, Karen W. Ulrich, Cornelia M. Lutterbaugh, James D. Shrubsole, Martha J. Zheng, Wei Markowitz, Sanford D. Grady, William M. TI Differences in DNA Methylation Signatures Reveal Multiple Pathways of Progression From Adenoma to Colorectal Cancer SO GASTROENTEROLOGY LA English DT Article DE Epigenetic Modifications; Colon Cancer; Progression; Gene Regulation ID CPG ISLAND METHYLATION; HUMAN COLON; MICROSATELLITE INSTABILITY; SERRATED PATHWAY; BRAF MUTATION; PHENOTYPE; HYPERMETHYLATION; PATHOGENESIS; LESIONS; POLYPS AB BACKGROUND & AIMS: Genetic and epigenetic alterations contribute to the pathogenesis of colorectal cancer (CRC). There is considerable molecular heterogeneity among colorectal tumors, which appears to arise as polyps progress to cancer. This heterogeneity results in different pathways to tumorigenesis. Although epigenetic and genetic alterations have been detected in conventional tubular adenomas, little is known about how these affect progression to CRC. We compared methylomes of normal colon mucosa, tubular adenomas, and colorectal cancers to determine how epigenetic alterations might contribute to cancer formation. METHODS: We conducted genome-wide array-based studies and comprehensive data analyses of aberrantly methylated loci in 41 normal colon tissue, 42 colon adenomas, and 64 cancers using HumanMethylation450 arrays. RESULTS: We found genome-wide alterations in DNA methylation in the nontumor colon mucosa and cancers. Three classes of cancers and 2 classes of adenomas were identified based on their DNA methylation patterns. The adenomas separated into classes of high-frequency methylation and low-frequency methylation. Within the high-frequency methylation adenoma class a subset of adenomas had mutant KRAS. Additionally, the high-frequency methylation adenoma class had DNA methylation signatures similar to those of cancers with low or intermediate levels of methylation, and the low-frequency methylation adenoma class had methylation signatures similar to that of nontumor colon tissue. The CpG sites that were differentially methylated in these signatures are located in intragenic and intergenic regions. CONCLUSIONS: Genome-wide alterations in DNA methylation occur during early stages of progression of tubular adenomas to cancer. These findings reveal heterogeneity in the pathogenesis of colorectal cancer, even at the adenoma step of the process. C1 [Luo, Yanxin; Wang, Jianping] Sun Yat Sen Univ, Affiliated Hosp 6, Dept Colorectal Surg, Guangzhou 510655, Guangdong, Peoples R China. [Luo, Yanxin; Wong, Chao-Jen; Kaz, Andrew M.; Dzieciatkowski, Slavomir; Carter, Kelly T.; Morris, Shelli M.; Grady, William M.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA. [Kaz, Andrew M.] VA Puget Sound Hlth Care Syst, Res & Dev Serv, Seattle, WA USA. [Kaz, Andrew M.; Grady, William M.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Willis, Joseph E.] Case Comprehens Canc Ctr, Case Med Ctr, Dept Pathol, Cleveland, OH USA. [Willis, Joseph E.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Makar, Karen W.; Ulrich, Cornelia M.] Fred Hutchinson Canc Res Ctr, Publ Hlth Sci Div, Seattle, WA 98109 USA. [Ulrich, Cornelia M.] Heidelberg Univ, Natl Ctr Tumor Dis NCT, Heidelberg, Germany. [Ulrich, Cornelia M.] Heidelberg Univ, German Canc Res Ctr DKFZ, Heidelberg, Germany. [Lutterbaugh, James D.; Markowitz, Sanford D.] Case Western Reserve Univ, Sch Med, Dept Med, Cleveland, OH 44106 USA. [Lutterbaugh, James D.; Markowitz, Sanford D.] Case Western Reserve Univ, Ireland Canc Ctr, Sch Med, Cleveland, OH 44106 USA. [Lutterbaugh, James D.; Markowitz, Sanford D.] Case Med Ctr, Cleveland, OH USA. [Shrubsole, Martha J.; Zheng, Wei] Vanderbilt Univ, Sch Med, Dept Med, Vanderbilt Epidemiol Ctr,Div Epidemiol, Nashville, TN 37212 USA. RP Luo, YX (reprint author), Sun Yat Sen Univ, Affiliated Hosp 6, Dept Colorectal Surg, Guangzhou 510655, Guangdong, Peoples R China. EM luoyx25@mail.sysu.edu.cn; wgrady@fhcrc.org RI Shrubsole, Martha/K-5052-2015 OI Shrubsole, Martha/0000-0002-5591-7575 FU National Cancer Institute of the National Institutes of Health [RO1CA115513, P30CA15704, UO1CA152756, U54CA143862, P01CA077852, P50CA95103, R01CA121060, P30CA68485, K07CA122451]; Burroughs Wellcome Fund; Program of Introducing Talents of Discipline to Universities of China [B12003]; International Science & Technology Cooperation Program of China [2011DFA32570]; National Natural Science Foundation of China [81201920]; [5P50CA150964] FX This research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under award number RO1CA115513, P30CA15704, UO1CA152756, U54CA143862, and P01CA077852 (WMG), P50CA95103 (ZW), R01CA121060, P30CA68485, K07CA122451 (MJS). The content is solely the responsibility of the authors, and does not necessarily represent the official views of the National Institutes of Health. Support for these studies was also provided by a Burroughs Wellcome Fund Translational Research Award for Clinician Scientist (WMG), Program of Introducing Talents of Discipline to Universities of China (B12003, JW) and International Science & Technology Cooperation Program of China (2011DFA32570, JW), National Natural Science Foundation of China (81201920, YL); and 5P50CA150964 (SDM). NR 52 TC 36 Z9 36 U1 1 U2 18 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD AUG PY 2014 VL 147 IS 2 BP 418 EP + DI 10.1053/j.gastro.2014.04.039 PG 20 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AN2WX UT WOS:000340447800030 PM 24793120 ER PT J AU Redmann, M Dodson, M Boyer-Guittaut, M Darley-Usmar, V Zhang, JH AF Redmann, Matthew Dodson, Matthew Boyer-Guittaut, Michael Darley-Usmar, Victor Zhang, Jianhua TI Mitophagy mechanisms and role in human diseases SO INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY LA English DT Article DE Mitochondria; Parkinson's disease; Cancer; Mitophagy; Heart disease ID MITOCHONDRIAL QUALITY-CONTROL; OXIDATIVE STRESS; PARKINSONS-DISEASE; HEPATOCELLULAR-CARCINOMA; BREAST-CANCER; PINK1/PARKIN-MEDIATED MITOPHAGY; ADRENOCORTICAL TUMORS; DAMAGED MITOCHONDRIA; ATTENUATES MITOPHAGY; SELECTIVE AUTOPHAGY AB Mitophagy is a process of mitochondrial turnover through lysosomal mediated autophagy activities. This review will highlight recent studies that have identified mediators of mitophagy in response to starvation, loss of mitochondrial membrane potential or perturbation of mitochondrial integrity. Furthermore, we will review evidence of mitophagy dysfunction in various human diseases and discuss the potential for therapeutic interventions that target mitophagy processes. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Redmann, Matthew; Dodson, Matthew; Darley-Usmar, Victor; Zhang, Jianhua] Univ Alabama Birmingham, Ctr Free Radical Biol, Birmingham, AL 35294 USA. [Redmann, Matthew; Dodson, Matthew; Darley-Usmar, Victor; Zhang, Jianhua] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. [Zhang, Jianhua] Birmingham VA Med Ctr, Dept Vet Affairs, Birmingham, AL 35294 USA. [Boyer-Guittaut, Michael] Univ Franche Comte, Biochim Lab, EA3922, SFR IBCT FED4234, F-25030 Besancon, France. RP Zhang, JH (reprint author), Univ Alabama Birmingham, Dept Pathol, BMRII 534,901 19th St S, Birmingham, AL 35294 USA. EM zhanja@uab.edu OI Zhang, Jianhua/0000-0002-2128-9574 FU NIH [R01-NS064090]; VA FX This work was supported by NIH R01-NS064090 and a VA merit award (to JZ). NR 113 TC 33 Z9 34 U1 4 U2 26 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1357-2725 EI 1878-5875 J9 INT J BIOCHEM CELL B JI Int. J. Biochem. Cell Biol. PD AUG PY 2014 VL 53 BP 127 EP 133 DI 10.1016/j.biocel.2014.05.010 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AN1KE UT WOS:000340340400016 PM 24842106 ER PT J AU Margolis, JM Chu, BC Wang, ZXJ Copher, R Cavazos, JE AF Margolis, Jay M. Chu, Bong-Chul Wang, Zhixiao J. Copher, Ronda Cavazos, Jose E. TI Effectiveness of Antiepileptic Drug Combination Therapy for Partial-Onset Seizures Based on Mechanisms of Action SO JAMA NEUROLOGY LA English DT Article ID TONIC CLONIC SEIZURES; CARBAMAZEPINE; EPILEPSY; ADULTS AB IMPORTANCE To our knowledge, the current study is the first to describe antiepileptic drug (AED) combination therapy patterns according to their mechanism of action (MOA) in a real-world setting and to evaluate the differences in outcomes comparing different-MOA combination therapy with same-MOA combination therapy for patients with partial-onset seizure. OBJECTIVE To compare treatment persistence and health care use with AED combinations categorized by MOA in patients with partial-onset seizures. DESIGN, SETTING, AND PARTICIPANTS Using the Truven Health MarketScan Commercial Claims Database containing 96 million covered lives from July 1, 2004, through March 31, 2011, adults with concomitant use of 2 different AEDs and a recent partial-onset seizure diagnosis were selected. Antiepileptic drugs were categorized by MOA: sodium channel blockers (SC), gamma-aminobutyric acid analogs (G), synaptic vesicle protein 2A binding (SV2), and multiple mechanisms (M). Patients were assigned a combination category based on their concomitant AED use. MAIN OUTCOMES AND MEASURES Treatment persistence was measured from the start of AED combination therapy until the end of the combination. Health care resource use was measured during the combination treatment duration. Multivariate analyses evaluated AED discontinuation risk and health care use according to MOA combinations. RESULTS Distribution of 8615 selected patients by combination was 3.3% for G+G, 7.5% for G+SV2, 8.6% for G+M, 13.9% for SC+SC, 19.0% for G+SC, 21.5% for SC+M, and 26.3% for SC+SV2. The same-MOA (G+G and SC+SC) combinations had the shortest persistence (mean [SD], 344 [345] days and 513 [530] days, respectively) and greater hazard of discontinuation compared with different-MOA combinations. Patients with different-MOA G combinations had a significantly lower risk for inpatient admission (odds ratio, 0.716; 95% CI, 0.539-0.952; P = .02) compared with G+G combinations. Patients with different-MOA SC combinations had significantly lower risks for emergency department visits (odds ratio, 0.853; 95% CI, 0.742-0.980; P = .03) compared with SC+SC combinations. CONCLUSIONS AND RELEVANCE The findings suggest that AED combinations with different MOAs have greater effectiveness as measured by treatment persistence and lower risks for hospitalization and emergency department visits. Further research is needed to more fully understand the role of the MOA in achieving optimal outcomes. C1 [Margolis, Jay M.] Truven Hlth Analyt, Bethesda, MD USA. [Chu, Bong-Chul] Truven Hlth Analyt, Santa Barbara, CA USA. [Wang, Zhixiao J.] Eisai Inc, Woodcliff Lake, NJ USA. [Copher, Ronda] Eisai Inc, Minneapolis, MN USA. [Cavazos, Jose E.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX USA. [Cavazos, Jose E.] South Texas Vet Hlth Care Syst, San Antonio Epilepsy Ctr Excellence, San Antonio, TX USA. RP Margolis, JM (reprint author), Truven Hlth Analyt, 332 Bryn Mawr Ave, Bala Cynwyd, PA 19004 USA. EM jay.margolis@truvenhealth.com RI Cavazos, Jose/J-4122-2016 OI Cavazos, Jose/0000-0001-5777-2608 FU Eisai Inc, Woodcliff Lake, New Jersey FX This research was sponsored by Eisai Inc, Woodcliff Lake, New Jersey. NR 15 TC 21 Z9 21 U1 1 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6149 EI 2168-6157 J9 JAMA NEUROL JI JAMA Neurol. PD AUG PY 2014 VL 71 IS 8 BP 985 EP 993 DI 10.1001/jamaneurol.2014.808 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA AN3IW UT WOS:000340481800008 PM 24911669 ER PT J AU Makam, AN Auerbach, AD Steinman, MA AF Makam, Anil N. Auerbach, Andrew D. Steinman, Michael A. TI Blood culture use in the emergency department in patients hospitalized with respiratory symptoms due to a nonpneumonia illness SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article ID COMMUNITY-ACQUIRED PNEUMONIA; HOLD-UP; MANAGEMENT; SCRUTINY; NHAMCS; RULE AB BACKGROUND Guidelines and performance measures recommend obtaining blood cultures in selected patients hospitalized with community-acquired pneumonia (CAP). Due to inherent diagnostic uncertainty, there may be spillover effects of these recommendations on other conditions that resemble pneumonia. METHODS Using data from the 2002 to 2010 National Hospital Ambulatory Medical Care Survey, a nationally representative sample of emergency department (ED) visits in the United States, we analyzed trends in obtaining cultures in patients hospitalized with respiratory symptoms due to a nonpneumonia illness using linear regression. RESULTS The most common primary admission diagnoses for these visits included heart failure (16%), chronic obstructive pulmonary disease (13%), and chest pain (12%). The proportion of cultures collected in the ED during these visits increased from 10% (95% confidence interval [CI]: 7%-14%) in 2002 to 20% (95% CI: 16%-26%) in 2010 (P<0.001 for the trend). This represented a parallel increase compared to patients hospitalized with CAP (P=0.12 for the difference in trends). CONCLUSIONS The increase in collecting cultures in the ED in patients hospitalized with respiratory symptoms due to a nonpneumonia illness suggests an important potential unintended consequence of blood culture recommendations for CAP. More attention to the judicious use of blood cultures to reduce harm and costs is needed. Journal of Hospital Medicine 2014;9:521-524. (c) 2014 Society of Hospital Medicine C1 [Makam, Anil N.] Univ Texas SW Med Ctr Dallas, Div Gen Internal Med, Dallas, TX 75390 USA. [Auerbach, Andrew D.] Univ Calif San Francisco, Div Hosp Med, San Francisco, CA 94143 USA. [Steinman, Michael A.] San Francisco VA Med Ctr, Div Geriatr, San Francisco, CA USA. [Steinman, Michael A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Makam, AN (reprint author), 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM anil.makam@utsouthwestern.edu OI Makam, Anil/0000-0001-7072-9946 FU NRSA [T32HP19025-07-00] FX Dr. Makam's work on this project was completed while he was a Primary Care Research Fellow at the University of California San Francisco, funded by an NRSA training grant (T32HP19025-07-00). The authors report no conflicts of interest. NR 17 TC 3 Z9 3 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1553-5592 EI 1553-5606 J9 J HOSP MED JI J. Hosp. Med. PD AUG PY 2014 VL 9 IS 8 BP 521 EP 524 DI 10.1002/jhm.2205 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA AN3YM UT WOS:000340524800007 PM 24753399 ER PT J AU Bailey, FA Williams, BR Goode, PS Woodby, LL Granstaff, US Echt, KV Redden, DT Kvale, E Burgio, KL AF Bailey, F. Amos Williams, Beverly R. Goode, Patricia S. Woodby, Lesa L. Granstaff, U. Shanette Echt, Katharina V. Redden, David T. Kvale, Elizabeth Burgio, Kathryn L. TI Impact of a Hospice Emergency Kit for Veterans and Their Caregivers: A Prospective Cohort Study SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID MANAGING MEDICATIONS; CARE; HOME; SUPPORT AB Background: Although hospice emergency kits (HEKs) are provided by many home hospice agencies, little is known about their use, side effects, and perceived impact. Objective: To evaluate HEK medication utilization, side effects, and impact as perceived by home hospice patients and their caregivers. Methods: We conducted a prospective longitudinal cohort study. Participants included 43 veterans and their family/caregivers referred to community home hospices with a Veterans Affairs (VA)-provided HEK. Measurements included patient/family reports based on weekly telephone interviews, electronic medical record (EMR) review, and after-death caregiver interviews. Results: The HEK was used by 27 of 43 patients/caregivers (62.8%). In 11 cases, they reported using the kit on more than one occasion. The most commonly used medications were morphine concentrate (30.2% of patients), lorazepam (20.9%), and levofloxacin (16.3%). In 15 cases (34.9%), the family thought the HEK may have helped the patient stay at home. Nineteen of the 43 patients made at least one visit to the emergency department (ED) and 22 were hospitalized. Most admissions through the ED were due to uncontrolled pain and/or gastrointestinal problems, such as nausea or bowel obstruction. In after-death interviews, opinions of the HEK were uniformly positive. Respondents described the HEK's usefulness and felt supported and empowered by its presence in the home. Minor side effects were reported in four cases. Conclusions: Findings provide promising evidence that HEKs are a feasible and well-tolerated method for achieving timely relief of emergent symptoms in home hospice patients and possibly avoiding unwanted ED visits and hospitalizations. C1 [Bailey, F. Amos; Williams, Beverly R.; Goode, Patricia S.; Woodby, Lesa L.; Granstaff, U. Shanette; Echt, Katharina V.; Redden, David T.; Kvale, Elizabeth; Burgio, Kathryn L.] Birmingham Atlanta Geriatr Res Educ & Clin Ctr, Dept Vet Affairs, Birmingham, AL USA. [Bailey, F. Amos; Williams, Beverly R.; Goode, Patricia S.; Woodby, Lesa L.; Granstaff, U. Shanette; Echt, Katharina V.; Redden, David T.; Kvale, Elizabeth; Burgio, Kathryn L.] Birmingham Atlanta Geriatr Res Educ & Clin Ctr, Dept Vet Affairs, Atlanta, GA USA. [Bailey, F. Amos; Williams, Beverly R.; Goode, Patricia S.; Woodby, Lesa L.; Granstaff, U. Shanette; Redden, David T.; Kvale, Elizabeth; Burgio, Kathryn L.] Univ Alabama Birmingham, Birmingham, AL USA. [Echt, Katharina V.] Emory Univ, Atlanta, GA 30322 USA. RP Burgio, KL (reprint author), Birmingham VA Med Ctr, Geriatr Res Educ & Clin Ctr, 11G 700 South 19th St, Birmingham, AL 35233 USA. EM kburgio@uabmc.edu FU Birmingham/Atlanta Geriatric Research, Education, and Clinical Center (GRECC); Research Enhancement Award Program (REAP), Department of Veterans Affairs FX This research was supported by the Birmingham/Atlanta Geriatric Research, Education, and Clinical Center (GRECC) and Research Enhancement Award Program (REAP), Department of Veterans Affairs. NR 19 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 EI 1557-7740 J9 J PALLIAT MED JI J. Palliat. Med. PD AUG PY 2014 VL 17 IS 8 BP 931 EP 938 DI 10.1089/jpm.2013.0395 PG 8 WC Health Care Sciences & Services SC Health Care Sciences & Services GA AN4BP UT WOS:000340532900013 PM 24927070 ER PT J AU Stey, AM Ko, CY Hall, BL Louie, R Lawson, EH Gibbons, MM Zingmond, DS Russell, MM AF Stey, Anne M. Ko, Clifford Y. Hall, Bruce Lee Louie, Rachel Lawson, Elise H. Gibbons, Melinda M. Zingmond, David S. Russell, Marcia M. TI Are Procedures Codes in Claims Data a Reliable Indicator of Intraoperative Splenic Injury Compared with Clinical Registry Data? SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID OF-VETERANS-AFFAIRS; QUALITY IMPROVEMENT PROGRAM; SURGEONS NATIONAL DATABASES; BYPASS GRAFT-SURGERY; ADMINISTRATIVE DATA; SURGICAL QUALITY; ACS-NSQIP; COMPLICATION RATES; DECADES EXPERIENCE; ADVERSE EVENTS AB BACKGROUND: Identifying iatrogenic injuries using existing data sources is important for improved transparency in the occurrence of intraoperative events. There is evidence that procedure codes are reliably recorded in claims data. The objective of this study was to assess whether concurrent splenic procedure codes in patients undergoing colectomy procedures are reliably coded in claims data as compared with clinical registry data. STUDY DESIGN: Patients who underwent colectomy procedures in the absence of neoplastic diagnosis codes were identified from American College of Surgeons (ACS) NSQIP data linked with Medicare inpatient claims data file (2005 to 2008). A kappa statistic was used to assess coding concordance between ACS NSQIP and Medicare inpatient claims, with ACS NSQIP serving as the reference standard. RESULTS: A total of 11,367 colectomy patients were identified from 212 hospitals. There were 114 patients (1%) who had a concurrent splenic procedure code recorded in either ACS NSQIP or Medicare inpatient claims. There were 7 patients who had a splenic injury diagnosis code recorded in either data source. Agreement of splenic procedure codes between the data sources was substantial (kappa statistic 0.72; 95% CI, 0.64-0.79). Medicare inpatient claims identified 81% of the splenic procedure codes recorded in ACS NSQIP, and 99% of the patients without a splenic procedure code. CONCLUSIONS: It is feasible to use Medicare claims data to identify splenic injuries occurring during colectomy procedures, as claims data have moderate sensitivity and excellent specificity for capturing concurrent splenic procedure codes compared with ACS NSQIP. (C) 2014 by the American College of Surgeons C1 [Stey, Anne M.] Mt Sinai Med Ctr, Icahn Sch Med, New York, NY 10029 USA. [Stey, Anne M.; Ko, Clifford Y.; Louie, Rachel; Lawson, Elise H.; Gibbons, Melinda M.; Zingmond, David S.; Russell, Marcia M.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA. [Ko, Clifford Y.; Russell, Marcia M.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Ko, Clifford Y.; Hall, Bruce Lee] Amer Coll Surg, Chicago, IL USA. [Hall, Bruce Lee] Washington Univ, St Louis VA Med Ctr, Dept Surg, Olin Business Sch, St Louis, MO USA. [Hall, Bruce Lee] Washington Univ, St Louis VA Med Ctr, Ctr Hlth Policy, St Louis, MO USA. [Hall, Bruce Lee] BJC Healthcare St Louis, St Louis, MO USA. RP Stey, AM (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, 10940 Wilshire Blvd,Suite 710, Los Angeles, CA 90024 USA. EM as013j@gmail.com FU Robert Wood Johnson Foundation; US Department of Veterans Affairs FX Dr Stey's time for this publication was supported by The Robert Wood Johnson Foundation Clinical Scholars program and the US Department of Veterans Affairs. NR 35 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 EI 1879-1190 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD AUG PY 2014 VL 219 IS 2 BP 237 EP U207 DI 10.1016/j.jamcollsurg.2014.02.029 PG 9 WC Surgery SC Surgery GA AN3LM UT WOS:000340489600013 PM 24891210 ER PT J AU Maggiore, RJ Dale, W Gross, CP Feng, T Tew, WP Mohile, SG Owusu, C Klepin, HD Lichtman, SM Gajra, A Ramani, R Katheria, V Zavala, L Hurria, A AF Maggiore, Ronald J. Dale, William Gross, Cary P. Feng, Tao Tew, William P. Mohile, Supriya G. Owusu, Cynthia Klepin, Heidi D. Lichtman, Stuart M. Gajra, Ajeet Ramani, Rupal Katheria, Vani Zavala, Laura Hurria, Arti CA Canc Aging Res Grp TI Polypharmacy and Potentially Inappropriate Medication Use in Older Adults with Cancer Undergoing Chemotherapy: Effect on Chemotherapy-Related Toxicity and Hospitalization During Treatment SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE polypharmacy; cancer; elderly; chemotherapy; toxicity ID ADVERSE DRUG-REACTIONS; ELDERLY-PATIENTS; BEERS CRITERIA; PREVALENCE; QUALITY; PEOPLE; APPROPRIATENESS; METAANALYSIS; POPULATION; MANAGEMENT AB OBJECTIVES: To evaluate the prevalence of polypharmacy and potentially inappropriate medication (PIM) use and the association between these and chemotherapy-related adverse events in older adults with cancer undergoing chemotherapy. DESIGN: Secondary analysis of prospectively collected data. SETTING: Outpatient oncology clinics in seven academic medical centers. PARTICIPANTS: Adults aged 65 and older with cancer undergoing chemotherapy. MEASUREMENTS: Measures included number of daily medications (polypharmacy); PIM use based on three indices (Beers, Zhan, and Drugs to Avoid in the Elderly criteria), and use of six "high risk" medication classes for adverse drug events (anticoagulants, antiplatelet agents, opioids, insulin, oral hypoglycemics, antiarrhythmics). Using multivariate logistic regression, the relations were evaluated between these criteria and Grade 3 to 5 chemotherapy-related toxicity and between these criteria and hospitalization during chemotherapy. RESULTS: Participants (N = 500; mean age 73, 61% Stage IV disease) took a mean of 5 +/- 4 daily medications (range 0-23). PIM use was common (up to 29% according to Beers criteria). No association was found between number of daily medications (reference 0-3 medications) and toxicity (4-9 medications, odds ratio (OR) = 1.34, 95% confidence interval (CI) = 0.92-1.97; >= 10 medications, OR = 0.82, 95% CI = 0.45-1.49) or hospitalization (>= 4 medications, OR = 1.34, 95% CI = 0.82-2.18, P = .24). There was also no association between PIM use and toxicity (P = .93) or hospitalization (P = .98). No medication class was associated with either outcome. CONCLUSIONS: Polypharmacy and PIM use were common but were not associated with chemotherapy-related toxicity or hospitalization in older adults with cancer. C1 [Maggiore, Ronald J.] Portland VA Med Ctr, Portland, OR USA. [Maggiore, Ronald J.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Dale, William] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. [Gross, Cary P.] Yale Univ, Ctr Comprehens Canc, New Haven, CT USA. [Gross, Cary P.] Yale Univ, Sch Med, New Haven, CT USA. [Feng, Tao; Ramani, Rupal; Katheria, Vani; Zavala, Laura; Hurria, Arti] City Hope Natl Med Ctr, Ctr Comprehens Canc, Duarte, CA 91001 USA. [Tew, William P.; Lichtman, Stuart M.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Mohile, Supriya G.] Univ Rochester, Rochester, NY USA. [Owusu, Cynthia] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Klepin, Heidi D.] Wake Forest Univ, Winston Salem, NC 27109 USA. [Gajra, Ajeet] SUNY Upstate Med Univ, Syracuse, NY 13210 USA. [Gajra, Ajeet] Syracuse Vet Affairs Med Ctr, Syracuse, NY USA. RP Hurria, A (reprint author), City Hope Natl Med Ctr, Canc & Aging Res Program, 1500 E Duarte Rd, Duarte, CA 91001 USA. EM ahurria@coh.org FU Paul Beeson Career Development Award in Aging Research [K23 AG026749-01, 1 K08 AG24842]; American Society of Clinical Oncology; Association of Specialty Professors; Junior Development Award in Geriatric Oncology; National Institute on Aging Geriatric Research Training Grant [T32 AG19134]; John A. Hartford Center of Excellence in Geriatrics FX This research was supported by Paul Beeson Career Development Award in Aging Research K23 AG026749-01, (PI: Dr. Hurria) and American Society of Clinical Oncology, Association of Specialty Professors, Junior Development Award in Geriatric Oncology (PI: Dr. Hurria). Dr. Maggiore's efforts are supported by National Institute on Aging Geriatric Research Training Grant T32 AG19134 under the guidance of Drs. Gross, Hurria, and Thomas Gill. Dr. Dale's efforts are supported by the John A. Hartford Center of Excellence in Geriatrics. Dr. Gross's efforts are supported by Paul Beeson Career Development Award in Aging Research 1 K08 AG24842. NR 38 TC 17 Z9 17 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD AUG PY 2014 VL 62 IS 8 BP 1505 EP 1512 DI 10.1111/jgs.12942 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AN3JE UT WOS:000340482800011 PM 25041361 ER PT J AU Gillespie, SM Brandt, LE Chang, A Chao, SH Corcoran, AM Miller, R Harper, GM Levine, SA Medina-Walpole, A AF Gillespie, Suzanne M. Brandt, Lynsey E. Chang, Anna Chao, Serena H. Corcoran, Amy M. Miller, Rachel Harper, G. Michael Levine, Sharon A. Medina-Walpole, Annette TI Staying in the Game: The 10-Step Approach to Sustaining Geriatrics Education in Hospitalists and Subspecialty Providers SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE geriatrics education; Donald W. Reynolds Foundation; hospitalist and subspecialist education ID FACULTY-DEVELOPMENT PROGRAM; MEDICAL-STUDENTS; CURRICULUM; PATIENT; CARE AB Geriatrics as a field has been fortunate to have the support of several philanthropic organizations to advance geriatrics education and training in the past two decades. Awardees of such grants were presented with unparalleled opportunities to develop new and innovative educational initiatives affecting learners at multiple levels and in multiple disciplines and specialties. The lessons learned from the Donald W. Reynolds Foundation initiatives about effect and sustainability are invaluable to the ongoing strategic development of geriatrics nationally. This article highlights successful educational initiatives developed at four institutions with past and current Donald W. Reynolds Foundation funding. Following an ice hockey playbook, this article identifies 10 strategies and initiatives to "stay in the geriatrics game" by training hospitalists and subspecialty providers. The authors' collective experience suggests that geriatrics educational initiatives can not only influence provider education, but also improve the care of older adults in multiple settings. C1 [Gillespie, Suzanne M.; Medina-Walpole, Annette] Univ Rochester, Sch Med & Dent, Rochester, NY USA. [Brandt, Lynsey E.; Corcoran, Amy M.; Miller, Rachel] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Chang, Anna; Harper, G. Michael] Univ Calif San Francisco, Sch Med, San Francisco, CA USA. [Chang, Anna; Harper, G. Michael] San Francisco VA Med Ctr, San Francisco, CA USA. [Chao, Serena H.; Levine, Sharon A.] Boston Univ, Sch Med, Boston, MA 02118 USA. RP Medina-Walpole, A (reprint author), Monroe Community Hosp, 435 East Henrietta Rd, Rochester, NY 14620 USA. EM annette_medinawalpole@urmc.rochester.edu FU Donald W. Reynold's Foundation FX Sponsor's Role: The educational initiatives described in this manuscript were developed through financial support from the Donald W. Reynold's Foundation. NR 20 TC 1 Z9 1 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD AUG PY 2014 VL 62 IS 8 BP 1575 EP 1582 DI 10.1111/jgs.12934 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AN3JE UT WOS:000340482800021 PM 25040491 ER PT J AU Kannan, TR Krishnan, M Ramasamy, K Becker, A Pakhomova, ON Hart, PJ Baseman, JB AF Kannan, Thirumalai R. Krishnan, Manickam Ramasamy, Kumaraguruparan Becker, Argentina Pakhomova, Olga N. Hart, P. John Baseman, Joel B. TI Functional mapping of community-acquired respiratory distress syndrome (CARDS) toxin of Mycoplasma pneumoniae defines regions with ADP-ribosyltransferase, vacuolating and receptor-binding activities SO MOLECULAR MICROBIOLOGY LA English DT Article ID TOXIGENIC ESCHERICHIA-COLI; PROTEIN HOMOLOGY DETECTION; SITE-DIRECTED MUTAGENESIS; HEAT-LABILE ENTEROTOXIN; CHOLERA-TOXIN; PERTUSSIS TOXIN; HELICOBACTER-PYLORI; RIBOSYLATING TOXINS; ASTHMA; INFECTIONS AB Community-acquired respiratory distress syndrome (CARDS) toxin from Mycoplasma pneumoniae is a 591-amino-acid virulence factor with ADP-ribosyltransferase (ADPRT) and vacuolating activities. It is expressed at low levels during in vitro growth and at high levels during colonization of the lung. Exposure of experimental animals to purified recombinant CARDS toxin alone is sufficient to recapitulate the cytopathology and inflammatory responses associated with M. pneumoniae infection in humans and animals. Here, by molecular modelling, serial truncations and site-directed mutagenesis, we show that the N-terminal region is essential for ADP-ribosylating activity. Also, by systematic truncation and limited proteolysis experiments we identified a portion of the C-terminal region that mediates toxin binding to mammalian cell surfaces and subsequent internalization. In addition, the C-terminal region alone induces vacuolization in a manner similar to full-length toxin. Together, these data suggest that CARDS toxin has a unique architecture with functionally separable N-terminal and C-terminal domains. C1 [Kannan, Thirumalai R.; Krishnan, Manickam; Ramasamy, Kumaraguruparan; Baseman, Joel B.] Univ Texas Hlth Sci Ctr San Antonio, Ctr Airway Inflammat Res, Dept Microbiol & Immunol, San Antonio, TX 78229 USA. [Becker, Argentina; Pakhomova, Olga N.; Hart, P. John] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA. [Hart, P. John] South Texas Vet Hlth Care Syst, Dept Vet Affairs, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78229 USA. RP Kannan, TR (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Ctr Airway Inflammat Res, Dept Microbiol & Immunol, San Antonio, TX 78229 USA. EM kannan@uthscsa.edu; baseman@uthscsa.edu FU National Institute of Allergy and Infectious Diseases [U19AI070412]; Kleberg Foundation; Robert A. Welch Foundation [AQ-1399]; National Center for Research Resources at the National Institute of Health [RR-15301]; US Department of Energy, Office of Basic Energy Sciences [W-31-109-ENG-38]; Cancer Therapy & Research Center (CTRC) Cancer Center Support Grant [NCI P30CA054174]; UTHSCSA Executive Research Committee FX We thank Tiffany McDonald Marsh, Pramod Gowda, Brandon Guin and Dr Sowmya Balasubramanian for their technical assistance. We would like to thank Rose Garza for assembling the manuscript. This work was supported by Award Number U19AI070412 from the National Institute of Allergy and Infectious Diseases, The Kleberg Foundation, and the Robert A. Welch Foundation Grant AQ-1399 (PJH). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases or the National Institutes of Health. This work is partially the result of research conducted at the Northeastern Collaborative Access Team (NE-CAT) beam lines of the Advanced Photon Source, supported by award RR-15301 from the National Center for Research Resources at the National Institute of Health. Use of the Advanced Photon Source is supported by the US Department of Energy, Office of Basic Energy Sciences, under contract No. W-31-109-ENG-38. This work was also supported in part by the Cancer Therapy & Research Center (CTRC) Cancer Center Support Grant, NCI P30CA054174 and support for the X-ray Crystallography Core Laboratory by the UTHSCSA Executive Research Committee is gratefully acknowledged. NR 52 TC 8 Z9 9 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0950-382X EI 1365-2958 J9 MOL MICROBIOL JI Mol. Microbiol. PD AUG PY 2014 VL 93 IS 3 BP 568 EP 581 DI 10.1111/mmi.12680 PG 14 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA AN1VF UT WOS:000340371200014 PM 24948331 ER PT J AU Chong, EW Guymer, RH Klein, R Klein, BE Cotch, MF Wang, JJ Shlipak, MG Wong, TY AF Chong, Elaine W. Guymer, Robyn H. Klein, Ronald Klein, Barbara E. Cotch, Mary Frances Wang, Jie Jin Shlipak, Michael G. Wong, Tien Y. TI Is Renal Function Associated with Early Age-Related Macular Degeneration? SO OPTOMETRY AND VISION SCIENCE LA English DT Article DE age-related macular degeneration; kidney; renal function ID CHRONIC KIDNEY-DISEASE; GLOMERULAR-FILTRATION-RATE; COMPLEMENT-FACTOR-H; BLUE-MOUNTAINS-EYE; GLOMERULONEPHRITIS TYPE-II; SERUM CYSTATIN-C; BEAVER DAM EYE; FUNDUS CHANGES; RISK; PREVALENCE AB Purpose. Age-related macular degeneration (AMD) and chronic kidney disease both involve immune dysregulation and may share underlying pathophysiologic changes to systemic homeostasis. Hence, we aim to evaluate associations between impaired kidney function and early AMD, in a search for urinary biomarkers for AMD. Methods. A population-based, cross-sectional analysis of persons aged 45 to 84 years was conducted with renal function measured using serum creatinine and cystatin C levels and the estimated glomerular filtration rate (eGFR) calculated. Age-related macular degeneration status was ascertained from retinal photographs. Results. Of 5874 participants, 221 had early AMD. High serum cystatin C and low eGFR (<= 60 ml/min/1.73 m(2)) were not associated with early AMD in our multivariate analyses. Among normotensive persons, however, highest versus other deciles of cystatin C were associated with an increased prevalence of early AMD (odds ratio, 1.80; 95% confidence interval, 1.00 to 3.23). Conclusions. Results could not confirm an association between kidney function and early AMD. The borderline association between cystatin C and early AMD in normotensive persons require further verification. C1 [Chong, Elaine W.; Guymer, Robyn H.; Wang, Jie Jin; Wong, Tien Y.] Univ Melbourne, Ctr Eye Res Australia, East Melbourne, Vic 3002, Australia. [Klein, Ronald; Klein, Barbara E.] Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI USA. [Cotch, Mary Frances] NEI, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20892 USA. [Wang, Jie Jin] Univ Sydney, Ctr Vis Res, Sydney, NSW 2006, Australia. [Shlipak, Michael G.] Univ Calif San Francisco, Dept Med, San Francisco VA Med Ctr, San Francisco, CA USA. [Shlipak, Michael G.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. [Wong, Tien Y.] Natl Univ Singapore, Yong Loo Lin Sch Med, Singapore Eye Res Inst, Singapore 117595, Singapore. RP Chong, EW (reprint author), Univ Melbourne, Ctr Eye Res Australia, 32 Gisborne St, East Melbourne, Vic 3002, Australia. EM elainechongwt@alumni.unimelb.edu.au RI Wang, Jie Jin/P-1499-2014 OI Wang, Jie Jin/0000-0001-9491-4898; Cotch, Mary Frances/0000-0002-2046-4350 FU National Heart, Lung, and Blood Institute [N01-HC-95159, N01-HC-95165, N01-HC-95169] FX This study was supported by contracts N01-HC-95159 through N01-HC-95165 and N01-HC-95169 from the National Heart, Lung, and Blood Institute. NR 40 TC 3 Z9 3 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-5488 EI 1538-9235 J9 OPTOMETRY VISION SCI JI Optom. Vis. Sci. PD AUG PY 2014 VL 91 IS 8 BP 860 EP 864 PG 5 WC Ophthalmology SC Ophthalmology GA AN4KL UT WOS:000340556500008 PM 24879085 ER PT J AU Coltrera, MD AF Coltrera, Marc D. TI Clinician-Performed Thyroid Ultrasound SO OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA LA English DT Article DE Ultrasound; Office-based; Thyroid cancer; Training; Validation; Competency ID FINE-NEEDLE-ASPIRATION; PREDICTIVE-VALUE; 3 SETS; NODULES; CARCINOMA; PAPILLARY; SONOGRAPHY; MANAGEMENT; BIOPSY; GUIDELINES AB This article is intended to demystify the process for those with a potential interest in acquiring ultrasound skills. It is not intended to be a comprehensive review of head and neck ultrasound but, rather, is focused on the bare minimum requirements and considerations involved in clinician-performed ultrasound. The article covers the initial diagnosis and the unparalleled usefulness of ultrasound for surgical planning just before incision. Further readings are listed at the end of the article to direct the reader to some excellent texts to help build confidence and experience. C1 [Coltrera, Marc D.] Univ Washington, Dept OTO HNS, Seattle, WA 98195 USA. [Coltrera, Marc D.] VA Puget Sound, OTO HNS Div, Seattle, WA 98108 USA. RP Coltrera, MD (reprint author), Univ Washington, Dept OTO HNS, 1959 Northeast Pacific,Box 356515, Seattle, WA 98195 USA. EM Coltrera@u.washington.edu NR 37 TC 4 Z9 4 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0030-6665 EI 1557-8259 J9 OTOLARYNG CLIN N AM JI Otolaryngol. Clin. N. Am. PD AUG PY 2014 VL 47 IS 4 BP 491 EP + DI 10.1016/j.otc.2014.04.001 PG 18 WC Otorhinolaryngology SC Otorhinolaryngology GA AN2UH UT WOS:000340440800005 PM 25041953 ER PT J AU Banks, CA Schlosser, RJ Wang, EW Casey, SE Mulligan, RM Mulligan, JK AF Banks, Caroline A. Schlosser, Rodney J. Wang, Eric W. Casey, Sarah E. Mulligan, Ryan M. Mulligan, Jennifer K. TI Macrophage Infiltrate Is Elevated in CRSwNP Sinonasal Tissue Regardless of Atopic Status SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article DE macrophage; chronic rhinosinusitis; nasal polyps; atopy ID RELATIVE CORTICOSTEROID INSENSITIVITY; CHRONIC RHINOSINUSITIS; DENDRITIC CELLS; NASAL POLYPS; ALLERGIC RHINITIS; ALTERNATIVE ACTIVATION; ALVEOLAR MACROPHAGES; CHRONIC SINUSITIS; SEVERE ASTHMA; DISEASE AB Objective. Macrophages are major producers of inflammatory cytokines; however, their role in chronic rhinosinusitis (CRS) has not been clearly defined. The aim of this study was to quantify macrophages in sinus tissue of patients with various subtypes of CRS and determine the impact of atopic status on macrophage infiltrate. Study Design. Prospective immunohistochemical study of human sinonasal tissue. Setting. Academic medical center. Subjects and Methods. Human sinonasal tissue was taken from patients with CRS with nasal polyposis (CRSwNP, n = 8), CRS without nasal polyposis (CRSsNP, n = 8), and controls (n = 8) undergoing surgery for CSF leak repair or endoscopic excision of non-secreting pituitary tumor. Samples were immunohistochemically stained for macrophage/monocyte markers Mac387 and CD68. Results. CRSwNP patients had significantly increased numbers of Mac387 and CD68 cells compared to control patients (P < .05) or CRSsNP patients (P < .01). CRSsNP had significantly increased number of cells staining for CD68 compared to controls (P < .05). The increased presence of macrophages measured by either marker in CRSwNP was independent of atopic status. Conclusion. Macrophages are increased in CSRwNP patients regardless of atopic status and may contribute to the immunopathology of CRS. C1 [Banks, Caroline A.; Schlosser, Rodney J.; Mulligan, Jennifer K.] Med Univ S Carolina, Dept Otolaryngol, Charleston, SC 29425 USA. [Schlosser, Rodney J.] Ralph H Johnson VA Med Ctr, Dept Surg, Charleston, SC USA. [Wang, Eric W.] Univ Pittsburgh, Dept Otolaryngol, Pittsburgh, PA 15260 USA. [Casey, Sarah E.; Mulligan, Ryan M.] Med Univ S Carolina, Charleston, SC 29425 USA. [Mulligan, Jennifer K.] Ralph H Johnson VA Med Ctr, Res Serv, Charleston, SC USA. [Mulligan, Jennifer K.] Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. RP Banks, CA (reprint author), Med Univ S Carolina, Dept Otolaryngol, 135 Rutledge Ave,MSC 550, Charleston, SC 29425 USA. EM Caroline_Banks@MEEI.HARVARD.EDU OI Wang, Eric/0000-0002-1180-5854 NR 39 TC 3 Z9 3 U1 1 U2 3 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0194-5998 EI 1097-6817 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD AUG PY 2014 VL 151 IS 2 BP 215 EP 220 DI 10.1177/0194599814528672 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA AN2YZ UT WOS:000340453300005 PM 24705220 ER PT J AU Davis, KS Byrd, JK Mehta, V Chiosea, SI Kim, S Ferris, RL Johnson, JT Duvvuri, U AF Davis, Kara S. Byrd, J. Kenneth Mehta, Vikas Chiosea, Simon I. Kim, Seungwon Ferris, Robert L. Johnson, Jonas T. Duvvuri, Umamaheswar TI Occult Primary Head and Neck Squamous Cell Carcinoma: Utility of Discovering Primary Lesions SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article DE unknown primary tumor; oropharyngeal; HPV; cervical metastases; squamous cell carcinoma; unknown primary; human papilloma virus; base of tongue; tonsil; oropharyngeal cancer ID HUMAN-PAPILLOMAVIRUS; UNKNOWN PRIMARY; OROPHARYNGEAL CANCER; POSITIVE HEAD; MANAGEMENT; SURVIVAL; HPV; DIAGNOSIS; STRATEGY; TUMORS AB Objective. Cancer of an unknown primary (CUP) squamous cell carcinoma metastatic to cervical lymph nodes is a challenging problem for the treating physician. Our aim is to determine if identification of the primary tumor is associated with improved oncologic outcomes and/or tumor characteristics including human papilloma virus (HPV) status. Study Design. Retrospective, matched-pairs analysis contrasting 2 cohorts based upon discovery of primary lesion. Setting. Tertiary teaching hospital. Subjects and Methods. Records of 136 patients initially diagnosed as carcinoma of unknown primary were retrospectively reviewed (1980-2010) and divided into 2 cohorts based on discovery of the primary lesion. Primary outcome measures were overall survival and time to recurrence according to Kaplan-Meier analysis. A nested subset of 22 patients in which the primary was discovered were matched to 22 patients remaining undiscovered according to nodal stage and age. Results. Discovered lesions were more likely to exhibit HPV positivity (P < .001). Matched-pairs analyses demonstrated that discovery of the primary was associated with better overall survival (HR = 0.125; 95% confidence interval [CI], 0.019-0.822; P = .030). Discovery of the primary was associated with improved cause-specific survival (HR = 0.142; 95% CI, 0.021-0.93; P = .0418) and disease-free survival (HR = 0.25; 95% CI, 0.069-0.91; P = .03). Conclusion. HPV positivity is associated with discovery of the primary tumor. Discovery of the primary lesion is associated with improved overall survival, cause-specific survival, and disease-free survival in patients initially presenting as CUP in matched-pair and cohort comparison analyses. C1 [Davis, Kara S.; Byrd, J. Kenneth; Kim, Seungwon; Ferris, Robert L.; Johnson, Jonas T.; Duvvuri, Umamaheswar] Univ Pittsburgh, Med Ctr, Dept Otolaryngol Head & Neck Surg, Pittsburgh, PA 15213 USA. [Mehta, Vikas] Louisiana State Univ, Hlth Sci Ctr Shreveport, Dept Otolaryngol Head & Neck Surg, Shreveport, LA 71105 USA. [Chiosea, Simon I.] Univ Pittsburgh, Med Ctr, Dept Pathol, Pittsburgh, PA USA. [Duvvuri, Umamaheswar] VA Pittsburgh Hlth Syst, Pittsburgh, PA USA. RP Davis, KS (reprint author), Univ Pittsburgh, Med Ctr, Dept Otolaryngol Head & Neck Surg, 200 Lothrop St Suite 500, Pittsburgh, PA 15213 USA. EM davisks@upmc.edu FU NIH [UL1 RR024153, UL1TR000005]; Department of Veterans Affairs, BLS RD; PNC Foundation FX NIH grants (UL1 RR024153 and UL1TR000005) funded statistical analysis. This was supported in part by funds from the Department of Veterans Affairs, BLS R&D and the PNC Foundation (U.D.). NR 20 TC 13 Z9 13 U1 0 U2 2 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0194-5998 EI 1097-6817 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD AUG PY 2014 VL 151 IS 2 BP 272 EP 278 DI 10.1177/0194599814533494 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA AN2YZ UT WOS:000340453300014 PM 24812081 ER PT J AU Maglione, MA Das, L Raaen, L Smith, A Chari, R Newberry, S Shanman, R Perry, T Goetz, MB Gidengil, C AF Maglione, Margaret A. Das, Lopamudra Raaen, Laura Smith, Alexandria Chari, Ramya Newberry, Sydne Shanman, Roberta Perry, Tanja Goetz, Matthew Bidwell Gidengil, Courtney TI Safety of Vaccines Used for Routine Immunization of US Children: A Systematic Review SO PEDIATRICS LA English DT Review DE evidence-based medicine; vaccine/immunization; infectious disease ID HUMAN ROTAVIRUS VACCINE; INACTIVATED INFLUENZA VACCINE; MUMPS-RUBELLA VACCINATION; CONJUGATE VACCINE; DOUBLE-BLIND; DATALINK PROJECT; HEALTHY INFANTS; UNITED-STATES; THROMBOCYTOPENIC PURPURA; POSTMARKETING EVALUATION AB BACKGROUND: Concerns about vaccine safety have led some parents to decline recommended vaccination of their children, leading to the resurgence of diseases. Reassurance of vaccine safety remains critical for population health. This study systematically reviewed the literature on the safety of routine vaccines recommended for children in the United States. METHODS: Data sources included PubMed, Advisory Committee on Immunization Practices statements, package inserts, existing reviews, manufacturer information packets, and the 2011 Institute of Medicine consensus report on vaccine safety. We augmented the Institute of Medicine report with more recent studies and increased the scope to include more vaccines. Only studies that used active surveillance and had a control mechanism were included. Formulations not used in the United States were excluded. Adverse events and patient and vaccine characteristics were abstracted. Adverse event collection and reporting was evaluated by using the McHarm scale. We were unable to pool results. Strength of evidence was rated as high, moderate, low, or insufficient. RESULTS: Of 20 478 titles identified, 67 were included. Strength of evidence was high for measles/mumps/rubella (MMR) vaccine and febrile seizures; the varicella vaccine was associated with complications in immunodeficient individuals. There is strong evidence that MMR vaccine is not associated with autism. There is moderate evidence that rotavirus vaccines are associated with intussusception. Limitations of the study include that the majority of studies did not investigate or identify risk factors for AEs; and the severity of AEs was inconsistently reported. CONCLUSIONS: We found evidence that some vaccines are associated with serious AEs; however, these events are extremely rare and must be weighed against the protective benefits that vaccines provide. C1 [Maglione, Margaret A.; Das, Lopamudra; Raaen, Laura; Smith, Alexandria; Chari, Ramya; Newberry, Sydne; Shanman, Roberta; Perry, Tanja; Gidengil, Courtney] RAND Corp, Santa Monica, CA 90407 USA. [Goetz, Matthew Bidwell] Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Goetz, Matthew Bidwell] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Gidengil, Courtney] Boston Childrens Hosp, Boston, MA USA. RP Maglione, MA (reprint author), RAND Corp, 1776 Main St Mailstop 4W, Santa Monica, CA 90407 USA. EM maglione@rand.org OI Goetz, Matthew/0000-0003-4542-992X FU Agency for Healthcare Research and Quality [HHSA290200710062I]; US Department of Health and Human Services FX Supported under Contract No. HHSA290200710062I from the Agency for Healthcare Research and Quality, US Department of Health and Human Services. NR 97 TC 35 Z9 38 U1 12 U2 229 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD AUG PY 2014 VL 134 IS 2 BP 325 EP 337 DI 10.1542/peds.2014-1079 PG 13 WC Pediatrics SC Pediatrics GA AN0HS UT WOS:000340266000059 PM 25086160 ER PT J AU Xu, S Shetterly, S Raebel, MA Ho, PM Tsai, TT Magid, D AF Xu, Stanley Shetterly, Susan Raebel, Marsha A. Ho, P. Michael Tsai, Thomas T. Magid, David TI Estimating the effects of time-varying exposures in observational studies using Cox models with stabilized weights adjustment SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE drug-eluting stent; clopidogrel; time-varying exposure; Cox model; stabilized weights; pharmacoepidemiology ID MARGINAL STRUCTURAL MODELS; PROPENSITY SCORE; COVARIANCE ANALYSIS; COUNTING-PROCESSES; REGRESSION-MODEL; SURVIVAL-DATA; CLOPIDOGREL; THERAPY; STENT; IMPLANTATION AB Purpose Assessing the safety and effectiveness of medical products with observational electronic medical record data is challenging when the treatment is time-varying. The objective of this paper is to develop a Cox model stratified by event times with stabilized weights (SWs) adjustment to examine the effect of time-varying treatment in observational studies. Methods Time-varying SWs are calculated at unique event times and are used in a Cox model stratified by event times to estimate the effect of time-varying treatment. We applied this method in examining the effect of an antiplatelet agent, clopidogrel, on events, including bleeding, myocardial infarction, and death after a drug-eluting stent was implanted in coronary artery. Clopidogrel use may change over time on the basis of patients' behavior (e. g., non-adherence) and physicians' recommendations (e. g., end of duration of therapy). We also compared the results with those from a Cox model for counting processes adjusting for all covariates used in creating SWs. Results We demonstrate that the (i) results from the stratified Cox model without SWs adjustment and the Cox model for counting processes without covariate adjustment are identical in analyzing the clopidogrel data; and (ii) the effects of clopidogrel on bleeding, myocardial infarction, and death are larger in the stratified Cox model with SWs adjustment compared with those from the Cox model for counting processes with covariate adjustment. Conclusions The Cox model stratified by event times with time-varying SWs adjustment is useful in estimating the effect of time-varying treatments in observational studies while balancing for known confounders. Copyright (C) 2014 John Wiley & Sons, Ltd. C1 [Xu, Stanley; Shetterly, Susan; Raebel, Marsha A.; Ho, P. Michael; Tsai, Thomas T.; Magid, David] Kaiser Permanente Colorado, Inst Hlth Res, Denver, CO 80237 USA. [Xu, Stanley; Raebel, Marsha A.; Ho, P. Michael; Tsai, Thomas T.; Magid, David] Univ Colorado, Denver, CO 80202 USA. [Ho, P. Michael; Tsai, Thomas T.] Denver VA Med Ctr, Denver, CO USA. RP Xu, S (reprint author), Kaiser Permanente Colorado, Inst Hlth Res, POB 378066, Denver, CO 80237 USA. EM stan.xu@kp.org FU Strategic Initiatives Funds of Kaiser Permanente Colorado; Agency for Healthcare Research and Quality, US Department of Health and Human Services as part of the Developing Evidence to Inform Decisions about Effectiveness 16 (DEcIDE) program [290-05-0033]; National Institutes of Health (NIH)/National Center for Advancing Translational Sciences (NCATS) Colorado Clinical and Translational Sciences Institute [UL1 TR001082] FX This project was supported by the Strategic Initiatives Funds of Kaiser Permanente Colorado and funded under Contract No. 290-05-0033 from the Agency for Healthcare Research and Quality, US Department of Health and Human Services as part of the Developing Evidence to Inform Decisions about Effectiveness 16 (DEcIDE) program. Xu was also supported by National Institutes of Health (NIH)/National Center for Advancing Translational Sciences (NCATS) Colorado Clinical and Translational Sciences Institute Grant Number UL1 TR001082. Contents are the authors' sole responsibility and do not necessarily represent official NIH views. NR 36 TC 2 Z9 2 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2014 VL 23 IS 8 BP 812 EP 818 DI 10.1002/pds.3601 PG 7 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA AN1PG UT WOS:000340355200005 PM 24596337 ER PT J AU Van Hyfte, GJ Kozak, LE Lepore, M AF Van Hyfte, Gregory J. Kozak, Leila E. Lepore, Michael TI A Survey of the Use of Complementary and Alternative Medicine in Illinois Hospice and Palliative Care Organizations SO AMERICAN JOURNAL OF HOSPICE & PALLIATIVE MEDICINE LA English DT Article DE complementary and alternative medicine; integrative palliative care; complementary therapies; hospice care; hospice administration; end-of-life care; family caregivers; service delivery ID THERAPY; CANCER AB This research assesses complementary and alternative medicine (CAM) use and administration for patients and family caregivers in Illinois hospice and palliative care organizations. An online survey was administered to a sample of 108 contacts of Illinois organizations listed in the National Hospice and Palliative Care Organization website, and 90.3% of the responding organizations offered some type of CAM. The top 5 most frequently offered CAM modalities to patients were pet therapy (64.5%), music therapy (61.3%), massage therapy (54.8%), art therapy (29.0%), and energy therapies (25.8%); these were the same top 5 offered to families but with different frequencies. Findings regarding utilization, administration, financing, and spiritual/ cultural competency are discussed with policy recommendations for data collection, administrative improvements, and integration of CAM providers into service delivery. C1 [Van Hyfte, Gregory J.] Dept Hlth Educ, Chicago, IL 60622 USA. [Kozak, Leila E.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. [Kozak, Leila E.] Univ Washington, Sch Publ Hlth, Dept Hlth Serv, Seattle, WA 98195 USA. [Lepore, Michael] Planetree, Dept Qual Res & Evaluat, Derby, CT USA. [Lepore, Michael] Brown Univ, Dept Hlth Serv Policy & Practice, Providence, RI 02912 USA. RP Van Hyfte, GJ (reprint author), Dept Hlth Educ, 2611W Chicago Ave, Chicago, IL 60622 USA. EM gregory@uchicago.edu FU Arthur Quern Fellowship at the University of Chicago; Graduate Program in Health Administration; Policy in the School of Social Service Administration; VA Puget Sound Health Care System, Seattle, Washington through Health Services Research and Development Service as part of Dr Kozak's fellowship [TPP 61-61-023] FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research was supported by the Arthur Quern Fellowship at the University of Chicago, Graduate Program in Health Administration and Policy in the School of Social Service Administration. Dr Kozak's work was supported in part by resources from the VA Puget Sound Health Care System, Seattle, Washington through Health Services Research and Development Service as part of Dr Kozak's fellowship, grant # TPP 61-61-023. NR 19 TC 0 Z9 0 U1 2 U2 16 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1049-9091 EI 1938-2715 J9 AM J HOSP PALLIAT ME JI Am. J. Hosp. Palliat. Med. PD AUG PY 2014 VL 31 IS 5 BP 553 EP 561 DI 10.1177/1049909113500378 PG 9 WC Health Care Sciences & Services SC Health Care Sciences & Services GA AM8BV UT WOS:000340095200013 PM 23943631 ER PT J AU Borson, S Chodosh, J AF Borson, Soo Chodosh, Joshua TI Developing Dementia-Capable Health Care Systems: A 12-Step Program SO CLINICS IN GERIATRIC MEDICINE LA English DT Article DE Dementia; Alzheimer disease; Primary care; Comprehensive management; Care coordination; Partnership; Quality measurement; Annual wellness visit ID AMERICAN GERIATRICS SOCIETY; RANDOMIZED CONTROLLED-TRIAL; PATIENT-CENTERED CARE; SERVICES-TASK-FORCE; OLDER-ADULTS; ALZHEIMERS-DISEASE; COGNITIVE IMPAIRMENT; MANAGEMENT INTERVENTION; MEDICAL HOME; DIABETES-MELLITUS AB Improving the quality, comprehensiveness, and coordination of health care for people with dementia is a primary goal of the National Alzheimer's Plan. In this article, the key principles of high-quality dementia care for nonspecialist clinicians and health care leaders are synthesized, a framework for operationalizing its components is presented, and simple steps for developing dementia-capable health care systems are offered. C1 [Borson, Soo] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Borson, Soo] Univ Washington, Sch Nursing, Dept Psychosocial & Community Hlth, Seattle, WA 98195 USA. [Chodosh, Joshua] Univ Calif Los Angeles, David Geffen Sch Med, V CAMP, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Borson, S (reprint author), 2375 South Toledo Ave, Palm Springs, CA 92264 USA. EM soob@uw.edu OI Chodosh, Joshua/0000-0001-7784-4306 NR 92 TC 4 Z9 4 U1 6 U2 23 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0749-0690 EI 1879-8853 J9 CLIN GERIATR MED JI Clin. Geriatr. Med. PD AUG PY 2014 VL 30 IS 3 BP 395 EP + DI 10.1016/j.cger.2014.05.001 PG 27 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA AM7UH UT WOS:000340073700002 PM 25037288 ER PT J AU Wang, LY Borisovskaya, A Maxwell, AL Pascualy, M AF Wang, Lucy Y. Borisovskaya, Anna Maxwell, Andrea L. Pascualy, Marcella TI Common Psychiatric Problems in Cognitively Impaired Older Patients Causes and Management SO CLINICS IN GERIATRIC MEDICINE LA English DT Article DE Dementia; Behavioral and psychological symptoms; Agitation; Depression; Psychosis; Anxiety ID RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED-TRIAL; NURSING-HOME RESIDENTS; SEVERE ALZHEIMERS-DISEASE; PSYCHOLOGICAL SYMPTOMS; DOUBLE-BLIND; NEUROPSYCHIATRIC SYMPTOMS; BEHAVIORAL SYMPTOMS; ATYPICAL ANTIPSYCHOTICS; GENERALIZED ANXIETY AB Although dementias are defined by their cognitive and functional deficits, psychiatric problems are common, contribute to patient distress and burden, and precipitate institutionalization. Successful treatment involves understanding that physiologic, psychological, and environmental factors can contribute to the development of these symptoms. By carefully assessing each of these factors, clinicians can individualize treatment and flexibly use nonpharmacologic and pharmacologic approaches tailored to patients and the context of care. Although there exist limitations to many treatment options, clinicians can still adapt current knowledge to develop a multifaceted treatment approach that improves the quality of life for patients and their caregivers. C1 [Wang, Lucy Y.; Borisovskaya, Anna; Maxwell, Andrea L.; Pascualy, Marcella] VA Puget Sound Healthcare Syst, Mental Hlth Serv, Seattle, WA 98108 USA. [Wang, Lucy Y.; Borisovskaya, Anna; Maxwell, Andrea L.; Pascualy, Marcella] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98108 USA. RP Wang, LY (reprint author), VA Puget Sound Healthcare Syst, Mental Hlth Serv, 1660 South Columbian Way,S-116, Seattle, WA 98108 USA. EM lucy.wang@va.gov FU VA Clinical Science Research and Development (CSR&D) Career Development Award Program [3125]; VA Puget Sound Health Care System, Seattle, Washington FX This work is supported by resources from the VA Puget Sound Health Care System, Seattle, Washington. Dr. Wang is supported by the VA Clinical Science Research and Development (CSR&D) Career Development Award Program (Project ID: 3125). NR 105 TC 3 Z9 3 U1 2 U2 10 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0749-0690 EI 1879-8853 J9 CLIN GERIATR MED JI Clin. Geriatr. Med. PD AUG PY 2014 VL 30 IS 3 BP 443 EP + DI 10.1016/j.cger.2014.04.002 PG 26 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA AM7UH UT WOS:000340073700004 PM 25037290 ER PT J AU Merel, S DeMers, S Vig, E AF Merel, Susan DeMers, Shaune Vig, Elizabeth TI Palliative Care in Advanced Dementia SO CLINICS IN GERIATRIC MEDICINE LA English DT Article DE Dementia; Palliative care; End-of-life care; Cognitive impairment; Skilled nursing facilities; Advance directives ID NURSING-HOME RESIDENTS; OF-LIFE CARE; PERCUTANEOUS ENDOSCOPIC GASTROSTOMY; SURROGATE DECISION-MAKERS; PLACEBO-CONTROLLED TRIAL; FEEDING-TUBE INSERTION; NEUROPSYCHIATRIC SYMPTOMS; ALZHEIMER-DISEASE; HOSPICE CARE; MEDICATION USE AB Because neurodegenerative dementias are progressive and ultimately fatal, a palliative approach focusing on comfort, quality of life, and family support can have benefits for patients, families, and the health system. Elements of a palliative approach include discussion of prognosis and goals of care, completion of advance directives, and a thoughtful approach to common complications of advanced dementia. Physicians caring for patients with dementia should formulate a plan for end-of-life care in partnership with patients, families, and caregivers, and be prepared to manage common symptoms at the end of life in dementia, including pain and delirium. C1 [Merel, Susan] Univ Washington, Dept Med, Div Gen Internal Med, Seattle, WA 98195 USA. [DeMers, Shaune] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Vig, Elizabeth] Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Vig, Elizabeth] Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA USA. RP Merel, S (reprint author), Univ Washington, Dept Med, Div Gen Internal Med, 1959 NE Pacific St,Box 356429, Seattle, WA 98195 USA. EM smerel@uw.edu NR 114 TC 2 Z9 2 U1 9 U2 34 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0749-0690 EI 1879-8853 J9 CLIN GERIATR MED JI Clin. Geriatr. Med. PD AUG PY 2014 VL 30 IS 3 BP 469 EP + DI 10.1016/j.cger.2014.04.004 PG 25 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA AM7UH UT WOS:000340073700005 PM 25037291 ER PT J AU Inampudi, C Parvataneni, S Morgan, CJ Deedwania, P Fonarow, GC Prabhu, SD Butler, J Zile, MR Aronow, WS Sanders, PW Allman, RM Ahmed, A AF Inampudi, Chakradhari Parvataneni, Sridivya Morgan, Charity J. Deedwania, Prakash Fonarow, Gregg C. Prabhu, Sumanth D. Butler, Javed Zile, Michael R. Aronow, Wilbert S. Sanders, Paul W. Allman, Richard M. Ahmed, Ali TI Lack of Association Between Spironolactone Use and 30-Day All-Cause Readmission In Hospitalized Medicare Beneficiaries With Systolic Heart Failure Eligible for Spironolactone Therapy SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 18th Annual Scientific Meeting of the Heart-Failure-Society-of-America (HFSA) CY SEP 14-17, 2014 CL Las Vegas, NV SP Heart Failure Soc Amer C1 [Inampudi, Chakradhari] Univ Iowa Hosp & Clin, Iowa City, IA 52242 USA. [Parvataneni, Sridivya; Morgan, Charity J.; Prabhu, Sumanth D.; Sanders, Paul W.; Ahmed, Ali] Univ Alabama Birmingham, Birmingham, AL USA. [Deedwania, Prakash] Univ Calif San Francisco, Fresno, CA USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Los Angeles, CA USA. [Prabhu, Sumanth D.; Ahmed, Ali] Birmingham VA Med Ctr, Birmingham, AL USA. [Butler, Javed] Emory Univ, Atlanta, GA 30322 USA. [Zile, Michael R.] Med Univ S Carolina, Charleston, SC 29425 USA. [Aronow, Wilbert S.] Westchester Cty Med Ctr, Valhalla, NY 10595 USA. [Allman, Richard M.] Dept Vet Affairs Geriatr & Extended Care Serv, Washington, DC USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 EI 1532-8414 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2014 VL 20 IS 8 SU S MA 141 BP S58 EP S58 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AM9PS UT WOS:000340214100140 ER PT J AU Zamani, P Rawat, D Kumar, PS Geraci, S Bhuva, R Konda, P Doulias, PT Ischiropoulos, H Chirinos, JA AF Zamani, Payman Rawat, Deepa Kumar, Prithvi Shiva Geraci, Sam Bhuva, Rushik Konda, Prasad Doulias, Paschalis-Thomas Ischiropoulos, Harry Chirinos, Julio A. TI Inorganic Nitrate Supplementation Improves Exercise Capacity in Subjects with HF with Preserved EF - A Pilot Study SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 18th Annual Scientific Meeting of the Heart-Failure-Society-of-America (HFSA) CY SEP 14-17, 2014 CL Las Vegas, NV SP Heart Failure Soc Amer C1 [Zamani, Payman; Kumar, Prithvi Shiva; Konda, Prasad; Chirinos, Julio A.] Hosp Univ Penn, Philadelphia, PA 19104 USA. [Rawat, Deepa; Kumar, Prithvi Shiva; Geraci, Sam; Bhuva, Rushik; Chirinos, Julio A.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Doulias, Paschalis-Thomas; Ischiropoulos, Harry] Childrens Hosp Philadelphia, Res Inst, Philadelphia, PA 19104 USA. NR 0 TC 2 Z9 2 U1 1 U2 5 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 EI 1532-8414 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2014 VL 20 IS 8 SU S MA 009 BP S4 EP S4 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AM9PS UT WOS:000340214100010 ER PT J AU Fung, SJ Chase, MH AF Fung, Simon J. Chase, Michael H. TI Control of hypoglossal motoneurones during naturally occurring sleep and wakefulness in the intact, unanaesthetized cat: a field potential study SO JOURNAL OF SLEEP RESEARCH LA English DT Article DE atonia; excitability; genioglossus; obstructive sleep apnea; rapid eye movement sleep; sleep-disordered breathing ID REM-SLEEP; GENIOGLOSSUS MUSCLE; MOTO-NEURONS; WAKE STATES; NUCLEUS; MICRODIALYSIS; EXCITABILITY; INHIBITION; ATONIA; APNEA AB The present electrophysiological study was designed to determine the discharge threshold of hypoglossal motoneurones during naturally occurring states of sleep and wakefulness in the intact, unanaesthetized cat. The antidromic field potential, which reflects the net level of membrane excitability of motoneurones and therefore their discharge threshold, was recorded in the hypoglossal nucleus following stimulation of the hypoglossal nerve. The amplitude of the antidromic field potential was larger during wakefulness and non-rapid eye movement (NREM) sleep compared with REM sleep. There was no significant difference in the amplitude of the field potential when wakefulness was compared with NREM sleep (P = 0.103, df = 3, t = 2.324). However, there was a 46% reduction in amplitude during REM sleep compared with NREM sleep (P < 0.001, df = 10, t = 6.421) or wakefulness (P < 0.01, df = 4, t = -4.598). These findings indicate that whereas the excitability of motoneurones that comprise the hypoglossal motor pool is relatively constant during wakefulness and NREM sleep, their excitability is significantly reduced during REM sleep. This state-dependent pattern of control of hypoglossal motoneurones during REM sleep is similar to that reported for motoneurones in other motor nuclei at all levels of the neuraxis. The decrease in the evoked response of hypoglossal motoneurones, which reflects a significant increase in the discharge threshold of individual motoneurones, results in atonia of the lingual and related muscles during REM sleep. C1 [Fung, Simon J.; Chase, Michael H.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Fung, Simon J.; Chase, Michael H.] WebSci Int, Los Angeles, CA 90024 USA. [Chase, Michael H.] Univ Calif Los Angeles, Sch Med, Dept Physiol, Los Angeles, CA 90024 USA. RP Fung, SJ (reprint author), WebSci Int, 1251 Westwood Blvd, Los Angeles, CA 90024 USA. EM sfung@websciences.org FU [1\01BX00819]; [TGS-109219]; [1R01HL116845] FX We are grateful to Francisco Morales, Jack Yamuy, MingChu Xi and Pablo Torterolo for their collaborative support in successfully developing the intact, unanaesthetized cat preparation employed in the present study. We are also indebted to Peter Soja and Ron Harper for their advice with respect to the fabrication of the cuff electrode for the hypoglossal nerve implant. We also thank Ida Shakhverdyan, Pandi Perumal, Naira Manukian, Andrui Nazarian and Reza Khorsan for their excellent technical assistance. This work was supported by grants 1 vertical bar 01BX00819, TGS-109219 and 1R01HL116845. NR 40 TC 3 Z9 3 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0962-1105 EI 1365-2869 J9 J SLEEP RES JI J. Sleep Res. PD AUG PY 2014 VL 23 IS 4 BP 469 EP 474 DI 10.1111/jsr.12137 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AN0EL UT WOS:000340256000014 PM 24605864 ER PT J AU Wong, ES Hebert, PL Maciejewski, ML Perkins, M Bryson, CL Au, DH Liu, CF AF Wong, Edwin S. Hebert, Paul L. Maciejewski, Matthew L. Perkins, Mark Bryson, Chris L. Au, David H. Liu, Chuan-Fen TI Does Favorable Selection Among Medicare Advantage Enrollees Affect Measurement of Hospital Readmission Rates? SO MEDICAL CARE RESEARCH AND REVIEW LA English DT Article DE Veterans; Medicare; readmission; risk adjustment; selection bias ID AFFAIRS HEALTH-CARE; SAMPLE SELECTION; HEART-FAILURE; VETERANS-AFFAIRS; ENROLLMENT; HMOS; PROGRAM; PLANS; BIAS; DISENROLLMENT AB Literature indicates favorable selection among Medicare Advantage (MA) enrollees compared with fee-for-service (FFS) enrollees. This study examined whether favorable selection into MA affected readmission rates among Medicare-eligible veterans following hospitalization for congestive heart failure in the Veterans Affairs Health System (VA). We measured total (VA + Medicare FFS) 30-day all-cause readmission rates across hospitals and all of VA. We used Heckman's correction to adjust readmission rates to be representative of all Medicare-eligible veterans, not just FFS-enrolled veterans. The adjusted all-cause readmission rate among FFS veterans was 27.1% (95% confidence interval [CI] = 26.5% to 27.7%), while the adjusted readmission rate among Medicare-eligible veterans was 25.3% (95% CI = 23.6% to 27.1%) after correcting for favorable selection. Readmission rate estimates among FFS veterans generalize to all Medicare-eligible veterans only after accounting for favorable selection into MA. Estimation of quality metrics should carefully consider sample selection to produce valid policy inferences. C1 [Wong, Edwin S.; Hebert, Paul L.; Perkins, Mark; Bryson, Chris L.; Au, David H.; Liu, Chuan-Fen] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Wong, Edwin S.; Hebert, Paul L.; Bryson, Chris L.; Au, David H.; Liu, Chuan-Fen] Univ Washington, Seattle, WA 98195 USA. [Maciejewski, Matthew L.] Durham VA Med Ctr, Durham, NC USA. [Maciejewski, Matthew L.] Duke Univ, Durham, NC USA. RP Wong, ES (reprint author), Ctr Innovat Vet Ctr & Value Driven Care, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM edwin.wong@va.gov FU Health Services Research and Development (HSR&D) Service, Office of Research and Development, Department of Veterans Affairs [IIR 09-354]; VA HSR&D Career Development Award [CDA 13-024] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research was supported by the Health Services Research and Development (HSR&D) Service, Office of Research and Development, Department of Veterans Affairs, IIR 09-354. Dr. Wong is supported by a VA HSR&D Career Development Award (CDA 13-024). Dr. Maciejewski is a VA Research Career Scientist (RCS 10-391). NR 30 TC 1 Z9 1 U1 0 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1077-5587 EI 1552-6801 J9 MED CARE RES REV JI Med. Care Res. Rev. PD AUG PY 2014 VL 71 IS 4 BP 367 EP 383 DI 10.1177/1077558714533823 PG 17 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA AM8IA UT WOS:000340115600004 PM 24811933 ER PT J AU Egede, LE Gebregziabher, M Zhao, YM Dismuke, CE Walker, RJ Hunt, KJ Axon, RN AF Egede, Leonard E. Gebregziabher, Mulugeta Zhao, Yumin Dismuke, Clara E. Walker, Rebekah J. Hunt, Kelly J. Axon, R. Neal TI Impact of Mental Health Visits on Healthcare Cost in Patients with Diabetes and Comorbid Mental Health Disorders SO PLOS ONE LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; RANDOMIZED-TRIAL; PSYCHOLOGICAL DISTRESS; MEDICAL-CARE; VETERANS; INDIVIDUALS; DEPRESSION; OUTCOMES; TELEPSYCHIATRY; MANAGEMENT AB Purpose: To assess the impact of mental health visits (MHV) on the cost of care for Veterans with diabetes and comorbid mental health conditions. Methods: A national cohort of 120,852 Veterans with diabetes and at least one mental health diagnosis (i.e., substance abuse, depression or psychoses) in 2002 was followed through 2006. Outcomes were pharmacy, inpatient and outpatient costs in 2012 dollars. Results: Least-square covariate adjusted estimates from the joint model of total VA costs of the number of MHV using December 31, 2012 value dollars indicate that relative to those with fewer MHV, those with 3+ MHV had the lowest mean inpatient cost ($21,406), but the highest mean outpatient and pharmacy cost ($9,727 and $2,015, respectively). If all Veterans who received zero MHV actually received 3+ MHV, we estimate through simulated scenarios that between $32,272,329 and $181,460,247 in inpatient costs would be saved. However, these savings would be offset by additional expenditures of between $1,166,017,547 and $1,166,224,787 in outpatient costs and between $151,604,683 and $161,439,632 in pharmacy costs. Conclusions: Among Veterans with diabetes and comorbid mental disorders having three or more mental health visits is associated with marginally decreased inpatient cost, but these potential savings seem to be offset by increased outpatient and pharmacy costs. C1 [Gebregziabher, Mulugeta; Zhao, Yumin; Dismuke, Clara E.; Walker, Rebekah J.; Hunt, Kelly J.; Axon, R. Neal] Ralph H Johnson Dept Vet Affairs Med Ctr, Hlth Equity & Rural Outreach Innovat Ctr, Charleston, SC USA. [Egede, Leonard E.; Zhao, Yumin; Dismuke, Clara E.; Walker, Rebekah J.; Axon, R. Neal] Med Univ S Carolina, Div Gen Internal Med, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. [Gebregziabher, Mulugeta; Hunt, Kelly J.] Med Univ S Carolina, Div Biostat & Epidemiol, Charleston, SC 29425 USA. RP Egede, LE (reprint author), Med Univ S Carolina, Div Gen Internal Med, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. EM egedel@musc.edu OI Gebregziabher, Mulugeta/0000-0002-4826-481X FU VHA Health Services Research and Development (HSRD) program [IIR-06-219] FX This study was supported by grant #IIR-06-219 funded by the VHA Health Services Research and Development (HSR&D) program. The funding agency did not participate in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. NR 26 TC 3 Z9 3 U1 0 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD AUG 1 PY 2014 VL 9 IS 8 AR e103804 DI 10.1371/journal.pone.0103804 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AM4JL UT WOS:000339819800081 PM 25083903 ER PT J AU Ikeda, AJ Grabowski, AM Lindsley, A Sadeghi-Demneh, E Reisinger, KD AF Ikeda, Andrea J. Grabowski, Alena M. Lindsley, Alida Sadeghi-Demneh, Ebrahim Reisinger, Kim D. TI A scoping literature review of the provision of orthoses and prostheses in resource-limited environments 2000-2010. Part one: Considerations for success SO PROSTHETICS AND ORTHOTICS INTERNATIONAL LA English DT Review DE Orthotics; prosthetics; developing countries; developing world; low-income countries ID TRANS-TIBIAL AMPUTEES; CIR CASTING SYSTEM; PONSETI METHOD; DEVELOPING-WORLD; TRANSTIBIAL PROSTHESES; CLUBFOOT DEFORMITY; SOCKETS; FOOT; LIMB; STRENGTH AB Study Design: Literature Review Background: We estimate that over 29 million people worldwide in resource-limited environments (RLEs) are in need of orthotic and prosthetic (O&P) devices and services. Objectives: Our goal was to ascertain the current state of O&P provision in RLEs and identify factors that may lead to more successful O&P provision. Methods: We conducted a comprehensive scoping literature review of all information related to O&P provision in RLEs published from 2000 to 2010. We targeted Vietnam, Cambodia, Tanzania, Malawi, Colombia, and the Navajo Nation, but also included information about developing countries in general. We searched academic databases and grey literature. We extracted information from each article in the areas of design, manufacturing, distribution, service provision, and technology transfer. Results: We identified commonly reported considerations and strategies for O&P provision from 431 articles. Analysis of expert consensus documents revealed recurring themes for improving O&P provision. We found that some suggestions from the consensus documents are being followed, but many are overlooked or have not yet been implemented. Conclusions: Areas for improvement include conducting field testing during the design process, providing services to rural environments, offering follow-up services, considering government collaboration, and encouraging an active role of the orthosis/prosthesis user. Outcomes and research studies will be further discussed in Part Two. C1 [Ikeda, Andrea J.; Lindsley, Alida; Reisinger, Kim D.] San Francisco State Univ, Whirlwind Wheelchair Int, San Francisco, CA 94132 USA. [Grabowski, Alena M.] Univ Colorado, Dept Integrat Physiol, Boulder, CO 80309 USA. [Sadeghi-Demneh, Ebrahim] Isfahan Univ Med Sci, Orthot & Prosthet Dept, Musculoskeletal Res Ctr, Esfahan, Iran. US Dept Vet Affairs, Eastern Colorado Healthcare Syst, Denver, CO USA. RP Ikeda, AJ (reprint author), San Francisco State Univ, Whirlwind Wheelchair Int, 1600 Holloway Ave,SCI 251, San Francisco, CA 94132 USA. EM andrea@whirlwindwheelchair.org RI Sadeghi-Demenh, Ebrahim/E-8110-2012 OI Sadeghi-Demenh, Ebrahim/0000-0003-0590-8512; GRABOWSKI, ALENA/0000-0002-4432-618X FU U.S. Department of Education, National Institute on Disability and Rehabilitation Research [H133A090020] FX This work was supported by the U.S. Department of Education, National Institute on Disability and Rehabilitation Research [grant number H133A090020]. NR 137 TC 0 Z9 0 U1 2 U2 9 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0309-3646 EI 1746-1553 J9 PROSTHET ORTHOT INT JI Prosthet. Orthot. Int. PD AUG PY 2014 VL 38 IS 4 BP 269 EP 286 DI 10.1177/0309364613500690 PG 18 WC Orthopedics; Rehabilitation SC Orthopedics; Rehabilitation GA AM8WM UT WOS:000340159500001 PM 24026045 ER PT J AU Kaatz, A Gutierrez, B Carnes, M AF Kaatz, Anna Gutierrez, Belinda Carnes, Molly TI Threats to objectivity in peer review: the case of gender SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Editorial Material ID SHIFTING STANDARDS; PUBLICATION; STEREOTYPES; BIAS C1 [Kaatz, Anna; Gutierrez, Belinda; Carnes, Molly] Univ Wisconsin, Ctr Womens Hlth Res, Madison, WI 53715 USA. [Gutierrez, Belinda; Carnes, Molly] William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Madison, WI USA. [Carnes, Molly] Univ Wisconsin, Dept Ind & Syst Engn, Madison, WI 53715 USA. [Carnes, Molly] Univ Wisconsin, Dept Med, Madison, WI 53715 USA. [Carnes, Molly] Univ Wisconsin, Dept Psychiat, Madison, WI 53715 USA. RP Carnes, M (reprint author), Univ Wisconsin, Ctr Womens Hlth Res, Madison, WI 53715 USA. EM mlcarnes@wisc.edu FU NIGMS NIH HHS [R01 GM111002] NR 17 TC 11 Z9 11 U1 1 U2 15 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD AUG PY 2014 VL 35 IS 8 BP 371 EP 373 DI 10.1016/j.tips.2014.06.005 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AN1KQ UT WOS:000340341600002 PM 25086743 ER PT J AU Smucny, J Wylie, KP Tregellas, JR AF Smucny, Jason Wylie, Korey P. Tregellas, Jason R. TI Functional magnetic resonance imaging of intrinsic brain networks for translational drug discovery SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Review DE biomarker; connectivity; graph theory; neuroimaging; resting state; schizophrenia ID RESTING-STATE NETWORKS; DEFAULT-MODE NETWORK; BOLD HEMODYNAMIC-RESPONSES; SMALL-WORLD NETWORKS; SCHIZOPHRENIA; CONNECTIVITY; FMRI; ARCHITECTURE; MODULATION; SYSTEMS AB Developing translational biomarkers is a priority for psychiatry research. Task-independent functional brain imaging is a relatively novel technique that allows examination of the brain's intrinsic networks, defined as functionally and (often) structurally connected populations of neurons whose properties reflect fundamental neurobiological organizational principles of the central nervous system. The ability to study the activity and organization of these networks has opened a promising new avenue for translational investigation, because they can be analogously examined across species and disease states. Interestingly, imaging studies have revealed shared spatial and functional characteristics of the intrinsic network architecture of the brain across species, including mice, rats, non-human primates, and humans. Using schizophrenia as an example, we show how intrinsic networks may show similar abnormalities in human diseases and animal models of these diseases, supporting their use as biomarkers in drug development. C1 [Smucny, Jason; Tregellas, Jason R.] Denver VA Med Ctr, Res Serv, Denver, CO 80220 USA. [Smucny, Jason; Wylie, Korey P.; Tregellas, Jason R.] Univ Colorado, Dept Psychiat, Aurora, CO USA. [Smucny, Jason; Tregellas, Jason R.] Univ Colorado, Neurosci Program, Aurora, CO USA. RP Tregellas, JR (reprint author), Denver VA Med Ctr, Res Serv, Denver, CO 80220 USA. EM Jason.tregellas@ucdenver.edu RI Tregellas, Jason/J-3637-2015 OI Smucny, Jason/0000-0001-5656-7987 FU NIMH NIH HHS [F31 MH102879] NR 64 TC 23 Z9 23 U1 1 U2 15 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD AUG PY 2014 VL 35 IS 8 BP 397 EP 403 DI 10.1016/j.tips.2014.05.001 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AN1KQ UT WOS:000340341600005 PM 24906509 ER PT J AU Yehuda, R Daskalakis, NP Lehrner, A Desarnaud, F Bader, HN Makotkine, I Flory, JD Bierer, LM Meaney, MJ AF Yehuda, Rachel Daskalakis, Nikolaos P. Lehrner, Amy Desarnaud, Frank Bader, Heather N. Makotkine, Iouri Flory, Janine D. Bierer, Linda M. Meaney, Michael J. TI Influences of Maternal and Paternal PTSD on Epigenetic Regulation of the Glucocorticoid Receptor Gene in Holocaust Survivor Offspring SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; PARENTAL PTSD; CHILDHOOD; METHYLATION; DEPRESSION; TRAUMA; MALTREATMENT; VALIDATION; RESPONSES; EXPOSURE AB Objective: Differential effects of maternal and paternal posttraumatic stress disorder (PTSD) have been observed in adult offspring of Holocaust survivors in both glucocorticoid receptor sensitivity and vulnerability to psychiatric disorder. The authors examined the relative influences of maternal and paternal PTSD on DNA methylation of the exon 1(F) promoter of the glucocorticoid receptor (GR-1(F)) gene (NR3C1) in peripheral blood mononuclear cells and its relationship to glucocorticoid receptor sensitivity in Holocaust offspring. Method: Adult offspring with at least one Holocaust survivor parent (N=80) and demographically similar participants without parental Holocaust exposure or parental PTSD (N=15) completed clinical interviews, self-report measures, and biological procedures. Blood samples were collected for analysis of GR-1(F) promoter methylation and of cortisol levels in response to low-dose dexamethasone, and two-way analysis of covariance was performed using maternal and paternal PTSD as main effects. Hierarchical clustering analysis was used to permit visualization of maternal compared with paternal PTSD effects on clinical variables and GR-1(F). promoter methylation. Results: A significant interaction demonstrated that in the absence of maternal PTSD, offspring with paternal PTSD showed higher GR-1(F) promoter methylation, whereas offspring with both maternal and paternal PTSD showed lower methylation. Lower GR-1(F) promoter methylation was significantly associated with greater post-dexamethasone cortisol suppression. The clustering analysis revealed that maternal and paternal PTSD effects were differentially associated with clinical indicators and GR-1(F) promoter methylation. Conclusions: This is the first study to demonstrate alterations of GR-1(F) promoter methylation in relation to parental PTSD and neuroendocrine outcomes. The moderation of paternal PTSD effects by maternal PTSD suggests different mechanisms for the intergenerational transmission of trauma-related vulnerabilities. C1 [Yehuda, Rachel] James J Peters Vet Affairs Med Ctr, Bronx, NY 10468 USA. Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY 10029 USA. McGill Univ, Douglas Mental Hlth Univ Inst, Ludmer Ctr Neuroinformat & Mental Hlth, Montreal, PQ, Canada. Agcy Sci Technol & Res, Singapore Inst Clin Sci, Singapore, Singapore. RP Yehuda, R (reprint author), James J Peters Vet Affairs Med Ctr, Bronx, NY 10468 USA. EM rachel.yehuda@va.gov RI Daskalakis, Nikolaos/B-7930-2014 OI Daskalakis, Nikolaos/0000-0003-1660-9112 FU NIMH [1RC1MH088101-01]; National Center for Advancing Translational Sciences (NCATS), a component of NIH [UL1TR000067] FX Supported by a grant from NIMH (1RC1MH088101-01) and by grant UL1TR000067 from the National Center for Advancing Translational Sciences (NCATS), a component of NIH. NIMH, NIH, and NCATS had no role in the study design, in the collection, analysis, and interpretation of the data, in writing the study, or in the decision to submit the study for publication. NR 40 TC 74 Z9 76 U1 11 U2 65 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X EI 1535-7228 J9 AM J PSYCHIAT JI Am. J. Psychiat. PD AUG PY 2014 VL 171 IS 8 BP 872 EP 880 DI 10.1176/appi.ajp.2014.13121571 PG 9 WC Psychiatry SC Psychiatry GA AM6QE UT WOS:000339988900013 PM 24832930 ER PT J AU Elvington, M Blichmann, P Qiao, F Scheiber, M Wadsworth, C Luzinov, I Lucero, J Vertegel, A Tomlinson, S AF Elvington, M. Blichmann, P. Qiao, F. Scheiber, M. Wadsworth, C. Luzinov, I. Lucero, J. Vertegel, A. Tomlinson, S. TI A novel protocol allowing oral delivery of a protein complement inhibitor that subsequently targets to inflamed colon mucosa and ameliorates murine colitis SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE colitis; complement; mouse model; oral delivery ID INFLAMMATORY-BOWEL-DISEASE; SODIUM-INDUCED COLITIS; DECAY-ACCELERATING FACTOR; DEXTRAN ESTER PRODRUGS; ULCERATIVE-COLITIS; CROHNS-DISEASE; GI TRACT; ACTIVATION; EXPRESSION; EPITHELIUM AB While there is evidence of a pathogenic role for complement in inflammatory bowel disease, there is also evidence for a protective role that relates to host defence and protection from endotoxaemia. There is thus concern regarding the use of systemic complement inhibition as a therapeutic strategy. Local delivery of a complement inhibitor to the colon by oral administration would ameliorate such concerns, but while formulations exist for oral delivery of low molecular weight drugs to the colon, they have not been used successfully for oral delivery of proteins. We describe a novel pellet formulation consisting of cross-linked dextran coated with an acrylic co-polymer that protects the complement inhibitor CR2-Crry from destruction in the gastrointestinal tract. CR2-Crry containing pellets administered by gavage, were characterized using a therapeutic protocol in a mouse model of dextran sulphate sodium (DSS)-induced colitis. Oral treatment of established colitis over a 5-day period significantly reduced mucosal inflammation and injury, with similar therapeutic benefit whether or not the proton pump inhibitor, omeprazole, was co-administered. Reduction in injury was associated with the targeting of CR2-Crry to the mucosal surface and reduced local complement activation. Treatment had no effect on systemic complement activity. This novel method for oral delivery of a targeted protein complement inhibitor will reduce systemic effects, thereby decreasing the risk of opportunistic infection, as well as lowering the required dose and treatment cost and improving patient compliance. Furthermore, the novel delivery system described here may provide similar benefits for administration of other protein-based drugs, such as anti-tumour necrosis factor-a antibodies. C1 [Elvington, M.; Qiao, F.; Scheiber, M.; Wadsworth, C.; Tomlinson, S.] Med Univ S Carolina, Dept Microbiol & Immunol, Darby Childrens Res Inst, Charleston, SC 29425 USA. [Tomlinson, S.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Blichmann, P.; Lucero, J.; Vertegel, A.] Clemson Univ, Dept Bioengn, Clemson, SC USA. [Luzinov, I.] Clemson Univ, Dept Mat Sci & Engn, Clemson, SC USA. RP Tomlinson, S (reprint author), Med Univ S Carolina, Dept Microbiol & Immunol, 173 Ashley Ave, Charleston, SC 29425 USA. EM tomlinss@musc.edu FU Crohn's and Colitis Foundation of America FX This work was supported by the Crohn's and Colitis Foundation of America. NR 30 TC 2 Z9 2 U1 0 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0009-9104 EI 1365-2249 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD AUG PY 2014 VL 177 IS 2 BP 500 EP 508 DI 10.1111/cei.12350 PG 9 WC Immunology SC Immunology GA AL9SI UT WOS:000339480700014 PM 24730624 ER PT J AU Deyo, RA Dworkin, SF Amtmann, D Andersson, G Borenstein, D Carragee, E Carrino, J Chou, R Cook, K DeLitto, A Goertz, C Khalsa, P Loeser, J Mackey, S Panagis, J Rainville, J Tosteson, T Turk, D Von Korff, M Weiner, DK AF Deyo, Richard A. Dworkin, Samuel F. Amtmann, Dagmar Andersson, Gunnar Borenstein, David Carragee, Eugene Carrino, John Chou, Roger Cook, Karon DeLitto, Anthony Goertz, Christine Khalsa, Partap Loeser, John Mackey, Sean Panagis, James Rainville, James Tosteson, Tor Turk, Dennis Von Korff, Michael Weiner, Debra K. TI Focus Article Report of the NIH Task Force on Research Standards for Chronic Low Back Pain SO CLINICAL JOURNAL OF PAIN LA English DT Article DE low back pain; chronic low back pain; research standards; minimum dataset; NIH Task Force ID CLINICAL-PRACTICE GUIDELINE; DEFINING CHRONIC PAIN; INFORMATION-SYSTEM PROMIS; FUNCTION ITEM BANK; QUALITY-OF-LIFE; PRIMARY-CARE; PROGNOSTIC APPROACH; SCREENING TOOL; START BACK; OUTCOME MEASURES AB Background: Despite rapidly increasing intervention, functional disability due to chronic low back pain (cLBP) has increased in recent decades. We often cannot identify mechanisms to explain the major negative impact cLBP has on patients' lives. Such cLBP is often termed non-specific and may be due to multiple biologic and behavioral etiologies. Researchers use varied inclusion criteria, definitions, baseline assessments, and outcome measures, which impede comparisons and consensus. Methods: The NIH Pain Consortium therefore charged a Research Task Force (RTF) to draft standards for research on cLBP. The resulting multidisciplinary panel developed a 3-stage process, each with a 2-day meeting. Results: The panel recommended using 2 questions to define cLBP; classifying cLBP by its impact (defined by pain intensity, pain interference, and physical function); use of a minimum dataset to describe research participants (drawing heavily on the PROMIS methodology); reporting "responder analyses" in addition to mean outcome scores; and suggestions for future research and dissemination. The Pain Consortium has approved the recommendations, which investigators should incorporate into NIH grant proposals. Conclusions: The RTF believes these recommendations will advance the field, help to resolve controversies, and facilitate future research addressing the genomic, neurologic, and other mechanistic substrates of chronic low back pain. Greater consistency in reporting should facilitate comparisons among studies and the development of phenotypes. We expect that the RTF recommendations will become a dynamic document and undergo continual improvement. C1 [Deyo, Richard A.; Chou, Roger] Oregon Hlth & Sci Univ, Portland, OR 97239 USA. [Dworkin, Samuel F.; Amtmann, Dagmar; Loeser, John; Turk, Dennis] Univ Washington, Seattle, WA 98195 USA. [Andersson, Gunnar] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Borenstein, David] George Washington Univ, Washington, DC USA. [Carragee, Eugene; Mackey, Sean] Stanford Univ, Stanford, CA 94305 USA. [Carrino, John] Johns Hopkins Univ, Baltimore, MD USA. [Cook, Karon] Northwestern Univ, Evanston, IL USA. [DeLitto, Anthony; Weiner, Debra K.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [DeLitto, Anthony; Weiner, Debra K.] Univ Pittsburgh, Pittsburgh, PA USA. [Goertz, Christine] Palmer Coll Chiropract, Davenport, IA USA. [Khalsa, Partap] Natl Ctr Complementary & Alternat Med, Bethesda, MD USA. [Panagis, James] NIAMSD, Bethesda, MD 20892 USA. [Rainville, James] New England Baptist Hosp, Roxbury Crossing, MA USA. [Tosteson, Tor] Dartmouth Coll, Hanover, NH USA. [Von Korff, Michael] Grp Hlth Res Inst, Seattle, WA USA. RP Deyo, RA (reprint author), Oregon Hlth & Sci Univ, 3181 SW Sam Jackson Pk Rd,Mail Code FM, Portland, OR 97239 USA. EM deyor@ohsu.edu FU National Center for Complementary and Alternative Medicine; National Institute for Arthritis, Musculoskeletal, and Skin Diseases FX This study was supported by the National Center for Complementary and Alternative Medicine and the National Institute for Arthritis, Musculoskeletal, and Skin Diseases. The authors declare no conflict of interest. NR 124 TC 4 Z9 5 U1 9 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0749-8047 EI 1536-5409 J9 CLIN J PAIN JI Clin. J. Pain PD AUG PY 2014 VL 30 IS 8 BP 701 EP 712 PG 12 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA AM2DI UT WOS:000339658900008 PM 24988192 ER PT J AU Cameron, MH Bethoux, F Davis, N Frederick, M AF Cameron, Michelle H. Bethoux, Francois Davis, Nina Frederick, Meredith TI Botulinum Toxin for Symptomatic Therapy in Multiple Sclerosis SO CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS LA English DT Review DE Multiple sclerosis; Spasticity; Botulinum toxin; Tremor; Incontinence ID NEUROGENIC DETRUSOR OVERACTIVITY; URINARY-INCONTINENCE; CONTROLLED-TRIAL; DOUBLE-BLIND; A TOXIN; SPASTICITY; INJECTIONS; TREMOR; ONABOTULINUMTOXINA; NEUROTOXIN AB Botulinumtoxin (BT) is a neurotoxin that paralyzes muscles by inhibiting release of acetylcholine from presynaptic vesicles at the neuromuscular junction. In people with multiple sclerosis (MS), clinical experience and research studies show that local injection of minute quantities of BT can temporarily control skeletal muscle spasticity, bladder detrusor hyperreflexia, and tremor. Specifically, BT injections have been shown to reduce muscle tone and improve passive function, and possibly improve active function, in patients with spasticity. Injection of BT into the bladder wall is a uniquely effective, safe, and durable treatment in patients with neurogenic detrusor hyperreflexia due to MS who have insufficient response or who do not tolerate oral antimuscarinic medications. This procedure has markedly reduced the need for indwelling catheters and bladder surgery. In addition, a recent study suggests BT may be effective for select patients with MS-associated upper extremity tremor. Appropriate use of BT can improve quality of life for many patients with MS. C1 [Cameron, Michelle H.; Frederick, Meredith] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Cameron, Michelle H.; Davis, Nina; Frederick, Meredith] Portland VA Med Ctr, Portland, OR USA. [Bethoux, Francois] Cleveland Clin, Mellen Ctr MS Treatment & Res, Cleveland, OH 44195 USA. [Davis, Nina] Oregon Hlth & Sci Univ, Dept Urol, Portland, OR 97201 USA. RP Cameron, MH (reprint author), Oregon Hlth & Sci Univ, Dept Neurol, 3181 SW Sam Jackson Pk Rd,L226, Portland, OR 97201 USA. EM cameromi@ohsu.edu; bethouf@ccf.org; davisni@ohsu.edu; frederim@ohsu.edu FU Concert Pharmaceuticals; Merz Pharma; Medtronic; GW Pharma; Allergan for development of educational presentations; Astellas Pharmaceuticals for development of educational presentations FX Francois Bethoux has received consultancy fees from Concert Pharmaceuticals, Merz Pharma, Medtronic, and GW Pharma, along with grants from Merz Pharma and Medtronic. He has also received payments from Allergan for development of educational presentations.; Nina Davis has received payments from Astellas Pharmaceuticals for development of educational presentations. NR 33 TC 4 Z9 4 U1 1 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1528-4042 EI 1534-6293 J9 CURR NEUROL NEUROSCI JI Curr. Neurol. Neurosci. Rep. PD AUG PY 2014 VL 14 IS 8 AR 463 DI 10.1007/s11910-014-0463-7 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AM3EB UT WOS:000339734100011 PM 24952479 ER PT J AU Cristancho, MA Thase, ME AF Cristancho, Mario A. Thase, Michael E. TI Drug safety evaluation of olanzapine/fluoxetine combination SO EXPERT OPINION ON DRUG SAFETY LA English DT Review DE bipolar depression; olanzapine-fluoxetine combination; safety and tolerability; treatment-resistant depression ID TREATMENT-RESISTANT DEPRESSION; BIPOLAR-I DEPRESSION; DOUBLE-BLIND; RANDOMIZED-TRIALS; BINDING PROFILE; OPEN-LABEL; FLUOXETINE; OLANZAPINE; DISORDER; MONOTHERAPY AB Introduction: Bipolar disorder and treatment-resistant depression (TRD) are common and recurrent conditions associated with significant disability, morbidity and mortality. Despite the clear need for effective treatments, only a few medications have been approved in the US for these indications. The combined formulation of olanzapine-fluoxetine (OFC) has been available for a decade now, thus a review on its safety profile and comparative efficacy is timely and can help clinicians to determine the benefit/risk profile of OFC within the context of other treatment alternatives. Areas covered: This paper summarizes the rationale and evidence supporting the use of OFC for both bipolar I depressive episodes and TRD with a focus on safety and tolerability. Product labels and the search engine PubMed was used to obtain relevant information on this subject. Expert opinion: Although further comparative studies are needed, the literature confirms that the OFC is an effective treatment for bipolar I depressive episodes, as well as major depressive episodes that have not responded to several adequate courses of antidepressant therapy. Its use as a first-line treatment for bipolar I depressive episodes and at a higher rung of algorithms for patients with TRD is limited by its propensity to cause weight gain and associated metabolic symptoms. C1 [Cristancho, Mario A.; Thase, Michael E.] Univ Penn, Perelman Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Thase, Michael E.] Philadelphia Vet Affairs Med Ctr, Dept Psychiat, Philadelphia, PA 19104 USA. RP Thase, ME (reprint author), Univ Penn, Perelman Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. EM thase@mail.med.upenn.edu FU Agency for Healthcare Research and Quality; Eli Lilly and Co.; Forest Pharmaceuticals; National Institute of Mental Health; Otsuka Pharmaceuticals FX M Thase has participated as an advisor/consultant for Alkermes, AstraZeneca, Bristol-Myerb Squibb, Eli Lilly & Co, Forest Laboratories (Incl PGx), Gerson Lehman Group, GlaxoSmithKline, Guidepoint Global, H. Lundbeck A/S, Janssen Pharmaceuticals, MedAvante, Inc., Merck and Co., Inc. (Incl Schering Plough and Organon), Neuronetics, Inc., Ortho-McNeil Pharmaceuticals (Incl Johnson & Johnson), Otsuka, Pfizer (Ind Wyeth Ayerst Pharmaceuticals, Roche, Shire US, Inc., Sunovion Pharmaceuticals, Inc., Takeda and Transcept Pharmaceuticals. He has received grant support from the Agency for Healthcare Research and Quality, Eli Lilly and Co., Forest Pharmaceuticals, the National Institute of Mental Health and Otsuka Pharmaceuticals. He has received honoraria for talks from AstraZeneca, Bristol-Myers Squibb Co., Eli Lilly & Co., Merck and Co., Inc., and Pfizer (Incl Wyeth Ayerst Pharmaceuticals). He has equity holdings in MedAvante, Inc. and has received royalties from the American Psychiatric Foundation, Guilford Publications, Herald House and W.W. Norton & Co., Inc. His spouse is employed by Peloton Advantage (formerly Advogent and Embryon) which does business with Pfizer/Wyeth. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 39 TC 2 Z9 2 U1 2 U2 5 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1474-0338 EI 1744-764X J9 EXPERT OPIN DRUG SAF JI Expert Opin. Drug Saf. PD AUG PY 2014 VL 13 IS 8 BP 1133 EP 1141 DI 10.1517/14740338.2014.933804 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AM4YM UT WOS:000339862100012 PM 24972823 ER PT J AU Ithapu, V Singh, V Lindner, C Austin, BP Hinrichs, C Carlsson, CM Bendlin, BB Johnson, SC AF Ithapu, Vamsi Singh, Vikas Lindner, Christopher Austin, Benjamin P. Hinrichs, Chris Carlsson, Cynthia M. Bendlin, Barbara B. Johnson, Sterling C. TI Extracting and Summarizing White Matter Hyperintensities Using Supervised Segmentation Methods in Alzheimer's Disease Risk and Aging Studies SO HUMAN BRAIN MAPPING LA English DT Article DE white matter hyperintensities; support vector machines; random forests; segmentation ID MILD COGNITIVE IMPAIRMENT; ASSOCIATION WORKGROUPS; DIAGNOSTIC GUIDELINES; LESION SEGMENTATION; NATIONAL INSTITUTE; IMAGE SEGMENTATION; MR-IMAGES; DEMENTIA; VOLUME; RECOMMENDATIONS AB Precise detection and quantification of white matter hyperintensities (WMH) observed in T2-weighted Fluid Attenuated Inversion Recovery (FLAIR) Magnetic Resonance Images (MRI) is of substantial interest in aging, and age-related neurological disorders such as Alzheimer's disease (AD). This is mainly because WMH may reflect co-morbid neural injury or cerebral vascular disease burden. WMH in the older population may be small, diffuse, and irregular in shape, and sufficiently heterogeneous within and across subjects. Here, we pose hyperintensity detection as a supervised inference problem and adapt two learning models, specifically, Support Vector Machines and Random Forests, for this task. Using texture features engineered by texton filter banks, we provide a suite of effective segmentation methods for this problem. Through extensive evaluations on healthy middle-aged and older adults who vary in AD risk, we show that our methods are reliable and robust in segmenting hyperintense regions. A measure of hyperintensity accumulation, referred to as normalized effective WMH volume, is shown to be associated with dementia in older adults and parental family history in cognitively normal subjects. We provide an open source library for hyperintensity detection and accumulation (interfaced with existing neuroimaging tools), that can be adapted for segmentation problems in other neuroimaging studies. (c) 2014 Wiley Periodicals, Inc. C1 [Ithapu, Vamsi; Singh, Vikas; Lindner, Christopher] Univ Wisconsin, Dept Comp Sci, Madison, WI 53706 USA. [Ithapu, Vamsi; Singh, Vikas; Austin, Benjamin P.; Carlsson, Cynthia M.; Bendlin, Barbara B.; Johnson, Sterling C.] Wisconsin Alzheimers Dis Res Ctr, Madison, WI USA. [Singh, Vikas] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI USA. [Austin, Benjamin P.; Carlsson, Cynthia M.; Bendlin, Barbara B.; Johnson, Sterling C.] Univ Wisconsin, Dept Med, Madison, WI USA. [Hinrichs, Chris] Univ Wisconsin, Dept Elect & Comp Engn, Madison, WI 53706 USA. [Johnson, Sterling C.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. RP Ithapu, V (reprint author), 5765 Med Sci Ctr, 1300 Univ Ave, Madison, WI 53706 USA. EM ithapu@wisc.edu OI Bendlin, Barbara/0000-0002-0580-9875 FU NIH [R01 AG040396, R01 G021155]; NSF [RI 1116584]; Wisconsin Partnership Fund, University of Wisconsin ADRC [P50 AG033514]; University of Wisconsin ICTR [1UL1RR025011]; Veterans Administration Merit Review Grant [I01CX000165]; CIBM [2T15LM007359] FX Contract grant sponsor: NIH; Contract grant numbers: R01 AG040396 and R01 G021155); Contract grant sponsor: NSF; Contract grant number: RI 1116584; Contract grant sponsor: Wisconsin Partnership Fund, University of Wisconsin ADRC; Contract grant number: P50 AG033514; Contract grant sponsor: University of Wisconsin ICTR; Contract grant number: 1UL1RR025011; Contract grant sponsor: Veterans Administration Merit Review Grant; Contract grant number: I01CX000165; Contract grant sponsor: CIBM postdoctoral fellowship via grant NLM; Contract grant number: 2T15LM007359 (to C. H.). NR 49 TC 14 Z9 14 U1 1 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1065-9471 EI 1097-0193 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD AUG PY 2014 VL 35 IS 8 BP 4219 EP 4235 DI 10.1002/hbm.22472 PG 17 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AL8YV UT WOS:000339426700049 PM 24510744 ER PT J AU Cao, H Yu, F Zhao, Y Zhang, XX Tai, J Lee, J Darehzereshki, A Bersohn, M Lien, CL Chi, NC Tai, YC Hsiai, TK AF Cao, Hung Yu, Fei Zhao, Yu Zhang, Xiaoxiao Tai, Joyce Lee, Juhyun Darehzereshki, Ali Bersohn, Malcolm Lien, Ching-Ling Chi, Neil C. Tai, Yu-Chong Hsiai, Tzung K. TI Wearable multi-channel microelectrode membranes for elucidating electrophysiological phenotypes of injured myocardium SO INTEGRATIVE BIOLOGY LA English DT Article ID HEART REGENERATION; ZEBRAFISH HEART; APOPTOSIS AB Understanding the regenerative capacity of small vertebrate models has provided new insights into the plasticity of injured myocardium. Here, we demonstrate the application of flexible microelectrode arrays (MEAs) in elucidating electrophysiological phenotypes of zebrafish and neonatal mouse models of heart regeneration. The 4-electrode MEA membranes were designed to detect electrical signals in the aquatic environment. They were micro-fabricated to adhere to the non-planar body surface of zebrafish and neonatal mice. The acquired signals were processed to display an electrocardiogram (ECG) with high signal-to-noise-ratios, and were validated via the use of conventional micro-needle electrodes. The 4-channel MEA provided signal stability and spatial resolution, revealing the site-specific electrical injury currents such as ST-depression in response to ventricular cryo-injury. Thus, our polymer-based and wearable MEA membranes provided electrophysiological insights into long-term conduction phenotypes for small vertebral models of heart injury and regeneration with a translational implication for monitoring cardiac patients. C1 [Cao, Hung; Yu, Fei; Lee, Juhyun; Hsiai, Tzung K.] Univ So Calif, Dept Biomed Engn, Los Angeles, CA 90089 USA. [Cao, Hung; Lee, Juhyun; Bersohn, Malcolm; Hsiai, Tzung K.] Univ Calif Los Angeles, Sch Med, Dept Med, Div Cardiol, Los Angeles, CA 90073 USA. [Zhao, Yu; Zhang, Xiaoxiao; Tai, Yu-Chong] CALTECH, Dept Elect Engn, Pasadena, CA 91125 USA. [Tai, Joyce] Tufts Univ, Medford, MA 02155 USA. [Darehzereshki, Ali; Lien, Ching-Ling] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Chi, Neil C.] Univ Calif San Diego, Sch Med, Dept Med, Div Cardiol, La Jolla, CA 92093 USA. [Cao, Hung; Lee, Juhyun; Bersohn, Malcolm; Hsiai, Tzung K.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Hsiai, TK (reprint author), Univ Calif Los Angeles, Henry Samueli Sch Engn & Appl Sci, David Geffen Sch Med, Dept Med Cardiol Bioengn & Physiol, Los Angeles, CA 90073 USA. EM THsiai@mednet.ucla.edu FU National Institutes of Health [HL-068689, HL-083015, HD069305-01, 1R01HL111437-01, R01HL096121-03] FX These studies were supported by National Institutes of Health HL-068689 (T.K.H), HL-083015 (T.K.H.), HD069305-01 (N.C.C., T.K.H.), 1R01HL111437-01 (T.K.H., N.C.C.), and R01HL096121-03 (C.L.L) NR 21 TC 5 Z9 5 U1 1 U2 21 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1757-9694 EI 1757-9708 J9 INTEGR BIOL-UK JI Integr. Biol. PD AUG PY 2014 VL 6 IS 8 BP 789 EP 795 DI 10.1039/c4ib00052h PG 7 WC Cell Biology SC Cell Biology GA AM5WA UT WOS:000339930500006 PM 24945366 ER PT J AU Ullrich, PM Lavela, SL Evans, CT Miskevics, S Weaver, FM Goldstein, B AF Ullrich, Philip M. Lavela, Sherri L. Evans, Charlesnika T. Miskevics, Scott Weaver, Frances M. Goldstein, Barry TI Associations between perceptions of evidence and adoption of H1N1 influenza infection prevention strategies among healthcare workers providing care to persons with spinal cord injury SO JOURNAL OF ADVANCED NURSING LA English DT Article DE adherence; evidence; guideline implementation; influenza prevention; promoting action on research implementation in health services; nursing ID PARIHS FRAMEWORK; IMPLEMENTATION STRATEGIES; ORGANIZATIONAL READINESS; GUIDELINE DISSEMINATION; UNIVERSAL PRECAUTIONS; DECISION-MAKING; INFORMATION; VACCINATION; ATTITUDES; SERVICES AB Aim. To examine associations between perceptions of evidence (research evidence, clinical expertise, patient preferences) and outcomes of a nationwide programme to implement H1N1 influenza prevention guidelines. Background. Healthcare workers do not consistently adhere to recommended infection control practices and this may be associated with their perceptions of evidence sources. Design. Cross-sectional mailed survey. Method. A survey of healthcare workers was administered in August 2010 after implementation of H1N1 prevention guidelines. Outcomes of interest were ratings of adherence to H1N1 prevention guidelines. Findings. Respondents with complete data (N = 283) were included in analyses. Facility-level adherence to guidelines was associated with opinions of clinical experts. Healthcare workers who rated clinical expertise as aligning with recommendations also rated their facilities as being more adherent to guidelines. Perceptions of research evidence and patient preferences were not associated with facility adherence. Personal adherence was not associated with perceptions of evidence, except among those healthcare workers who rated both clinical experts and patients as unsupportive of guidelines; these practitioners were less likely to adhere to recommended personal hygiene practices. Conclusion. Efforts to implement guidelines might be most effective when capitalizing on the influence of clinical experts. To better explain variability in guideline adherence, inclusion of a broader array of variables is recommended for future studies. C1 [Ullrich, Philip M.] Spinal Cord Injury Qual Enhancement Res Initiat S, Seattle, WA 98108 USA. [Ullrich, Philip M.; Goldstein, Barry] VA Puget Sound Healthcare Syst, Seattle, WA USA. [Lavela, Sherri L.; Evans, Charlesnika T.; Miskevics, Scott; Weaver, Frances M.] SCI QUERI, Hines, IL USA. [Lavela, Sherri L.; Evans, Charlesnika T.; Miskevics, Scott; Weaver, Frances M.] VA Hosp, Edward Hines Jr Dept Vet Affairs, Ctr Innovat Complex Chron Healthcare, Hines, IL USA. [Goldstein, Barry] SCI QUERI, Seattle, WA USA. RP Ullrich, PM (reprint author), Spinal Cord Injury Qual Enhancement Res Initiat S, Seattle, WA 98108 USA. EM philip.ullrich@va.gov FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service, Spinal Cord Injury Quality Enhancement Initiative (SCI QUERI) [RRP 10-046] FX This research was supported by a grant from the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service, Spinal Cord Injury Quality Enhancement Initiative (SCI QUERI, RRP 10-046). This paper presents the views of the authors; it does not necessarily represent the views or policies of the Department of Veterans Affairs or the Health Services Research and Development Service. NR 28 TC 0 Z9 0 U1 2 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0309-2402 EI 1365-2648 J9 J ADV NURS JI J. Adv. Nurs. PD AUG PY 2014 VL 70 IS 8 BP 1793 EP 1800 DI 10.1111/jan.12336 PG 8 WC Nursing SC Nursing GA AL9VW UT WOS:000339492500011 PM 24341504 ER PT J AU Ather, S Iqbal, F Gulotta, J Aljaroudi, W Heo, J Iskandrian, AE Hage, FG AF Ather, Sameer Iqbal, Fahad Gulotta, John Aljaroudi, Wael Heo, Jaekyeong Iskandrian, Ami E. Hage, Fadi G. TI Comparison of three commercially available softwares for measuring left ventricular perfusion and function by gated SPECT myocardial perfusion imaging SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Article DE Myocardial perfusion imaging; single-photon emission-computed tomography; left ventricular ejection fraction; perfusion defect size ID EMISSION COMPUTED-TOMOGRAPHY; CORONARY-ARTERY-DISEASE; EJECTION FRACTION; NUCLEAR CARDIOLOGY; AUTOMATIC QUANTIFICATION; PACKAGES; DEFECTS; VALIDATION; 4D-MSPECT; ACCURACY AB The three softwares, Quantitative Perfusion SPECT (QPS), Emory Cardiac Toolbox, and 4 Dimension-Myocardial SPECT (4DM) are widely used with myocardial perfusion imaging (MPI) to determine perfusion defect size (PDS) and left ventricular (LV) function. There are limited data on the degree of agreement between these methods in quantifying the LV perfusion pattern and function. In 120 consecutive patients who had abnormal regadenoson SPECT MPI with a visually derived summed stress score a parts per thousand yen4, the correlation between the softwares for measurements of PDS, reversible, and fixed defects was poor to fair (Spearman's rho = 0.18-0.72). Overall, estimation of defect size was smaller by QPS and larger by 4DM. There was discordance among the softwares in 62% of the cases in defining PDS as small/moderate/large. The correlation between the softwares was better for measuring LVEF, volumes and mass (rho = 0.84-0.97), and discrepant results for defining normal/mild-moderate/severe LV systolic dysfunction were prevalent in 28% of the patients. There are significant differences between the softwares in measuring PDS as well as LV function, and more importantly in defining small, moderate, or large ischemic burden. These results suggest the necessity of using the same software when assessing interval changes by serial imaging. C1 [Ather, Sameer; Heo, Jaekyeong; Iskandrian, Ami E.; Hage, Fadi G.] Univ Alabama Birmingham, Div Cardiovasc Dis, Birmingham, AL 35294 USA. [Iqbal, Fahad] Univ Minnesota, Med Ctr, Div Cardiovasc Dis, Minneapolis, MN 55455 USA. [Gulotta, John] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Aljaroudi, Wael] Amer Univ Beirut, Beirut, Lebanon. [Hage, Fadi G.] Birmingham Vet Affairs Med Ctr, Cardiol Sect, Birmingham, AL USA. RP Hage, FG (reprint author), Univ Alabama Birmingham, Div Cardiovasc Dis, Birmingham, AL 35294 USA. EM fadihage@uab.edu OI ather, sameer/0000-0002-5579-0658; Hage, Fadi/0000-0002-1397-4942 FU Astellas Pharma USA FX Dr Iskandrian is a scientific advisor for Rapidscan, Pharma and has received research grants from Astellas Pharma USA. Dr Hage is a scientific advisor for Astellas Pharma USA and has received investigator-initiated grant support from Astellas Pharma USA. The other authors report no financial disclosures. NR 32 TC 7 Z9 7 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1071-3581 EI 1532-6551 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD AUG PY 2014 VL 21 IS 4 BP 673 EP 681 DI 10.1007/s12350-014-9885-5 PG 9 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA AM6EU UT WOS:000339956900002 PM 24715622 ER PT J AU Aggarwal, H AlJaroudi, WA Mehta, S Mannon, R Heo, J Iskandrian, AE Hage, FG AF Aggarwal, Himanshu AlJaroudi, Wael A. Mehta, Shikha Mannon, Roslyn Heo, Jaekyeong Iskandrian, Ami E. Hage, Fadi G. TI The prognostic value of left ventricular mechanical dyssynchrony using gated myocardial perfusion imaging in patients with end-stage renal disease SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Article DE LV dyssynchrony; Phase analysis; End-stage renal disease; Myocardial perfusion imaging; Left ventricular ejection fraction ID EMISSION COMPUTED-TOMOGRAPHY; PHASE-ANALYSIS; SURVIVAL; THERAPY; SPECT AB Prior studies show that left ventricular mechanical dyssynchrony (LVD), measured by gated SPECT myocardial perfusion imaging (MPI), identifies patients with end-stage renal disease (ESRD) at higher risk for all-cause mortality but these were in small number of patients. We sought to assess the interaction between LVD and LV perfusion pattern in risk-stratification of a large sample size of patients with ESRD. From the renal transplantation database maintained at the University of Alabama at Birmingham, we identified consecutive patients with ESRD who had gated SPECT MPI between 2003 and 2007. MPIs were reprocessed to derive LV ejection fraction (EF), perfusion defect size, and LVD [phase bandwidth (BW) and phase standard deviation (SD)]. The primary end-point was all-cause mortality, which was prospectively collected and verified against the social security death index database. There were 828 patients aged 52.6 +/- A 0.36 years (45% were women and 60% had diabetes mellitus). The LVEF was 54.8 +/- A 0.4% and the perfusion pattern was abnormal in 334 patients (41%). During a follow-up period of 61 +/- A 0.9 months, 230 patients (28%) received renal transplants and 290 patients (35%) died. The phase BW (73.1 +/- A 2.6A degrees vs 66.3 +/- A 1.8A degrees, P = .02) and SD (25.2 +/- A 0.8A degrees vs 23.4 +/- A 0.5A degrees, P = .06) were greater in patients who died than those who survived indicating greater dyssynchrony. Patients with phase BW > 56A degrees or SD a parts per thousand yen21A degrees (median values) had worse 5-year survival (64% vs 72%, and 66% vs 71%, log-rank P = .005 and P = .07, respectively). After adjusting for demographics, co-morbidities, LVEF, and perfusion pattern, phase BW was associated with worse outcome (hazard ratio 1.289 95% CI 1.010-1.644, P = .04). LVD by phase analysis of gated SPECT MPI provides prognostic value in ESRD beyond myocardial perfusion and EF. C1 [Aggarwal, Himanshu; Heo, Jaekyeong; Iskandrian, Ami E.; Hage, Fadi G.] Univ Alabama Birmingham, Div Cardiovasc Dis, Birmingham, AL 35294 USA. [AlJaroudi, Wael A.] Amer Univ Beirut, Div Cardiovasc Dis, Med Ctr, Beirut, Lebanon. [Mehta, Shikha; Mannon, Roslyn] Univ Alabama Birmingham, Div Nephrol, Birmingham, AL 35294 USA. [Hage, Fadi G.] Birmingham Vet Affairs Med Ctr, Div Cardiol, Birmingham, AL USA. RP Hage, FG (reprint author), Univ Alabama Birmingham, Div Cardiovasc Dis, Birmingham, AL 35294 USA. EM fadihage@uab.edu OI Hage, Fadi/0000-0002-1397-4942 FU Astellas Pharma USA FX Dr Iskandrian is a scientific advisor for Rapidscan, Pharma and has received research grants from the Astellas Pharma USA. Dr Hage has received research grants from the Astellas Pharma USA. Dr Hage is a scientific advisor for Astellas Pharma USA. The other authors report no financial disclosures. NR 23 TC 11 Z9 11 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1071-3581 EI 1532-6551 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD AUG PY 2014 VL 21 IS 4 BP 739 EP 746 DI 10.1007/s12350-014-9886-4 PG 8 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA AM6EU UT WOS:000339956900011 PM 24858622 ER PT J AU Okon, L Werth, VP AF Okon, Lauren Werth, Victoria P. TI Challenges in measuring outcomes: Size assessment of an individual cutaneous lesion SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Editorial Material ID SURFACE-AREA; ULCERS C1 [Okon, Lauren; Werth, Victoria P.] Univ Penn, Perelman Sch Med, Dept Dermatol, Philadelphia, PA 19104 USA. [Werth, Victoria P.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Werth, VP (reprint author), Perelman Ctr Adv Med, Dept Dermatol, Ste 1-330A,3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM werth@mail.med.upenn.edu FU NIAMS NIH HHS [K24-AR 02207] NR 11 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD AUG PY 2014 VL 71 IS 2 BP 402 EP 404 DI 10.1016/j.jaad.2014.04.032 PG 3 WC Dermatology SC Dermatology GA AM6TJ UT WOS:000339997700049 PM 25037795 ER PT J AU Kottyan, LC Davis, BP Sherrill, JD Liu, K Rochman, M Kaufman, K Weirauch, MT Vaughn, S Lazaro, S Rupert, AM Kohram, M Stucke, EM Kemme, KA Magnusen, A He, H Dexheimer, P Chehade, M Wood, RA Pesek, RD Vickery, BP Fleischer, DM Lindbad, R Sampson, HA Mukkada, VA Putnam, PE Abonia, JP Martin, LJ Harley, JB Rothenberg, ME AF Kottyan, Leah C. Davis, Benjamin P. Sherrill, Joseph D. Liu, Kan Rochman, Mark Kaufman, Kenneth Weirauch, Matthew T. Vaughn, Samuel Lazaro, Sara Rupert, Andrew M. Kohram, Mojtaba Stucke, Emily M. Kemme, Katherine A. Magnusen, Albert He, Hua Dexheimer, Phillip Chehade, Mirna Wood, Robert A. Pesek, Robbie D. Vickery, Brian P. Fleischer, David M. Lindbad, Robert Sampson, Hugh A. Mukkada, Vincent A. Putnam, Phil E. Abonia, J. Pablo Martin, Lisa J. Harley, John B. Rothenberg, Marc E. TI Genome-wide association analysis of eosinophilic esophagitis provides insight into the tissue specificity of this allergic disease SO NATURE GENETICS LA English DT Article ID INTERLEUKIN-4 RECEPTOR-ALPHA; REGULATORY T-CELLS; SUSCEPTIBILITY LOCI; ATOPIC-DERMATITIS; GENE-EXPRESSION; CHROMOSOME 11Q13.5; EPITHELIAL-CELLS; DIETARY THERAPY; METAANALYSIS; VARIANTS AB Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder associated with allergic hypersensitivity to food. We interrogated >1.5 million genetic variants in EoE cases of European ancestry and subsequently in a multi-site cohort with local and out-of-study control subjects. In addition to replicating association of the 5q22 locus (meta-analysis P = 1.9 x 10(-16)), we identified an association at 2p23 spanning CAPN14 (P = 2.5 x 10(-10)). CAPN14 was specifically expressed in the esophagus, was dynamically upregulated as a function of disease activity and genetic haplotype and after exposure of epithelial cells to interleukin (IL)-13, and was located in an epigenetic hotspot modified by IL-13. Genes neighboring the top 208 EoE-associated sequence variants were enriched for esophageal expression, and multiple loci for allergic sensitization were associated with EoE susceptibility (4.8 x 10(-2) < P < 5.1 x 10(-11)). We propose a model to explain the tissue-specific nature of EoE that involves the interplay of allergic sensitization with an EoE-specific, IL-13-inducible esophageal response involving CAPN14. C1 [Kottyan, Leah C.; Kaufman, Kenneth; Weirauch, Matthew T.; Vaughn, Samuel; Lazaro, Sara; Magnusen, Albert; Harley, John B.] Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Ctr Autoimmune Genom & Etiol,Div Rheumatol, Cincinnati, OH USA. [Kottyan, Leah C.; Kaufman, Kenneth; Lazaro, Sara; Magnusen, Albert; Harley, John B.] US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA. [Kottyan, Leah C.; Davis, Benjamin P.; Sherrill, Joseph D.; Liu, Kan; Rochman, Mark; Stucke, Emily M.; Kemme, Katherine A.; Abonia, J. Pablo; Rothenberg, Marc E.] Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Div Allergy & Immunol, Cincinnati, OH 45220 USA. [Weirauch, Matthew T.; Kohram, Mojtaba; Dexheimer, Phillip] Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Div Biomed Informat, Cincinnati, OH USA. [He, Hua; Martin, Lisa J.] Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Div Human Genet, Cincinnati, OH USA. [Chehade, Mirna; Sampson, Hugh A.] Icahn Sch Med Mt Sinai, Dept Pediat, New York, NY 10029 USA. [Wood, Robert A.] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA. [Pesek, Robbie D.] Univ Arkansas Med Sci, Arkansas Childrens Hosp, Dept Pediat, Little Rock, AR 72205 USA. [Vickery, Brian P.] Univ N Carolina, Dept Pediat, Chapel Hill, NC USA. [Fleischer, David M.] Natl Jewish Hlth, Dept Pediat, Denver, CO USA. [Lindbad, Robert] EMMES Corp, Rockville, MD USA. [Mukkada, Vincent A.; Putnam, Phil E.] Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Div Gastroenterol Hepatol & Nutr, Cincinnati, OH USA. RP Rothenberg, ME (reprint author), Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Div Allergy & Immunol, Cincinnati, OH 45220 USA. EM rothenberg@cchmc.org RI ; Martin, Lisa/E-2425-2016 OI Abonia, Juan/0000-0003-3788-6485; Martin, Lisa/0000-0001-8702-9946; Kottyan, Leah/0000-0003-3979-2220 FU US NIH, National Institute of Allergy and Infectious Diseases (NIAID), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Heart, Lung, and Blood Institute (NHLBI); National Human Genome Research Institute (NHGRI) [U19 AI066738, U01 HG006828, U01 HG006828-S1, U01 HG006828-S2, U01 AI066560, R37 AI024717, P01 AI083194, T32 HL7752-19, K23 AI099083, P01 AR049084]; US NIH from NIAID and NIDDK [U19 AI066738]; National Center for Research Resources (NCRR), a component of the US NIH [UL1 TR001082, UL1 TR-000067, UL1 TR-000039, UL1 TR-000083, UL1 TR-000424]; US Department of Veteran Affairs [IMMA 9]; US Department of Defense [PR094002]; Cincinnati Children's Research Foundation and its Cincinnati Genomic Control Cohort; Campaign Urging Research for Eosinophilic Diseases (CURED); Buckeye Foundation; Food Allergy Research Education (FARE) Foundation; Foundation of the American College of Allergy, Asthma and Immunology FX Funding for this project was provided by the US NIH, National Institute of Allergy and Infectious Diseases (NIAID), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Heart, Lung, and Blood Institute (NHLBI) and National Human Genome Research Institute (NHGRI) (U19 AI066738, U01 HG006828, U01 HG006828-S1, U01 HG006828-S2, U01 AI066560, R37 AI024717, P01 AI083194, T32 HL7752-19, K23 AI099083 and P01 AR049084). The CoFAR arm of the study was supported by US NIH grant U19 AI066738 from NIAID and NIDDK. The project was also supported by several grants from the National Center for Research Resources (NCRR), a component of the US NIH: UL1 TR001082 (National Jewish), UL1 TR-000067 (Mount Sinai), UL1 TR-000039 (Arkansas), UL1 TR-000083 (University of North Carolina) and UL1 TR-000424 (Johns Hopkins). Support was also received from the US Department of Veteran Affairs (IMMA 9) and the US Department of Defense (PR094002). This research was supported in part by the Cincinnati Children's Research Foundation and its Cincinnati Genomic Control Cohort. Other support was derived from the Campaign Urging Research for Eosinophilic Diseases (CURED), the Buckeye Foundation, the Food Allergy Research Education (FARE) Foundation and the Foundation of the American College of Allergy, Asthma and Immunology. NR 53 TC 54 Z9 54 U1 2 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD AUG PY 2014 VL 46 IS 8 BP 895 EP 900 DI 10.1038/ng.3033 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA AM2TT UT WOS:000339704400021 PM 25017104 ER PT J AU Hepner, KA Paddock, SM Watkins, KE Solomon, J Blonigen, DM Pincus, HA AF Hepner, Kimberly A. Paddock, Susan M. Watkins, Katherine E. Solomon, Jacob Blonigen, Daniel M. Pincus, Harold Alan TI Veterans' Perceptions of Behavioral Health Care in the Veterans Health Administration: A National Survey SO PSYCHIATRIC SERVICES LA English DT Article ID PATIENT-CENTERED CARE; POSTTRAUMATIC-STRESS-DISORDER; INPATIENT CARE; MENTAL-HEALTH; UNITED-STATES; SATISFACTION; OUTCOMES; QUALITY; PERFORMANCE; IMPROVEMENT AB Objective: This study provided national estimates of perceptions of behavioral health care services among patients of the Veterans Health Administration (YHA) with a diagnosis of bipolar I disorder, major depression, posttraumatic stress disorder, schizophrenia, or substance use disorder. Methods: A stratified random sample of 6,190 patients completed telephone interviews from November 2008 through August 2009. Patients (N=5,185) who reported receiving VHA behavioral health care in the prior 12 months were asked about their need for housing and employment services, timeliness and recovery orientation of their care, satisfaction with care, and perceived improvement. Results: Half of patients reported always receiving routine appointments as soon as requested, and 42% were highly satisfied with their YHA mental health care. Approximately 74% of patients reported being helped by the treatment they received, yet only 32% reported that their symptoms had improved. After controlling for covariates, the analyses showed that patients with a substance use disorder reported lower satisfaction with care and perceived their treatment to be less helpful compared with patients without a substance use disorder. Conclusions: Although matched sample comparison data were not available, the results showed that overall patient perceptions of VHA mental health care were favorable, but there was significant room for improvement across all areas of assessment. A majority reported being helped by treatment, but few reported symptom improvement. Variations in perceptions among patients with different disorders suggest the potential importance of psychiatric diagnosis, particularly substance use disorder, in assessing patient perceptions of care. C1 [Hepner, Kimberly A.; Paddock, Susan M.; Watkins, Katherine E.; Solomon, Jacob; Pincus, Harold Alan] RAND Corp, Santa Monica, CA 90401 USA. [Pincus, Harold Alan] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. [Pincus, Harold Alan] New York Presbyterian Hosp, New York, NY USA. [Blonigen, Daniel M.] US Dept Vet Affairs, Ctr Hlth Care Evaluat, Palo Alto Hlth Care Syst, Palo Alto, CA USA. RP Hepner, KA (reprint author), RAND Corp, Santa Monica, CA 90401 USA. EM hepner@rand.org FU U.S. Department of Veterans Affairs (VA) [GS 10 F-0261K, 101-G67214/101-G67215]; Veterans Health Administration Mental Health Services; VA Substance Use Disorder Quality Enhancement Research Initiative [SUDQ-LIP 1206]; VA Office of Research and Development (Clinical Sciences Research and Development); Robert Wood Johnson Foundation; John A. Hartford Foundation; Heinz Endowments; Atlantic Philanthropies; UPMC Health Plan (Community Care Behavioral Health); Highmark Foundation; Staunton Farm Foundation; FISA Foundation; Eden Hall Foundation; SCAN Foundation; Graham Boeckh Foundation; Johnson and Johnson; Lifespan Health System; Alberta Innovates Health Solutions FX This project was funded by the U.S. Department of Veterans Affairs (VA) (contract number GS 10 F-0261K, 101-G67214/101-G67215; program evaluation of Veterans Health Administration Mental Health Services; and the VA Substance Use Disorder Quality Enhancement Research Initiative-SUDQ-LIP 1206). Dr. Blonigen was supported by a Career Development Award-2 from the VA Office of Research and Development (Clinical Sciences Research and Development). The authors thank Q. Burkhart, M.S., of the RAND Corporation for conducting study analyses. The opinions expressed here are the authors' and do not necessarily represent the views of the VA or any other entity of the U.S. government.; Dr. Pincus has received research funding from the Robert Wood Johnson Foundation, the John A. Hartford Foundation, the Heinz Endowments, the Atlantic Philanthropies, the UPMC Health Plan (Community Care Behavioral Health), the Highmark Foundation, the Staunton Farm Foundation, the FISA Foundation, the Eden Hall Foundation, the SCAN Foundation, and the Graham Boeckh Foundation; has served as a consultant or as a member of the advisory board for Value Options, Altarum Institute, and Manila Consulting; and has been paid for presentations by Johnson and Johnson, the Lifespan Health System, and Alberta Innovates Health Solutions. The other authors report no competing interests. NR 40 TC 5 Z9 5 U1 1 U2 6 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 EI 1557-9700 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD AUG PY 2014 VL 65 IS 8 BP 988 EP 996 DI 10.1176/appi.ps.201200385 PG 9 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA AM3TU UT WOS:000339776500006 PM 24733444 ER PT J AU Shaikh, H Morales, D Laghi, F AF Shaikh, Hameeda Morales, Daniel Laghi, Franco TI Weaning from Mechanical Ventilation SO SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Review DE mechanical ventilation; weaning; monitoring; diagnostic tests; screening; extubation ID INTENSIVE-CARE-UNIT; RANDOMIZED CONTROLLED-TRIAL; CRITICALLY-ILL PATIENTS; PRESSURE SUPPORT VENTILATION; CUFF-LEAK TEST; OBSTRUCTIVE PULMONARY-DISEASE; SPONTANEOUS BREATHING TRIAL; POSITIVE AIRWAY PRESSURE; POSTEXTUBATION STRIDOR; NATRIURETIC PEPTIDE AB For many critically ill patients admitted to an intensive care unit, the insertion of an endotracheal tube and the initiation of mechanical ventilation (MV) can be lifesaving procedures. Subsequent patient care often requires intensivists to manage the complex interaction of multiple failing organ systems. The shift in the intensivists' focus toward the discontinuation of MV can thus occur late in the course of critical illness. The dangers of MV, however, make it imperative to wean patients at the earliest possible time. Premature weaning trials, however, trigger significant respiratory distress, which can cause setbacks in the patient's clinical course. Premature extubation is also risky. To reduce delayed weaning and premature extubation, a three-step diagnostic strategy is suggested: measurement of weaning predictors, a trial of unassisted breathing (T-tube trial), and a trial of extubation. Since each step constitutes a diagnostic test, clinicians must not only command a thorough understanding of each test but must also be aware of the principles of clinical decision making when interpreting the information generated by each step. Many difficult aspects of pulmonary pathophysiology encroach on weaning management. Accordingly, weaning commands sophisticated, individualized care. Few other responsibilities of an intensivist require a more analytical effort and carry more promise for improving patient outcome than the application of physiologic principles in the weaning of patients. C1 [Shaikh, Hameeda; Laghi, Franco] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Hines, IL 60141 USA. [Morales, Daniel; Laghi, Franco] Loyola Univ, Div Pulm & Crit Care, Maywood, IL 60153 USA. RP Laghi, F (reprint author), Loyola Univ Chicago, Div Pulm & Crit Care Med, Dept Med, Stritch Sch Med,Edward Hines Jr VA Hosp, 111N,5th Ave & Roosevelt Rd, Hines, IL 60141 USA. EM flaghi@lumc.edu FU Veterans Administration Research Service FX This study was supported by grants from the Veterans Administration Research Service. NR 135 TC 0 Z9 0 U1 0 U2 14 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 1069-3424 EI 1098-9048 J9 SEMIN RESP CRIT CARE JI Semin. Respir. Crit. Care Med. PD AUG PY 2014 VL 35 IS 4 BP 451 EP 468 DI 10.1055/s-0034-1381953 PG 18 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA AM4YW UT WOS:000339863100006 PM 25141162 ER PT J AU Kranzler, HR AF Kranzler, Henry R. TI Commentary on Garbutt et al. (2014): Can we predict who benefits from naltrexone in the treatment of alcohol dependence? SO ADDICTION LA English DT Editorial Material DE Clinical predictors; critical review; family history of alcoholism; moderators; naltrexone; pharmacogenetics ID PROJECT MATCH C1 [Kranzler, Henry R.] Univ Penn, Perelman Sch Med, Ctr Studies Addict, Dept Psychiat, Philadelphia, PA 19104 USA. [Kranzler, Henry R.] Philadelphia VA Med Ctr, VISN Mental Illness Res Educ & Clin Ctr 4, Philadelphia, PA USA. RP Kranzler, HR (reprint author), Univ Penn, Perelman Sch Med, Ctr Studies Addict, Dept Psychiat, Philadelphia, PA 19104 USA. EM kranzler@mail.med.upenn.edu FU NIAAA NIH HHS [K24 AA013736, R01 AA021164] NR 9 TC 2 Z9 2 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0965-2140 EI 1360-0443 J9 ADDICTION JI Addiction PD AUG PY 2014 VL 109 IS 8 BP 1285 EP 1286 DI 10.1111/add.12618 PG 2 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA AL9QV UT WOS:000339476700014 PM 25041200 ER PT J AU Wong, ES Bryson, CL Hebert, PL Liu, CF AF Wong, Edwin S. Bryson, Chris L. Hebert, Paul L. Liu, Chuan-Fen TI Estimating the Impact of Oral Diabetes Medication Adherence on Medical Costs in VA SO ANNALS OF PHARMACOTHERAPY LA English DT Article DE medication adherence; diabetes; medical costs; instrumental variables; Department of Veterans Affairs ID HEALTH-CARE COST; ISSUES; HOSPITALIZATION; IDENTIFICATION; NONADHERENCE; ENDOGENEITY; MORTALITY; VETERANS; MODELS; RISK AB Background: Despite evidence demonstrating clinical benefits of oral hypoglycemic agents (OHAs), adherence to OHAs is generally poor. The economic benefit of OHA adherence among patients in the Veterans Affairs Health System (VA) is unknown. Objective: This study assessed the impact of OHA adherence on medical costs and hospitalization probability in a VA population. Methods: This retrospective cohort study included 26 051 VA patients with diabetes who completed the 2006 Survey of Health Care Experiences of Patients. We calculated total costs in fiscal year (FY) 2007 from the VA perspective as the sum of costs for all inpatient and outpatient services provided by VA. We measured adherence using the medication possession ratio (MPR), which reflected the proportion of days covered in FY2007. Patients were classified as adherent if MPR >= 80%. Analyses using instrumental variables (IVs) addressed potential biases from unobserved confounding. Results: On average, adherent patients incurred lower total medical costs ($4051 vs $5133, P < 0.001) and were less likely to be hospitalized (4.6% vs 7.2%, P < 0.001) compared with nonadherent patients. After covariate adjustment, adherence was associated with a $170 reduction in total costs (P < 0.011) and a 1.5 percentage point decrease (P < 0.001) in hospitalization probability. IV estimates indicated that the impacts of OHA adherence were larger in magnitude. Conclusion: On average, OHA adherence was associated with lower medical costs of at least $170 per patient over a I-year period. Results from this study are important for informing policy decisions to broadly disseminate programs to promote diabetes medication adherence, particularly in a VA setting. C1 [Wong, Edwin S.; Bryson, Chris L.; Hebert, Paul L.; Liu, Chuan-Fen] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Wong, Edwin S.; Bryson, Chris L.; Hebert, Paul L.; Liu, Chuan-Fen] Univ Washington, Seattle, WA 98195 USA. RP Wong, ES (reprint author), Ctr Innovat Vet Ctr & Value Driven Care, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM edwin.wong@va.gov FU Health Services Research and Development Service, Office of Research and Development, Department of Veterans Affairs [IIR 07-068]; VA Health Services Research and Development Career Development Award [CDA 13-024] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: All authors are employed by the Department of Veterans Affairs. This research was supported by the Health Services Research and Development Service, Office of Research and Development, Department of Veterans Affairs (IIR 07-068). Dr Wong is supported by VA Health Services Research and Development Career Development Award (CDA 13-024). The views expressed are those of the authors and do not necessarily reflect the views of the Department of Veterans Affairs and the University of Washington. NR 30 TC 7 Z9 7 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1060-0280 EI 1542-6270 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD AUG PY 2014 VL 48 IS 8 BP 978 EP 985 DI 10.1177/1060028014536981 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AL9LE UT WOS:000339461800004 PM 24847159 ER PT J AU Adams, TG Badour, CL Cisler, JM Feldner, MT AF Adams, Thomas G., Jr. Badour, Christal L. Cisler, Joshua M. Feldner, Matthew T. TI Contamination Aversion and Posttraumatic Stress Symptom Severity Following Sexual Trauma SO COGNITIVE THERAPY AND RESEARCH LA English DT Article DE Contamination; Sexual assault; Aversion; PTSD; OCD ID OBSESSIVE-COMPULSIVE DISORDER; ADMINISTERED PTSD SCALE; MENTAL CONTAMINATION; LATENT STRUCTURE; DISGUST; MEDIATION; PRODUCT; ASSAULT; MODELS; FEAR AB Contamination concerns have been linked to increased posttraumatic stress symptoms. The present study offered a preliminary test of the roles of domain-specific contamination aversions in posttraumatic stress. Fifty women with a history of sexual or physical assault were recruited from the community and assessed for posttraumatic stress symptom severity and individual differences in mental contamination, direct contamination aversion [aversion to normative contaminants (e.g., garbage)], indirect contamination aversion [aversion to perceived contaminants (e.g., handrails)], and symptoms of contamination-based obsessive-compulsive disorder. We observed large and significant relations between posttraumatic stress symptoms and all forms of contamination fears and aversions among participants reporting sexual trauma, but minimal and non-significant relations among victims of physical assault. Exploratory tests revealed that the effects of basic contamination aversions on posttraumatic stress symptom severity were largely mediated by mental contamination. The present study suggests that contamination fears and aversions (i.e., normal or perceived) are highly related to posttraumatic stress symptoms among sexual trauma victims and highlights the importance of assessing and targeting feelings and evaluations related to contamination when treating posttraumatic stress symptoms among sexual trauma victims. C1 [Adams, Thomas G., Jr.; Badour, Christal L.; Feldner, Matthew T.] Univ Arkansas, Fayetteville, AR 72701 USA. [Adams, Thomas G., Jr.; Badour, Christal L.] Med Univ S Carolina, Charleston, SC 29425 USA. [Adams, Thomas G., Jr.; Badour, Christal L.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Cisler, Joshua M.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Feldner, Matthew T.] Laureate Inst Brain Res, Tulsa, OK USA. RP Adams, TG (reprint author), Univ Arkansas, 212 Mem Hall, Fayetteville, AR 72701 USA. EM tomadams@uark.edu; mfelde@uark.edu NR 43 TC 0 Z9 0 U1 2 U2 7 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0147-5916 EI 1573-2819 J9 COGNITIVE THER RES JI Cogn. Ther. Res. PD AUG PY 2014 VL 38 IS 4 BP 449 EP 457 DI 10.1007/s10608-014-9609-9 PG 9 WC Psychology, Clinical SC Psychology GA AL8IO UT WOS:000339382000009 ER PT J AU Halpern, NA Shaz, D AF Halpern, Neil A. Shaz, David TI Return on Investment: Just Knowing the Price Is Not Enough! SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE critical care; healthcare informatics; return on investment ID INTENSIVE-CARE-UNIT; TECHNOLOGY; SAFETY; SYSTEM; COST C1 [Halpern, Neil A.; Shaz, David] Mem Sloan Kettering Canc Ctr, Dept Anesthesiol & Crit Care, New York, NY 10021 USA. [Shaz, David] James J Peters VA Med Ctr, Dept Med, Bronx, NY USA. RP Halpern, NA (reprint author), Mem Sloan Kettering Canc Ctr, Dept Anesthesiol & Crit Care, 1275 York Ave, New York, NY 10021 USA. NR 18 TC 0 Z9 0 U1 3 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD AUG PY 2014 VL 42 IS 8 BP 1952 EP 1953 DI 10.1097/CCM.0000000000000422 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA AL7QV UT WOS:000339330700055 PM 25029139 ER PT J AU Ho, EY Cozen, ML Shen, H Lerrigo, R Trimble, E Ryan, JC Corvera, CU Monto, A AF Ho, Edith Y. Cozen, Myrna L. Shen, Hui Lerrigo, Robert Trimble, Erica Ryan, James C. Corvera, Carlos U. Monto, Alexander CA HOVAS Grp Hepatocellular Carcinoma TI Expanded use of aggressive therapies improves survival in early and intermediate hepatocellular carcinoma SO HPB LA English DT Article ID HEPATITIS-C INFECTION; UNITED-STATES; LIVER-TRANSPLANTATION; RADIOFREQUENCY ABLATION; RESECTION; VETERANS; CHEMOEMBOLIZATION; MULTICENTER; POPULATION; RECURRENCE AB Background: Despite the increasing annual incidence of hepatocellular carcinoma (HCC) in the USA, now estimated at 2.7 cases per 100 000 population, only a small proportion of patients receive treatment and 5-year survival rates range from 9% to 17%. Objectives: The present study examines the effects of multimodal treatment on survival in a mixed-stage HCC cohort, focusing on the impact of radical therapy in patients with Barcelona Clinic Liver Cancer (BCLC) stage B disease. Methods: A retrospective review of the medical records of 254 patients considered for HCC treatment between 2003 and 2011 at a large tertiary referral centre was conducted. Results: A total of 195 (76.8%) patients were treated with a median of two liver-directed interventions. Median survival time was 16 months. In proportional hazards analysis, radiofrequency ablation (RFA) and resection were associated with significantly improved 1- and 5-year survival among patients with BCLC stage 0-A disease. In patients with BCLC stage B disease, RFA conferred a survival benefit at 1 year and resection was associated with significantly improved survival at 5 years. Conclusions: As one of few studies to track the complete course of sequential HCC therapies, the findings of the present study suggest that HCC patients with intermediate-stage (BCLC stage B) disease may benefit from aggressive interventions not currently included in societal guidelines. C1 [Ho, Edith Y.; Monto, Alexander] Univ Calif San Francisco, Dept Med, Div Gastroenterol, San Francisco, CA USA. [Cozen, Myrna L.; Shen, Hui; Lerrigo, Robert; Ryan, James C.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Corvera, Carlos U.] Univ Calif San Francisco, Dept Surg, San Francisco, CA USA. [Cozen, Myrna L.; Shen, Hui; Trimble, Erica; Ryan, James C.] San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA. [Corvera, Carlos U.] San Francisco VA Med Ctr, Dept Surg, San Francisco, CA USA. [Monto, Alexander] San Francisco VA Med Ctr, Dept Med, Div Gastroenterol, San Francisco, CA USA. RP Monto, A (reprint author), San Francisco VA Med Ctr, Gastroenterol Sect 111 B, 4150 Clement St, San Francisco, CA 94121 USA. EM alexander.monto@va.gov FU Veterans Affairs Merit Award Program [1I01-CX000295-01A1]; Veterans Affairs Hepatitis C Resource Center FX Veterans Affairs Merit Award Program (1I01-CX000295-01A1) and Veterans Affairs Hepatitis C Resource Center. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. NR 38 TC 6 Z9 6 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1365-182X EI 1477-2574 J9 HPB JI HPB PD AUG PY 2014 VL 16 IS 8 BP 758 EP 767 DI 10.1111/hpb.12214 PG 10 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA AM2FQ UT WOS:000339665600010 PM 24467780 ER PT J AU Jin, J Zhang, X Lu, Z Li, Y Lopes-Virella, MF Yu, H Haycraft, CJ Li, Q Kirkwood, KL Huang, Y AF Jin, J. Zhang, X. Lu, Z. Li, Y. Lopes-Virella, M. F. Yu, H. Haycraft, C. J. Li, Q. Kirkwood, K. L. Huang, Y. TI Simvastatin inhibits lipopolysaccharide-induced osteoclastogenesis and reduces alveolar bone loss in experimental periodontal disease SO JOURNAL OF PERIODONTAL RESEARCH LA English DT Article DE alveolar bone; inflammation; lipopolysaccharide; periodontal disease; simvastatin ID NF-KAPPA-B; CARDIOVASCULAR-DISEASE; OVARIECTOMIZED RATS; MONONUCLEAR-CELLS; STATIN THERAPY; IN-VIVO; EXPRESSION; SUPPRESSES; ACTIVATION; MECHANISMS AB Background and Objective: Statins are inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase and have anti-inflammatory effects independent of cholesterol lowering. Recent clinical studies have indicated that statin intake has a beneficial effect on periodontal disease. However, the underlying mechanisms have not been well understood. In the current study, we employed a rat model with lipopolysaccharide (LPS)-induced periodontal disease and determined the effect of simvastatin, a commonly prescribed statin, on osteoclastogenesis, gingival inflammation and alveolar bone loss. Material and Methods: Sprague-Dawley rats were injected with Aggregatibacter actinomycetemcomitans LPS in periodontal tissue three times per week for 8 wk and part of the rats with LPS injection were also given simvastatin via gavage. After the treatments, the rat maxillae were scanned by microcomputed tomography and the images were analyzed to determine alveolar bone loss. To explore the underlying mechanisms, the effect of simvastatin on osteoclastogenesis and gingival expression of proinflammatory cytokines were also determined by tartrate-resistant acid phosphatase staining and real-time polymerase chain reaction assays, respectively. Results: Results showed that LPS treatment markedly increased bone loss, but administration of simvastatin significantly alleviated the bone loss. Results also showed that LPS treatment stimulated osteoclastogenesis and the expression of inflammatory cytokines, but simvastatin significantly modulates the stimulatory effect of LPS on osteoclastogenesis and cytokine expression. Conclusion: This study demonstrated that simvastatin treatment inhibits LPS-induced osteoclastogenesis and gingival inflammation and reduces alveolar bone loss, indicating that the intake of simvastatin may hinder the progression of periodontal disease. C1 [Jin, J.; Zhang, X.; Lu, Z.; Li, Y.; Lopes-Virella, M. F.; Huang, Y.] Med Univ S Carolina, Coll Med, Dept Med, Div Endocrinol Diabet & Med Genet, Charleston, SC 29425 USA. [Lopes-Virella, M. F.; Huang, Y.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Yu, H.; Haycraft, C. J.; Li, Q.; Kirkwood, K. L.] Med Univ S Carolina, Coll Dent Med, Dept Craniofacial Biol, Charleston, SC 29425 USA. RP Huang, Y (reprint author), Ralph H Johnson Vet Aairs Med Ctr, 114 Doughty St, Charleston, SC 29403 USA. EM huangyan@musc.edu FU National Institutes of Health [DE016353]; Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs; National Institute of General Medicine [P30 GM103331] FX This work was supported by National Institutes of Health grant DE016353 and the Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs (to Y.H.). This project used facilities, resources and/or technical assistance of the Laboratory of the Center for Oral Health Research (L-COHR) that is supported by the National Institute of General Medicine grant P30 GM103331. NR 39 TC 6 Z9 8 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3484 EI 1600-0765 J9 J PERIODONTAL RES JI J. Periodont. Res. PD AUG PY 2014 VL 49 IS 4 BP 518 EP 526 DI 10.1111/jre.12132 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA AM0AB UT WOS:000339503800012 PM 24117880 ER PT J AU Norton, S Matthews, FE Barnes, DE Yaffe, K Brayne, C AF Norton, Sam Matthews, Fiona E. Barnes, Deborah E. Yaffe, Kristine Brayne, Carol TI Potential for primary prevention of Alzheimer's disease: an analysis of population-based data SO LANCET NEUROLOGY LA English DT Article ID PUBLIC-HEALTH IMPACT; RISK-FACTOR; COGNITIVE FUNCTION; UNITED-STATES; DEMENTIA; PREVALENCE; METAANALYSIS; PROJECTIONS; DEPRESSION AB Background Recent estimates suggesting that over half of Alzheimer's disease burden worldwide might be attributed to potentially modifiable risk factors do not take into account risk-factor non-independence. We aimed to provide specific estimates of preventive potential by accounting for the association between risk factors. Methods Using relative risks from existing meta-analyses, we estimated the population-attributable risk (PAR) of Alzheimer's disease worldwide and in the USA, Europe, and the UK for seven potentially modifiable risk factors that have consistent evidence of an association with the disease (diabetes, midlife hypertension, midlife obesity, physical inactivity, depression, smoking, and low educational attainment). The combined PAR associated with the risk factors was calculated using data from the Health Survey for England 2006 to estimate and adjust for the association between risk factors. The potential of risk factor reduction was assessed by examining the combined effect of relative reductions of 10% and 20% per decade for each of the seven risk factors on projections for Alzheimer's disease cases to 2050. Findings Worldwide, the highest estimated PAR was for low educational attainment (19.1%, 95% CI 12.3-25.6). The highest estimated PAR was for physical inactivity in the USA (21.0%, 95% CI 5.8-36.6), Europe (20.3%, 5.6-35.6), and the UK (21.8%, 6.1-37.7). Assuming independence, the combined worldwide PAR for the seven risk factors was 49.4% (95% CI 25.7-68.4), which equates to 16.8 million attributable cases (95% CI 8.7-23.2 million) of 33.9 million cases. However, after adjustment for the association between the risk factors, the estimate reduced to 28.2% (95% CI 14.2-41.5), which equates to 9.6 million attributable cases (95% CI 4.8-14.1 million) of 33.9 million cases. Combined PAR estimates were about 30% for the USA, Europe, and the UK. Assuming a causal relation and intervention at the correct age for prevention, relative reductions of 10% per decade in the prevalence of each of the seven risk factors could reduce the prevalence of Alzheimer's disease in 2050 by 8.3% worldwide. Interpretation After accounting for non-independence between risk factors, around a third of Alzheimer's diseases cases worldwide might be attributable to potentially modifiable risk factors. Alzheimer's disease incidence might be reduced through improved access to education and use of effective methods targeted at reducing the prevalence of vascular risk factors (eg, physical inactivity, smoking, midlife hypertension, midlife obesity, and diabetes) and depression. C1 [Norton, Sam] Kings Coll London, Inst Psychiat, Dept Psychol, London, England. [Matthews, Fiona E.] Inst Publ Hlth, Med Res Council Biostat, Cambridge, England. [Barnes, Deborah E.; Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Barnes, Deborah E.; Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Barnes, Deborah E.; Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA. [Brayne, Carol] Univ Cambridge, Inst Publ Hlth, Cambridge CB2 0SR, England. RP Brayne, C (reprint author), Univ Cambridge, Inst Publ Hlth, Cambridge CB2 0SR, England. EM carol.brayne@medschl.cam.ac.uk RI Norton, Sam/A-1898-2009 OI Norton, Sam/0000-0003-1714-9963; Matthews, Fiona/0000-0002-1728-2388 FU National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care for Cambridgeshire and Peterborough FX National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care for Cambridgeshire and Peterborough. NR 32 TC 250 Z9 256 U1 21 U2 128 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1474-4422 EI 1474-4465 J9 LANCET NEUROL JI Lancet Neurol. PD AUG PY 2014 VL 13 IS 8 BP 788 EP 794 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA AL9JB UT WOS:000339456300013 PM 25030513 ER PT J AU Tse, JR Long, JL AF Tse, Justin R. Long, Jennifer L. TI Microstructure Characterization of a Decellularized Vocal Fold Scaffold for Laryngeal Tissue Engineering SO LARYNGOSCOPE LA English DT Article DE Vocal folds; Young's modulus; scaffolds; tissue engineering; decellularized ID BOVINE ACELLULAR SCAFFOLD; EXTRACELLULAR-MATRIX; CANINE MODEL; STEM-CELLS; RECONSTRUCTION; COLLAGEN; ELASTIN; SCAR AB Objectives/Hypothesis: One potential treatment for vocal fold injury or neoplasia is to replace the entire vocal fold with a tissue-engineered scaffold. This scaffold should ideally have similar mechanical properties and extracellular matrix composition as the native vocal fold. As one approach toward this goal, we decellularized human vocal folds and characterized their mechanical properties and extracellular matrix microstructure. Study Design: Basic science investigation. Methods: Human vocal folds were dissected from the laryngeal framework and treated with sodium dodecyl sulfate (SDS) to remove all cells. Mechanical properties were measured by indentation before and after SDS treatment. The extracellular matrix components of collagen, laminin, elastin, and hyaluronic acid were also characterized before and after decellularization using histology and immunofluorescence. Results: After 4 days of SDS treatment, we obtained a scaffold that retained the original geometry of the vocal fold but was devoid of cells. The elastic modulus of the vocal folds did not change significantly before and after decellularization. Upon qualitative inspection, the decellularized vocal folds retained the original collagen, elastin, and laminin content and orientation but lost the original hyaluronic acid. Conclusions: Vocal folds can be decellularized using SDS without adversely affecting its mechanical stiffness and fibrous extracellular matrix. This preliminary study demonstrates the potential of a decellularized scaffold to serve as a tissue-engineered construct for vocal fold replacement. C1 [Long, Jennifer L.] Univ Calif Los Angeles, Dept Head & Neck Surg, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Long, Jennifer L.] VA Greater Los Angeles Med Ctr, Los Angeles, CA USA. RP Long, JL (reprint author), Univ Calif Los Angeles, Dept Head & Neck Surg, CHS Room 62-132,650 Charles Young Dr, Los Angeles, CA 90095 USA. EM jlong@mednet.ucla.edu OI Long, Jennifer/0000-0002-4185-2328 FU National Institute of Child Health and Human Development FX The authors thank Drs. Melody Xuan, Zhaoyan Zhang, and Ivan Lopez for their technical support. The laminin B2 monoclonal antibody developed by J. R. Sanes was obtained from the Developmental Studies Hybridoma Bank, developed under the auspices of the National Institute of Child Health and Human Development and maintained by the University of Iowa, Department of Biology, Iowa City, Iowa. NR 28 TC 7 Z9 7 U1 0 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X EI 1531-4995 J9 LARYNGOSCOPE JI Laryngoscope PD AUG PY 2014 VL 124 IS 8 BP E326 EP E331 DI 10.1002/lary.24605 PG 6 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA AL9ST UT WOS:000339482100005 PM 24448829 ER PT J AU Kertesz, SG Pollio, DE Jones, RN Steward, J Stringfellow, EJ Gordon, AJ Johnson, NK Kim, TA Daigle, SG Austin, EL Young, AS Chrystal, JG Davis, LL Roth, DL Holt, CL AF Kertesz, Stefan G. Pollio, David E. Jones, Richard N. Steward, Jocelyn Stringfellow, Erin J. Gordon, Adam J. Johnson, Nancy K. Kim, Theresa A. Daigle, Shanette G. Austin, Erika L. Young, Alexander S. Chrystal, Joya G. Davis, Lori L. Roth, David L. Holt, Cheryl L. TI Development of the Primary Care Quality-Homeless (PCQ-H) Instrument A Practical Survey of Homeless Patients' Experiences in Primary Care SO MEDICAL CARE LA English DT Article DE patient satisfaction; item response theory; patient-centered care; survey methodology; patient-centered outcomes research; homeless persons; homeless health care ID HEALTH-CARE; PSYCHOMETRIC PROPERTIES; CONSUMER ASSESSMENT; COMPARING HOMELESS; MEDICAL-CARE; ADULTS; VETERANS; SERVICES; PERCEPTIONS; PERFORMANCE AB Background: Homeless patients face unique challenges in obtaining primary care responsive to their needs and context. Patient experience questionnaires could permit assessment of patient-centered medical homes for this population, but standard instruments may not reflect homeless patients' priorities and concerns. Objectives: This report describes (a) the content and psychometric properties of a new primary care questionnaire for homeless patients; and (b) the methods utilized in its development. Methods: Starting with quality-related constructs from the Institute of Medicine, we identified relevant themes by interviewing homeless patients and experts in their care. A multidisciplinary team drafted a preliminary set of 78 items. This was administered to homeless-experienced clients (n = 563) across 3 VA facilities and 1 non-VA Health Care for the Homeless Program. Using Item Response Theory, we examined Test Information Function (TIF) curves to eliminate less informative items and devise plausibly distinct subscales. Results: The resulting 33-item instrument (Primary Care Quality-Homeless) has 4 subscales: Patient-Clinician Relationship (15 items), Cooperation among Clinicians (3 items), Access/Coordination (11 items), and Homeless-specific Needs (4 items). Evidence for divergent and convergent validity is provided. TIF graphs showed adequate informational value to permit inferences about groups for 3 subscales (Relationship, Cooperation, and Access/Coordination). The 3-item Cooperation subscale had lower informational value (TIF < 5) but had good internal consistency (alpha = 0.75) and patients frequently reported problems in this aspect of care. Conclusions: Systematic application of qualitative and quantitative methods supported the development of a brief patient-reported questionnaire focused on the primary care of homeless patients and offers guidance for future population-specific instrument development. C1 [Kertesz, Stefan G.] Univ Alabama Birmingham, Sch Med, Birmingham VA Med Ctr, Birmingham, AL USA. [Pollio, David E.] Univ Alabama Birmingham, Dept Social Work, Birmingham, AL USA. [Jones, Richard N.] Brown Univ, Alpert Sch Med, Providence, RI 02912 USA. [Steward, Jocelyn] Univ Alabama Birmingham, Sch Hlth Related Profess, Birmingham, AL USA. [Stringfellow, Erin J.] Washington Univ, George Warren Brown Sch Social Work, St Louis, MO 63130 USA. [Gordon, Adam J.] Univ Pittsburgh, Sch Med, Ctr Hlth Equ Res & Promot, VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. [Johnson, Nancy K.; Austin, Erika L.] Birmingham VA Med Ctr, Birmingham, AL USA. [Kim, Theresa A.] Boston Univ, Sch Med, Boston Hlth Care Homeless Program, Boston, MA 02118 USA. [Daigle, Shanette G.] Univ Alabama Birmingham, Dept Vet Affairs, Birmingham Atlanta Geriatr Res Educ & Clin Ctr GR, Birmingham, AL USA. [Young, Alexander S.; Chrystal, Joya G.] Univ Calif Los Angeles, VA Desert Pacific Mental Illness Res Educ & Clin, Los Angeles, CA USA. [Young, Alexander S.; Chrystal, Joya G.] Univ Calif Los Angeles, Dept Psychiat, Greater Los Angeles VA Healthcare Ctr, Los Angeles, CA USA. [Davis, Lori L.] Tuscaloosa VA Med Ctr, Tuscaloosa, AL USA. [Roth, David L.] Johns Hopkins Univ, Ctr Aging & Hlth, Baltimore, MD USA. [Holt, Cheryl L.] Univ Maryland, Sch Publ Hlth, College Pk, MD 20742 USA. RP Kertesz, SG (reprint author), Div Prevent Med, MT 608,1720 2nd Ave S, Birmingham, AL 35294 USA. EM skertesz@uabmc.edu RI Jones, Richard/J-3488-2013 OI Jones, Richard/0000-0002-1049-218X; Kertesz, Stefan/0000-0001-6101-8421 FU VA Health Services Research and Development FX The authors are obligated both to acknowledge their funding (VA Health Services Research and Development) and a VA disclaimer to indicate that the views are their own and not those of the Federal Government. NR 63 TC 3 Z9 3 U1 2 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD AUG PY 2014 VL 52 IS 8 BP 734 EP 742 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AL7RQ UT WOS:000339332900011 PM 25023918 ER PT J AU Gulati, T Ramanathan, DS Wong, CC Ganguly, K AF Gulati, Tanuj Ramanathan, Dhakshin S. Wong, Chelsea C. Ganguly, Karunesh TI Reactivation of emergent task-related ensembles during slow-wave sleep after neuroprosthetic learning SO NATURE NEUROSCIENCE LA English DT Article ID MOTOR MEMORY CONSOLIDATION; BRAIN-COMPUTER INTERFACE; SUBSEQUENT SLEEP; CELL ASSEMBLIES; NEURONS; CORTEX; RAT; ARM; TETRAPLEGIA; PLASTICITY AB Brain-machine interfaces can allow neural control over assistive devices. They also provide an important platform for studying neural plasticity. Recent studies have suggested that optimal engagement of learning is essential for robust neuroprosthetic control. However, little is known about the neural processes that may consolidate a neuroprosthetic skill. On the basis of the growing body of evidence linking slow-wave activity (SWA) during sleep to consolidation, we examined whether there is 'offline' processing after neuroprosthetic learning. Using a rodent model, we found that, after successful learning, task-related units specifically experienced increased locking and coherency to SWA during sleep. Moreover, spike-spike coherence among these units was substantially enhanced. These changes were not present with poor skill acquisition or after control awake periods, demonstrating the specificity of our observations to learning. Notably, the time spent in SWA predicted the performance gains. Thus, SWA appears to be involved in offline processing after neuroprosthetic learning. C1 [Gulati, Tanuj; Ramanathan, Dhakshin S.; Wong, Chelsea C.; Ganguly, Karunesh] San Francisco VA Med Ctr, Neurol & Rehabil Dept, San Francisco, CA 94121 USA. [Gulati, Tanuj; Wong, Chelsea C.; Ganguly, Karunesh] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Ramanathan, Dhakshin S.] San Francisco VA Med Ctr, Dept Psychiat, San Francisco, CA USA. [Ramanathan, Dhakshin S.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. RP Ganguly, K (reprint author), San Francisco VA Med Ctr, Neurol & Rehabil Dept, San Francisco, CA 94121 USA. EM karunesh.ganguly@ucsf.edu FU Department of Veterans Affairs [B6674]; Burroughs Wellcome Fund [1009855]; American Heart/Stroke Association [0875016N]; VA Psychiatric Research Advanced Fellowship FX This work was supported by the Department of Veterans Affairs (B6674 to KG.), the Burroughs Wellcome Fund (1009855 to K.G.), the American Heart/Stroke Association (0875016N to K.G.) and a VA Psychiatric Research Advanced Fellowship (to D.S.R.). NR 45 TC 18 Z9 18 U1 1 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 EI 1546-1726 J9 NAT NEUROSCI JI Nat. Neurosci. PD AUG PY 2014 VL 17 IS 8 BP 1107 EP 1113 DI 10.1038/nn.3759 PG 7 WC Neurosciences SC Neurosciences & Neurology GA AM1XA UT WOS:000339641400017 PM 24997761 ER PT J AU Merkow, RP Bilimoria, KY Tomlinson, JS Paruch, JL Fleming, JB Talamonti, MS Ko, CY Bentrem, DJ AF Merkow, Ryan P. Bilimoria, Karl Y. Tomlinson, James S. Paruch, Jennifer L. Fleming, Jason B. Talamonti, Mark S. Ko, Clifford Y. Bentrem, David J. TI Postoperative Complications Reduce Adjuvant Chemotherapy Use in Resectable Pancreatic Cancer SO ANNALS OF SURGERY LA English DT Article DE ACS NSQIP; adjuvant therapy; complications; NCDB; pancreatic cancer; surgery ID RANDOMIZED CONTROLLED-TRIAL; PHASE-III TRIAL; PERIAMPULLARY REGION; CURATIVE RESECTION; COOPERATIVE GROUP; SURGICAL QUALITY; PATIENT SAFETY; UNITED-STATES; RISK; SURGERY AB Objective: To assess the impact of postoperative complications on the receipt of adjuvant chemotherapy. Background: Randomized trials have demonstrated that adjuvant chemotherapy is associated with improved long-term survival. However, pancreatic surgery is associated with significant morbidity and the degree to which complications limit subsequent treatment options is unknown. Methods: Patients from the American College of Surgeons National Surgical Quality Improvement Program and the National Cancer Data Base who underwent pancreatic resection for cancer were linked (2006-2009). The associations between complications and adjuvant chemotherapy use or treatment delay (>= 70 days from surgery) were assessed using multivariable regression methods. Results: From 149 hospitals, 2047 patients underwent resection for stage I-III pancreatic adenocarcinoma of which 23.2% had at least 1 serious complication. Overall adjuvant chemotherapy receipt was 57.7%: 61.8% among patients not experiencing any complication and 43.6% among those who had a serious complication. Serious complications increased the likelihood of not receiving adjuvant therapy over twofold [odds ratio (OR) = 2.20, 95% confidence interval (CI): 1.73-2.80]. Specific complications associated with adjuvant chemotherapy omission were reintubation (OR = 7.79, 95% CI: 3.59-16.87), prolonged ventilation (OR = 5.92, 95% CI: 3.23-10.86), pneumonia (OR = 2.83, 95% CI: 1.63-4.90), sepsis/shock (OR = 2.76, 95% CI: 2.02-3.76), organ space/deep surgical site infection (OR = 2.19, 95% CI: 1.53-3.13), venous thromboembolism (OR = 1.92, 95% CI: 1.08-3.43), and urinary tract infection (OR = 1.61, 95% CI: 1.02-2.54). Serious complications also doubled the likelihood of delaying adjuvant treatment administration (OR = 2.08, 95% CI: 1.42-3.05). Sensitivity analysis in a younger, healthier patient cohort demonstrated similar associations. Conclusions: Postoperative complications are common following pancreatic surgery and are associated with adjuvant chemotherapy omission and treatment delays. C1 [Merkow, Ryan P.; Bilimoria, Karl Y.; Paruch, Jennifer L.; Ko, Clifford Y.] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL 60611 USA. [Merkow, Ryan P.; Bilimoria, Karl Y.; Bentrem, David J.] Northwestern Univ, Feinberg Sch Med, Surg Outcomes & Qual Improvement Ctr, Chicago, IL 60611 USA. [Merkow, Ryan P.; Bilimoria, Karl Y.; Bentrem, David J.] Northwestern Univ, Dept Surg, Northwestern Inst Comparat Effectiveness Res NICE, Feinberg Sch Med, Chicago, IL 60611 USA. [Merkow, Ryan P.; Paruch, Jennifer L.; Talamonti, Mark S.] Univ Chicago, Pritzker Sch Med, Dept Surg, Chicago, IL 60637 USA. [Tomlinson, James S.; Ko, Clifford Y.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. [Tomlinson, James S.; Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Fleming, Jason B.] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. [Talamonti, Mark S.] Northshore Univ Hlth Syst, Dept Surg, Evanston, IL USA. [Bentrem, David J.] Jesse Brown Vet Affairs Med Ctr, Dept Surg, Chicago, IL USA. RP Merkow, RP (reprint author), Amer Coll Surg, Div Res & Optimal Patient Care, 633 N St Clair St,22nd Floor, Chicago, IL 60611 USA. EM RMerkow@facs.org FU American Cancer Society [280521]; Genetech FX The authors have no conflicts of interest to disclose. This study was supported by a grant from the American Cancer Society (No. 280521) to R. P. M. and K.Y.B. J.L.P. is supported by a grant from Genetech. NR 30 TC 24 Z9 24 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD AUG PY 2014 VL 260 IS 2 BP 372 EP 377 DI 10.1097/SLA.0000000000000378 PG 6 WC Surgery SC Surgery GA AL5KW UT WOS:000339173500033 PM 24374509 ER PT J AU Pensinger, DA Aliota, MT Schaenzer, AJ Boldon, KM Ansari, IU Vincent, WJB Knight, B Reniere, ML Striker, R Sauer, JD AF Pensinger, Daniel A. Aliota, Matthew T. Schaenzer, Adam J. Boldon, Kyle M. Ansari, Israr-ul H. Vincent, William J. B. Knight, Benjamin Reniere, Michelle L. Striker, Rob Sauer, John-Demian TI Selective Pharmacologic Inhibition of a PASTA Kinase Increases Listeria monocytogenes Susceptibility to beta-Lactam Antibiotics SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID SERINE/THREONINE PROTEIN-KINASE; STAPHYLOCOCCUS-AUREUS; SER/THR KINASE; ANTIMICROBIAL SUSCEPTIBILITY; MYCOBACTERIUM-TUBERCULOSIS; ENTEROCOCCUS-FAECALIS; MEDICAL-CENTERS; PKNB; RESISTANCE; BACTERIA AB While beta-lactam antibiotics are a critical part of the antimicrobial arsenal, they are frequently compromised by various resistance mechanisms, including changes in penicillin binding proteins of the bacterial cell wall. Genetic deletion of the penicillin binding protein and serine/threonine kinase-associated protein (PASTA) kinase in methicillin-resistant Staphylococcus aureus (MRSA) has been shown to restore beta-lactam susceptibility. However, the mechanism remains unclear, and whether pharmacologic inhibition would have the same effect is unknown. In this study, we found that deletion or pharmacologic inhibition of the PASTA kinase in Listeria monocytogenes by the nonselective kinase inhibitor staurosporine results in enhanced susceptibility to both aminopenicillin and cephalosporin antibiotics. Resistance to vancomycin, another class of cell wall synthesis inhibitors, or antibiotics that inhibit protein synthesis was unaffected by staurosporine treatment. Phosphorylation assays with purified kinases revealed that staurosporine selectively inhibited the PASTA kinase of L. monocytogenes ( PrkA). Importantly, staurosporine did not inhibit a L. monocytogenes kinase without a PASTA domain (Lmo0618) or the PASTA kinase from MRSA (Stk1). Finally, inhibition of PrkA with a more selective kinase inhibitor, AZD5438, similarly led to sensitization of L. monocytogenes to beta-lactam antibiotics. Overall, these results suggest that pharmacologic targeting of PASTA kinases can increase the efficacy of beta-lactam antibiotics. C1 [Pensinger, Daniel A.; Aliota, Matthew T.; Schaenzer, Adam J.; Boldon, Kyle M.; Vincent, William J. B.; Knight, Benjamin; Striker, Rob; Sauer, John-Demian] Univ Wisconsin, Dept Med Microbiol & Immunol, Madison, WI 53706 USA. [Aliota, Matthew T.; Schaenzer, Adam J.; Boldon, Kyle M.; Ansari, Israr-ul H.; Striker, Rob] Univ Wisconsin, Dept Med, Madison, WI USA. [Striker, Rob] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Reniere, Michelle L.] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. RP Sauer, JD (reprint author), Univ Wisconsin, Dept Med Microbiol & Immunol, Madison, WI 53706 USA. EM sauer3@wisc.edu FU Hartwell Foundation; NIH [U54 AI57153] FX This work was supported by an individual biomedical research award from The Hartwell Foundation to R. S. and by an NIH grant (U54 AI57153) to J.-D.S. NR 42 TC 7 Z9 8 U1 0 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 EI 1098-6596 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD AUG PY 2014 VL 58 IS 8 BP 4486 EP 4494 DI 10.1128/AAC.02396-14 PG 9 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA AL6RA UT WOS:000339259200029 PM 24867981 ER PT J AU Egelund, EF Weiner, M Singh, RP Prihoda, TJ Gelfond, JAL Derendorf, H Mac Kenzie, WR Peloquin, CA AF Egelund, Eric F. Weiner, Marc Singh, Rajendra P. Prihoda, Thomas J. Gelfond, Jonathon A. L. Derendorf, Hartmut Mac Kenzie, William R. Peloquin, Charles A. TI Protein Binding of Rifapentine and Its 25-Desacetyl Metabolite in Patients with Pulmonary Tuberculosis SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID SERUM-ALBUMIN; MYCOBACTERIUM-TUBERCULOSIS; RIFAMPICIN; PLASMA; HIV AB Rifapentine is highly protein bound in blood, but the free, unbound drug is the microbiologically active fraction. In this exploratory study, we characterized the free plasma fraction of rifapentine in 41 patients with tuberculosis. We found a lower total rifapentine concentration but significantly higher free rifapentine levels in African patients of black race compared to non-Africans. These data support larger pharmacokinetic/pharmacodynamic studies to confirm these findings and assess free rifapentine in relation to microbiological and clinical outcomes. C1 [Egelund, Eric F.; Derendorf, Hartmut; Peloquin, Charles A.] Univ Florida, Coll Pharm, Gainesville, FL USA. [Weiner, Marc] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Weiner, Marc] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Singh, Rajendra P.] GlaxoSmithKline, Clin Pharmacol Modeling & Simulat, King Of Prussia, PA USA. [Prihoda, Thomas J.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Gelfond, Jonathon A. L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol, San Antonio, TX 78229 USA. [Gelfond, Jonathon A. L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Biostat, San Antonio, TX 78229 USA. [Mac Kenzie, William R.] Ctr Dis Control & Prevent, Div TB Eliminat, Atlanta, GA USA. RP Weiner, M (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. EM weiner@uthscsa.edu FU Centers for Disease Control and Prevention through the Tuberculosis Trials Consortium; Veterans Affairs Administration FX This work was supported by the Centers for Disease Control and Prevention through the Tuberculosis Trials Consortium and the Veterans Affairs Administration. NR 16 TC 5 Z9 5 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 EI 1098-6596 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD AUG PY 2014 VL 58 IS 8 BP 4904 EP 4910 DI 10.1128/AAC.01730-13 PG 7 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA AL6RA UT WOS:000339259200078 PM 24841270 ER PT J AU Bentov, I Damodarasamy, M Plymate, S Reed, MJ AF Bentov, Itay Damodarasamy, Mamatha Plymate, Stephen Reed, May J. TI Decreased proliferative capacity of aged dermal fibroblasts in a three dimensional matrix is associated with reduced IGF1R expression and activation SO BIOGERONTOLOGY LA English DT Article DE Dermal fibroblasts; IGF1R; IGF-1; 3D matrix; Proliferation; Erk phosphorylation ID GROWTH-FACTOR-I; LIFE-SPAN; FACTOR RECEPTOR; HUMAN-CELLS; SKIN; INSULIN; GENE; SENESCENCE; ADHESIONS; MIGRATION AB Skin aging results in increased susceptibility to injury and impaired wound healing. Proliferation of fibroblasts is reduced in aged dermis, which contributes to delays in wound closure. Age-associated differences are regulated, in part, by local or systemic factors such as the IGF-1/IGF1R system. The aim of this study was to determine if expression and activation of IGF1R in aged human dermal fibroblasts, when compared to young fibroblasts, is associated with altered proliferative capacity in a 3D collagen matrix that better simulates the dermal extracellular matrix in vivo. The proliferation of young and aged human dermal fibroblasts in 3D collagen and its association with baseline levels of IGF1R expression were measured. The effect of stimulation and inhibition of Erk phosphorylation on the proliferative capacity of fibroblasts in a 3D collagen matrix was defined. Our results show that proliferation and Erk phosphorylation is reduced in aged dermal fibroblasts relative to young fibroblasts. Activation of Erk phosphorylation in aged fibroblasts is associated with a significant increase in fibroblast proliferation in 3D collagen. C1 [Bentov, Itay] Univ Washington, Dept Anesthesiol & Pain Med, Harborview Med Ctr, Seattle, WA 98104 USA. [Damodarasamy, Mamatha; Plymate, Stephen; Reed, May J.] Univ Washington, Div Gerontol & Geriatr Med, Dept Med, Seattle, WA 98104 USA. [Plymate, Stephen] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Bentov, I (reprint author), Univ Washington, Dept Anesthesiol & Pain Med, Harborview Med Ctr, Box 359724,325 Ninth Ave, Seattle, WA 98104 USA. EM itayb@uw.edu FU ITHS; Department of Anesthesiology & Pain Medicine pilot grant; [R03 AG042353]; [R21 AG33391] FX This work was supported by R03 AG042353 (I. B.), ITHS and Department of Anesthesiology & Pain Medicine pilot grant (I. B.), and R21 AG33391 (M.J.R.). We would like to thank Dr. Kathryn Houmiel for her technical assistance. NR 38 TC 5 Z9 5 U1 1 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1389-5729 EI 1573-6768 J9 BIOGERONTOLOGY JI Biogerontology PD AUG PY 2014 VL 15 IS 4 BP 329 EP 337 DI 10.1007/s10522-014-9501-8 PG 9 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA AL7UW UT WOS:000339342500002 PM 24770843 ER PT J AU Bates, BS Rodriguez, AL Felts, AS Morrison, RD Venable, DF Blobaum, AL Byers, FW Lawson, KP Daniels, JS Niswender, CM Jones, CK Conn, PJ Lindsley, CW Emmitte, KA AF Bates, Brittney S. Rodriguez, Alice L. Felts, Andrew S. Morrison, Ryan D. Venable, Daryl F. Blobaum, Anna L. Byers, Frank W. Lawson, Kera P. Daniels, J. Scott Niswender, Colleen M. Jones, Carrie K. Conn, P. Jeffrey Lindsley, Craig W. Emmitte, Kyle A. TI Discovery of VU0431316: A negative allosteric modulator of mGlu(5) with activity in a mouse model of anxiety SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE Glutamate; CNS; mGlu(5); Allosteric modulator; Anxiety ID MGLUR5 ANTAGONIST MPEP; METABOTROPIC GLUTAMATE-RECEPTOR-5 ANTAGONIST; ESOPHAGEAL SPHINCTER RELAXATIONS; CUE-INDUCED REINSTATEMENT; RECEPTOR ANTAGONIST; GLUTAMATE RECEPTORS; GASTROESOPHAGEAL-REFLUX; NUCLEUS-ACCUMBENS; SQUIRREL-MONKEYS; SEEKING BEHAVIOR AB Development of SAR in an aryl ether series of mGlu(5) NAMs leading to the identification of pyrazine analog VU0431316 is described in this Letter. VU0431316 is a potent and selective non-competitive antagonist of mGlu(5) that binds at a known allosteric binding site. VU0431316 demonstrates an attractive DMPK profile, including moderate clearance and good bioavailability in rats. Intraperitoneal (IP) dosing of V1J0431316 in a mouse marble burying model of anxiety, an assay known to be sensitive to mGlu(5) antagonists and other anxiolytics, produced dose proportional effects. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Bates, Brittney S.; Rodriguez, Alice L.; Felts, Andrew S.; Morrison, Ryan D.; Venable, Daryl F.; Blobaum, Anna L.; Byers, Frank W.; Lawson, Kera P.; Daniels, J. Scott; Niswender, Colleen M.; Jones, Carrie K.; Conn, P. Jeffrey; Lindsley, Craig W.; Emmitte, Kyle A.] Vanderbilt Univ, Med Ctr, Vanderbilt Ctr Neurosci Drug Discovery, Nashville, TN 37232 USA. [Bates, Brittney S.; Rodriguez, Alice L.; Felts, Andrew S.; Morrison, Ryan D.; Venable, Daryl F.; Blobaum, Anna L.; Byers, Frank W.; Lawson, Kera P.; Daniels, J. Scott; Niswender, Colleen M.; Jones, Carrie K.; Conn, P. Jeffrey; Lindsley, Craig W.; Emmitte, Kyle A.] Vanderbilt Univ, Med Ctr, Dept Pharmacol, Nashville, TN 37232 USA. [Lindsley, Craig W.; Emmitte, Kyle A.] Vanderbilt Univ, Dept Chem, Nashville, TN 37232 USA. [Jones, Carrie K.] US Dept Vet Affairs, Tennessee Valley Healthcare Syst, Nashville, TN 37212 USA. RP Emmitte, KA (reprint author), Vanderbilt Univ, Med Ctr, Vanderbilt Ctr Neurosci Drug Discovery, Nashville, TN 37232 USA. EM kyle.a.emmitte@vanderbilt.edu FU NIDA [R01 DA023947]; Seaside Therapeutics [VUMC33842] FX We thank NIDA (R01 DA023947) and Seaside Therapeutics (VUMC33842) for their support of our programs in the development of non-competitive antagonist of mGlu5. We also thank Tammy S. Santomango for technical contributions with the protein binding assays. NR 70 TC 2 Z9 2 U1 1 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X EI 1464-3405 J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD AUG 1 PY 2014 VL 24 IS 15 BP 3307 EP 3314 DI 10.1016/j.bmcl.2014.06.003 PG 8 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA AL6FT UT WOS:000339228700017 PM 24969015 ER PT J AU Yazdany, J Trupin, L Schmajuk, G Katz, PP Yelin, EH AF Yazdany, Jinoos Trupin, Laura Schmajuk, Gabriela Katz, Patricia P. Yelin, Edward H. TI Quality of care in systemic lupus erythematosus: the association between process and outcome measures in the Lupus Outcomes Study SO BMJ QUALITY & SAFETY LA English DT Article ID LARGE OBSERVATIONAL COHORT; ACTIVITY QUESTIONNAIRE; HEALTH PLANS; OSTEOPOROSIS; DISPARITIES; INDICATORS; VALIDATION; DISEASE AB Objectives Although process measures to assess quality of care in systemic lupus erythematosus (SLE) are available, their relationship to long-term outcomes has not been studied. Using a prospective, longitudinal cohort study, we examined the associations between high-quality care and two important SLE outcomes, disease activity and damage. Methods Data were derived from the University of California, San Francisco Lupus Outcomes Study. Participants were followed from 2009 through 2013, responding to yearly surveys. Primary outcomes in this study were clinically meaningful increases in disease activity and damage, assessed by the Systemic Lupus Activity Questionnaire (SLAQ) and the Brief Index of Lupus Damage (BILD), respectively. Using multivariable regression, we examined the relationship between high performance on 13 validated quality measures (receipt of >= 85% of quality measures), and disease outcomes, adjusting for disease status, sociodemographic characteristics, healthcare services and follow-up time. Results The 737 participants were eligible for a mean of five quality measures (SD 2, range 2-12). There were 155 and 162 participants who had clinically meaningful increases in SLAQ and BILD, respectively. In our models, we found no statistically significant relationship between performance on quality measures and changes in SLAQ. However, receiving higher-quality SLE care was significantly protective against increased disease damage (adjusted OR 0.4, 95% CI 0.4 to 0.7), even after adjusting for covariates. Discussion In this community-based cohort, we illustrate for the first time a strong link between processes of care, defined by SLE quality measures, and the subsequent accumulation of disease damage, an important outcome. C1 [Yazdany, Jinoos; Trupin, Laura; Katz, Patricia P.; Yelin, Edward H.] Univ Calif San Francisco, Div Rheumatol, Dept Med, San Francisco, CA 94143 USA. [Schmajuk, Gabriela] Univ Calif San Francisco, Dept Med, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. [Katz, Patricia P.; Yelin, Edward H.] Univ Calif San Francisco, Inst Hlth Policy Studies, San Francisco, CA 94143 USA. RP Yazdany, J (reprint author), Univ Calif San Francisco, Div Rheumatol, Box 0920, San Francisco, CA 94143 USA. EM jinoos.yazdany@ucsf.edu FU National Institute of Arthritis and Musculoskeletal and Skin diseases [K23 AR060259, P60 AR053308, 2R01 AR056476] FX Research reported in this manuscript was supported by the National Institute of Arthritis and Musculoskeletal and Skin diseases under award numbers K23 AR060259, P60 AR053308 and 2R01 AR056476. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 24 TC 8 Z9 8 U1 0 U2 4 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-5415 EI 2044-5423 J9 BMJ QUAL SAF JI BMJ Qual. Saf. PD AUG PY 2014 VL 23 IS 8 BP 659 EP 666 DI 10.1136/bmjqs-2013-002494 PG 8 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA AL5MC UT WOS:000339176900008 PM 24614054 ER PT J AU Connizzo, BK Yannascoli, SM Tucker, JJ Caro, AC Riggin, CN Mauck, RL Soslowsky, LJ Steinberg, DR Bernstein, J AF Connizzo, Brianne K. Yannascoli, Sarah M. Tucker, Jennica J. Caro, Adam C. Riggin, Corinne N. Mauck, Robert L. Soslowsky, Louis J. Steinberg, David R. Bernstein, Joseph TI The Detrimental Effects of Systemic Ibuprofen Delivery on Tendon Healing Are Time-Dependent SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; ROTATOR CUFF TEARS; COMPOSITIONAL PROPERTIES; MECHANICAL-PROPERTIES; INSERTION SITE; ANIMAL-MODEL; RAT MODEL; FRACTURE; REPAIR; INHIBITION AB Current clinical treatment after tendon repairs often includes prescribing NSAIDs to limit pain and inflammation. The negative influence of NSAIDs on bone repair is well documented, but their effects on tendon healing are less clear. While NSAIDs may be detrimental to early tendon healing, some evidence suggests that they may improve healing if administered later in the repair process. We asked whether the biomechanical and histologic effects of systemic ibuprofen administration on tendon healing are influenced by either immediate or delayed drug administration. After bilateral supraspinatus detachment and repair surgeries, rats were divided into groups and given ibuprofen orally for either Days 0 to 7 (early) or Days 8 to 14 (delayed) after surgery; a control group did not receive ibuprofen. Healing was evaluated at 1, 2, and 4 weeks postsurgery through biomechanical testing and histologic assessment. Biomechanical evaluation resulted in decreased stiffness and modulus at 4 weeks postsurgery for early ibuprofen delivery (mean +/- SD [95% CI]: 10.8 +/- 6.4 N/mm [6.7-14.8] and 8.9 +/- 5.9 MPa [5.4-12.3]) when compared to control repair (20.4 +/- 8.6 N/mm [16.3-24.5] and 15.7 +/- 7.5 MPa [12.3-19.2]) (p = 0.003 and 0.013); however, there were no differences between the delayed ibuprofen group (18.1 +/- 7.4 N/mm [14.2-22.1] and 11.5 +/- 5.6 MPa [8.2-14.9]) and the control group. Histology confirmed mechanical results with reduced fiber reorganization over time in the early ibuprofen group. Early administration of ibuprofen in the postoperative period was detrimental to tendon healing, while delayed administration did not affect tendon healing. Historically, clinicians have often prescribed ibuprofen after tendon repair, but this study suggests that the timing of ibuprofen administration is critical to adequate tendon healing. This research necessitates future clinical studies investigating the use of ibuprofen for pain control after rotator cuff repair and other tendon injuries. C1 [Connizzo, Brianne K.; Yannascoli, Sarah M.; Tucker, Jennica J.; Caro, Adam C.; Riggin, Corinne N.; Mauck, Robert L.; Soslowsky, Louis J.] Univ Penn, McKay Orthopaed Res Lab, Philadelphia, PA 19104 USA. [Steinberg, David R.; Bernstein, Joseph] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Soslowsky, LJ (reprint author), Univ Penn, McKay Orthopaed Res Lab, 424 Stemmler Hall,34th & Hamilton Walk, Philadelphia, PA 19104 USA. EM soslowsk@mail.med.upenn.edu FU Penn Center for Musculoskeletal Disorders (Philadelphia, PA, USA) (NIH Grant) [P30 AR050950]; NIH (Bethesda, MD, USA) (NIH Training Grant) [T32 AR007132]; Orthopaedic Research and Education Foundation (Rosemont, IL, USA) (OREF Resident Clinician Scientist Training Grant) [12-027] FX The institution of one or more of the authors (BKC, SMY, JJT, ACC, CNR, RLM, LJS) has received, during the study period, funding from the Penn Center for Musculoskeletal Disorders (Philadelphia, PA, USA) (NIH Grant P30 AR050950) and the NIH (Bethesda, MD, USA) (NIH Training Grant T32 AR007132). One of the authors certifies that she (SMY), or a member of her immediate family, has received or may receive, during the study period, funding from the Orthopaedic Research and Education Foundation (Rosemont, IL, USA) (OREF Resident Clinician Scientist Training Grant 12-027). Each author certifies that he or she, or a member of his or her immediate family, has no funding or commercial associations (eg, consultancies, stock ownership, equity interest, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article. NR 34 TC 17 Z9 17 U1 1 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X EI 1528-1132 J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD AUG PY 2014 VL 472 IS 8 BP 2433 EP 2439 DI 10.1007/s11999-013-3258-2 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA AL3AK UT WOS:000338997100021 PM 23982408 ER PT J AU Glasgow, SC Heafner, TA Watson, JDB Aden, JK Perry, WB AF Glasgow, Sean C. Heafner, Thomas A. Watson, J. Devin B. Aden, James K. Perry, W. Brian TI Initial Management and Outcome of Modern Battlefield Anal Trauma SO DISEASES OF THE COLON & RECTUM LA English DT Article DE Anorectal surgery; Ostomy; Outcomes research; Colorectal surgery; General surgery; Trauma ID OPERATION IRAQI FREEDOM; RECTAL INJURIES; SURGICAL-MANAGEMENT; ENDURING FREEDOM; SPHINCTER REPAIR; COMBAT WOUNDS; COLOSTOMY; EPIDEMIOLOGY; COLON AB BACKGROUND: Despite the potential for morbidity and permanent lifestyle alteration, few reports exist examining traumatic injury to the anal canal, particularly among modern-day combatants. OBJECTIVE: The aim of this study was to document the incidence, initial surgical management, and long-term outcomes of wartime anal trauma. DESIGN: This study is a retrospective review. DATA SOURCES: Data were compiled from multiple electronic medical record systems, including the Department of Defense Trauma Registry, the Patient Administration Systems and Biostatistics Activity, and the Armed Forces Health Longitudinal Tracking Application. SETTINGS: Combatants were treated at military treatment facilities with surgical capability during the wars in Iraq and Afghanistan, 2003 through early 2011. PATIENTS: All US and coalition combatants sustaining trauma to the anal canal or sphincter musculature were included. MAIN OUTCOME MEASURES: The quantification of incidence, the evaluation of initial treatment approach, and the determination of clinical and surgical factors correlating with restoration or preservation of GI tract continuity were the primary outcomes measured. RESULTS: Anal trauma occurred in 46 combatants, predominantly from blast injury (76.1%). Most (36, 78.2%) underwent fecal diversion. Concurrent severe systemic or intra-abdominal injuries correlated with colostomy creation. Acute anoplasty was attempted in 11 patients (23.7%) but did not influence eventual colostomy reversal. Among 33 US personnel, the permanent colostomy rate was 30.3%. Concurrent injury to the abdomen strongly predicted long-term colostomy (p = 0.009), along with hypogastric arterial ligation (p = 0.05) and pelvic fracture (p = 0.06). LIMITATIONS: This study was limited by the potential underdiagnosis of anal injury and the restricted follow-up of non-US personnel. CONCLUSIONS: Other injuries besides anal trauma typically have guided the decision for fecal diversion, and acute anal repair has rarely been indicated. The majority of patients with anal trauma regained normal GI continuity, although certain pelvic injuries increased the likelihood of permanent colostomy. C1 [Glasgow, Sean C.] St Louis Univ, Dept Surg, St Louis, MO 63110 USA. [Glasgow, Sean C.] US Air Force, Ctr Sustainment Trauma & Readiness Skills, St Louis, MO USA. [Heafner, Thomas A.; Watson, J. Devin B.] San Antonio Mil Med Ctr, Dept Surg, Ft Sam Houston, TX USA. [Aden, James K.] US Army, Inst Surg Res, Ft Sam Houston, TX 78234 USA. [Perry, W. Brian] Audie L Murphy Vet Hosp, San Antonio, TX USA. RP Glasgow, SC (reprint author), St Louis Univ, Dept Surg, 3635 Vista & Grand Blvd,3 FDT, St Louis, MO 63110 USA. EM glasgowsc@slu.edu FU Defense Health Program [6.7 FY12] FX Research was funded in part by Defense Health Program 6.7 FY12 grant, "Quality of Life and Obstacles to Care in Injured Personnel with Ostomies," principle investigator Major Sean C. Glasgow. NR 32 TC 1 Z9 1 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0012-3706 EI 1530-0358 J9 DIS COLON RECTUM JI Dis. Colon Rectum PD AUG PY 2014 VL 57 IS 8 BP 1012 EP 1018 DI 10.1097/DCR.0000000000000141 PG 7 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA AL6KO UT WOS:000339241500015 PM 25003297 ER PT J AU Wechsler, RT Leroy, R Van Cott, A Hammer, AE Vuong, A Huffman, R VanLandingham, K Messenheinner, JA AF Wechsler, Robert T. Leroy, Robert Van Cott, Anne Hammer, Anne E. Vuong, Alain Huffman, Russell VanLandingham, Kevan Messenheinner, John A. TI Lamotrigine extended-release as adjunctive therapy with optional conversion to monotherapy in older adults with epilepsy SO EPILEPSY RESEARCH LA English DT Article DE Lamottigine; Extended-release; Epilepsy; Elderly; Monotherapy ID NEWLY-DIAGNOSED EPILEPSY; TONIC-CLONIC SEIZURES; NEW-ONSET EPILEPSY; IMMEDIATE-RELEASE; ELDERLY-PATIENTS; CLINICAL-TRIAL; DOUBLE-BLIND; CARBAMAZEPINE; SAFETY; MULTICENTER AB Purpose: To determine the tolerability and efficacy of lamotrigine extended-release (LTG XR) as adjunctive therapy with optional conversion to monotherapy in patients ages >= 65 years with epilepsy. Methods: This open-label study included the standard LTG XR dose escalation, an 8-week Adjunctive Maintenance Phase (AMP), a 13-week Adjunctive Optimization Phase or Conversion and Monotherapy Phase, and a Taper/Follow-Up Phase. At the end of the AMP, patients on a single concomitant antiepileptic drug (AED) were converted to LTG XR monotherapy over 5 weeks and then remained in the Monotherapy Maintenance Phase for 8 weeks. All other patients remained in the study on concomitant AEDs for an additional 13 weeks in the Adjunctive Optimization Phase. Key findings: The number of patients who took >= 1 dose of study medication was 121. Of the 92 patients completing the AMP, 68 patients (74%) were deemed by their treating physician to be eligible to proceed with monotherapy; the remaining 24 patients (26%) continued in the Adjunctive Optimization Phase. The types of adverse events reported with LTG XR were similar to those in studies of LTG XR in younger adult patients with epilepsy and studies of LTG immediate-release (IR) across age groups with epilepsy. No serious rashes were reported. For subjects who were not seizure free at baseline (n=55), the median baseline seizure frequency was 0.5 seizures per week. During the entire treatment period, the median percent change from baseline was 90% (p < 0.0001). Fifty-two (52) patients (76%) of the 68 who entered the monotherapy phase successfully converted to monotherapy. Significance: In this small open label study, LTG-XR was safe and effective when added to the AED regimen of older patients with epilepsy. Many patients were able to be converted to LTG-XR monotherapy. (C) 2014 Elsevier B.V. All rights reserved. C1 [Wechsler, Robert T.] Idaho Comprehens Epilepsy Ctr, Boise, ID USA. [Leroy, Robert] Texas Epilepsy Grp, Dallas, TX USA. [Van Cott, Anne] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Van Cott, Anne] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Hammer, Anne E.; Vuong, Alain; Huffman, Russell; VanLandingham, Kevan; Messenheinner, John A.] GlaxoSmithKline, Brentford, England. RP Wechsler, RT (reprint author), Consultants Epilepsy & Neurol PLLC, Idaho Comprehens Epilepsy Ctr, 1499 West Hays St, Boise, ID 83702 USA. EM rtw@idahoepilepsy.com FU GlaxoSmithKline FX Jane Saiers, PhD (The WriteMedicine Inc.) assisted with development of initial drafts of the manuscript in collaboration with all co-authors. Dr. Saiers' work was funded by GlaxoSmithKline. NR 41 TC 2 Z9 2 U1 2 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 EI 1872-6844 J9 EPILEPSY RES JI Epilepsy Res. PD AUG PY 2014 VL 108 IS 6 BP 1128 EP 1136 DI 10.1016/j.eplepsyres.2014.04.009 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA AL4XS UT WOS:000339138700015 PM 24888248 ER PT J AU Sprenger, CCT Plymate, SR AF Sprenger, Cynthia C. T. Plymate, Stephen R. TI The Link Between Androgen Receptor Splice Variants and Castration-Resistant Prostate Cancer SO HORMONES & CANCER LA English DT Review ID INCREASED SURVIVAL; AR-45 VARIANT; CELL-LINES; GROWTH; GENE; DOMAIN; MODEL; TRANSCRIPTION; ENZALUTAMIDE; ABIRATERONE AB Resistance to the latest advanced prostate cancer therapies, including abiraterone and enzalutamide, is associated with increased expression of constitutively active androgen receptor splice variants (AR-Vs). The exact mechanism by which these therapies result in AR-Vs is unknown, but may include genomic rearrangement of the androgen receptor gene as well as alternative splicing of the AR pre-messenger RNA (mRNA). An additional complication that hinders further development of effective AR strategies is that the mechanisms by which the directed therapies are bypassed may vary. Finally, the question must be addressed as to whether the androgen receptor remains to be the driver of most castration resistant disease or whether truly AR-independent tumors arise after successful androgen ablation therapy. In this review, we will examine androgen receptor splice variants as an alternative mechanism by which prostate cancer becomes resistant to androgen receptor-directed therapy. C1 [Sprenger, Cynthia C. T.; Plymate, Stephen R.] Univ Washington, Dept Med, Seattle, WA 98104 USA. [Plymate, Stephen R.] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Sprenger, Cynthia C. T.] Univ Washington, Seattle, WA 98104 USA. RP Sprenger, CCT (reprint author), Univ Washington, Harborview Res & Training Bldg,325 9th Ave,Box 35, Seattle, WA 98104 USA. EM cts2501@u.washington.edu FU NCI NIH HHS [P01 CA085859, P01 CA163227, P50 CA097186] NR 60 TC 24 Z9 25 U1 2 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1868-8497 EI 1868-8500 J9 HORM CANCER-US JI Horm. Cancer PD AUG PY 2014 VL 5 IS 4 BP 207 EP 217 DI 10.1007/s12672-014-0177-y PG 11 WC Oncology; Endocrinology & Metabolism SC Oncology; Endocrinology & Metabolism GA AL7QW UT WOS:000339330800002 PM 24798453 ER PT J AU Ibrahim, MK Barnes, JL Osorio, EY Anstead, GM Jimenez, F Osterholzer, JJ Travi, BL Ahuja, SS White, AC Melby, PC AF Ibrahim, Marwa K. Barnes, Jeffrey L. Osorio, E. Yaneth Anstead, Gregory M. Jimenez, Fabio Osterholzer, John J. Travi, Bruno L. Ahuja, Seema S. White, A. Clinton, Jr. Melby, Peter C. TI Deficiency of Lymph Node-Resident Dendritic Cells (DCs) and Dysregulation of DC Chemoattractants in a Malnourished Mouse Model of Leishmania donovani Infection SO INFECTION AND IMMUNITY LA English DT Article ID INNATE IMMUNE-RESPONSE; VISCERAL LEISHMANIASIS; BONE-MARROW; IN-VIVO; CONDUIT SYSTEM; RISK-FACTOR; MALNUTRITION; MONOCYTES; MIGRATION; RECRUITMENT AB Malnutrition is thought to contribute to more than one-third of all childhood deaths via increased susceptibility to infection. Malnutrition is a significant risk factor for the development of visceral leishmaniasis, which results from skin inoculation of the intracellular protozoan Leishmania donovani. We previously established a murine model of childhood malnutrition and found that malnutrition decreased the lymph node barrier function and increased the early dissemination of L. donovani. In the present study, we found reduced numbers of resident dendritic cells (conventional and monocyte derived) but not migratory dermal dendritic cells in the skin-draining lymph nodes of L. donovani-infected malnourished mice. Expression of chemokines and their receptors involved in trafficking of dendritic cells and their progenitors to the lymph nodes was dysregulated. C-C chemokine receptor type 2 (CCR2) and its ligands (CCL2 and CCL7) were reduced in the lymph nodes of infected malnourished mice, as were CCR2-bearing monocytes/macrophages and monocyte-derived dendritic cells. However, CCR7 and its ligands (CCL19 and CCL21) were increased in the lymph node and CCR7 was increased in lymph node macrophages and dendritic cells. CCR2-deficient mice recapitulated the profound reduction in the number of resident (but not migratory dermal) dendritic cells in the lymph node but showed no alteration in the expression of CCL19 and CCL21. Collectively, these results suggest that the malnutrition-related reduction in the lymph node barrier to dissemination of L. donovani is related to insufficient numbers of lymph node-resident but not migratory dermal dendritic cells. This is likely driven by the altered activity of the CCR2 and CCR7 chemoattractant pathways. C1 [Ibrahim, Marwa K.; Melby, Peter C.] Univ Texas Hlth Sci Ctr San Antonio, Dept Microbiol & Immunol, San Antonio, TX 78229 USA. [Ibrahim, Marwa K.; Barnes, Jeffrey L.; Anstead, Gregory M.; Jimenez, Fabio; Ahuja, Seema S.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Ibrahim, Marwa K.] Natl Res Ctr, Genet Engn Div, Dept Microbial Biotechnol, Giza, Egypt. [Barnes, Jeffrey L.; Anstead, Gregory M.; Jimenez, Fabio; Ahuja, Seema S.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Osterholzer, John J.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Osterholzer, John J.] VA Ann Arbor Healthcare Syst, Ann Arbor, MI USA. [Osorio, E. Yaneth; Travi, Bruno L.; White, A. Clinton, Jr.; Melby, Peter C.] Univ Texas, Med Branch, Dept Internal Med, Galveston, TX USA. [Osorio, E. Yaneth; Travi, Bruno L.; White, A. Clinton, Jr.; Melby, Peter C.] Univ Texas, Med Branch, Ctr Trop Dis, Galveston, TX USA. [Travi, Bruno L.; Melby, Peter C.] Univ Texas, Med Branch Galveston, Dept Microbiol & Immunol, Galveston, TX USA. [Melby, Peter C.] Univ Texas, Med Branch Galveston, Dept Pathol, Galveston, TX USA. RP Melby, PC (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Microbiol & Immunol, San Antonio, TX 78229 USA. EM pcmelby@utmb.edu OI White, A Clinton/0000-0002-9668-4632; Ibrahim, Marwa/0000-0002-2603-8280 FU U.S. Department of Veterans Affairs; Department of Internal Medicine at the University of Texas Medical Branch FX This work was supported by funding from the U.S. Department of Veterans Affairs and the Department of Internal Medicine at the University of Texas Medical Branch (to P.C.M.). NR 68 TC 3 Z9 3 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 EI 1098-5522 J9 INFECT IMMUN JI Infect. Immun. PD AUG PY 2014 VL 82 IS 8 BP 3098 EP 3112 DI 10.1128/IAI.01778-14 PG 15 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AL5GK UT WOS:000339161400002 PM 24818662 ER PT J AU Pfeiffer, CD Beldavs, ZG AF Pfeiffer, Christopher D. Beldavs, Zintars G. TI Much to Do about Carbapenem-Resistant Enterobacteriaceae: Why Supplementing Surveillance May Be the Key to Stopping Spread SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Editorial Material ID KLEBSIELLA-PNEUMONIAE; INTERVENTION; HOSPITALS; REGION C1 [Pfeiffer, Christopher D.] Portland VA Med Ctr, Dept Hosp & Specialty Med, Portland, OR 97239 USA. [Pfeiffer, Christopher D.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. [Beldavs, Zintars G.] Oregon Hlth Author, Publ Hlth Div, Portland, OR USA. RP Pfeiffer, CD (reprint author), Portland VA Med Ctr, POB 1034 P3-ID, Portland, OR 97239 USA. EM pfeiffec@ohsu.edu NR 18 TC 2 Z9 2 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X EI 1559-6834 J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD AUG PY 2014 VL 35 IS 8 BP 984 EP 986 DI 10.1086/677158 PG 3 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA AL3RQ UT WOS:000339046900007 PM 25026613 ER PT J AU Singh, A Bartsch, SM Muder, RR Lee, BY AF Singh, Ashima Bartsch, Sarah M. Muder, Robert R. Lee, Bruce Y. TI An Economic Model: Value of Antimicrobial-Coated Sutures to Society, Hospitals, and Third-Party Payers in Preventing Abdominal Surgical Site Infections SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID RANDOMIZED-CONTROLLED-TRIAL; STERNAL WOUND INFECTIONS; POLYGLACTIN 910 VICRYL; COLORECTAL SURGERY; TOPICAL ANTIBIOTICS; ACQUIRED INFECTION; COST-EFFECTIVENESS; TRICLOSAN; CLOSURE; RISK AB BACKGROUND. While the persistence of high surgical site infection (SSI) rates has prompted the advent of more expensive sutures that are coated with antimicrobial agents to prevent SSIs, the economic value of such sutures has yet to be determined. METHODS. Using Tree Age Pro, we developed a decision analytic model to determine the cost-effectiveness of using antimicrobial sutures in abdominal incisions from the hospital, third-party payer, and societal perspectives. Sensitivity analyses systematically varied the risk of developing an SSI (range, 5%-20%), the cost of tridosan-coated sutures (range, $5-$25/inch), and triclosan-coated suture efficacy in preventing infection (range, 5%-50%) to highlight the range of costs associated with using such sutures. RESULTS. Triclosan-coated sutures saved $4,109-$13,975 (hospital perspective), $4,133-$14,297 (third-party payer perspective), and $40,127-$53,244 (societal perspective) per SSI prevented, when a surgery had a 15% SSI risk, depending on their efficacy. If the SSI risk was no more than 5% and the efficacy in preventing SSIs was no more than 10%, tridosan-coated sutures resulted in extra expenditure for hospitals and third-party payers (resulting in extra costs of $1,626 and $1,071 per SSI prevented for hospitals and third-party payers, respectively; SSI risk, 5%; efficacy, 10%). CONCLUSIONS. Our results suggest that switching to triclosan-coated sutures from the uncoated sutures can both prevent SSIs and save substantial costs for hospitals, third-party payers, and society, as long as efficacy in preventing SSIs is at least 10% and SSI risk is at least 10%. C1 [Singh, Ashima] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Bartsch, Sarah M.; Lee, Bruce Y.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. [Muder, Robert R.] Univ Pittsburgh, Div Infect Dis, Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Lee, BY (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, 855 North Wolfe St,Suite 600, Baltimore, MD 21205 USA. EM bruceleemdmba@gmail.com FU National Institute of General Medical Sciences; Pennsylvania Department of Health FX This study was supported by the National Institute of General Medical Sciences Models of Infectious Disease Agent Study and the Pennsylvania Department of Health. The funders had no role in the design and conduct of the study; the collection, management, analysis, and interpretation of the data; or the preparation, review, or approval of the manuscript. NR 60 TC 10 Z9 10 U1 3 U2 8 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X EI 1559-6834 J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD AUG PY 2014 VL 35 IS 8 BP 1013 EP 1020 DI 10.1086/677163 PG 8 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA AL3RQ UT WOS:000339046900012 PM 25026618 ER PT J AU Garrett, SM Whitaker, RM Beeson, CC Schnellmann, RG AF Garrett, Sara M. Whitaker, Ryan M. Beeson, Craig C. Schnellmann, Rick G. TI Agonism of the 5-Hydroxytryptamine 1F Receptor Promotes Mitochondrial Biogenesis and Recovery from Acute Kidney Injury SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID ISCHEMIA-REPERFUSION INJURY; PGC-1-ALPHA MESSENGER-RNA; PROXIMAL TUBULE CELLS; INDUCED LIVER-INJURY; 5-HT1F RECEPTOR; SKELETAL-MUSCLE; MIGRAINE TREATMENT; ENDOTHELIAL-CELLS; ACTIVATION; DYSFUNCTION AB Many acute and chronic conditions, such as acute kidney injury, chronic kidney disease, heart failure, and liver disease, involve mitochondrial dysfunction. Although we have provided evidence that drug-induced stimulation of mitochondrial biogenesis (MB) accelerates mitochondrial and cellular repair, leading to recovery of organ function, only a limited number of chemicals have been identified that induce MB. The goal of this study was to assess the role of the 5-hydroxytryptamine 1F (5-HT1F) receptor in MB. Immunoblot and quantitative polymerase chain reaction analyses revealed 5-HT1F receptor expression in renal proximal tubule cells (RPTC). A MB screening assay demonstrated that two selective 5-HT1F receptor agonists, LY334370 (4-fluoro-N-[3-(1-methyl- 4-piperidinyl)-1H-indol-5-yl] benzamide) and LY344864 (N-[(3R)-3-(dimethylamino)-2,3,4,9-tetrahydro-1H-carbazol-6-yl]- 4-fluorobenzamide; 1-100 nM) increased carbonylcyanide-p-trifluoromethoxyphenylhydrazone-uncoupled oxygen consumption in RPTC, and validation studies confirmed both agonists increased mitochondrial proteins [e.g., ATP synthase beta, cytochrome c oxidase 1 (Cox1), and NADH dehydrogenase (ubiquinone) 1 beta subcomplex subunit 8 (NDUFB8)] in vitro. Small interfering RNA knockdown of the 5-HT1F receptor blocked agonist-induced MB. Furthermore, LY344864 increased peroxisome proliferator-activated receptor coactivator 1-alpha, Cox1, and NDUFB8 transcript levels and mitochondrial DNA (mtDNA) copy number in murine renal cortex, heart, and liver. Finally, LY344864 accelerated recovery of renal function, as indicated by decreased blood urea nitrogen and kidney injury molecule 1 and increased mtDNA copy number following ischemia/reperfusion-induced acute kidney injury (AKI). In summary, these studies reveal that the 5-HT1F receptor is linked to MB, 5-HT1F receptor agonism promotes MB in vitro and in vivo, and 5-HT1F receptor agonism promotes recovery from AKI injury. Induction of MB through 5-HT1F receptor agonism represents a new target and approach to treat mitochondrial organ dysfunction. C1 [Garrett, Sara M.; Whitaker, Ryan M.; Beeson, Craig C.; Schnellmann, Rick G.] Med Univ S Carolina, Dept Drug Discovery & Biomed Sci, Ctr Cell Death Injury & Regenerat, Charleston, SC 29425 USA. [Schnellmann, Rick G.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Schnellmann, RG (reprint author), Med Univ S Carolina, Dept Drug Discovery & Biomed Sci, 280 Calhoun St,MSC140, Charleston, SC 29425 USA. EM schnell@musc.edu FU National Institutes of Health National Institute of General Medical Sciences [R01-GM084147]; National Institutes of Health National Center for Research Resources [UL1RR029882]; Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs [1BX000851]; South Carolina Clinical and Translational Research Institute; Medical University of South Carolina; National Institutes of Health Ruth L. Kirschstein National Research Service Award [5T32-DK083262-03]; National Institutes of Health [C06-RR015455] FX This work was supported by the National Institutes of Health National Institute of General Medical Sciences [Grant R01-GM084147]; the National Institutes of Health National Center for Research Resources [Grant UL1RR029882]; the Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs [1BX000851]; the South Carolina Clinical and Translational Research Institute, with an academic home at the Medical University of South Carolina; and the National Institutes of Health Ruth L. Kirschstein National Research Service Award [Grant 5T32-DK083262-03]. Animal facilities were funded by the National Institutes of Health National Center for Research Resources [Grant C06-RR015455]. NR 51 TC 7 Z9 7 U1 1 U2 9 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 EI 1521-0103 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD AUG PY 2014 VL 350 IS 2 BP 257 EP 264 DI 10.1124/jpet.114.214700 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AL6VJ UT WOS:000339270800008 PM 24849926 ER PT J AU Lin, XC Kraut, JA Wu, DM AF Lin, Xinchun Kraut, Jeffrey A. Wu, Dongmei TI Coadministration of a Na+-H+ exchange inhibitor and sodium bicarbonate for the treatment of asphyxia-induced cardiac arrest in piglets SO PEDIATRIC RESEARCH LA English DT Article ID LACTIC-ACIDOSIS; BLOOD-FLOW; REPERFUSION INJURY; RESUSCITATION; DYSFUNCTION; ACTIVATION; SABIPORIDE; ISCHEMIA; SM-20220; THERAPY AB BACKGROUND: The present study tested the hypothesis that addition of an inhibitor of Na+/H+ exchanger (NHE1) to sodium bicarbonate might improve the response to base therapy from prolonged asphyxial cardiac arrest in piglets. METHODS: Asphyxial cardiac arrest was induced by endotracheal tube clamping. Animals were randomly assigned to four study groups: (i) vehicle control, (ii) administration of sabiporide (NHE1 inhibitor), (iii) administration of sodium bicarbonate, and (iv) administration of sabiporide and sodium bicarbonate. RESULTS: Administration of sodium bicarbonate alone did not affect survival, hemodynamic measures, and regional blood flow to critical tissues such as brain, heart, kidney, liver, and spleen. In contrast, sabiporide given alone or combined with sodium bicarbonate improved these. Furthermore, treatment with sabiporide reduced accumulation of neutrophils, reduced cytokine production in the lung, and reduced plasma levels of cardiac troponin-I, alanine aminotransferase, aspartate aminotransferase, and urea. In addition, the combined use of sabiporide and sodium bicarbonate had more profound reduction in interleukin (IL)-6 and IL-10, compared to sabiporide alone. CONCLUSION: These results suggest that addition of sabiporide to the administration of sodium bicarbonate might improve hemodynamic response and dampen the inflammatory cascade noted with cardiac arrest, and therefore being an attractive option in the treatment of cardiac arrest. C1 [Lin, Xinchun; Wu, Dongmei] Mt Sinai Med Ctr, Dept Res, Miami Beach, FL 33140 USA. [Kraut, Jeffrey A.] Vet Adm Greater Los Angeles Healthcare Syst, Med & Res Serv, Los Angeles, CA USA. [Kraut, Jeffrey A.] Vet Adm Greater Los Angeles Healthcare Syst, Div Nephrol, Los Angeles, CA USA. [Kraut, Jeffrey A.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Wu, Dongmei] Chonbuk Natl Univ, Dept Biotechnol Informat Sci & Nanotechnol BIN Fu, Jeonju, South Korea. RP Wu, DM (reprint author), Mt Sinai Med Ctr, Dept Res, Miami Beach, FL 33140 USA. EM dongmeiwu@bellsouth.net RI Wu, Dongmei/I-3213-2016 FU US Army Medical Research and Material Command [W81XWH-06-1-0719]; Basic Science Research Program of the National Research Foundation of Korea [NRF-2012007331] FX This work was supported in part by a US Army Medical Research and Material Command grant W81XWH-06-1-0719 (D.W.) and by the Basic Science Research Program of the National Research Foundation of Korea (NRF-2012007331). NR 40 TC 2 Z9 2 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0031-3998 EI 1530-0447 J9 PEDIATR RES JI Pediatr. Res. PD AUG PY 2014 VL 76 IS 2 BP 118 EP 126 DI 10.1038/pr.2014.65 PG 9 WC Pediatrics SC Pediatrics GA AL6GO UT WOS:000339230800001 PM 24796369 ER PT J AU Robinson, ES Okawa, J Feng, R Payne, AS Werth, V AF Robinson, E. S. Okawa, J. Feng, R. Payne, A. S. Werth, V. TI The incidence of herpes zoster in patients with cutaneous lupus erythematosus, dermatomyositis, and pemphigus vulgaris is increased compared to the average US population SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology (SID) CY MAY 07-10, 2014 CL Albuquerque, NM SP Soc Invest Dermatol C1 [Robinson, E. S.; Okawa, J.; Werth, V.] Vet Affairs Med Ctr, Philadelphia, PA USA. [Robinson, E. S.; Okawa, J.; Payne, A. S.; Werth, V.] Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. [Feng, R.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2014 VL 134 IS 8 MA LB827 BP S6 EP S6 PG 1 WC Dermatology SC Dermatology GA AL4SW UT WOS:000339126100073 ER PT J AU Xu, J Jiang, Y Wang, J Shi, X Liu, Q Liu, Z Li, Y Scott, MJ Xiao, G Li, S Fan, L Billiar, TR Wilson, MA Fan, J AF Xu, J. Jiang, Y. Wang, J. Shi, X. Liu, Q. Liu, Z. Li, Y. Scott, M. J. Xiao, G. Li, S. Fan, L. Billiar, T. R. Wilson, M. A. Fan, J. TI Macrophage endocytosis of high-mobility group box 1 triggers pyroptosis SO CELL DEATH AND DIFFERENTIATION LA English DT Article ID GLYCATION END-PRODUCTS; CELL-DEATH; INFLAMMASOME ACTIVATION; NLRP3 INFLAMMASOME; NALP3 INFLAMMASOME; NEURITE OUTGROWTH; ENDOTHELIAL-CELLS; LATE MEDIATOR; RECEPTOR; HMGB1 AB Macrophages can be activated and regulated by high-mobility group box 1 (HMGB1), a highly conserved nuclear protein. Inflammatory functions of HMGB1 are mediated by binding to cell surface receptors, including the receptor for advanced glycation end products (RAGE), Toll-like receptor (TLR)2, TLR4, and TLR9. Pyroptosis is a caspase-1-dependent programmed cell death, which features rapid plasma membrane rupture, DNA fragmentation, and release of proinflammatory intracellular contents. Pyroptosis can be triggered by various stimuli, however, the mechanism underlying pyroptosis remains unclear. In this study, we identify a novel pathway of HMGB1-induced macrophage pyroptosis. We demonstrate that HMGB1, acting through RAGE and dynamin-dependent signaling, initiates HMGB1endocytosis, which in turn induces cell pyroptosis. The endocytosis of HMGB1 triggers a cascade of molecular events, including cathepsin B release from ruptured lysosomes followed by pyroptosome formation and caspase-1 activation. We further confirm that HMGB1-induced macrophage pyroptosis also occurs in vivo during endotoxemia, suggesting a pathophysiological significance for this form of pyroptosis in the development of inflammation. These findings shed light on the regulatory role of ligand-receptor internalization in directing cell fate, which may have an important role in the progress of inflammation following infection and injury. C1 [Xu, J.; Wang, J.; Shi, X.; Liu, Z.; Li, Y.; Scott, M. J.; Billiar, T. R.; Wilson, M. A.; Fan, J.] Univ Pittsburgh, Sch Med, Dept Surg, Pittsburgh, PA USA. [Xu, J.; Jiang, Y.; Wang, J.; Liu, Z.] Southern Med Univ, Dept Pathophysiol, Guangzhou 510515, Guangdong, Peoples R China. [Shi, X.] Xi An Jiao Tong Univ, Coll Med, Dept Pharmacol, Xian 710049, Peoples R China. [Liu, Q.] Univ Pittsburgh, Sch Med, Thomas E Starzl Transplantat Inst, Dept Surg, Pittsburgh, PA USA. [Liu, Q.] Harbin Med Univ, Affiliated Hosp 2, Dept Cardiovasc Surg, Harbin, Peoples R China. [Xiao, G.] Rush Univ, Med Ctr, Dept Biochem, Chicago, IL 60612 USA. [Li, S.] Univ Pittsburgh, Sch Pharm, Ctr Pharmacogenet, Dept Pharmaceut Sci, Pittsburgh, PA USA. [Fan, L.] Univ Pittsburgh, Sch Arts & Sci, Pittsburgh, PA USA. [Billiar, T. R.; Fan, J.] Univ Pittsburgh, McGowan Inst Regenerat Med, Pittsburgh, PA USA. [Wilson, M. A.; Fan, J.] Vet Affairs Pittsburgh Healthcare Syst, Res & Dev, Pittsburgh, PA USA. RP Jiang, Y (reprint author), Southern Med Univ, Dept Pathophysiol, Guangzhou 510515, Guangdong, Peoples R China. EM jiang48231@163.com; jif7@pitt.edu FU National Institutes of Health [R01-HL-079669, P50-GM-53789]; VA Merit Award; National Key Basic Research Program (China) [2010CB529704]; PCSIRT [IRT0731]; National Natural Science Foundation of China [30670828] FX This work was supported by the National Institutes of Health Grant R01-HL-079669 (JF and MAW), National Institutes of Health Center Grant P50-GM-53789 (TRB and JF), a VA Merit Award (JF), National Key Basic Research Program 2010CB529704 (YJ, China), PCSIRT IRT0731 (YJ), and National Natural Science Foundation of China 30670828 (YJ). NR 37 TC 24 Z9 26 U1 4 U2 26 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1350-9047 EI 1476-5403 J9 CELL DEATH DIFFER JI Cell Death Differ. PD AUG PY 2014 VL 21 IS 8 BP 1229 EP 1239 DI 10.1038/cdd.2014.40 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AK8UQ UT WOS:000338704500005 PM 24769733 ER PT J AU Sonnenberg, A AF Sonnenberg, Amnon TI Ubiquitous occurrence of birth-cohort patterns in inflammatory bowel disease SO EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY LA English DT Article DE birth-cohort pattern; Crohn's disease; death rates; ethnicity; time trends; ulcerative colitis ID ULCERATIVE-COLITIS; CROHNS-DISEASE; TIME TRENDS; PREVALENCE; MORTALITY AB Background and aims The aim of the present study was to demonstrate the ubiquitous occurrence of the birth-cohort phenomenon of inflammatory bowel disease among US whites and nonwhites, as well as males and females. Methods Mortality from Crohn's disease and ulcerative colitis in the USA between 1950 and 2010 were analyzed to discern underlying birth-cohort patterns affecting both their time trends. Age-standardized cohort mortality ratio was used as a summary statistic to represent the overall mortality associated with consecutive birth-cohorts. Results The cohort-age contours of Crohn's disease aligned to form one hyperbola with an initial rise between 1865 and 1935 and a subsequent decline. This pattern was confirmed by the time trends of the corresponding standardized cohort mortality ratio values. In ulcerative colitis, the individual cohort-age contours also aligned into one hyperbola that appeared shifted towards earlier generations by about 30 years when compared with Crohn's disease. Similar trends were observed in men and women or whites and nonwhites analyzed separately. Conclusion The birth-cohort patterns indicate that exposure to two separate risk factors must have occurred in both diseases during an early period of life. In the USA, these exposures have changed over historical times similarly in both sexes and different ethnic groups. Eur J Gastroenterol Hepatol 26: 888- 893 (C) 2014 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [Sonnenberg, Amnon] Portland VA Med Ctr, Portland, OR USA. [Sonnenberg, Amnon] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr P3 GI, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu NR 10 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0954-691X EI 1473-5687 J9 EUR J GASTROEN HEPAT JI Eur. J. Gastroenterol. Hepatol. PD AUG PY 2014 VL 26 IS 8 BP 888 EP 893 DI 10.1097/MEG.0000000000000118 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AK9BK UT WOS:000338722300009 PM 24987824 ER PT J AU Akber, A Portale, AA Johansen, KL AF Akber, Aalia Portale, Anthony A. Johansen, Kirsten L. TI Use of pedometers to increase physical activity among children and adolescents with chronic kidney disease SO PEDIATRIC NEPHROLOGY LA English DT Article DE Physical activity; Children; Adolescents; Health-related quality of life; Physical performance ID QUALITY-OF-LIFE; AMBULATORY PATIENTS; PEDIATRIC-PATIENTS; HEALTH; HEMODIALYSIS; TRANSPLANT; STEPS/DAY; DIALYSIS; EXERCISE; ADULTS AB Children and adolescents with chronic kidney disease (CKD) are inactive relative to their peers. Forty-four children and adolescents aged 7-20 years with CKD, end-stage renal disease (ESRD) on dialysis or a kidney transplant participated in a 12-week pedometer-based intervention to increase physical activity. Patients recorded daily step counts and reported them weekly. Pediatric Quality of Life Inventory (PedsQL) and 6-min walk (6 MW) were administered at baseline and after 12 weeks. Age was 15.1 +/- 3.4 years; 27 % had CKD, 16 % were receiving dialysis, and 57 % had received a kidney transplant. Mean daily step count did not change significantly (+48, 95 % CI -48 to +145 steps/day per week). Transplant recipients and patients with CKD increased their activity by 100 steps/day (95 % CI -14 to 208) and 73 steps/day (95 % CI -115 to 262) each week, respectively, and patients on dialysis decreased by 133 steps/day (95 % CI -325 to 58; p value for interaction 0.03) in multivariable analysis. Change in physical activity was associated with change in 6 MW distance (r = 0.74, p < 0.001) and change in physical functioning (r = 0.53, p = 0.001). Youths with CKD did not significantly increase their activity over 12 weeks of a pedometer-based intervention. However, changes in physical activity were associated with changes in physical functioning and performance. C1 [Akber, Aalia] Kaiser Oakland Med Ctr, Div Nephrol, Dept Pediat, Oakland, CA USA. [Portale, Anthony A.] Univ Calif San Francisco, Dept Pediat, Div Nephrol, San Francisco, CA USA. [Johansen, Kirsten L.] Univ Calif San Francisco, Dept Med, Div Nephrol, San Francisco, CA USA. [Johansen, Kirsten L.] San Francisco VA Med Ctr, Nephrol Sect, San Francisco, CA 94121 USA. RP Johansen, KL (reprint author), San Francisco VA Med Ctr, Nephrol Sect, 111J,4150 Clement St, San Francisco, CA 94121 USA. EM kirsten.johansen@ucsf.edu FU Genzyme Corp; Abbott Laboratories FX Dr. Johansen serves on the National Nephrology Advisory Board of Amgen and as Deputy Editor for the Clinical Journal of the American Society of Nephrology. Dr. Portale receives research support from Genzyme Corp and Abbott Laboratories. NR 25 TC 2 Z9 2 U1 2 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0931-041X EI 1432-198X J9 PEDIATR NEPHROL JI Pediatr. Nephrol. PD AUG PY 2014 VL 29 IS 8 BP 1395 EP 1402 DI 10.1007/s00467-014-2787-6 PG 8 WC Pediatrics; Urology & Nephrology SC Pediatrics; Urology & Nephrology GA AK8TH UT WOS:000338700400014 PM 24648129 ER PT J AU Le, H Khankhanian, P Joshi, N Maa, J Crevensten, H AF Le, Hai Khankhanian, Pouya Joshi, Neha Maa, John Crevensten, Henry TI Patients Recovering From Abdominal Surgery Who Walked With Volunteers Had Improved Postoperative Recovery Profiles during Their Hospitalization SO WORLD JOURNAL OF SURGERY LA English DT Article ID COLORECTAL SURGERY; ENHANCED RECOVERY; CARE; PATHWAY; LENGTH; STAY AB Early walking as part of a perioperative care program benefits patients who have had surgery. However, the impact of early walking by itself on the mental and physical recovery of postoperative patients has not been examined. We established a program called walking to recovery (WTR) in which college volunteers provided walking assistance to patients recovering after abdominal surgery. Patients who participated in the program were compared with patients who did not. The postoperative recovery profile survey (PRP-17) was administered on day of discharge to 15 participants and 15 non-participants. Medical records were reviewed to obtain indication for surgery, type of surgery, length of hospital stay, and postoperative complications. At 1 month post-discharge, a short form (SF)-12v2 questionnaire was administered by telephone to assess postoperative quality of life as defined by mental and physical level of function and measured with the mental component score (MCS) and the physical component score (PCS). The average age of participants and non-participants was similar (48.9 +/- A 9.8 vs. 51.4 +/- A 8.7 years; p = 0.28). When the two groups were approximately matched by type and severity of surgery, participants had lower PRP-17 composite scores (9.9 vs. 12.5, p = 0.003) and higher indicator sums (9.8 vs. 8.4, p = 0.04) than non-participants, both of which indicate better postoperative recovery in participants. The mean immobilization score was significantly lower in participants (0.3 vs. 0.8, p = 0.04). Postoperative length of stay and MCS did not differ between the two groups, but in participants there was a trend for higher scores in the PCS. Walking with volunteers was associated with a better PRP during the hospitalization period but not at 1 month follow-up. The WTR program is a sustainable, cost-effective model program for other hospitals to emulate as part of the standard of care of postoperative patients. C1 [Le, Hai; Khankhanian, Pouya; Joshi, Neha] Univ Calif San Francisco, Sch Med, San Francisco, CA 94115 USA. [Maa, John] Univ Calif San Francisco, Dept Surg, San Francisco, CA USA. [Crevensten, Henry] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Crevensten, Henry] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. RP Le, H (reprint author), Univ Calif San Francisco, Sch Med, San Francisco, CA 94115 USA. EM hai.le@ucsf.edu; hcrevensten@medicine.ucsf.edu NR 15 TC 2 Z9 2 U1 2 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2313 EI 1432-2323 J9 WORLD J SURG JI World J.Surg. PD AUG PY 2014 VL 38 IS 8 BP 1961 EP 1965 DI 10.1007/s00268-014-2491-5 PG 5 WC Surgery SC Surgery GA AK7WV UT WOS:000338639300015 PM 24615609 ER PT J AU Bensing, BA Seepersaud, R Yen, YT Sullam, PM AF Bensing, Barbara A. Seepersaud, Ravin Yen, Yihfen T. Sullam, Paul M. TI Selective transport by SecA2: An expanding family of customized motor proteins SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Review DE Accessory Sec system; Glycoprotein transport; Bacterial glycoprotein; Asp1; Asp2; S-layer ID STREPTOCOCCUS-GORDONII DL1; ACID-BINDING ADHESIN; ALGA CYANIDIOSCHYZON-MEROLAE; SIGNAL-SEQUENCE RECOGNITION; SURFACE GLYCOPROTEINS GSPB; FIMBRIA-ASSOCIATED ADHESIN; RICH REPEAT GLYCOPROTEIN; STAPHYLOCOCCUS-AUREUS; TRANSLOCATION CHANNEL; LISTERIA-MONOCYTOGENES AB The SecA2 proteins are a special class of transport-associated ATPases that are related to the SecA component of the general Sec system, and are found in an increasingly large number of Gram-positive bacterial species. The SecA2 substrates are typically linked to the cell wall, but may be lipid-linked, peptidoglycan-linked, or non-covalently associated S-layer proteins. These substrates can have a significant impact on virulence of pathogenic organisms, but may also aid colonization by commensals. The SecA2 orthologues range from being highly similar to their SecA paralogues, to being distinctly different in apparent structure and function. Two broad classes of SecA2 are evident One transports multiple substrates, and may interact with the general Sec system, or with an as yet unidentified transmembrane channel. The second type transports a single substrate, and is a component of the accessory Sec system, which includes the SecY paralogue SecY2 along with the accessory Sec proteins Asp1-3. Recent studies indicate that the latter three proteins may have a unique role in coordinating post-translational modification of the substrate with transport by SecA2. Comparative functional and phylogenetic analyses suggest that each SecA2 may be uniquely adapted for a specific type of substrate. This article is part of a Special Issue entitled: Protein trafficking and secretion in bacteria. Guest Editors: Anastassios Economou and Ross Dalbey. Published by Elsevier B.V. C1 San Francisco VA Med Ctr, San Francisco, CA 94121 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Bensing, BA (reprint author), VA Med Ctr 111W2, Div Infect Dis, 4150 Clement St, San Francisco, CA 94121 USA. EM barbara.bensing@ucsf.edu FU Department of Veterans Affairs; VA Merit Review program; Northern California Institute for Research and Education; NIH [R01-AI41513]; American Heart Association (AHA), Western Affiliate FX This work was supported by the Department of Veterans Affairs and the VA Merit Review program; the Northern California Institute for Research and Education; grant R01-AI41513 from the NIH (P.M.S.); and a Fellowship Award from the American Heart Association (AHA), Western Affiliate (YY). NR 97 TC 13 Z9 13 U1 2 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 EI 0006-3002 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD AUG PY 2014 VL 1843 IS 8 SI SI BP 1674 EP 1686 DI 10.1016/j.bbamcr.2013.10.019 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AK7GE UT WOS:000338595800025 PM 24184206 ER PT J AU Wang, JY Shi, YJ Zhang, LL Zhang, F Hu, XM Zhang, WT Leak, RK Gao, YQ Chen, L Chen, J AF Wang, Jiayin Shi, Yejie Zhang, Lili Zhang, Feng Hu, Xiaoming Zhang, Wenting Leak, Rehana K. Gao, Yanqin Chen, Ling Chen, Jun TI Omega-3 polyunsaturated fatty acids enhance cerebral angiogenesis and provide long-term protection after stroke SO NEUROBIOLOGY OF DISEASE LA English DT Article DE Angiogenesis; Angiopoietin 2; Astrocyte; Neuroprotection; Omega-3 polyunsaturated fatty acids; Stroke; VEGF ID ENDOTHELIAL GROWTH-FACTOR; BLOOD-BRAIN-BARRIER; DOCOSAHEXAENOIC ACID; ISCHEMIC-STROKE; VASCULAR-PERMEABILITY; CELL TRANSPLANTATION; SIGNALING PATHWAY; FISH-OIL; IN-VIVO; INJURY AB Stroke is a devastating neurological disorder and one of the leading causes of death and serious disability. After cerebral ischemia, revascularization in the ischemic boundary zone provides nutritive blood flow as well as various growth factors to promote the survival and activity of neurons and neural progenitor cells. Enhancement of angiogenesis and the resulting improvement of cerebral microcirculation are key restorative mechanisms and represent an important therapeutic strategy for ischemic stroke. In the present study, we tested the hypothesis that post-stroke angiogenesis would be enhanced by omega-3 polyunsaturated fatty acids (n - 3 PUFAs), a major component of dietary fish oil. To this end, we found that transgenic fat-1 mice that overproduce n - 3 PUFAs exhibited long-term behavioral and histological protection against transient focal cerebral ischemia (tECI). Importantly, fat-1 transgenic mice also exhibited robust improvements in revascularization and angiogenesis compared to wild type littermates, suggesting a potential role for n - 3 fatty acids in post-stroke cerebrovascular remodeling. Mechanistically, n - 3 PUFAs induced upregulation of angiopoietin 2 (Ang 2) in astrocytes after tFCI and stimulated extracellular Ang 2 release from cultured astrocytes after oxygen and glucose deprivation. Ang 2 facilitated endothelial proliferation and barrier formation in vitro by potentiating the effects of VEGF on phospholipase C gamma 1 and Src signaling. Consistent with these findings, blockade of Src activity in post-stroke fat-1 mice impaired n - 3 PUFA-induced angiogenesis and exacerbated long-term neurological outcomes. Taken together, our findings strongly suggest that n - 3 PUPA supplementation is a potential angiogenic treatment capable of augmenting brain repair and improving long-term functional recovery after cerebral ischemia. (C) 2014 Elsevier Inc All rights reserved. C1 [Wang, Jiayin; Shi, Yejie; Zhang, Lili; Zhang, Feng; Hu, Xiaoming; Zhang, Wenting; Leak, Rehana K.; Gao, Yanqin; Chen, Ling; Chen, Jun] Vet Affairs Pittsburgh Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA 15261 USA. [Wang, Jiayin; Zhang, Feng; Hu, Xiaoming; Chen, Jun] Capital Med Univ, Xuanwu Hosp, Cell Therapy Ctr, Beijing 100053, Peoples R China. [Chen, Ling] Chinese Peoples Liberat Army Gen Hosp, Dept Neurosurg, Beijing 100853, Peoples R China. [Chen, Ling] Chinese Peoples Liberat Army Gen Hosp, PLA Inst Neurosurg, Beijing 100853, Peoples R China. [Leak, Rehana K.] Duquesne Univ, Grad Sch Pharmaceut Sci, Pittsburgh, PA 15282 USA. [Shi, Yejie; Zhang, Lili; Zhang, Feng; Hu, Xiaoming; Leak, Rehana K.; Gao, Yanqin; Chen, Jun] Univ Pittsburgh, Sch Med, Ctr Cerebrovasc Dis Res, Pittsburgh, PA 15213 USA. RP Chen, L (reprint author), Chinese Peoples Liberat Army Gen Hosp, Dept Neurosurg, 28 Fuxing Rd, Beijing 100853, Peoples R China. EM chlyz34@163.com; chenj2@upmc.edu RI Gao, Yanqin/I-6790-2016 OI Gao, Yanqin/0000-0002-4915-9819; Leak, Rehana/0000-0003-2817-7417; Shi, Yejie/0000-0001-7502-9201 FU NIH [NS036736, NS045048, NS056118]; Research Career Scientist Award from Department of Veterans Affairs; VA RR D Merit Review; High Level Talent Fund of the Beijing Healthcare System [2011-3-093]; Program for New Century Excellent Talents in University [NCET-12-0612]; National Natural Science Foundation of China [81301066]; Beijing Nova Program [XX2013019] FX This project was supported by NIH grants NS036736, NS045048, and NS056118 (to J.C.), the Research Career Scientist Award from Department of Veterans Affairs and the VA RR & D Merit Review (to J.C.). L.C. was supported by the High Level Talent Fund of the Beijing Healthcare System (Grant No. 2011-3-093) and the Program for New Century Excellent Talents in University (Grant No. NCET-12-0612). J.W. was supported by the National Natural Science Foundation of China (Grant No. 81301066) and Beijing Nova Program (Grant No. XX2013019). The authors are indebted to Carol Culver for excellent editorial assistance and Pat Strickler for excellent administrative support. NR 56 TC 17 Z9 17 U1 1 U2 21 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 EI 1095-953X J9 NEUROBIOL DIS JI Neurobiol. Dis. PD AUG PY 2014 VL 68 BP 91 EP 103 DI 10.1016/j.nbd.2014.04.014 PG 13 WC Neurosciences SC Neurosciences & Neurology GA AJ8XV UT WOS:000337992300009 PM 24794156 ER PT J AU Back, SE Gros, DF McCauley, JL Flanagan, JC Cox, E Barth, KS Brady, KT AF Back, Sudie E. Gros, Daniel F. McCauley, Jenna L. Flanagan, Julianne C. Cox, Elizabeth Barth, Kelly S. Brady, Kathleen T. TI Laboratory-induced cue reactivity among individuals with prescription opioid dependence SO ADDICTIVE BEHAVIORS LA English DT Article DE Prescription opioids; Opiates; Prescription drugs; Drug cue reactivity; Drug cue paradigm ID DRUG-RELATED CUES; ADDICTION RESEARCH; HEROIN-ADDICTS; OPIATE ADDICTS; ALCOHOL; SMOKING; RELAPSE; ABUSE; METAANALYSIS; EXPOSURE AB Prescription opioid (PO) dependence is a critical health problem. Although examination of drug cue reactivity paradigms has advanced the understanding of risk factors for relapse for a variety of substances (e.g., cocaine, alcohol, nicotine), no PO specific drug cue paradigm has been developed. The current study addressed this gap in the literature and evaluated the ability of a newly developed PO drug cue paradigm to elicit subjective, physiological, and neuroendocrine changes among PO-dependent participants (n = 20) as compared to controls (n = 17). The drug cue paradigm included an induction script, viewing and handling paraphernalia (e.g., bottle of oxycontin pills, pill crusher) and watching a video depicting people using POs as well as places related to POs (e.g., pharmacies). Consistent with hypotheses, the PO group demonstrated significant pre- to post-cue increases on subjective ratings of craving, difficulty resisting POs, stress, and anger. The control group did not demonstrate significant changes on any of the subjective measures. Both the PO group and the control group evidenced significant pre- to post-cue increases in physiological responses (e.g., blood pressure, skin conductance), as expected given the arousing nature of the drug cue stimuli. The PO group, but not the control group, evidenced a significant pre- to post-cue increase in heart rate and salivary cortisol levels. The development and validation of a drug cue paradigm for POs may help inform future research and treatment development efforts for patients with PO dependence. Published by Elsevier Ltd. C1 [Back, Sudie E.; Gros, Daniel F.; McCauley, Jenna L.; Flanagan, Julianne C.; Barth, Kelly S.; Brady, Kathleen T.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Clin Neurosci Div, Charleston, SC 29425 USA. [Back, Sudie E.; Gros, Daniel F.; Brady, Kathleen T.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. [Cox, Elizabeth] Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27514 USA. RP Back, SE (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, Clin Neurosci Div, 67 President St,MSC861, Charleston, SC 29425 USA. EM backs@musc.edu FU National Institute on Drug Abuse [K23 DA021228, K12 DA031974, K12 HD055885]; National Institute of Health [5 UL1 RR029882] FX This work was supported in part by grants K23 DA021228 (Back), K12 DA031974 (Brady), and K12 HD055885 (Brady) from the National Institute on Drug Abuse, and National Institute of Health grant 5 UL1 RR029882 (Brady). NIDA and NIH had no further role in the study design, collection, analysis or interpretation of the data, writing the manuscript, or the decision to submit the paper for publication. NR 67 TC 3 Z9 3 U1 8 U2 21 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 EI 1873-6327 J9 ADDICT BEHAV JI Addict. Behav. PD AUG PY 2014 VL 39 IS 8 BP 1217 EP 1223 DI 10.1016/j.addbeh.2014.04.007 PG 7 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA AI8YD UT WOS:000337212000002 PM 24813546 ER PT J AU Denneson, LM Corson, K Helmer, DA Bair, MJ Dobscha, SK AF Denneson, Lauren M. Corson, Kathryn Helmer, Drew A. Bair, Matthew J. Dobscha, Steven K. TI Mental health utilization of new-to-care Iraq and Afghanistan Veterans following suicidal ideation assessment SO PSYCHIATRY RESEARCH LA English DT Article DE Depression; Risk assessment; Suicide; Delivery of health care ID SERVICES TASK-FORCE; OEF/OIF VETERANS; ENDURING FREEDOM; DEPRESSION; RISK; PHQ-9; VA; THOUGHTS; VALIDITY; SCREENS AB We evaluated the impact of brief structured suicidal ideation (SI) assessments on mental health care among new-to-care Operations Enduring Freedom and Iraqi Freedom (OEF/OIF) veterans. National datasets provided military, demographic, and clinical information. For all new-to-care OEF/OIF veterans administered depression screens (PHQ-2: Patient Health Questionnaire-2) and structured SI assessments in primary care or ambulatory mental health settings of three Veterans Affairs (VA) Medical Centers between April 2008 and September 2009 (N=465), generalized estimating equations were used to examine associations between SI and number of subsequent-year specialty mental health visits and antidepressant prescriptions. Approximately one-third of the veterans reported SI. In multivariate models, PTSD and anxiety diagnoses, severe depression symptoms, being married, and SI assessment by a mental health clinician were associated with more mental health visits in the subsequent year. Depression, PTSD, and anxiety diagnoses, and SI assessment by a mental health clinician were associated with receiving antidepressants. Presence of SI did not significantly affect subsequent year mental health utilization when adjusting for diagnostic and clinician variables, but inaugural visits involving mental health clinicians were consistently associated with subsequent mental health care. Published by Elsevier Ireland Ltd. C1 [Denneson, Lauren M.; Corson, Kathryn; Dobscha, Steven K.] Portland VA Med Ctr, Portland Ctr Improve Vet Involvement Care CIVIC, Portland, OR 97207 USA. [Denneson, Lauren M.; Corson, Kathryn; Dobscha, Steven K.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. [Helmer, Drew A.] VA New Jersey Hlth Care Syst, War Related Illness & Injury Study Ctr, E Orange, NJ USA. [Helmer, Drew A.] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Med & Dent, Newark, NJ 07103 USA. [Bair, Matthew J.] Richard L Roudebush Vet Affairs Med Ctr, Indianapolis, IN 46202 USA. RP Denneson, LM (reprint author), Portland VA Med Ctr, POB 1034 R&D66, Portland, OR 97207 USA. EM lauren.denneson@va.gov FU U.S. Department of Veterans Affairs, Veterans Health Administration; Health Services Research and Development Service Project [DHI-08-096]; Center to Improve Veteran Involvement in Care (CIVIC) at the Portland VA Medical Center; Department of Veterans Affairs or the United States government FX This material is based upon work supported by the U.S. Department of Veterans Affairs, Veterans Health Administration, and Health Services Research and Development Service Project DHI-08-096. Dr. Denneson is a core investigator in the Center to Improve Veteran Involvement in Care (CIVIC) at the Portland VA Medical Center. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government. NR 37 TC 2 Z9 2 U1 2 U2 14 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD JUL 30 PY 2014 VL 217 IS 3 BP 147 EP 153 DI 10.1016/j.psychres.2014.03.017 PG 7 WC Psychiatry SC Psychiatry GA AI5AS UT WOS:000336878400004 PM 24726814 ER PT J AU Gupta, A Wang, YF Spertus, JA Geda, M Lorenze, N Nkonde-Price, C D'Onofrio, G Lichtman, JH Krumholz, HM AF Gupta, Aakriti Wang, Yongfei Spertus, John A. Geda, Mary Lorenze, Nancy Nkonde-Price, Chileshe D'Onofrio, Gail Lichtman, Judith H. Krumholz, Harlan M. TI Trends in Acute Myocardial Infarction in Young Patients and Differences by Sex and Race, 2001 to 2010 SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE acute myocardial infarction; hospitalization; sex differences; trends; young women ID CORONARY-HEART-DISEASE; UNITED-STATES; CARDIOVASCULAR-DISEASE; MORTALITY-RATES; RISK-FACTORS; PREVALENCE; WOMEN; HOSPITALIZATION AB BACKGROUND Various national campaigns launched in recent years have focused on young women with acute myocardial infarctions (AMIs). Contemporary longitudinal data about sex differences in clinical characteristics, hospitalization rates, length of stay (LOS), and mortality have not been examined. OBJECTIVES This study sought to determine sex differences in clinical characteristics, hospitalization rates, LOS, and in-hospital mortality by age group and race among young patients with AMIs using a large national dataset of U.S. hospital discharges. METHODS Using the National Inpatient Sample, clinical characteristics, AMI hospitalization rates, LOS, and in-hospital mortality were compared for patients with AMI across ages 30 to 54 years, dividing them into 5-year subgroups from 2001 to 2010, using survey data analysis techniques. RESULTS A total of 230,684 hospitalizations were identified with principal discharge diagnoses of AMI in 30- to 54-year-old patients from Nationwide Inpatient Sample data, representing an estimated 1,129,949 hospitalizations in the United States from 2001 to 2010. No statistically significant declines in AMI hospitalization rates were observed in the age groups <55 years or stratified by sex. Prevalence of comorbidities was higher in women and increased among both sexes through the study period. Women had longer LOS and higher in-hospital mortality than men across all age groups. However, observed in-hospital mortality declined significantly for women from 2001 to 2010 (from 3.3% to 2.3%, relative change 30.5%; p for trend < 0.0001) but not for men (from 2% to 1.8%, relative change 8.6%; p for trend = 0.60). CONCLUSIONS AMI hospitalization rates for young people have not declined over the past decade. Young women with AMIs have more comorbidity, longer LOS, and higher in-hospital mortality than young men, although their mortality rates are decreasing. (C) 2014 by the American College of Cardiology Foundation C1 [Gupta, Aakriti; Wang, Yongfei; Geda, Mary; Lorenze, Nancy; Lichtman, Judith H.; Krumholz, Harlan M.] Yale New Haven Med Ctr, Ctr Outcomes Res & Evaluat, New Haven, CT 06504 USA. [Gupta, Aakriti] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. [Wang, Yongfei; Nkonde-Price, Chileshe; Krumholz, Harlan M.] Yale Univ, Sch Med, Dept Internal Med, Sect Cardiovasc Med, New Haven, CT 06510 USA. [Spertus, John A.] St Lukes Mid Amer Heart Inst, Kansas City, MO USA. [Spertus, John A.] Univ Missouri, Kansas City, MO 64110 USA. [Nkonde-Price, Chileshe] Philadelphia VA Med Ctr, VA Ctr Hlth Equity & Res Promot, Philadelphia, PA USA. [Nkonde-Price, Chileshe] Univ Penn, Dept Internal Med, Robert Wood Johnson Fdn Clin Scholars Program, Philadelphia, PA 19104 USA. [D'Onofrio, Gail] Yale Univ, Sch Med, Dept Emergency Med, New Haven, CT 06510 USA. [Lichtman, Judith H.] Yale Univ, Sch Med, Dept Chron Dis Epidemiol, New Haven, CT 06510 USA. [Krumholz, Harlan M.] Yale Univ, Sch Med, Robert Wood Johnson Fdn Clin Scholars Program, New Haven, CT 06510 USA. [Krumholz, Harlan M.] Yale Univ, Sch Publ Hlth, Dept Hlth Policy & Management, New Haven, CT 06510 USA. RP Krumholz, HM (reprint author), Yale Univ, Sch Med, Dept Internal Med, 1 Church St,Suite 200, New Haven, CT 06510 USA. EM harlan.krumholz@yale.edu OI D'Onofrio, Gail/0000-0002-3833-1871 FU Center for Cardiovascular Outcomes Research at Yale University [U01 HL105270-04]; Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients [R01 LH081153-06]; Genentech; National Heart, Lung, and Blood Institute; Eli Lilly and Company FX This work was supported by grant U01 HL105270-04 (Center for Cardiovascular Outcomes Research at Yale University) and grant R01 LH081153-06 (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients), both from the National Heart, Lung, and Blood Institute. Dr. Spertus has received research grants from Genentech and Eli Lilly and Company. Dr. Krumholz has a research agreement to share data with Johnson & Johnson; and is chair of a scientific advisory board of UnitedHealthcare. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 20 TC 60 Z9 62 U1 4 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JUL 29 PY 2014 VL 64 IS 4 BP 337 EP 345 DI 10.1016/j.jacc.2014.04.054 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AM9ZN UT WOS:000340240700001 PM 25060366 ER PT J AU Merlin, LR Horak, HA Milligan, TA Kraakevik, JA Ali, II AF Merlin, Lisa R. Horak, Holli A. Milligan, Tracey A. Kraakevik, Jeff A. Ali, Imran I. TI A competency-based longitudinal core curriculum in medical neuroscience SO NEUROLOGY LA English DT Article ID NEUROLOGY CLERKSHIP; CLINICAL SKILLS; BASIC SCIENCES; EDUCATION; PERFORMANCE; SIMULATION; CARE AB Current medical educational theory encourages the development of competency-based curricula. The Accreditation Council for Graduate Medical Education's 6 core competencies for resident education (medical knowledge, patient care, professionalism, interpersonal and communication skills, practice-based learning, and systems-based practice) have been embraced by medical schools as the building blocks necessary for becoming a competent licensed physician. Many medical schools are therefore changing their educational approach to an integrated model in which students demonstrate incremental acquisition and mastery of all competencies as they progress through medical school. Challenges to medical schools include integration of preclinical and clinical studies as well as development of learning objectives and assessment measures for each competency. The Undergraduate Education Subcommittee (UES) of the American Academy of Neurology (AAN) assembled a group of neuroscience educators to outline a longitudinal competency-based curriculum in medical neuroscience encompassing both preclinical and clinical coursework. In development of this curriculum, the committee reviewed United States Medical Licensing Examination content outlines, Liaison Committee on Medical Education requirements, prior AAN-mandated core curricula for basic neuroscience and clinical neurology, and survey responses from educators in US medical schools. The newly recommended curriculum provides an outline of learning objectives for each of the 6 competencies, listing each learning objective in active terms. Documentation of experiences is emphasized, and assessment measures are suggested to demonstrate adequate achievement in each competency. These guidelines, widely vetted and approved by the UES membership, aspire to be both useful as a stand-alone curriculum and also provide a framework for neuroscience educators who wish to develop a more detailed focus in certain areas of study. C1 [Merlin, Lisa R.] Suny Downstate Med Ctr, Brooklyn, NY 11203 USA. [Merlin, Lisa R.] Kings Cty Hosp, Brooklyn, NY USA. [Horak, Holli A.] Univ Arizona, Tucson, AZ USA. [Milligan, Tracey A.] Harvard Univ, Sch Med, Boston, MA USA. [Milligan, Tracey A.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Kraakevik, Jeff A.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Kraakevik, Jeff A.] Portland VA Med Ctr, Portland, OR USA. [Ali, Imran I.] Univ Toledo, Toledo, OH USA. RP Merlin, LR (reprint author), Suny Downstate Med Ctr, Brooklyn, NY 11203 USA. EM lisa.merlin@downstate.edu NR 24 TC 3 Z9 4 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD JUL 29 PY 2014 VL 83 IS 5 BP 456 EP 462 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA AN0DV UT WOS:000340253900017 PM 24975860 ER PT J AU Gold, MC McLaren, JE Reistetter, JA Smyk-Pearson, S Ladell, K Swarbrick, GM Yu, YYL Hansen, TH Lund, O Nielsen, M Gerritsen, B Kesmir, C Miles, JJ Lewinsohn, DA Price, DA Lewinsohn, DM AF Gold, Marielle C. McLaren, James E. Reistetter, Joseph A. Smyk-Pearson, Sue Ladell, Kristin Swarbrick, Gwendolyn M. Yu, Yik Y. L. Hansen, Ted H. Lund, Ole Nielsen, Morten Gerritsen, Bram Kesmir, Can Miles, John J. Lewinsohn, Deborah A. Price, David A. Lewinsohn, David M. TI MR1-restricted MAIT cells display ligand discrimination and pathogen selectivity through distinct T cell receptor usage SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID VITAMIN-B METABOLITES; BACTERIAL-INFECTION; ALPHA-CHAIN; RECOGNITION; MR1; EXPRESSION AB Mucosal-associated invariant T (MAIT) cells express a semi-invariant T cell receptor (TCR) that detects microbial metabolites presented by the nonpolymorphic major histocompatibility complex (MHC)-like molecule MR1. The highly conserved nature of MR1 in conjunction with biased MAIT TCR. chain usage is widely thought to indicate limited ligand presentation and discrimination within a pattern-like recognition system. Here, we evaluated the TCR repertoire of MAIT cells responsive to three classes of microbes. Substantial diversity and heterogeneity were apparent across the functional MAIT cell repertoire as a whole, especially for TCR beta chain sequences. Moreover, different pathogen-specific responses were characterized by distinct TCR usage, both between and within individuals, suggesting that MAIT cell adaptation was a direct consequence of exposure to various exogenous MR1-restricted epitopes. In line with this interpretation, MAIT cell clones with distinct TCRs responded differentially to a riboflavin metabolite. These results suggest that MAIT cells can discriminate between pathogen-derived ligands in a clonotype-dependent manner, providing a basis for adaptive memory via recruitment of specific repertoires shaped by microbial exposure.\ C1 [Gold, Marielle C.; Reistetter, Joseph A.; Smyk-Pearson, Sue; Lewinsohn, David M.] Oregon Hlth & Sci Univ, Div Pulm & Crit Care Med, Portland, OR 97239 USA. [Gold, Marielle C.; Lewinsohn, Deborah A.; Lewinsohn, David M.] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97239 USA. [Swarbrick, Gwendolyn M.; Lewinsohn, Deborah A.] Oregon Hlth & Sci Univ, Dept Pediat, Portland, OR 97239 USA. [Gold, Marielle C.; Lewinsohn, David M.] Portland VA Med Ctr, Portland, OR 97239 USA. [McLaren, James E.; Ladell, Kristin; Miles, John J.; Price, David A.] Cardiff Univ, Sch Med, Inst Infect & Immun, Cardiff CF14 4XN, S Glam, Wales. [Yu, Yik Y. L.; Hansen, Ted H.] Washington Univ, St Louis Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. [Lund, Ole; Nielsen, Morten] Tech Univ Denmark, Dept Syst Biol, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark. [Nielsen, Morten] Univ Nacl San Martin, Inst Invest Biotecnol, RA-1650 Buenos Aires, DF, Argentina. [Gerritsen, Bram; Kesmir, Can] Univ Utrecht, Theoret Biol & Bioinformat Grp, NL-3584 CH Utrecht, Netherlands. [Miles, John J.] QIMR Berghofer Med Res Inst, Brisbane, Qld 4006, Australia. [Price, David A.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Gold, MC (reprint author), Oregon Hlth & Sci Univ, Div Pulm & Crit Care Med, Portland, OR 97239 USA. EM goldm@ohsu.edu; lewinsod@ohsu.edu RI Lund, Ole/F-4437-2014; Price, David/C-7876-2013; Ladell, Kristin/C-8301-2013; Kesmir, Can/B-9410-2011; Lewinsohn, David/I-4936-2013 OI Lund, Ole/0000-0003-1108-0491; Price, David/0000-0001-9416-2737; Ladell, Kristin/0000-0002-9856-2938; Lewinsohn, David/0000-0001-9906-9494; Nielsen, Morten/0000-0001-7885-4311 FU Department of Veterans Affairs with resources and facility access provided by the Portland VA Medical Center; National Institutes of Health (NIH) via the Mucosal Immunology Studies Team (MIST) - National Institute of Allergy and Infectious Diseases (NIH grant) [U01 AI095776-01, AI046553]; Wellcome Trust (UK); Wellcome Trust Senior Investigator FX This work was supported by the Department of Veterans Affairs with resources and facility access provided by the Portland VA Medical Center, the National Institutes of Health (NIH) via the Mucosal Immunology Studies Team (MIST) U01 AI095776-01 funded by the National Institute of Allergy and Infectious Diseases (NIH grant AI046553), and the Wellcome Trust (UK). D.A. Price is a Wellcome Trust Senior Investigator. NR 29 TC 49 Z9 49 U1 4 U2 16 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 EI 1540-9538 J9 J EXP MED JI J. Exp. Med. PD JUL 28 PY 2014 VL 211 IS 8 BP 1601 EP 1610 DI 10.1084/jem.20140507 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA AQ4DV UT WOS:000342743500010 PM 25049333 ER PT J AU Mathes, DW Chang, J Hwang, B Graves, SS Storer, BE Butts-Miwongtum, T Sale, GE Storb, R AF Mathes, David W. Chang, Jeff Hwang, Billanna Graves, Scott S. Storer, Barry E. Butts-Miwongtum, Tiffany Sale, George E. Storb, Rainer TI Simultaneous Transplantation of Hematopoietic Stem Cells and a Vascularized Composite Allograft Leads to Tolerance SO TRANSPLANTATION LA English DT Article DE Dog; Nonmyeloablative conditioning regimen; Hematopoietic cell transplantation; Vascularized composite allograft; Skin allograft; FoxP3; Tolerance ID PRECLINICAL CANINE MODEL; LONG-TERM TOLERANCE; TISSUE-TRANSPLANTATION; RENAL-TRANSPLANTATION; HAND TRANSPLANTATION; KIDNEY ALLOGRAFTS; MINIATURE SWINE; BONE-MARROW; CHIMERISM; REJECTION AB Background. We have previously demonstrated that tolerance to a vascularized composite allograft (VCA) can be achieved after the establishment of mixed chimerism. We test the hypothesis that tolerance to a VCA in our dog leukocyte antigen-matched canine model is not dependent on the previous establishment of mixed chimerism and can be induced coincident with hematopoietic cell transplantation (HCT). Methods. Eight dog leukocyte antigen-matched, minor antigen mismatched dogs received 200 cGy of radiation and a VCA transplant. Four dogs received donor bone marrow at the time of VCA transplantation (group 1), whereas a second group of four dogs did not (group 2). All recipients received a limited course of postgrafting immunosuppression. All dogs that received HCT and VCA were given donor, third-party, and autologous skin grafts. Results. All group 1 recipients were tolerant to their VCA (962 weeks). Three of the four dogs in group 2 rejected their VCA transplants after the cessation of immunosuppression. Biopsies obtained from the muscle and skin of VCA from group 1 showed few infiltrating cells compared with extensive infiltrates in biopsies of VCA from group 2. Compared with autologous skin and muscle, elevated levels of CD3+ FoxP3+ T-regulatory cells were found in the skin and muscle obtained from the VCA of HCT recipients. All group 1 animals were tolerant to their donor skin graft and promptly rejected the third-party skin grafts. Conclusion. These data demonstrated that donor-specific tolerance to all components of the VCA can be established through simultaneous nonmyeloablative allogeneic HCT and VCA transplantation protocol. C1 [Mathes, David W.; Chang, Jeff; Hwang, Billanna; Graves, Scott S.; Storer, Barry E.; Butts-Miwongtum, Tiffany; Sale, George E.; Storb, Rainer] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA. [Mathes, David W.; Chang, Jeff] Univ Washington, Dept Surg, Seattle, WA 98195 USA. [Mathes, David W.] VA Puget Sound Hlth Care Syst, Plast Surg Serv, Seattle, WA USA. [Graves, Scott S.; Storb, Rainer] Univ Washington, Dept Med, Seattle, WA USA. [Storer, Barry E.] Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA. [Sale, George E.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. RP Mathes, DW (reprint author), Fred Hutchinson Canc Res Ctr, Div Clin Res, POB 19024,D1-100 1100 Fairview Ave N, Seattle, WA 98109 USA. EM dwmathes@fhcrc.org FU National Institutes of Health, Bethesda, MD [P01CA078902, P30CA015704]; Plastic Surgery Foundation FX This study received research funding from the National Institutes of Health, Bethesda, MD, grants P01CA078902 and P30CA015704. In addition, D.W.M. received support from the National Endowment for Plastic Surgery Grant from the Plastic Surgery Foundation. This study was neither prepared nor funded in any part by a commercial organization, including educational grants. NR 29 TC 10 Z9 11 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 EI 1534-6080 J9 TRANSPLANTATION JI Transplantation PD JUL 27 PY 2014 VL 98 IS 2 BP 131 EP 138 DI 10.1097/TP.0000000000000204 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA AL6SB UT WOS:000339262000009 PM 24918616 ER PT J AU Karasawa, H Yakabi, S Wang, LX Tache, Y AF Karasawa, Hiroshi Yakabi, Seiichi Wang, Lixin Tache, Yvette TI Orexin-1 receptor mediates the increased food and water intake induced by intracerebroventricular injection of the stable somatostatin pan-agonist, ODT8-SST in rats SO NEUROSCIENCE LETTERS LA English DT Article DE Food intake; Orexin-A; ODT8-SST; SB-334867; Somatostatin 2 receptor; Water intake ID MELANIN-CONCENTRATING HORMONE; NEUROPEPTIDE-Y; HYPOTHALAMUS; DRINKING; STIMULATION; NEURONS; BEHAVIOR; BRAIN; HYPOCRETIN/OREXIN; LOCALIZATION AB Intracerebroventricular (icv) injection of the stable somatostatin pan-agonist, ODT8-SST induces a somatostatin 2 receptor (sst(2)) mediated robust feeding response that involves neuropeptide Y and opioid systems in rats. We investigated whether the orexigenic system driven by orexin also plays a role. Food and water intake after icv injection was measured concomitantly in non-fasted and non-water deprived rats during the light phase. In vehicle treated rats (100% DMSO, icv), ODT8-SST (1 mu g/rat, icv) significantly increased the 2-h food and water intake compared to icv vehicle plus saline (5.1 +/- 1.0 g vs. 1.2 +/- 0.4 g and 11.3 +/- 1.9 mL vs. 2.5 +/- 1.2 mL, respectively). The orexin-1 receptor antagonist, SB-334867 (16 mu g/rat, icv) completely inhibited the 2-h food and water intake induced by icv ODT8-SST. In contrast, the icv pretreatment with the selective somatostatin sst(2) antagonist, S-406-028, established to block the orexigenic effect of icv ODT8-SST, did not modify the increased food and water intake induced by icv orexin-A (10.7 mu g/rat). These data indicate that orexin-1 receptor signaling system is part of the brain neurocircuitry contributing to the orexigenic and dipsogenic responses induced by icv ODT8-SST and that orexin-A stimulates food intake independently from brain sst(2) activation. Published by Elsevier Ireland Ltd. C1 [Karasawa, Hiroshi; Yakabi, Seiichi; Wang, Lixin; Tache, Yvette] Univ Calif Los Angeles, CURE Digest Dis Ctr, Dept Med, Los Angeles, CA 90073 USA. [Karasawa, Hiroshi; Yakabi, Seiichi; Wang, Lixin; Tache, Yvette] Univ Calif Los Angeles, Ctr Neurobiol, Stress Digest Dis Div, Los Angeles, CA 90073 USA. [Karasawa, Hiroshi; Yakabi, Seiichi; Wang, Lixin; Tache, Yvette] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Tache, Y (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, CURE Digest Dis Ctr, Bldg 115,Rm 117B,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM ytache@mednet.ucla.edu FU Veterans Administration Research Career Scientist Award; NIH [DK 33061]; [NIDDK-41303] FX The authors thank Mrs. Honghui Liang for excellent technical support. This work was supported by NIDDK-41303 (Animal core, YT, LW) and Veterans Administration Research Career Scientist Award (YT) and NIH DK 33061. We thank Dr. Jean Rivier (Clayton Foundation Laboratories for Biological Sciences, Salk Institutes, La Jolla, CA) for the generous supply of peptides. NR 43 TC 2 Z9 3 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 EI 1872-7972 J9 NEUROSCI LETT JI Neurosci. Lett. PD JUL 25 PY 2014 VL 576 BP 88 EP 92 DI 10.1016/j.neulet.2014.05.063 PG 5 WC Neurosciences SC Neurosciences & Neurology GA AN8KU UT WOS:000340853900017 PM 24915296 ER PT J AU Qin, WP Pan, JP Qin, YW Lee, DN Bauman, WA Cardozo, C AF Qin, Weiping Pan, Jiangping Qin, Yiwen Lee, David N. Bauman, William A. Cardozo, Christopher TI Identification of functional glucocorticoid response elements in the mouse FoxO1 promoter SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE FoxO1; Glucocorticoids; Glucocorticoid response element; Glucocorticoid receptor ID SKELETAL-MUSCLE ATROPHY; GENE-EXPRESSION; TRANSCRIPTION FACTORS; DENERVATION ATROPHY; UBIQUITIN LIGASES; RECEPTOR; INVOLVE; REDD1; MTOR AB Glucocorticoids stimulate muscle atrophy through a cascade of signals that includes activation of Fox transcription factors which then upregulate multiple genes to promote degradation of myofibrillar and other muscle proteins and inhibit protein synthesis. Our previous finding that glucocorticoids upregulate mRNA levels for FoxO1 in skeletal muscle led us to hypothesize that the FoxO1 gene contains one or more glucocorticoid response elements (GREs). Here we show that upregulation of FoxO1 expression by glucocorticoids requires the glucocorticoid receptor (GR) and binding of hormones to it. In cultured C2C12 myoblasts dexamethasone did not alter FoxO1 mRNA stability. Computational analysis predicted that the proximal promoter of the FoxO1 gene contained a cluster of eight GRE half sites and one highly conserved near-consensus SRE; the cluster is found between -800 and -2000 bp upstream of the first codon of the FoxO1 gene. A reporter gene constructed using the first 2 kb of the FoxO1 promoter was stimulated by dexamethasone. Removal of a 5' domain containing half of the GREs reduced reporter gene activity and removal of all GREs in this region ablated activation by dexamethasone. Restriction fragments of the cluster of 8 upstream GREs bound recombinant GR in gel shift assays. Collectively, the data demonstrate that the proximal promoter of the FoxO1 gene contains multiple functional GREs, indicating that upregulation of FoxO1 expression by glucocorticoids through GREs represents an additional mechanism by which the GR drives glucocorticoid-mediated muscle atrophy. These findings are also relevant to other physiological roles of FoxO1 such as regulation of hepatic metabolism. Published by Elsevier Inc. C1 [Qin, Weiping; Pan, Jiangping; Qin, Yiwen; Lee, David N.; Bauman, William A.; Cardozo, Christopher] James J Peters VA Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, Bronx, NY 10468 USA. [Qin, Weiping; Bauman, William A.; Cardozo, Christopher] Mt Sinai Sch Med, Dept Med, New York, NY USA. [Bauman, William A.; Cardozo, Christopher] Mt Sinai Sch Med, New York, NY USA. RP Qin, WP (reprint author), James J Peters VA Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, 130 West Kingsbridge Rd, Bronx, NY 10468 USA. EM weiping.qin@mssm.edu FU Department of Veterans Affairs Rehabilitation Research and Development Service [B9212C, B0687R, B1313R] FX Grant support: Department of Veterans Affairs Rehabilitation Research and Development Service B9212C, B0687R and B1313R. NR 22 TC 12 Z9 12 U1 0 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X EI 1090-2104 J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUL 25 PY 2014 VL 450 IS 2 BP 979 EP 983 DI 10.1016/j.bbrc.2014.06.080 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA AM4YD UT WOS:000339861200009 PM 24971545 ER PT J AU Friedberg, MW Schneider, EC Werner, RM AF Friedberg, Mark W. Schneider, Eric C. Werner, Rachel M. TI Evaluating a Multipayer Medical Home Intervention Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 [Friedberg, Mark W.; Schneider, Eric C.] RAND Corp, Boston, MA USA. [Werner, Rachel M.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Friedberg, MW (reprint author), 20 Pk Plaza,Ste 920, Boston, MA 02116 USA. EM mfriedbe@rand.org NR 0 TC 1 Z9 1 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 23 PY 2014 VL 312 IS 4 BP 436 EP 436 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA AL6QN UT WOS:000339257800034 PM 25038367 ER PT J AU Kaplan, DE Goldberg, DS AF Kaplan, David E. Goldberg, David S. TI Liver Transplants Among US Veterans Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 [Kaplan, David E.] Philadelphia VA Med Ctr, Gastroenterol Sect, Philadelphia, PA USA. [Goldberg, David S.] Univ Penn, Dept Med, Div Gastroenterol, Philadelphia, PA 19104 USA. RP Goldberg, DS (reprint author), Univ Penn, Dept Med, Div Gastroenterol, 423 Guardian Dr, Philadelphia, PA 19104 USA. EM david.goldberg@uphs.upenn.edu OI Kaplan, David E./0000-0002-3839-336X FU Intramural VA [VA999999] NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 23 PY 2014 VL 312 IS 4 BP 437 EP 437 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA AL6QN UT WOS:000339257800036 PM 25038369 ER PT J AU Barnes, DE Kaup, A Kirby, KA Byers, AL Diaz-Arrastia, R Yaffe, K AF Barnes, Deborah E. Kaup, Allison Kirby, Katharine A. Byers, Amy L. Diaz-Arrastia, Ramon Yaffe, Kristine TI Traumatic brain injury and risk of dementia in older veterans SO NEUROLOGY LA English DT Article ID ALZHEIMERS-DISEASE; HEAD-INJURY; COGNITIVE DECLINE; POPULATION; PLAYERS; DEATH; US AB Objectives: Traumatic brain injury (TBI) is common in military personnel, and there is growing concern about the long-term effects of TBI on the brain; however, few studies have examined the association between TBI and risk of dementia in veterans. Methods: We performed a retrospective cohort study of 188,764 US veterans aged 55 years or older who had at least one inpatient or outpatient visit during both the baseline (2000-2003) and follow-up (2003-2012) periods and did not have a dementia diagnosis at baseline. TBI and dementia diagnoses were determined using ICD-9 codes in electronic medical records. Fine-Gray proportional hazards models were used to determine whether TBI was associated with greater risk of incident dementia, accounting for the competing risk of death and adjusting for demographics, medical comorbidities, and psychiatric disorders. Results: Veterans were a mean age of 68 years at baseline. During the 9-year follow-up period, 16% of those with TBI developed dementia compared with 10% of those without TBI (adjusted hazard ratio, 1.57; 95% confidence interval: 1.35-1.83). There was evidence of an additive association between TBI and other conditions on risk of dementia. Conclusions: TBI in older veterans was associated with a 60% increase in the risk of developing dementia over 9 years after accounting for competing risks and potential confounders. Our results suggest that TBI in older veterans may predispose toward development of symptomatic dementia and raise concern about the potential long-term consequences of TBI in younger veterans and civilians. C1 [Barnes, Deborah E.; Kaup, Allison; Kirby, Katharine A.; Byers, Amy L.; Yaffe, Kristine] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Barnes, Deborah E.; Kaup, Allison; Kirby, Katharine A.; Byers, Amy L.; Yaffe, Kristine] San Francisco VA Med Ctr, Bethesda, MD USA. [Diaz-Arrastia, Ramon] Uniformed Serv Univ Hlth Sci, Bethesda, MD USA. [Diaz-Arrastia, Ramon] Ctr Neurosci & Regenerat Med, Bethesda, MD USA. RP Barnes, DE (reprint author), Univ Calif San Francisco, San Francisco, CA 94143 USA. EM Deborah.barnes@ucsf.edu FU Department of Defense/NCIRE [W81XWH-11-2-0189, 1610, 1614, W81XWH-12-1-0581]; NIH [K24 AG031155] FX Supported by the Department of Defense/NCIRE (Barnes: W81XWH-11-2-0189, project 1610; Byers: W81XWH-11-2-0189, project 1614; Yaffe: W81XWH-12-1-0581) and the NIH (Yaffe: K24 AG031155). The funders did not contribute to the design of the study, analysis or interpretation of data, or decision to publish. The views expressed do not necessarily reflect those of the funders. NR 39 TC 42 Z9 42 U1 2 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD JUL 22 PY 2014 VL 83 IS 4 BP 312 EP 319 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA AM9YH UT WOS:000340236500010 PM 24966406 ER PT J AU Kirschen, MP Tsou, A Nelson, SB Russell, JA Larriviere, D AF Kirschen, Matthew P. Tsou, Amy Nelson, Sarah Bird Russell, James A. Larriviere, Daniel CA Ethics Law Humanities Comm TI Legal and ethical implications in the evaluation and management of sports-related concussion SO NEUROLOGY LA English DT Article ID CHRONIC TRAUMATIC ENCEPHALOPATHY; HIGH-SCHOOL; PROFESSIONAL FOOTBALL; RECURRENT CONCUSSION; POSITION STATEMENT; BRAIN-INJURY; RUGBY UNION; PLAYERS; RISK; CARE AB Objective: To examine the ethical and legal issues physicians face when evaluating and managing athletes with sports-related concussions, and to offer guidance to physicians as they navigate these situations. Results: This position paper reviews and compares the components of sports-related concussion laws, including education, removal from play, and clearance for return to play. It highlights the challenges privacy laws present relevant to providing care to concussed athletes and suggests ways to help physicians overcome these obstacles. The report also explores the ethical considerations physicians should bear in mind as they evaluate and manage concussed athletes, addressing them through a framework that includes considerations of professionalism, informed decision-making, patient autonomy, beneficence, nonmaleficence, conflicts of interest, and distributive justice. Conclusions: Physicians caring for concussed athletes have an ethical obligation to ensure that their primary responsibility is to safeguard the current and future physical and mental health of their patients. Physicians have a duty to provide athletes and their parents with information about concussion risk factors, symptoms, and the risks for postconcussion neurologic impairments. Physicians should facilitate informed and shared decision-making among athletes, parents, and medical teams while protecting athletes from potential harm. Additionally, including concussion evaluation and management training in neurology residency programs, as well as developing a national concussion registry, will benefit patients by the development of policies and clinical guidelines that optimize prevention and treatment of concussive head injury. C1 [Kirschen, Matthew P.] Univ Penn, Perelman Sch Med, Dept Pediat, Div Neurol, Philadelphia, PA 19104 USA. [Kirschen, Matthew P.] Univ Penn, Perelman Sch Med, Dept Anesthesia & Crit Care Med, Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Tsou, Amy] Emergency Care Res Inst, Plymouth, PA USA. [Tsou, Amy] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Nelson, Sarah Bird] Amer Acad Neurol, Minneapolis, MN USA. [Russell, James A.] Tufts Univ, Sch Med, Lahey Clin, Dept Neurol, Boston, MA 02111 USA. [Larriviere, Daniel] Ochsner Med Ctr, Ochner Neurosci Inst, New Orleans, LA USA. RP Kirschen, MP (reprint author), Univ Penn, Perelman Sch Med, Dept Pediat, Div Neurol, Philadelphia, PA 19104 USA. EM kirschenm@chop.edu NR 38 TC 8 Z9 8 U1 3 U2 30 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD JUL 22 PY 2014 VL 83 IS 4 BP 352 EP 358 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA AM9YH UT WOS:000340236500017 PM 25008394 ER PT J AU Chen, Y Chiang, HC Litchfield, P Pena, M Juang, C Riley, DJ AF Chen, Yumay Chiang, Huai-Chin Litchfield, Patricia Pena, Michelle Juang, Charity Riley, Daniel J. TI Expression of Nek1 during kidney development and cyst formation in multiple nephron segments in the Nek1-deficient kat2J mouse model of polycystic kidney disease SO JOURNAL OF BIOMEDICAL SCIENCE LA English DT Article DE Kidney development; Primary cilium; Centromere ID DNA-DAMAGE RESPONSE; PLANAR CELL POLARITY; NIMA-RELATED KINASES; PROTEIN-KINASES; MURINE MODELS; ASPERGILLUS-NIDULANS; CHECKPOINT CONTROL; GENE-PRODUCT; PKD2; MUTATION AB Background: Neks, mammalian orthologs of the fungal protein kinase never-in-mitosis A, have been implicated in the pathogenesis of polycystic kidney disease. Among them, Nek1 is the primary protein inactivated in kat2J mouse models of PKD. Result: We report the expression pattern of Nek1 and characterize the renal cysts that develop in kat2J mice. Nek1 is detectable in all murine tissues but its expression in wild type and kat2J heterozygous kidneys decrease as the kidneys mature, especially in tubular epithelial cells. In the embryonic kidney, Nek1 expression is most prominent in cells that will become podocytes and proximal tubules. Kidney development in kat2J homozygous mice is aberrant early, before the appearance of gross cysts: developing cortical zones are thin, populated by immature glomeruli, and characterized by excessive apoptosis of several cell types. Cysts in kat2J homozygous mice form postnatally in Bowman's space as well as different tubular subtypes. Late in life, kat2J heterozygous mice form renal cysts and the cells lining these cysts lack staining for Nek1. The primary cilia of cells lining cysts in kat2J homozygous mice are morphologically diverse: in some cells they are unusually long and in others there are multiple cilia of varying lengths. Conclusion: Our studies indicate that Nek1 deficiency leads to disordered kidney maturation, and cysts throughout the nephron. C1 [Chen, Yumay; Juang, Charity] Univ Calif Irvine, Div Endocrinol, Dept Med, Irvine, CA 92697 USA. [Chiang, Huai-Chin; Litchfield, Patricia; Pena, Michelle; Riley, Daniel J.] Univ Texas Hlth Sci Ctr San Antonio, Div Nephrol, Dept Med, San Antonio, TX 78229 USA. [Riley, Daniel J.] Univ Texas Hlth Sci Ctr San Antonio, Univ Transplant Ctr, San Antonio, TX 78229 USA. [Riley, Daniel J.] South Texas Vet Hlth Care Syst, Renal Res Div, Audie L Murphy Div, San Antonio, TX 78229 USA. RP Chen, Y (reprint author), Univ Calif Irvine, Div Endocrinol, Dept Med, Gross Hall 1130,Mail Code 4086, Irvine, CA 92697 USA. EM yumayc@uci.edu; rileyd@uthscsa.edu FU PKD Foundation; American Society of Nephrology; National Kidney Foundation; NIH [RO1-DK067339, RO1-DK61626]; George M. O'Brien Kidney Research Center grant from the NIH [P50-DK061597] FX This work was initiated at University of Texas Health Science Center at San Antonio and completed at The University of California, Irvine. The work was supported by grants from the PKD Foundation, the American Society of Nephrology, the National Kidney Foundation, and the NIH (RO1-DK067339) to Y.C.; a George M. O'Brien Kidney Research Center grant from the NIH to Y.C. (P50-DK061597, Hanna E. Abboud, Program Director); and a grant from the NIH to D.J.R. (RO1-DK61626). We thank Rosaria Polci, and Sergio Garcia for assistance with early stages of the project and with technical matters; Dr. Phang-Lang Chen for critical reading the manuscript; and a Veterans Administration Renal Research Excellence Award Program to the South Texas Veterans Health Care System, Audie L. Murphy Division, for core facility support. NR 53 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1021-7770 EI 1423-0127 J9 J BIOMED SCI JI J. Biomed. Sci. PD JUL 17 PY 2014 VL 21 AR 63 DI 10.1186/s12929-014-0063-5 PG 14 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA AO1CJ UT WOS:000341049200001 PM 25030234 ER PT J AU Olfson, M Marcus, SC Bridge, JA AF Olfson, Mark Marcus, Steven C. Bridge, Jeffrey A. TI Addressing Suicide Risk in Emergency Department Patients Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID PREDICTORS C1 [Olfson, Mark] Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. [Marcus, Steven C.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Bridge, Jeffrey A.] Nationwide Childrens Hosp, Res Inst, Ctr Innovat Pediat Practice, Columbus, OH USA. RP Olfson, M (reprint author), Columbia Univ Coll Phys & Surg, Dept Psychiat, 1051 Riverside Dr, New York, NY 10032 USA. EM mo49@columbia.edu NR 6 TC 1 Z9 1 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 16 PY 2014 VL 312 IS 3 BP 298 EP 298 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA AL2FC UT WOS:000338940300036 PM 25027154 ER PT J AU Harden, WD Prochazka, AV AF Harden, Wesley D. Prochazka, Allan V. TI Review: Preoperative behavioral interventions increase smoking cessation and reduce postoperative complications SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material C1 [Harden, Wesley D.; Prochazka, Allan V.] Denver VA Med Ctr, Denver, CO 80220 USA. RP Harden, WD (reprint author), Denver VA Med Ctr, Denver, CO 80220 USA. NR 3 TC 0 Z9 0 U1 0 U2 2 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUL 15 PY 2014 VL 161 IS 2 AR JC2 DI 10.7326/0003-4819-161-2-201407150-02002 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA AM3PJ UT WOS:000339764600001 PM 25023268 ER PT J AU Abdulhadi, MA Perno, JR Melhem, ER Nucifora, PGP AF Abdulhadi, Mike A. Perno, Joseph R. Melhem, Elias R. Nucifora, Paolo G. P. TI Characteristics of Spondylotic Myelopathy on 3D Driven-Equilibrium Fast Spin Echo and 2D Fast Spin Echo Magnetic Resonance Imaging: A Retrospective Cross-Sectional Study SO PLOS ONE LA English DT Article ID CERVICAL COMPRESSION MYELOPATHY; INCREASED SIGNAL INTENSITY; PREDICT PROGNOSIS; CORD; MRI; SURGERY; SEQUENCES; IMAGES; STENOSIS; RECOVERY AB In patients with spinal stenosis, magnetic resonance imaging of the cervical spine can be improved by using 3D driven-equilibrium fast spin echo sequences to provide a high-resolution assessment of osseous and ligamentous structures. However, it is not yet clear whether 3D driven-equilibrium fast spin echo sequences adequately evaluate the spinal cord itself. As a result, they are generally supplemented by additional 2D fast spin echo sequences, adding time to the examination and potential discomfort to the patient. Here we investigate the hypothesis that in patients with spinal stenosis and spondylotic myelopathy, 3D driven-equilibrium fast spin echo sequences can characterize cord lesions equally well as 2D fast spin echo sequences. We performed a retrospective analysis of 30 adult patients with spondylotic myelopathy who had been examined with both 3D driven-equilibrium fast spin echo sequences and 2D fast spin echo sequences at the same scanning session. The two sequences were inspected separately for each patient, and visible cord lesions were manually traced. We found no significant differences between 3D driven-equilibrium fast spin echo and 2D fast spin echo sequences in the mean number, mean area, or mean transverse dimensions of spondylotic cord lesions. Nevertheless, the mean contrast-to-noise ratio of cord lesions was decreased on 3D driven-equilibrium fast spin echo sequences compared to 2D fast spin echo sequences. These findings suggest that 3D driven-equilibrium fast spin echo sequences do not need supplemental 2D fast spin echo sequences for the diagnosis of spondylotic myelopathy, but they may be less well suited for quantitative signal measurements in the spinal cord. C1 [Abdulhadi, Mike A.] Childrens Hosp & Clin Minnesota, Minneapolis, MN USA. [Perno, Joseph R.; Nucifora, Paolo G. P.] Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. [Melhem, Elias R.] Univ Maryland, Baltimore, MD 21201 USA. [Nucifora, Paolo G. P.] Univ Penn, Philadelphia, PA 19104 USA. RP Nucifora, PGP (reprint author), Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. EM paolo.nucifora@uphs.upenn.edu NR 40 TC 1 Z9 1 U1 0 U2 0 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUL 15 PY 2014 VL 9 IS 7 AR e100964 DI 10.1371/journal.pone.0100964 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AM6RN UT WOS:000339992400008 PM 25025170 ER PT J AU Kothari, A Morgan, M Haake, DA AF Kothari, Atul Morgan, Margie Haake, David A. TI Emerging Technologies for Rapid Identification of Bloodstream Pathogens SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE bloodstream infections; rapid diagnostics; molecular diagnostics; clinical microbiology; antimicrobial stewardship ID DESORPTION IONIZATION-TIME; IN-SITU HYBRIDIZATION; STAPHYLOCOCCUS-AUREUS BACTEREMIA; FLIGHT MASS-SPECTROMETRY; HUMAN SEPTIC SHOCK; METHICILLIN-RESISTANT; ANTIMICROBIAL THERAPY; CULTURE BOTTLES; CANDIDA-ALBICANS; CLINICAL IMPACT AB Technologies for rapid microbial identification are poised to revolutionize clinical microbiology and enable informed decision making for patients with life-threatening bloodstream infections. Species identification of microorganisms in positive blood cultures can be performed in minutes using commercial fluorescence in situ hybridization tests or mass spectroscopy. Microorganisms in positive blood cultures can also be identified within 1-2.5 hours using automated polymerase chain reaction-based systems that can also detect selected antibiotic resistance markers, such as methicillin resistance. When combined with antibiotic stewardship programs, these approaches improve clinical outcomes and reduce healthcare expenditures. Tests for direct detection in whole blood samples are highly desirable because of their potential to identify bloodstream pathogens without waiting 1-2 days for blood cultures to become positive. However, results for pathogen detection in whole blood do not overlap with those of conventional blood culture techniques and we are still learning how best to use these approaches. C1 [Kothari, Atul; Haake, David A.] VA Greater Los Angeles Healthcare Syst, Div Infect Dis, Los Angeles, CA 90073 USA. [Morgan, Margie] Cedars Sinai Med Ctr, Dept Pathol & Lab Med, Los Angeles, CA 90048 USA. [Haake, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Haake, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90095 USA. [Haake, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA. RP Kothari, A (reprint author), VA Greater Los Angeles Healthcare Syst, Infect Dis Sect, 111F,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM dratulkothari@gmail.com FU NIAID NIH HHS [R21 AI109889] NR 46 TC 23 Z9 23 U1 2 U2 16 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUL 15 PY 2014 VL 59 IS 2 BP 272 EP 278 DI 10.1093/cid/ciu292 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AM2FR UT WOS:000339665700021 PM 24771332 ER PT J AU Roman, BR Asch, DA AF Roman, Benjamin R. Asch, David A. TI Faded Promises: The Challenge of Deadopting Low-Value Care SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material C1 Univ Penn, Robert Wood Johnson Fdn Clin Scholars Program, Ctr Hlth Equity Res & Promot, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Ctr Hlth Equity Res & Promot, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Mem Sloan Kettering Canc Ctr, Head & Neck Serv, New York, NY 10021 USA. RP Asch, DA (reprint author), Blockley Hall 1123,423 Guardian Dr, Philadelphia, PA 19104 USA. EM asch@wharton.upenn.edu NR 8 TC 19 Z9 19 U1 0 U2 1 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUL 15 PY 2014 VL 161 IS 2 BP 149 EP + DI 10.7326/M14-0212 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA AM3PJ UT WOS:000339764600026 PM 24781317 ER PT J AU Gregory, CM Embry, A Perry, L Bowden, MG AF Gregory, Chris M. Embry, Aaron Perry, Lindsay Bowden, Mark G. TI Quantifying human movement across the continuum of care: From lab to clinic to community SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE Walking; Biomechanics; Motion analysis; Rehabilitation ID GROUND REACTION FORCES; HEMIPARETIC WALKING; AMBULATORY ACTIVITY; RELIABILITY; SPEED; VALIDATION; SYSTEM AB The ability to precisely quantify human movement within the laboratory setting provides researchers with data that comprehensively describe movement dysfunction in clinical cohorts. Furthermore, these data can be effectively utilized to identify potential underlying mechanisms as targets for therapeutic intervention. Although the utility of these methodologies is evidenced by the number of laboratories incorporating these techniques to understand clinical pathologies, the direct translation to clinical practice remains elusive and there exists an information gap between researchers studying these populations and the clinicians developing treatment for the individuals. Method: Recent technological advancements allow researchers and their clinician counterparts to measure certain elements of human movement outside of the laboratory. Specifically, the use of portable accelerometers allows for calculation of acceleration of the center of mass (COMa) during walking. COMa can be then be used to infer information about force generation by the individual during walking. This information may then be used by researchers to integrate with laboratory based results as well as by clinicians to partner with clinical findings, thus guiding clinical decision making as well as treatment design. The extent to which these types of measurement devices can be used to generate specific data describing human movement away from the lab is in the early stages of investigation, however, the potential for their use is something that could help advance research and patient care in the future. Published by Elsevier B.V. C1 [Gregory, Chris M.] Med Univ S Carolina, Dept Hlth Sci & Res, Charleston, SC 29425 USA. [Embry, Aaron] Med Univ S Carolina, Div Phys Therapy, Charleston, SC 29425 USA. [Perry, Lindsay; Bowden, Mark G.] Ralph H Johnson VAMC, Res Serv, Charleston, SC USA. RP Gregory, CM (reprint author), Med Univ S Carolina, Coll Hlth Profess, Dept Hlth Sci & Res, 77 President St,MSC 700, Charleston, SC 29425 USA. EM gregoryc@musc.edu FU RRD VA [IK2 RX000787] NR 16 TC 3 Z9 3 U1 2 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 EI 1872-678X J9 J NEUROSCI METH JI J. Neurosci. Methods PD JUL 15 PY 2014 VL 231 SI SI BP 18 EP 21 DI 10.1016/j.jneumeth.2014.04.029 PG 4 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA AL5BN UT WOS:000339148600004 PM 24797226 ER PT J AU Ruel, N Markova, DZ Adams, SL Scanzello, C Cs-Szabo, G Gerard, D Shi, P Anderson, DG Zack, M An, HS Chen, D Zhang, YJ AF Ruel, Nancy Markova, Dessislava Z. Adams, Sherrill L. Scanzello, Carla Cs-Szabo, Gabriella Gerard, David Shi, Peng Anderson, D. Greg Zack, Marc An, Howard S. Chen, Di Zhang, Yejia TI Fibronectin Fragments and the Cleaving Enzyme ADAM-8 in the Degenerative Human Intervertebral Disc SO SPINE LA English DT Article DE intervertebral disc; fibronectin fragments; ADAM-8; human ID IN-VITRO; DOMAIN; CHONDROGENESIS; CARTILAGE; MATRIX; CELLS; VIVO AB Study Design. The presence of fibronectin fragments (FN-fs) and the cleaving enzyme, A disintegrin and metalloproteinase domain-containing protein (ADAM)-8 were examined in human intervertebral disc (IVD) tissue in vitro. Objective. To investigate the presence and pathophysiological concentration of FN-fs and their cleaving enzyme, ADAM-8, in the human IVD tissue. Summary of Background Data. The 29-kDa FN-f has been shown to result in extracellular matrix loss in rabbit IVDs. However, the concentration of this biologically active fragment in the degenerative human IVD tissue has previously not been determined. Furthermore, it is critical to identify the enzyme(s) responsible for FN cleavage in the IVD. Methods. Human degenerative IVD tissues were removed during spinal surgery. A normal seeming young adult and an infant human cadaveric sample were obtained as controls. Soluble proteins were extracted, and analyzed by Western blotting using antibodies specific for the human FN neoepitope VRAA 271. A purified 29-kDa FN-f was used to allow estimation of the concentration of FN-fs in the tissues. ADAM-8, a FN-cleaving enzyme, was analyzed by Western blotting and immunostaining. Results. All adult IVD tissues contain many FN-f species, but these species were absent from the infant disc tissue. Moderately degenerative discs contained the highest amount of FN-fs; the concentration was estimated to be in the nanomolar range per gram of tissue. ADAM-8, known to cleave FN resulting in the VRAA(271) neoepitope, was present in the human disc. ADAM-8 primarily localized in the pericellular matrix of the nucleus pulposus tissue, as determined by immunostaining. Conclusion. This is the first report that N-terminal FN-fs are consistently present in IVD tissues from adult subjects. The pathophysiological concentration of these fragments is estimated to be at nanomolar range per gram of IVD tissue. Furthermore, ADAM-8, known to cleave FN, is present at the pericellular matrix of disc cells. C1 [Ruel, Nancy; Shi, Peng; An, Howard S.; Zhang, Yejia] Rush Univ, Med Ctr, Dept Orthoped Surg, Chicago, IL 60612 USA. [Markova, Dessislava Z.; Anderson, D. Greg] Thomas Jefferson Univ, Dept Orthoped Surg, Philadelphia, PA 19107 USA. [Adams, Sherrill L.] Univ Penn, Sch Dent Med, Dept Biochem, Philadelphia, PA 19104 USA. [Scanzello, Carla] Univ Penn, Perelman Sch Med, Dept Med, Rheumatol Sect, Philadelphia, PA 19104 USA. [Scanzello, Carla] Univ Penn, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Cs-Szabo, Gabriella; Gerard, David; Chen, Di] Rush Univ, Med Ctr, Dept Biochem, Chicago, IL 60612 USA. [Zhang, Yejia] Univ Penn, Perelman Sch Med, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Zhang, Yejia] Univ Penn, Perelman Sch Med, Dept Phys Med & Rehabil, Philadelphia, PA 19104 USA. [Zack, Marc] Dow Agrosci, Indianapolis, IN USA. RP Zhang, YJ (reprint author), Univ Penn, Perelman Sch Med, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. EM yejia.zhang@uphs.upenn.edu FU National Institute of Child Health and Human Development (NICHD) [1K08 HD049598-01] FX National Institute of Child Health and Human Development (NICHD, 1K08 HD049598-01) funds were received to support this work. NR 20 TC 4 Z9 5 U1 6 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 EI 1528-1159 J9 SPINE JI SPINE PD JUL 15 PY 2014 VL 39 IS 16 BP 1274 EP 1279 DI 10.1097/BRS.0000000000000397 PG 6 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA AL5IG UT WOS:000339166500011 PM 25010013 ER PT J AU Donnelly, J Wang, H Locke, J Mannon, R Baddley, J AF Donnelly, J. Wang, H. Locke, J. Mannon, R. Baddley, J. TI Healthcare Facility-Associated Clostridium difficile Infection in Solid Organ Transplant Recipients SO TRANSPLANTATION LA English DT Meeting Abstract CT World Transplant Congress CY JUL 26-31, 2014 CL San Francisco, CA SP Amer Soc Transplant Surg, Transplantat Soc, Amer Soc Transplantat C1 [Donnelly, J.; Wang, H.] Univ Alabama Birmingham, Dept Emergency Med, Birmingham, AL USA. [Locke, J.] Univ Alabama Birmingham, Dept Surg, Birmingham, AL 35294 USA. [Mannon, R.; Baddley, J.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Baddley, J.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. OI Donnelly, John/0000-0002-0646-9470 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 EI 1534-6080 J9 TRANSPLANTATION JI Transplantation PD JUL 15 PY 2014 VL 98 SU 1 MA D2397 BP 772 EP 772 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA AL4LN UT WOS:000339104605074 ER PT J AU Myaskovsky, L Pleis, J Dew, M Switzer, G Shapiro, R AF Myaskovsky, L. Pleis, J. Dew, M. Switzer, G. Shapiro, R. TI Race, Experience of Discrimination, and Other Non-Medical Factors Predict Differences in Acceptance for Kidney Transplantation. SO TRANSPLANTATION LA English DT Meeting Abstract CT World Transplant Congress CY JUL 26-31, 2014 CL San Francisco, CA SP Amer Soc Transplant Surg, Transplantat Soc, Amer Soc Transplantat C1 [Myaskovsky, L.; Pleis, J.; Switzer, G.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Myaskovsky, L.; Pleis, J.; Dew, M.; Switzer, G.; Shapiro, R.] Univ Pittsburgh, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 EI 1534-6080 J9 TRANSPLANTATION JI Transplantation PD JUL 15 PY 2014 VL 98 SU 1 MA B1197 BP 827 EP 827 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA AL4LN UT WOS:000339104605257 ER PT J AU Myaskovsky, L Pleis, J Ramkumar, M Langone, A Saha, S Thomas, C AF Myaskovsky, L. Pleis, J. Ramkumar, M. Langone, A. Saha, S. Thomas, C. TI Fewer Race Disparities in the National VA Kidney Transplant Program. SO TRANSPLANTATION LA English DT Meeting Abstract CT World Transplant Congress CY JUL 26-31, 2014 CL San Francisco, CA SP Amer Soc Transplant Surg, Transplantat Soc, Amer Soc Transplantat C1 [Myaskovsky, L.; Pleis, J.; Ramkumar, M.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Myaskovsky, L.; Pleis, J.; Ramkumar, M.] Univ Pittsburgh, Pittsburgh, PA USA. [Langone, A.] VA Tennessee Valley Healthcare Syst, Nashville, TN USA. [Saha, S.] Portland VA Med Ctr, Portland, OR USA. [Thomas, C.] Iowa City VA Healthcare Syst, Iowa City, IA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 EI 1534-6080 J9 TRANSPLANTATION JI Transplantation PD JUL 15 PY 2014 VL 98 SU 1 MA B1196 BP 827 EP 827 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA AL4LN UT WOS:000339104605256 ER PT J AU Manickam, N Patel, M Griendling, KK Gorin, Y Barnes, JL AF Manickam, Nagaraj Patel, Mandakini Griendling, Kathy K. Gorin, Yves Barnes, Jeffrey L. TI RhoA/Rho kinase mediates TGF-beta(1)-induced kidney myofibroblast activation through Poldip2/Nox4-derived reactive oxygen species SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE fibrosis; NADPH oxidase; oxidative stress; GTPase; myofibroblast differentiation; Rho kinase; transforming growth factor-beta(1); polymerase (DNA-directed) delta-interacting protein 2 ID UNILATERAL URETERAL OBSTRUCTION; I COLLAGEN EXPRESSION; GROWTH-FACTOR-BETA; ANGIOTENSIN-II; TGF-BETA; RHO-KINASE; MESANGIAL CELLS; NADPH OXIDASES; SIGNAL-TRANSDUCTION; OXIDATIVE STRESS AB The small G proteins Rac1 and RhoA regulate actin cytoskeleton, cell shape, adhesion, migration, and proliferation. Recent studies in our laboratory have shown that NADPH oxidase Nox4-derived ROS are involved in transforming growth factor (TGF)-beta(1)-induced rat kidney myofibroblast differentiation assessed by the acquisition of an alpha-smooth muscle actin (alpha-SMA) phenotype and expression of an alternatively spliced fibronectin variant (Fn-EIIIA). Rac1 and RhoA are essential in signaling by some Nox homologs, but their role as effectors of Nox4 in kidney myofibroblast differentiation is not known. In the present study, we explored a link among Rac1 and RhoA and Nox4-dependent ROS generation in TGF-beta(1)-induced kidney myofibroblast activation. TGF-beta(1) stimulated an increase in Nox4 protein expression, NADPH oxidase activity, and abundant alpha-SMA and Fn-EIIIA expression. RhoA but not Rac1 was involved in TGF-beta(1) induction of Nox4 signaling of kidney myofibroblast activation. TGF-beta(1) stimulated active RhoA-GTP and increased Rho kinase (ROCK). Inhibition of RhoA with small interfering RNA and ROCK using Y-27632 significantly reduced TGF-beta(1)-induced stimulation of Nox4 protein, NADPH oxidase activity, and alpha-SMA and Fn-EIIIA expression. Treatment with diphenyleneiodonium, an inhibitor of NADPH oxidase, did not decrease RhoA activation but inhibited TGF-beta(1)-induced alpha-SMA and Fn-EIIIA expression, indicating that RhoA is upstream of ROS generation. RhoA/ROCK also regulated polymerase (DNA-directed) delta-interacting protein 2 (Poldip2), a newly discovered Nox4 enhancer protein. Collectively, these data indicate that RhoA/ROCK is upstream of Poldip2-dependent Nox4 regulation and ROS production and induces redox signaling of kidney myofibroblast activation and may broader implications in the pathophysiology of renal fibrosis. C1 [Barnes, Jeffrey L.] South Texas Vet Hlth Care Syst, Audie Murphy Mem Vet Adm Hosp, Med Res Serv, San Antonio, TX USA. [Manickam, Nagaraj; Patel, Mandakini; Gorin, Yves; Barnes, Jeffrey L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Nephrol, San Antonio, TX 78229 USA. [Griendling, Kathy K.] Emory Univ, Sch Med, Dept Med, Div Cardiol, Atlanta, GA USA. RP Barnes, JL (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Nephrol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM barnesj@uthscsa.edu FU Veterans Administration Merit Review Program; National Institutes of Health (NIH) [RO1-DK-080106]; NIH George O'Brien Kidney Center and Morphology Core FX This work was supported by grants from the Veterans Administration Merit Review Program, National Institutes of Health (NIH) Grant RO1-DK-080106, and the NIH George O'Brien Kidney Center and Morphology Core. NR 67 TC 33 Z9 37 U1 0 U2 16 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X EI 1522-1466 J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD JUL 15 PY 2014 VL 307 IS 2 BP F159 EP F171 DI 10.1152/ajprenal.00546.2013 PG 13 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA AL1XZ UT WOS:000338921000005 PM 24872317 ER PT J AU Tregellas, JR AF Tregellas, Jason R. TI Neuroimaging Biomarkers for Early Drug Development in Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Review DE Biomarkers; default network; gamma; band; hippocampus; neuroimaging; schizophrenia ID DEFAULT MODE NETWORK; CEREBRAL-BLOOD-FLOW; FUNCTIONAL CONNECTIVITY; 1ST-EPISODE PSYCHOSIS; ACETYLCHOLINE-RECEPTOR; HIPPOCAMPAL-FORMATION; HEMODYNAMIC-RESPONSE; 1ST-DEGREE RELATIVES; GAMMA OSCILLATIONS; PREFRONTAL CORTEX AB Given the relative inability of currently available antipsychotic treatments to adequately provide sustained recovery and improve quality of life for patients with schizophrenia, new treatment strategies are urgently needed. One way to improve the therapeutic development process may be an increased use of biomarkers in early clinical trials. Reliable biomarkers that reflect aspects of disease pathophysiology can be used to determine if potential treatment strategies are engaging their desired biological targets. This review evaluates three potential neuroimaging biomarkers: hippocampal hyperactivity, gamma-band deficits, and default network abnormalities. These deficits have been widely replicated in the illness, correlate with measures of positive symptoms, are consistent with models of disease pathology, and have shown initial promise as biomarkers of biological response in early studies of potential treatment strategies. Two key features of these deficits, and a guiding rationale for the focus of this review, are that the deficits are not dependent upon patients' performance of specific cognitive tasks and they have analogues in animal models of schizophrenia, greatly increasing their appeal for use as biomarkers. Using neuroimaging biomarkers such as those proposed here to establish early in the therapeutic development process if treatment strategies are having their intended biological effect in humans may facilitate development of new treatments for schizophrenia. C1 [Tregellas, Jason R.] Univ Colorado, Sch Med, Denver Vet Affairs Med Ctr, Res Serv, Aurora, CO 80045 USA. [Tregellas, Jason R.] Univ Colorado, Sch Med, Dept Psychiat, Aurora, CO 80045 USA. RP Tregellas, JR (reprint author), Univ Colorado, Sch Med, Dept Psychiat, 13001 East 17th Pl,MS F546, Aurora, CO 80045 USA. EM Jason.tregellas@ucdenver.edu RI Tregellas, Jason/J-3637-2015 FU Veterans Affairs Clinical Science Research and Development Service; National Institutes of Health [R01DK089095]; Brain and Behavior Research Foundation; Blowitz-Ridgeway Foundation FX Dr. Tregellas is supported by the Veterans Affairs Clinical Science Research and Development Service, National Institutes of Health Grant R01DK089095, the Brain and Behavior Research Foundation, and the Blowitz-Ridgeway Foundation. NR 117 TC 16 Z9 16 U1 7 U2 20 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUL 15 PY 2014 VL 76 IS 2 BP 111 EP 119 DI 10.1016/j.biopsych.2013.08.025 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AK5FU UT WOS:000338450900006 PM 24094513 ER PT J AU Akl, TJ Wilson, MA Ericson, MN Farquhar, E Cote, GL AF Akl, Tony J. Wilson, Mark A. Ericson, M. Nance Farquhar, Ethan Cote, Gerard L. TI Wireless Monitoring of Liver Hemodynamics In Vivo SO PLOS ONE LA English DT Article ID NEAR-INFRARED SPECTROSCOPY; IMPLANTABLE SENSOR; CEREBRAL OXIMETRY; ALLOGRAFT FAILURE; PULSE OXIMETRY; OXYGENATION; PERFUSION; TRANSPLANTATION; NIRS; SIGNALS AB Liver transplants have their highest technical failure rate in the first two weeks following surgery. Currently, there are limited devices for continuous, real-time monitoring of the graft. In this work, a three wavelengths system is presented that combines near-infrared spectroscopy and photoplethysmography with a processing method that can uniquely measure and separate the venous and arterial oxygen contributions. This strategy allows for the quantification of tissue oxygen consumption used to study hepatic metabolic activity and to relate it to tissue stress. The sensor is battery operated and communicates wirelessly with a data acquisition computer which provides the possibility of implantation provided sufficient miniaturization. In two in vivo porcine studies, the sensor tracked perfusion changes in hepatic tissue during vascular occlusions with a root mean square error (RMSE) of 0.135 mL/min/g of tissue. We show the possibility of using the pulsatile wave to measure the arterial oxygen saturation similar to pulse oximetry. The signal is also used to extract the venous oxygen saturation from the direct current (DC) levels. Arterial and venous oxygen saturation changes were measured with an RMSE of 2.19% and 1.39% respectively when no vascular occlusions were induced. This error increased to 2.82% and 3.83% when vascular occlusions were induced during hypoxia. These errors are similar to the resolution of a commercial oximetry catheter used as a reference. This work is the first realization of a wireless optical sensor for continuous monitoring of hepatic hemodynamics. C1 [Akl, Tony J.; Cote, Gerard L.] Texas A&M Univ, Dept Biomed Engn, College Stn, TX 77843 USA. [Wilson, Mark A.] Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA. [Wilson, Mark A.] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Ericson, M. Nance; Farquhar, Ethan] Oak Ridge Natl Lab, Oak Ridge, TN USA. RP Akl, TJ (reprint author), Texas A&M Univ, Dept Biomed Engn, College Stn, TX 77843 USA. EM tja161@gmail.com RI Ericson, Milton/H-9880-2016 OI Ericson, Milton/0000-0002-6628-4865 FU National Institutes of Health (NIH) through a Bioengineering Research Partnership (BRP) grant [5R01-GM077150] FX This work was funded by the National Institutes of Health (NIH) through a Bioengineering Research Partnership (BRP) grant (#5R01-GM077150). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 32 TC 3 Z9 3 U1 0 U2 10 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUL 14 PY 2014 VL 9 IS 7 AR e102396 DI 10.1371/journal.pone.0102396 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AM1PC UT WOS:000339618600076 PM 25019160 ER PT J AU Jim, B Mehta, S Qipo, A Kim, K Cohen, HW Moore, RM He, JC Sharma, S AF Jim, Belinda Mehta, Swati Qipo, Andi Kim, Kwanghee Cohen, Hillel W. Moore, Robert M. He, John C. Sharma, Shuchita TI A Comparison of Podocyturia, Albuminuria and Nephrinuria in Predicting the Development of Preeclampsia: A Prospective Study SO PLOS ONE LA English DT Article ID ANTIANGIOGENIC FACTORS; ANGIOGENIC FACTORS; URINARY-EXCRETION; PROTEINURIA; BIOMARKERS; PREGNANCY; HYPERTENSION; DISEASE; WOMEN AB Preeclampsia, a hypertensive multisystem disease that complicates 5-8% of all pregnancy, is a major cause for maternal and fetal mortality and morbidity. The disease is associated with increased spontaneous and evoked preterm birth and remote cardio-renal disorders in the mother and offspring. Thus the ability to predict the disease should lead to earlier care and decreased morbidity. This has led to fervent attempts to identify early predictive biomarkers and research endeavors that have expanded as we learn more regarding possible causes of the disease. As preeclampsia is associated with specific renal pathology including podocyte injury, early urinary podocyte (podocyturia), or the podocyte specific proteinuria nephrin in the urine (nephrinuria), as well as the more easily measured urinary albumin (albuminuria), have all been suggested as predictive markers. We performed a prospective study recruiting 91 pregnant women (78 of whom were high risk) and studied the predictive ability of these three urinary biomarkers. The subjects were recruited between 15-38 weeks of gestation. Fourteen patients, all in the high-risk obstetric group, developed preeclampsia. The levels of podocyturia, nephrinuria, and albuminuria were variably higher in the high-risk pregnant patients who developed preeclampsia. The sensitivities and specificities for podocyturia were 70% and 43%, for albuminuria were 36% and 96%, and for nephrinuria were 57% and 58%, respectively. Also, abnormal nephrinuria (69%) and podocyturia (38%) were detected in low risk women who had uncomplicated gestations; none of these women exhibited albuminuria. In our study, none of the three urinary markers achieved the minimum predictive values required for clinical testing. The lack of excessive albuminuria, however, may indicate a preeclampsia-free gestation. Given a discrepant literature, further studies with larger sample size should be considered. C1 [Jim, Belinda; Qipo, Andi] Albert Einstein Coll Med, Jacobi Med Ctr, Dept Nephrol Med, Bronx, NY 10467 USA. [Mehta, Swati; He, John C.] James J Peters VA Med Ctr, Dept Nephrol Med, Bronx, NY USA. [Kim, Kwanghee] Providence Alaska Med Ctr, Anchorage, AK USA. [Cohen, Hillel W.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Moore, Robert M.] Albert Einstein Coll Med, Dept Obstet & Gynecol, Jacobi Med Ctr, Bronx, NY 10467 USA. [He, John C.; Sharma, Shuchita] Mt Sinai Sch Med, Dept Nephrol Med, New York, NY USA. RP Jim, B (reprint author), Albert Einstein Coll Med, Jacobi Med Ctr, Dept Nephrol Med, Bronx, NY 10467 USA. EM belindajim286@gmail.com OI Cohen, Hillel/0000-0002-4524-0898 FU CTSA from the National Center for Advancing Translational Sciences (NCATS), a component of the National Institutes of Health (NIH) [1 UL1 TR001073-01, 1 TL1 TR001072-01, 1 KL2 TR001071-01] FX This publication was supported in part by the CTSA Grant 1 UL1 TR001073-01, 1 TL1 TR001072-01, 1 KL2 TR001071-01 from the National Center for Advancing Translational Sciences (NCATS), a component of the National Institutes of Health (NIH). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 22 TC 7 Z9 8 U1 1 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUL 10 PY 2014 VL 9 IS 7 AR e101445 DI 10.1371/journal.pone.0101445 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AK9RG UT WOS:000338763800024 PM 25010746 ER PT J AU Perez, SM Carreno, FR Frazer, A Lodge, DJ AF Perez, Stephanie M. Carreno, Flavia R. Frazer, Alan Lodge, Daniel J. TI Vagal Nerve Stimulation Reverses Aberrant Dopamine System Function in the Methylazoxymethanol Acetate Rodent Model of Schizophrenia SO JOURNAL OF NEUROSCIENCE LA English DT Article DE dopamine; hippocampus; schizophrenia; vagal nerve stimulation ID TREATMENT-RESISTANT DEPRESSION; RAT DORSAL HIPPOCAMPUS; PREFRONTAL CORTEX; ELECTROPHYSIOLOGICAL CHARACTERIZATION; ANTIPSYCHOTIC-DRUGS; EPILEPSY PATIENTS; GENE-EXPRESSION; BRAIN; NOREPINEPHRINE; DEFICITS AB Vagal nerve stimulation (VNS) is an alternative therapy for epilepsy and treatment refractory depression. Here we examine VNS as a potential therapy for the treatment of schizophrenia in the methylozoxymethanol acetate (MAM) rodent model of the disease. We have previously demonstrated that hyperactivity within ventral regions of the hippocampus (vHipp) drives the dopamine system dysregulation in this model. Moreover, by targeting the vHipp directly, we can reverse aberrant dopamine system function and associated behaviors in the MAM model. Although the central effects of VNS have not been completely delineated, positron emission topographic measurements of cerebral blood flow in humans have consistently reported that VNS stimulation induces bilateral decreases in hippocampal activity. Based on our previous observations, we performed in vivo extracellular electrophysiological recordings in MAM-and saline-treated rats to evaluate the effect of chronic (2 week) VNS treatment on the activity of putative vHipp pyramidal neurons, as well as downstream dopamine neuron activity in the ventral tegmental area. Here we demonstrate that chronic VNS was able to reverse both vHipp hyperactivity and aberrant mesolimbic dopamine neuron function in the MAM model of schizophrenia. Additionally, VNS reversed a behavioral correlate of the positive symptoms of schizophrenia. Because current therapies for schizophrenia are far from adequate, with a large number of patients discontinuing treatment due to low efficacy or intolerable side effects, it is important to explore alternative nonpharmacological treatments. These data provide the first preclinical evidence that VNS may be a possible alternative therapeutic approach for the treatment of schizophrenia. C1 [Perez, Stephanie M.; Carreno, Flavia R.; Frazer, Alan; Lodge, Daniel J.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA. [Perez, Stephanie M.; Carreno, Flavia R.; Frazer, Alan; Lodge, Daniel J.] Univ Texas Hlth Sci Ctr San Antonio, Ctr Biomed Neurosci, San Antonio, TX 78229 USA. [Frazer, Alan] South Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX 78229 USA. RP Lodge, DJ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, 7703 Floyd Curl Dr,MC 7764, San Antonio, TX 78229 USA. EM LodgeD@uthscsa.edu RI Lodge, Daniel/K-4740-2014 OI Lodge, Daniel/0000-0002-6772-1748 FU NIH [R01 MH082933, R01 MH090067, F31 MH098564]; Cyberonics; Dey Pharmaceuticals FX This work was supported by NIH Grants R01 MH082933 (A.F.), R01 MH090067 (D.J.L.), and F31 MH098564 (S.M.P.).; S.M.P. and F.R.C. declare no competing financial interests. A.F. has served on advisory boards for Lundbeck, Takeda Pharmaceuticals International, and Eli Lilly; and as a consultant for Dey Pharmaceuticals. Previously, A.F. had received financial compensation as a consultant for Cyberonics and had also obtained grant support from them for a preclinical study. D.J.L. reports receiving consulting fees from Dey Pharmaceuticals. NR 51 TC 6 Z9 6 U1 0 U2 5 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUL 9 PY 2014 VL 34 IS 28 BP 9261 EP 9267 DI 10.1523/JNEUROSCI.0588-14.2014 PG 7 WC Neurosciences SC Neurosciences & Neurology GA AL5EJ UT WOS:000339156000010 PM 25009259 ER PT J AU Karimkhani, C Boyers, LN Margolis, DJ Naghavi, M Hay, RJ Williams, HC Naldi, L Coffeng, LE Weinstock, MA Dunnick, CA Pederson, H Vos, T Murray, CJL Dellavalle, RP AF Karimkhani, Chante Boyers, Lindsay N. Margolis, David J. Naghavi, Mohsen Hay, Roderick J. Williams, Hywel C. Naldi, Luigi Coffeng, Luc E. Weinstock, Martin A. Dunnick, Cory A. Pederson, Hannah Vos, Theo Murray, Christopher J. L. Dellavalle, Robert P. TI Comparing Cutaneous Research Funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases with 2010 Global Burden of Disease Results SO PLOS ONE LA English DT Article ID RESEARCH PRIORITIES; OF-HEALTH; LEPROSY; ASSOCIATION; PSORIASIS AB Importance: Disease burden data helps guide research prioritization. Objective: To determine the extent to which grants issued by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) reflect disease burden, measured by disability-adjusted life years (DALYs) from Global Burden of Disease (GBD) 2010 project. Design: Two investigators independently assessed 15 skin conditions studied by GBD 2010 in the NIAMS database for grants issued in 2013. The 15 skin diseases were matched to their respective DALYs from GBD 2010. Setting: The United States NIAMS database and GBD 2010 skin condition disability data. Main Outcome(s) and Measure(s): Relationship of NIAMS grant database topic funding with percent total GBD 2010 DALY and DALY rank for 15 skin conditions. Results: During fiscal year 2013, 1,443 NIAMS grants were issued at a total value of $424 million. Of these grants, 17.7% covered skin topics. Of the total skin disease funding, 82%(91 grants) were categorized as "general cutaneous research.'' Psoriasis, leprosy, and "other skin and subcutaneous diseases'' (ie; immunobullous disorders, vitiligo, and hidradenitis suppurativa) were over-represented when funding was compared with disability. Conversely, cellulitis, decubitus ulcer, urticaria, acne vulgaris, viral skin diseases, fungal skin diseases, scabies, and melanoma were under-represented. Conditions for which disability and funding appeared well-matched were dermatitis, squamous and basal cell carcinoma, pruritus, bacterial skin diseases, and alopecia areata. Conclusions and Relevance: Degree of representation in NIAMS is partly correlated with DALY metrics. Grant funding was well-matched with disability metrics for five of the 15 studied skin diseases, while two skin diseases were over-represented and seven were under-represented. Global burden estimates provide increasingly transparent and important information for investigating and prioritizing national research funding allocations. C1 [Karimkhani, Chante] Columbia Univ, Coll Phys & Surg, New York, NY USA. [Boyers, Lindsay N.] Georgetown Univ, Sch Med, Washington, DC USA. [Margolis, David J.] Univ Penn, Dept Biostat & Epidemiol & Dermatol, Philadelphia, PA 19104 USA. [Naghavi, Mohsen; Coffeng, Luc E.; Vos, Theo; Murray, Christopher J. L.] Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA. [Hay, Roderick J.] Kings Coll Hosp NHS Trust, Dept Dermatol, London, England. [Williams, Hywel C.] Univ Nottingham, Ctr Evidence Based Dermatol, Nottingham NG7 2RD, England. [Naldi, Luigi] Azienda Osped Papa Giovanni XXIII, Dept Dermatol, Bergamo, Italy. [Weinstock, Martin A.] Vet Affairs Med Ctr, Dermatoepidemiol Unit, Providence, RI USA. [Weinstock, Martin A.] Rode Isl Hosp, Dept Dermatol, Providence, RI USA. [Weinstock, Martin A.] Brown Univ, Dept Dermatol, Providence, RI 02912 USA. [Weinstock, Martin A.] Brown Univ, Dept Epidemiol, Providence, RI 02912 USA. [Dunnick, Cory A.; Dellavalle, Robert P.] Univ Colorado, Dept Dermatol, Aurora, CO 80045 USA. [Dunnick, Cory A.; Dellavalle, Robert P.] Eastern Colorado Hlth Care Syst, Dermatol Serv, US Dept Vet Affairs, Denver, CO USA. [Pederson, Hannah] Univ Colorado, Sch Med, Aurora, CO USA. [Dellavalle, Robert P.] Univ Colorado, Colorado Sch Publ Hlth, Dept Epidemiol, Aurora, CO USA. RP Dellavalle, RP (reprint author), Univ Colorado, Dept Dermatol, Anschutz Med Campus, Aurora, CO 80045 USA. EM robert.dellavalle@ucdenver.edu RI Naldi, Luigi/K-6343-2016 OI Naldi, Luigi/0000-0002-3160-2835 FU Bill and Melinda Gates Foundation; US Department of Veterans Affairs FX This study was supported in part by the Bill and Melinda Gates Foundation (PI: Christoper Murray) and the US Department of Veterans Affairs (salary for Drs. Dellavalle, Dunnick, Weinstock). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 32 TC 5 Z9 5 U1 1 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUL 8 PY 2014 VL 9 IS 7 AR e102122 DI 10.1371/journal.pone.0102122 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AL6KZ UT WOS:000339242700112 PM 25003335 ER PT J AU Zeidel, ML Hoenig, MP Palevsky, PM AF Zeidel, Mark L. Hoenig, Melanie P. Palevsky, Paul M. TI A New CJASN Series: Renal Physiology for the Clinician SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Editorial Material C1 [Zeidel, Mark L.; Hoenig, Melanie P.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Palevsky, Paul M.] VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA. [Palevsky, Paul M.] Univ Pittsburgh, Sch Med, Dept Med, Renal Electrolyte Div, Pittsburgh, PA 15213 USA. RP Zeidel, ML (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. EM mzeidel@bidmc.harvard.edu OI Palevsky, Paul/0000-0002-7334-5400 NR 2 TC 1 Z9 1 U1 1 U2 2 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 EI 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD JUL 7 PY 2014 VL 9 IS 7 BP 1271 EP 1271 DI 10.2215/CJN.10191012 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA AK7NP UT WOS:000338615300019 PM 25002526 ER PT J AU Rogal, SS Hu, A Bandi, R Shaikh, O AF Rogal, Shari S. Hu, Angela Bandi, Rupal Shaikh, Obaid TI Novel therapy for non-cirrhotic hyperammonemia due to a spontaneous splenorenal shunt SO WORLD JOURNAL OF GASTROENTEROLOGY LA English DT Article DE Splenorenal shunt; Gastric bypass; Hyperammonemia; Encephalopathy ID ENCEPHALOPATHY AB Spontaneous splenorenal shunts in the absence of cirrhosis have rarely been reported as a cause hyperammonemia with encephalopathy. Several closure techniques of such lesions have been described. Here we report a case of a patient with no history of liver disease who developed significant confusion. After an extensive workup, he was found to have hyperammonemia and encephalopathy due to formation of a spontaneous splenorenal shunt. There was no evidence of cirrhosis on biopsy or imaging and no portal hypertension when directly measured. The shunt was 18 mm and too large for embolization so the segment of the splenic vein between the portal vein and the shunt was occluded using an Amplatzer plug. Thus, the superior mesenteric flow was directed entirely to the liver. After interventional radiology closure of the shunt using this technique there was complete resolution of symptoms. The case represents the first report of a successful closure of splenorenal shunt via percutaneous embolization of the splenic vein with an amplatzer plug using a common femoral vein approach. (C) 2014 Baishideng Publishing Group Inc. All rights reserved. C1 [Rogal, Shari S.] Univ Pittsburgh, Med Ctr, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA 15213 USA. [Hu, Angela] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15213 USA. [Bandi, Rupal] Vet Affairs Pittsburgh Healthcare Syst, Dept Radiol, Pittsburgh, PA 15240 USA. [Shaikh, Obaid] Vet Affairs Pittsburgh Healthcare Syst, Div Gastroenterol, Pittsburgh, PA 15240 USA. RP Rogal, SS (reprint author), Univ Pittsburgh, Med Ctr, Div Gastroenterol Hepatol & Nutr, PUH, 200 Lothrop St,M Level,C Wing, Pittsburgh, PA 15213 USA. EM rogalss@upmc.edu FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development FX Supported by Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development NR 6 TC 2 Z9 4 U1 0 U2 2 PU BAISHIDENG PUBLISHING GROUP INC PI PLEASANTON PA 8226 REGENCY DR, PLEASANTON, CA 94588 USA SN 1007-9327 EI 2219-2840 J9 WORLD J GASTROENTERO JI World J. Gastroenterol. PD JUL 7 PY 2014 VL 20 IS 25 BP 8288 EP 8291 DI 10.3748/wjg.v20.i25.8288 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AK6EM UT WOS:000338520900038 PM 25009405 ER PT J AU Sanchez, SH Sethi, SS Santos, SL Boockvar, K AF Sanchez, Sadie H. Sethi, Sanjum S. Santos, Susan L. Boockvar, Kenneth TI Implementing medication reconciliation from the planner's perspective: a qualitative study SO BMC HEALTH SERVICES RESEARCH LA English DT Article DE Medication reconciliation; Adverse drug event; Patient safety; Implementation; National patient safety goals AB Background: Medication reconciliation can reduce adverse events associated with prescribing errors at transitions between sites of care. Though a U.S. Joint Commission National Patient Safety Goal since 2006, at present organizations continue to have difficulty implementing it. The objective of this study was to examine medication reconciliation implementation from the perspective of individuals involved in the planning process in order to identify recurrent themes, including facilitators and barriers, that might inform other organizations' planning and implementation efforts. Methods: We performed semi-structured interviews with individuals who had a role in planning medication reconciliation implementation at a large urban academic medical center in the U.S. and its affiliated Veterans Affairs hospital. We queried respondents' perceptions of the implementation process and their experience with facilitators and barriers. Transcripts were coded and analyzed using a grounded theory approach. The themes that emerged were subsequently categorized using the Consolidated Framework for Implementation Research (CFIR). Results: There were 13 respondents, each with one or more organizational roles in quality improvement, information technology, medication safety, and education. Respondents described a resource-and time-intensivemedication reconciliation planning process. The planning teams' membership and functioning were recognized as important factors to a successful planning process. Implementation was facilitated by planners' understanding of the principles of performance improvement, in particular, fitting the new process into the workflow of multiple disciplines. Nevertheless, a need for significant professional role changes was recognized. Staff training was recognized to be an important part of roll-out, but training had several limitations. Planners monitored compliance to help sustain the process, but acknowledged that this did not ensure that medication reconciliation actually achieved its primary goal of reducing errors. Study findings fit multiple constructs in the CFIR model. Conclusions: Study findings suggest that to improve the likelihood of a successful implementation of medication reconciliation, planners should, among other considerations, involve a multidisciplinary planning team, recognize the significant professional role changes that may be needed, and consider devoting resources not just to compliance monitoring but also to monitoring of the process' impact on prescribing. C1 [Sanchez, Sadie H.; Boockvar, Kenneth] Icahn Sch Med Mt Sinai, One Gustave L Levy Pl,Box 1057, New York, NY 10029 USA. [Sethi, Sanjum S.] Boston Univ, Sch Med, Div Cardiol, Boston, MA 02118 USA. [Santos, Susan L.] VA New Jersey Hlth Care Syst, War Related Illness & Injury Study Ctr East Orang, E Orange, NJ 07018 USA. [Santos, Susan L.] Rutgers State Univ, Sch Publ Hlth Piscataway, Piscataway, NJ USA. [Boockvar, Kenneth] James J Peters Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY 10468 USA. [Boockvar, Kenneth] Jewish Home Lifecare Res Inst Aging, New York, NY USA. RP Boockvar, K (reprint author), Icahn Sch Med Mt Sinai, One Gustave L Levy Pl,Box 1057, New York, NY 10029 USA. EM kenneth.boockvar@mssm.edu OI Boockvar, Kenneth/0000-0003-1165-5558 FU VA Health Services Research and Development [IAB-05-204, REA 08-260]; Greenwall Foundation FX The authors would like to acknowledge the contribution of Liz Rosen (Lehigh University) who helped enter and sort the coded files. This project was supported by VA Health Services Research and Development grants IAB-05-204 and REA 08-260. Dr. Boockvar was supported by the Greenwall Foundation. NR 23 TC 8 Z9 9 U1 2 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6963 J9 BMC HEALTH SERV RES JI BMC Health Serv. Res. PD JUL 4 PY 2014 VL 14 AR 290 DI 10.1186/1472-6963-14-290 PG 10 WC Health Care Sciences & Services SC Health Care Sciences & Services GA V42FM UT WOS:000209599700001 PM 24996538 ER PT J AU Wynn, JK Jahshan, C Green, MF AF Wynn, Jonathan K. Jahshan, Carol Green, Michael F. TI Multisensory integration in schizophrenia: a behavioural and eventrelated potential study SO COGNITIVE NEUROPSYCHIATRY LA English DT Article DE schizophrenia; multisensory integration; ERP; race model ID AUDIOVISUAL INTEGRATION; PROCESSING DEFICITS; RECOGNITION; INFORMATION; SPEECH; FACILITATION; PERSPECTIVE; STIMULI; BINDING; HUMANS AB IntroductionSuccessful processing of multisensory stimuli increases the likelihood of detection or identification of salient, biologically significant events faster and more efficiently than unisensory inputs. Schizophrenia (SZ) patients show deficits in unisensory processing, but it is unclear whether impairments are seen to multisensory stimuli, a process known as multisensory integration (MSI). We used behavioural and event-related potential (ERP) measures to examine MSI in SZ and healthy controls (HC).MethodsThirty-three SZ and 30 HC completed a target detection task with unisensory and multisensory stimuli. Reaction times (RT) were measured while their electroencephalogram (EEG) was recorded. Two auditory (N100 and P200) and visual (P100 and N160) ERPs were examined. MSI was analysed in terms of violations of RT to the race model and by comparing ERPs in the MSI condition to the sum of the unisensory ERPs.ResultsBoth groups showed faster RT in MSI compared to unisensory conditions. SZ had non-significantly fewer violations of the race model compared to HC. SZ had significantly smaller amplitudes to unisensory visual N160 and auditory P100 relative to HC; there were no significant group differences on any ERP measure of MSI.ConclusionsSZ showed relatively intact MSI with subtle (non-significant) differences at the neural and behavioural levels compared to HC. Our results suggest that neural processes associated with MSI are not an additional source of impairment in SZ. C1 [Wynn, Jonathan K.; Jahshan, Carol; Green, Michael F.] VA Greater Los Angeles Healthcare Syst, Mental Illness Res Educ & Clin Ctr, Los Angeles, CA 90073 USA. [Wynn, Jonathan K.; Green, Michael F.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90095 USA. RP Wynn, JK (reprint author), VA Greater Los Angeles Healthcare Syst, Mental Illness Res Educ & Clin Ctr, Los Angeles, CA 90073 USA. EM jkwynn@ucla.edu RI Wynn, Jonathan/H-3749-2014; Keil, Julian/I-3337-2016 OI Wynn, Jonathan/0000-0002-1763-8540; Keil, Julian/0000-0003-4195-7397 FU National Institute of Mental Health [MH043292, MH065707, MH091468] FX This work was supported by grants from the National Institute of Mental Health [grant number MH043292], [grant number MH065707] and [grant number MH091468]. NR 44 TC 2 Z9 2 U1 1 U2 10 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1354-6805 EI 1464-0619 J9 COGN NEUROPSYCHIATRY JI Cogn. Neuropsychiatry PD JUL 4 PY 2014 VL 19 IS 4 BP 319 EP 336 DI 10.1080/13546805.2013.866892 PG 18 WC Psychiatry SC Psychiatry GA AE5VW UT WOS:000334058400003 PM 24397788 ER PT J AU Rinne, ST Feemster, LC Collins, BF Au, DH Perkins, M Bryson, CL O'Riordan, TG Liu, CF AF Rinne, Seppo T. Feemster, Laura C. Collins, Bridget F. Au, David H. Perkins, Mark Bryson, Christopher L. O'Riordan, Thomas G. Liu, Chuan-Fen TI Thiazolidinediones and the risk of asthma exacerbation among patients with diabetes: a cohort study SO ALLERGY ASTHMA AND CLINICAL IMMUNOLOGY LA English DT Article DE Thiazolidinediones; Peroxisome proliferator-activated receptors; Glitazones; Asthma; Cohort study ID ACTIVATED-RECEPTOR-GAMMA; OBSTRUCTIVE PULMONARY-DISEASE; MURINE MODEL; PPAR-GAMMA; AIRWAY INFLAMMATION; ALLERGIC INFLAMMATION; AGONIST ROSIGLITAZONE; PIOGLITAZONE; SEVERITY; COSTS AB Background: Thiazolidinediones are oral diabetes medications that selectively activate peroxisome proliferator-activated receptor gamma and have potent anti-inflammatory properties. While a few studies have found improvements in pulmonary function with exposure to thiazolidinediones, there are no studies of their impact on asthma exacerbations. Our objective was to assess whether exposure to thiazolidinediones was associated with a decreased risk of asthma exacerbation. Methods: We performed a cohort study of diabetic Veterans who had a diagnosis of asthma and were taking oral diabetes medications during the period of 10/1/2005 - 9/30/2006. The risk of asthma exacerbations and oral steroid use during 10/1/2006 - 9/30/2007 was compared between patients who were prescribed thiazolidinediones and patients who were on alternative oral diabetes medications. Multivariable logistic regression and negative binomial regression analyses were used to characterize this risk. A sensitivity analysis was performed, restricting our evaluation to patients who were adherent to diabetes therapy. Results: We identified 2,178 patients who were on thiazolidinediones and 10,700 who were not. Exposure to thiazolidinediones was associated with significant reductions in the risk of asthma exacerbation (OR = 0.79, 95% CI, 0.62 - 0.99) and oral steroid prescription (OR = 0.73, 95% CI 0.63 - 0.84). Among patients who were adherent to diabetes medications, there were more substantial reductions in the risks for asthma exacerbation (OR = 0.64, 95% CI 0.47 - 0.85) and oral steroid prescription (OR = 0.68, 95% CI 0.57 - 0.81). Conclusions: Thiazolidinediones may provide a novel anti-inflammatory approach to asthma management by preventing exacerbations and decreasing the use of oral steroids. C1 [Rinne, Seppo T.; Feemster, Laura C.; Collins, Bridget F.; Au, David H.; Perkins, Mark; Bryson, Christopher L.; Liu, Chuan-Fen] VA Puget Sound Hlth Care Syst, Dept Vet Affairs, Hlth Serv Res & Dev, Seattle, WA 98104 USA. [Rinne, Seppo T.; Feemster, Laura C.; Collins, Bridget F.; Au, David H.] Univ Washington, Dept Pulm & Cri Care, Seattle, WA 98195 USA. [Bryson, Christopher L.] Univ Washington, Dept Med, Div Gen Internal Med, Seattle, WA USA. [O'Riordan, Thomas G.] Gilead Sci Inc, Seattle, WA USA. [Liu, Chuan-Fen] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. RP Rinne, ST (reprint author), VA Puget Sound Hlth Care Syst, Dept Vet Affairs, Hlth Serv Res & Dev, 1100 Olive Way Suite 1400, Seattle, WA 98104 USA. EM srinne@uw.edu FU VA HSRD [IIR 07-068-2]; Gilead Sciences Inc FX Research funding for this project was from a VA HSR&D grant (IIR 07-068-2) along with funding from Gilead Sciences Inc. Neither funding source had a role in the study design, analysis, or interpretation. NR 40 TC 3 Z9 3 U1 1 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1710-1484 EI 1710-1492 J9 ALLERGY ASTHMA CL IM JI Allerg Asthma Clin. Immunol. PD JUL 3 PY 2014 VL 10 AR 34 DI 10.1186/1710-1492-10-34 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA AL3GY UT WOS:000339016100001 PM 25024717 ER PT J AU Honavar, J Bradley, E Bradley, K Oh, JY Vallejo, MO Kelley, EE Cantu-Medellin, N Doran, S Dell'italia, LJ Matalon, S Patel, RP AF Honavar, Jaideep Bradley, Eddie Bradley, Kelley Oh, Joo Yeun Vallejo, Matthew O. Kelley, Eric E. Cantu-Medellin, Nadiezhda Doran, Stephen Dell'italia, Louis J. Matalon, Sadis Patel, Rakesh P. TI Chlorine gas exposure disrupts nitric oxide homeostasis in the pulmonary vasculature SO TOXICOLOGY LA English DT Article DE Halogen; Lung; Inflammation ID INDUCED LUNG INJURY; EPITHELIAL NA+ CHANNELS; TRAIN DERAILMENT; MURINE MODEL; MICE; INHALATION; MECHANISMS; MITIGATION; HYPERREACTIVITY; SUPEROXIDE AB Exposure to chlorine (Cl-2) gas during industrial accidents or chemical warfare leads to significant airway and distal lung epithelial injury that continues post exposure. While lung epithelial injury is prevalent, relatively little is known about whether Cl-2 gas also promotes injury to the pulmonary vasculature. To determine this, rats were subjected to a sub-lethal Cl-2 gas exposure (400 ppm, 30 min) and then brought back to room air. Pulmonary arteries (PA) were isolated from rats at various times post-exposure and contractile (phenylephrine) and nitric oxide (NO)-dependent vasodilation (acetylcholine and mahmanonoate) responses measured ex vivo. PA contractility did not change, however significant inhibition of NO-dependent vasodilation was observed that was maximal at 24-48 h post exposure. Superoxide dismutase restored NO-dependent vasodilation suggesting a role for increased superoxide formation. This was supported by similar to 2-fold increase in superoxide formation (measured using 2-hydroethidine oxidation to 2-OH-E+) from PA isolated from Cl-2 exposed rats. We next measured PA pressures in anesthetized rats. Surprisingly, PA pressures were significantly (similar to 4 mmHg) lower in rats that had been exposed to Cl-2 gas 24 h earlier suggesting that deficit in NO-signaling observed in isolated PA experiments did not manifest as increased PA pressures in vivo. Administration of the iNOS selective inhibitor 1400W, restored PA pressures to normal in Cl-2 exposed, but not control rats suggesting that any deficit in NO-signaling due to increased superoxide formation in the PA, is offset by increased NO-formation from iNOS. These data indicate that disruption of endogenous NO-signaling mechanisms that maintain PA tone is an important aspect of post-Cl-2 gas exposure toxicity. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Honavar, Jaideep; Bradley, Kelley; Oh, Joo Yeun; Vallejo, Matthew O.; Patel, Rakesh P.] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. [Bradley, Eddie; Dell'italia, Louis J.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Doran, Stephen; Matalon, Sadis] Univ Alabama Birmingham, Dept Anesthesiol, Birmingham, AL 35294 USA. [Matalon, Sadis; Patel, Rakesh P.] Univ Alabama Birmingham, Ctr Free Rad Biol, Birmingham, AL 35294 USA. [Matalon, Sadis; Patel, Rakesh P.] Univ Alabama Birmingham, Ctr Lung Injury & Repair, Birmingham, AL 35294 USA. [Kelley, Eric E.; Cantu-Medellin, Nadiezhda] Univ Pittsburgh, Dept Anesthesiol, Pittsburgh, PA 15260 USA. [Dell'italia, Louis J.] Birmingham VA Med Ctr, Birmingham, AL USA. RP Patel, RP (reprint author), Univ Alabama Birmingham, Dept Pathol, 901 19th St South,BMR 2,Room 532, Birmingham, AL 35294 USA. EM rakeshp@uab.edu OI Patel, Rakesh/0000-0002-1526-4303 FU CounterACT Program; Office of the Director; National Institute of Environmental Health Sciences [1U01ES023759, 5U01ES015676]; National Institute of Health [T32 HL007457] FX This research was supported by the CounterACT Program, National Institutes of Health, Office of the Director, and the National Institute of Environmental Health Sciences, Grant Numbers 1U01ES023759 and 5U01ES015676 and a fellowship from the National Institute of Health to MOV (T32 HL007457). NR 35 TC 6 Z9 6 U1 0 U2 17 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD JUL 3 PY 2014 VL 321 BP 96 EP 102 DI 10.1016/j.tox.2014.04.005 PG 7 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA AJ7IO UT WOS:000337870600011 PM 24769334 ER PT J AU Koenig, CJ Wingard, LM Sabee, C Olsher, D Vandergriff, I AF Koenig, Christopher J. Wingard, Leah M. Sabee, Christina Olsher, David Vandergriff, Ilona TI Managing Patient-centered Communication across the Type 2 Diabetes Illness Trajectory: A Grounded Practical Theory of Interactional Sensitivity SO JOURNAL OF APPLIED COMMUNICATION RESEARCH LA English DT Article DE Treatment Decision-making; Type 2 Diabetes; Health Communication; Conversation Analysis; Physician-Patient Interaction; Patient-centered Communication; Grounded Practical Theory ID HEALTH-CARE; TREATMENT RECOMMENDATIONS; PARENT RESISTANCE; INSULIN THERAPY; ATTACHMENT; CONSULTATIONS; CONVERSATION; PATERNALISM; ADHERENCE; DELIVERY AB This article uses the theoretical and methodological framework of Grounded Practical Theory (GPT) to provide a lens for analyzing and interpreting discourse as a situated form of social action in routine Type 2 diabetes visits. Drawing on a total data-set of 400 audio-recorded routine visits, we randomly selected 55 visits for qualitative analysis. In this article, we use Conversation Analysis to document communication techniques, which we in turn use as evidence to ground our claims within the GPT framework. We use two single cases of interaction to analyze communication techniques physicians use when recommending a change from oral medication to insulin. We argue treatment intensification is a key moment in health communication to reflect about patient centeredness because physicians can find themselves in an interactional dilemma: while insulin may effectively help control unstable disease, an insulin recommendation may simultaneously counter patient values and treatment preferences. Our analysis suggests that physicians use what we call interactional sensitivity to balance medical need and patient preferences when making medical decisions by tailoring their communication according to the local situation and the patient's larger illness trajectory. We propose that interactional sensitivity is a type of communication work and a quality of patient-centered communication characterized by the theoretical relationship between tailoring communication to the contingencies of the local interaction and the global illness trajectory. Overall, this article contributes to health communication scholarship by proposing a normative model for reflecting on how physicians negotiate challenging interactions with patients during routine chronic illness visits. C1 [Koenig, Christopher J.] San Francisco Vet Adm Med Ctr, Dept Med, San Francisco, CA 94121 USA. [Koenig, Christopher J.] Univ Calif San Francisco, Philip R Lee Inst Hlth Policy Studies, San Francisco, CA USA. [Wingard, Leah M.; Sabee, Christina] San Francisco State Univ, Dept Commun Studies, San Francisco, CA USA. [Olsher, David] San Francisco State Univ, Dept English, San Francisco, CA USA. [Vandergriff, Ilona] San Francisco State Univ, Dept Foreign Languages & Literatures, San Francisco, CA USA. RP Koenig, CJ (reprint author), San Francisco Vet Adm Med Ctr, Dept Med, 4150 Clement St,111-A1, San Francisco, CA 94121 USA. EM christopher.koenig@ucsf.edu OI Koenig, Christopher J./0000-0003-0884-4120 NR 62 TC 6 Z9 6 U1 0 U2 14 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0090-9882 EI 1479-5752 J9 J APPL COMMUN RES JI J. Appl. Commun. Res. PD JUL 3 PY 2014 VL 42 IS 3 SI SI BP 244 EP 267 DI 10.1080/00909882.2014.911943 PG 24 WC Communication SC Communication GA AH1MA UT WOS:000335883700002 ER PT J AU Meffert, SM Henn-Haase, C Metzler, TJ Qian, M Best, S Hirschfeld, A McCaslin, S Inslicht, S Neylan, TC Marmar, CR AF Meffert, Susan M. Henn-Haase, Clare Metzler, Thomas J. Qian, Meng Best, Suzanne Hirschfeld, Ayelet McCaslin, Shannon Inslicht, Sabra Neylan, Thomas C. Marmar, Charles R. TI Prospective Study of Police Officer Spouse/Partners: A New Pathway to Secondary Trauma and Relationship Violence? SO PLOS ONE LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; EMERGENCY SERVICES PERSONNEL; MALE VIETNAM VETERANS; COMBAT VETERANS; WAR VETERANS; PSYCHOLOGICAL DISTRESS; PARTNERS PERCEPTIONS; MISSISSIPPI SCALE; MENTAL-HEALTH; PTSD AB Introduction: It has been reported that posttraumatic stress disorder (PTSD) is associated with secondary spouse/partner (S/P) emotional distress and relationship violence. Objective: To investigate the relationships between PTSD, S/P emotional distress and relationship violence among police recruits using a prospective design. Methods: Two hypotheses were tested in 71 S/Ps: (1) Police officer reports of greater PTSD symptoms after 12 months of police service will be associated with greater secondary trauma symptoms among S/Ps; (2) Greater secondary trauma symptoms among S/Ps at 12 months will be associated with S/P reports of greater relationship violence. Methods: 71 police recruits and their S/Ps were assessed at baseline and 12 months after the start of police officer duty. Using linear and logistic regression, we analyzed explanatory variables for 12 month S/P secondary traumatic stress symptoms and couple violence, including baseline S/P variables and couple violence, as well as exposure and PTSD reports from both S/P and officer. Results: S/P perception of officer PTSD symptoms predicted S/P secondary traumatic stress. OS/P secondary trauma was significantly associated with both total couple violence (.34, p = .004) and S/P to officer violence (.35, p = .003). Conclusions: Although results from this relatively small study of young police officers and their S/Ps must be confirmed by larger studies in general populations, findings suggest that S/P perception of PTSD symptoms may play a key role in the spread of traumatic stress symptoms across intimate partner relationships and intimate partner violence in the context of PTSD. C1 [Meffert, Susan M.; Inslicht, Sabra; Neylan, Thomas C.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Metzler, Thomas J.; Hirschfeld, Ayelet; Inslicht, Sabra; Neylan, Thomas C.] San Francisco Vet Adm Med Ctr, Mental Hlth Serv, San Francisco, CA USA. [Henn-Haase, Clare; Qian, Meng; Marmar, Charles R.] NYU, Dept Psychiat, New York, NY 10016 USA. [Best, Suzanne] Lewis & Clark Coll, Grad Sch Educ & Counseling, Portland, OR 97219 USA. [McCaslin, Shannon] Natl Ctr PTSD, Disseminat & Training Div, Palo Alto, CA USA. RP Meffert, SM (reprint author), Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. EM susan.meffert@ucsf.edu OI meffert, susan/0000-0002-5882-7102 FU National Institute of Mental Health [R01 - MH056350-06] FX This research was supported by National Institute of Mental Health Grant (R01 - MH056350-06) to CRM. The funders had no role in the study design, data collection and analysis, decision to publish or preparation of this manuscript. NR 44 TC 0 Z9 0 U1 0 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUL 2 PY 2014 VL 9 IS 7 AR e100663 DI 10.1371/journal.pone.0100663 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AO5BA UT WOS:000341354100036 PM 24987848 ER PT J AU Chang, ET Wells, KB Young, AS Stockdale, S Johnson, MD Fickel, JJ Jou, K Rubenstein, LV AF Chang, Evelyn T. Wells, Kenneth B. Young, Alexander S. Stockdale, Susan Johnson, Megan D. Fickel, Jacqueline J. Jou, Kevin Rubenstein, Lisa V. TI The Anatomy of Primary Care and Mental Health Clinician Communication: A Quality Improvement Case Study SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE primary care; mental health; communication; quality improvement; ambulatory care; primary care redesign ID OF-VETERANS-AFFAIRS; RESPECT-DEPRESSION TRIAL; COLLABORATIVE CARE; BEHAVIORAL HEALTH; OUTPATIENT CLINICS; INTEGRATED CARE; UNITED-STATES; MEDICAL HOME; DISORDERS; IMPLEMENTATION AB The high prevalence of comorbid physical and mental illnesses among veterans is well known. Therefore, ensuring effective communication between primary care (PC) and mental health (MH) clinicians in the Veterans Affairs (VA) health care system is essential. The VA's Patient Aligned Care Teams (PACT) initiative has further raised awareness of the need for communication between PC and MH. Improving such communication, however, has proven challenging. To qualitatively understand barriers to PC-MH communication in an academic community-based clinic by using continuous quality improvement (CQI) tools and then initiate a change strategy. An interdisciplinary quality improvement (QI) work group composed of 11 on-site PC and MH providers, administrators, and researchers identified communication barriers and facilitators using fishbone diagrams and process flow maps. The work group then verified and provided context for the diagram and flow maps through medical record review (32 patients who received both PC and MH care), interviews (6 stakeholders), and reports from four previously completed focus groups. Based on these findings and a previous systematic review of interventions to improve interspecialty communication, the team initiated plans for improvement. Key communication barriers included lack of effective standardized communication processes, practice style differences, and inadequate PC training in MH. Clinicians often accessed advice or formal consultation based on pre-existing across-discipline personal relationships. The work group identified collocated collaborative care, joint care planning, and joint case conferences as feasible, evidence-based interventions for improving communication. CQI tools enabled providers to systematically assess local communication barriers and facilitators and engaged stakeholders in developing possible solutions. A locally tailored CQI process focusing on communication helped initiate change strategies and ongoing improvement efforts. C1 [Chang, Evelyn T.; Rubenstein, Lisa V.] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA USA. [Chang, Evelyn T.; Young, Alexander S.; Stockdale, Susan; Johnson, Megan D.; Fickel, Jacqueline J.; Rubenstein, Lisa V.] VA Ctr Study Healthcare Innovat Implementat & Pol, North Hills, CA USA. [Wells, Kenneth B.; Rubenstein, Lisa V.] Univ Calif Los Angeles, Dept Hlth Policy & Management, Fielding Sch Publ Hlth, Los Angeles, CA USA. [Wells, Kenneth B.; Young, Alexander S.] Univ Calif Los Angeles, Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90024 USA. [Johnson, Megan D.; Rubenstein, Lisa V.] RAND Corp, Santa Monica, CA USA. [Young, Alexander S.; Johnson, Megan D.; Jou, Kevin] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Psychiat, Los Angeles, CA USA. RP Chang, ET (reprint author), VA Greater Los Angeles Healthcare Syst, Dept GIM 111G, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM evelyn.chang@va.gov FU VA Office of Patient Care Services; VA Office of Academic Affiliations, Health Services Research and Development through the Health Services Fellowship Training Program [TMP 65-020] FX This work was undertaken as part of the Veterans Administration's PACT Demonstration Laboratory initiative, supporting and evaluating VA's transition to a patient-centered medical home. Funding for the PACT Demonstration Laboratory initiative is provided by the VA Office of Patient Care Services.; Funding support provided by VA Office of Academic Affiliations, Health Services Research and Development through the Health Services Fellowship Training Program (TMP 65-020). NR 54 TC 1 Z9 1 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2014 VL 29 SU 2 BP 598 EP 606 DI 10.1007/s11606-013-2731-7 PG 9 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AK3OS UT WOS:000338334700009 ER PT J AU Rinker, JR Salter, AR Cutter, GR AF Rinker, John R., II Salter, Amber R. Cutter, Gary R. TI Improvement of multiple sclerosis-associated tremor as a treatment effect of natalizunnab SO MULTIPLE SCLEROSIS AND RELATED DISORDERS LA English DT Article DE Multiple sclerosis; Tremor; Neurologic symptoms; Natatizumab; Self-report; Questionnaires ID PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; CEREBELLAR TREMOR; ISONIAZID THERAPY; MULTICENTER; DISABILITY; PREVALENCE; SYMPTOMS; CANNABIS; EFFICACY AB Background: Tremor is among the most physically disabling symptoms associated with MS. The effect of MS disease modifying therapies (DMTs) on the severity of MS tremor is unclear. Objective: To compare the change over time in scores reflecting tremor severity between subjects treated with natalizumab and other disease modifying drugs. Methods: Questionnaires were sent to North American Research Committee on MS registrants reporting mild or greater tremor on semiannual updates. Respondents on natalizumab and other MS therapies completed a survey which included tremor-specific scales to indicate tremor severity both currently and when the current therapy was initiated. Differences between natalizumab and non-natalizumab groups were compared using ANOVA. Results: Surveys were returned by 567 registrants, including 202 taking natalizumab. Subjects on natalizumab were more likely to report tremor improvement (29.6%) than those never (15.2%) or previously (14.8%, p=0.0002) on natalizumab. Over a mean recall period of 6.2+4.6 years, the Tremor Related Activities of Daily Living score worsened by 1.8 points among natalizumab-treated subjects, 3.3 points among those previously on natalizumab, and 5.3 points among those who never took natalizumab (p=0.009). Conclusion: Respondents taking natalizumab were more likely to experience tremor improvement than those taking other MS disease modifying therapies. Published by Elsevier B.V. C1 [Rinker, John R., II] Univ Alabama Birmingham, Dept Neurol, Birmingham, AL 35294 USA. [Rinker, John R., II] Birmingham VA Med Ctr, Birmingham, AL 35233 USA. [Salter, Amber R.; Cutter, Gary R.] Univ Alabama Birmingham, Dept Biostat, Birmingham, AL 35294 USA. RP Rinker, JR (reprint author), Univ Alabama Birmingham, Dept Neurol, 1720 7th Ave South,SC 440, Birmingham, AL 35294 USA. EM rinkerj@uab.edu FU Biogen Idec [US-TYS-11-10238] FX This study was funded by an Investigator Initiated Grant/Trial Award from Biogen Idec (US-TYS-11-10238). NR 30 TC 1 Z9 1 U1 1 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2211-0348 EI 2211-0356 J9 MULT SCLER RELAT DIS JI Mult. Scler. Relat. Disord. PD JUL PY 2014 VL 3 IS 4 BP 505 EP 512 DI 10.1016/j.msard.2014.04.001 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA CB5KC UT WOS:000349664900013 PM 25877063 ER PT J AU Zhou, YB Kucik, DF Szalais, AJ Edberg, JC AF Zhou, Yebin Kucik, Dennis F. Szalais, Alexander J. Edberg, Jeffrey C. TI Human Neutrophil Flow Chamber Adhesion Assay SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS LA English DT Article DE Immunology; Issue 89; neutrophil adhesion; flow chamber; human umbilical vein endothelial cell (HUVEC); purified ligand ID WALL SHEAR-STRESS; SUSCEPTIBILITY; MOLECULE-1; LFA-1 AB Neutrophil firm adhesion to endothelial cells plays a critical role in inflammation in both health and disease. The process of neutrophil firm adhesion involves many different adhesion molecules including members of the beta(2) integrin family and their counter-receptors of the ICAM family. Recently, naturally occurring genetic variants in both beta(2) integrins and ICAMs are reported to be associated with autoimmune disease. Thus, the quantitative adhesive capacity of neutrophils from individuals with varying allelic forms of these adhesion molecules is important to study in relation to mechanisms underlying development of autoimmunity. Adhesion studies in flow chamber systems can create an environment with fluid shear stress similar to that observed in the blood vessel environment in vivo. Here, we present a method using a flow chamber assay system to study the quantitative adhesive properties of human peripheral blood neutrophils to human umbilical vein endothelial cell ( HUVEC) and to purified ligand substrates. With this method, the neutrophil adhesive capacities from donors with different allelic variants in adhesion receptors can be assessed and compared. This method can also be modified to assess adhesion of other primary cell types or cell lines. C1 [Zhou, Yebin] Univ Alabama Birmingham, Genet & Genom Sci Grad Program, Birmingham, AL USA. [Kucik, Dennis F.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Kucik, Dennis F.] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL USA. [Kucik, Dennis F.] Univ Alabama Birmingham, Dept Biomed Engn, Birmingham, AL USA. [Szalais, Alexander J.; Edberg, Jeffrey C.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35233 USA. RP Edberg, JC (reprint author), Univ Alabama Birmingham, Dept Med, Birmingham, AL 35233 USA. EM jedberg@uab.edu OI Zhou, Yebin/0000-0002-4410-1909 FU Lupus Research Institute (NY, NY); NIH [P01-AR49084, R21-DA026956, UL1-TR00165] FX This work is sponsored by the Lupus Research Institute (NY, NY), NIH P01-AR49084, NIH R21-DA026956 and NIH UL1-TR00165. We thank Dr. Robert P. Kimberly for his continued support. NR 20 TC 0 Z9 0 U1 0 U2 2 PU JOURNAL OF VISUALIZED EXPERIMENTS PI CAMBRIDGE PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA SN 1940-087X J9 JOVE-J VIS EXP JI J. Vis. Exp. PD JUL PY 2014 IS 89 AR e51410 DI 10.3791/51410 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CB0DR UT WOS:000349296100023 ER PT J AU Smith, RT True, G AF Smith, R. Tyson True, Gala TI Warring Identities: Identity Conflict and the Mental Distress of American Veterans of the Wars in Iraq and Afghanistan SO SOCIETY AND MENTAL HEALTH LA English DT Article DE identity; military health; posttraumatic stress disorder; psychological distress; institutions ID POSTTRAUMATIC-STRESS-DISORDER; US MILITARY; HEALTH; CARE; SUICIDE; ILLNESS; MASCULINITY; SOCIOLOGY; DIAGNOSIS; PERSONNEL AB Drawing from 26 life story interviews of recent American veterans, this paper analyzes the identity struggle faced by soldiers returning from Operation Iraqi Freedom and Operation Enduring Freedom and reentering the civilian world. Instead of examining veterans' problems as a consequence of post-combat mental illnesses such as PTSD and major depression, we analyze the contrast between the participants' identities as soldiers and their identities as civilians. We find that the postwar transition causes adverse mental health effects that stem from contrasts between the military's demands for deindividuation, obedience, chain-of-command, and dissociation and the civilian identity expectations of autonomy, self-advocacy, and being relational. Veterans' reintegration to civilian society is further hindered by a culture that is perceived (by veterans) as having decreased understanding of the soldier/veteran experience itself. These identity conflicts-what we term warring identities-have an important yet understudied effect on veterans' combat-related mental health problems. C1 [Smith, R. Tyson] Brown Univ, Providence, RI 02912 USA. [True, Gala] CHERP, Philadelphia, PA USA. RP Smith, RT (reprint author), Brown Univ, 112 George St,Box 1916, Providence, RI 02912 USA. EM tyson321@gmail.com NR 75 TC 6 Z9 6 U1 6 U2 23 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 2156-8693 EI 2156-8731 J9 SOC MENT HEALTH JI Soc. Ment. Health PD JUL PY 2014 VL 4 IS 2 BP 147 EP 161 DI 10.1177/2156869313512212 PG 15 WC Sociology SC Sociology GA AY3EG UT WOS:000347466700005 ER PT J AU Arlehamn, CSL Lewinsohn, D Sette, A Lewinsohn, D AF Arlehamn, Cecilia S. Lindestam Lewinsohn, David Sette, Alessandro Lewinsohn, Deborah TI Antigens for CD4 and CD8 T Cells in Tuberculosis SO COLD SPRING HARBOR PERSPECTIVES IN MEDICINE LA English DT Article ID IMMUNODEFICIENCY-VIRUS-INFECTION; MEDIATED IMMUNE-RESPONSES; MYCOBACTERIUM-BOVIS BCG; VACCINE DEVELOPMENT; PROTECTIVE IMMUNITY; INTERFERON-GAMMA; SECRETED ANTIGENS; ESAT-6 ANTIGEN; IFN-GAMMA; PULMONARY TUBERCULOSIS AB Tuberculosis (TB), caused by infection with Mycobacterium tuberculosis (MTB), represents an important cause of morbidity and mortality worldwide for which an improved vaccine and immunodiagnostics are urgently needed. CD4(+) and CD8(+) T cells play an important role in host defense to TB. Definition of the antigens recognized by these T cells is critical for improved understanding of the immunobiology of TB and for development of vaccines and diagnostics. Herein, the antigens and epitopes recognized by classically HLA class I- and II-restricted CD4(+) and CD8(+) T cells in humans infected with MTB are reviewed. Immunodominant antigens and epitopes have been defined using approaches targeting particular TB proteins or classes of proteins and by genome-wide discovery approaches. Antigens and epitopes recognized by classically restricted CD4(+) and CD8(+) T cells show extensive breadth and diversity in MTB-infected humans. C1 [Arlehamn, Cecilia S. Lindestam; Sette, Alessandro] La Jolla Inst Allergy & Immunol, La Jolla, CA 92037 USA. [Lewinsohn, David; Lewinsohn, Deborah] Oregon Hlth & Sci Univ, Portland, OR 97239 USA. [Lewinsohn, David] Portland VA Med Ctr, Portland, OR 97239 USA. RP Lewinsohn, D (reprint author), Oregon Hlth & Sci Univ, Portland, OR 97239 USA. EM lewinsde@ohsu.edu RI Lewinsohn, David/I-4936-2013 OI Lewinsohn, David/0000-0001-9906-9494; Lindestam Arlehamn, Cecilia/0000-0001-7302-8002 NR 155 TC 13 Z9 13 U1 0 U2 7 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 2157-1422 J9 CSH PERSPECT MED JI Cold Spring Harb. Perspect. Med. PD JUL PY 2014 VL 4 IS 7 AR a018465 DI 10.1101/cshperspect.a018465 PG 15 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AW8NB UT WOS:000346518000006 ER PT J AU Knight, EM Gandy, S AF Knight, E. M. Gandy, S. TI Immunomodulation and AD - Down But Not Out SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Article DE Alzheimer's disease; immunotherapy; immunoglobulin; IVIG; oligomer ID AMYLOID-BETA-PEPTIDE; MODERATE ALZHEIMERS-DISEASE; HUMAN INTRAVENOUS IMMUNOGLOBULIN; MOUSE MODEL; SIGNALING PATHWAY; NATURAL OLIGOMERS; HUMAN-ANTIBODIES; IMMUNIZATION; PATHOLOGY; MEMORY AB Alzheimer's disease (AD) is a progressive neurodegenerative disorder and is the most common cause of dementia in the elderly. Interventions that remove existing fibrillar and oligomeric amyloid-beta (A beta) are believed to be essential for the success of any attempt at stabilization of brain function and mitigation of cognitive decline. Many of these strategies have focused on A beta vaccination and administration of anti-A beta antibodies. Both active and passive immunotherapies have been successful in mouse models, but both have had limited effect in clinical trials. Intravenous immunoglobulin (IVIG) has been proposed as a potential treatment for AD following evidence for behavioral benefit in AD models and cognitive benefit in early phase 1 and phase 2 clinical trials. A phase 3 trial IVIG trial failed to meet its primary outcomes. While there was a statistically significant benefit in moderate stage AD patients who carried an APOE epsilon 4 allele, this stabilization of cognition was evident only on neuropsychological examination. No benefit on activities of daily living was evident, therefore failing to qualify AD as a new indication for IVIG. Identifying the biologically active component (s) responsible for the neuropsychological benefit in APOE epsilon 4-positive AD patients could enable the development of a compound with greater potency that would qualify for FDA (US Food and Drug Administration) registration. C1 [Knight, E. M.; Gandy, S.] Icahn Sch Med Mt Sinai, Dept Neurol, New York, NY 10029 USA. [Knight, E. M.; Gandy, S.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Knight, E. M.; Gandy, S.] Icahn Sch Med Mt Sinai, Alzheimers Dis Res Ctr, New York, NY 10029 USA. [Gandy, S.] James J Peters Vet Affairs Med Ctr, Bronx, NY 10468 USA. RP Gandy, S (reprint author), Icahn Sch Med Mt Sinai, Dept Neurol, New York, NY 10029 USA. EM elysse.knight@mssm.edu; samuel.gandy@mssm.edu FU Baxter Pharmaceuticals; Amicus Therapeutics; Constellation Wines FX SG serves on SABs for the Pfizer-Janssen Alzheimer's Immunotherapy Alliance, for Cerora, and for Diagenic. He has received research grant support from Baxter Pharmaceuticals, Amicus Therapeutics, and Constellation Wines. NR 41 TC 5 Z9 5 U1 0 U2 1 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 EI 1573-2592 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD JUL PY 2014 VL 34 SU 1 BP S70 EP S73 DI 10.1007/s10875-014-0039-y PG 4 WC Immunology SC Immunology GA AU3KN UT WOS:000345512100012 PM 24781637 ER PT J AU Hockemeyer, K Janetopoulos, C Terekhov, A Hofmeister, W Vilgelm, A Costa, L Wikswo, JP Richmond, A AF Hockemeyer, K. Janetopoulos, C. Terekhov, A. Hofmeister, W. Vilgelm, A. Costa, Lino Wikswo, J. P. Richmond, A. TI Engineered three-dimensional microfluidic device for interrogating cell-cell interactions in the tumor microenvironment SO BIOMICROFLUIDICS LA English DT Article ID BREAST-CANCER CELLS; IN-VITRO; CULTURE MODEL; 3D; CHEMOKINES; METASTASIS; ANGIOGENESIS; FIBROBLASTS; MIGRATION; GROWTH AB Stromal cells in the tumor microenvironment play a key role in the metastatic properties of a tumor. It is recognized that cancer-associated fibroblasts (CAFs) and endothelial cells secrete factors capable of influencing tumor cell migration into the blood or lymphatic vessels. We developed a microfluidic device that can be used to image the interactions between stromal cells and tumor cell spheroids in a three dimensional (3D) microenvironment while enabling external control of interstitial flow at an interface, which supports endothelial cells. The apparatus couples a 200-mu m channel with a semicircular well to mimic the interface of a blood vessel with the stroma, and the design allows for visualization of the interactions of interstitial flow, endothelial cells, leukocytes, and fibroblasts with the tumor cells. We observed that normal tissue-associated fibroblasts (NAFs) contribute to the "single file" pattern of migration of tumor cells from the spheroid in the 3D microenvironment. In contrast, CAFs induce a rapid dispersion of tumor cells out of the spheroid with migration into the 3D matrix. Moreover, treatment of tumor spheroid cultures with the chemokine CXCL12 mimics the effect of the CAFs, resulting in similar patterns of dispersal of the tumor cells from the spheroid. Conversely, addition of CXCL12 to co-cultures of NAFs with tumor spheroids did not mimic the effects observed with CAF co-cultures, suggesting that NAFs produce factors that stabilize the tumor spheroids to reduce their migration in response to CXCL12. (C) 2014 AIP Publishing LLC. C1 [Hockemeyer, K.; Vilgelm, A.; Richmond, A.] US Dept Vet Affairs, Tennessee Valley Healthcare Syst, Nashville, TN 37212 USA. [Hockemeyer, K.; Janetopoulos, C.; Hofmeister, W.; Wikswo, J. P.; Richmond, A.] Vanderbilt Univ, Vanderbilt Inst Integrat Biosyst Res & Educ, Nashville, TN 37235 USA. [Hockemeyer, K.; Vilgelm, A.; Richmond, A.] Vanderbilt Univ, Sch Med, Dept Canc Biol, Nashville, TN 37232 USA. [Hockemeyer, K.; Janetopoulos, C.] Vanderbilt Univ, Dept Biol Sci, Nashville, TN 37232 USA. [Hockemeyer, K.; Janetopoulos, C.] Vanderbilt Univ, Dept Cell & Dev Biol, Nashville, TN 37232 USA. [Terekhov, A.; Hofmeister, W.; Costa, Lino] Univ Tennessee, Inst Space, Ctr Laser Applicat, Tullahoma, TN 37388 USA. [Hofmeister, W.; Costa, Lino] Univ Tennessee, Dept Mat Sci & Engn, Knoxville, TN 37996 USA. [Wikswo, J. P.] Vanderbilt Univ, Dept Biomed Engn, Nashville, TN 37235 USA. [Wikswo, J. P.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Nashville, TN 37235 USA. [Wikswo, J. P.] Vanderbilt Univ, Dept Phys & Astron, Nashville, TN 37235 USA. RP Richmond, A (reprint author), US Dept Vet Affairs, Tennessee Valley Healthcare Syst, Nashville, TN 37212 USA. EM ann.richmond@vanderbilt.edu FU TVHS; Department of Veterans Affairs through MERIT; Senior Research Career Scientist Awards; NIH [R01 CA34590, K12-CA90625]; Tennessee Higher Education Commission grant; Vanderbilt Discovery Award; [RO1GM080370] FX We thank Kevin Seale and the team in VIIBRE and SyBBURE for all their support, guidance, and encouragement. We are thankful to Hal Moses and Simon Hayward at Vanderbilt for the human CAF and NAF cultures isolated and cultured from breast tissue. We thank Melody Swartz at the Laboratory of Lymphatic and Cancer Bioengineering, EPFL Institute, Lausanne, Switzerland for her advice and guidance in the initial development of the devices. Thanks to Tammy Sobolik and Linda Horton who provided technical support and guidance. This work was supported by grants from the TVHS and the Department of Veterans Affairs through MERIT and Senior Research Career Scientist Awards to A. R.; NIH grants R01 CA34590 (A. R.) and K12-CA90625 (A. V.); Tennessee Higher Education Commission grant to the Center for Laser Applications at UT Space Institute (W. H.); RO1GM080370 (C.J.) and Vanderbilt Discovery Award (C.J. and W.H.). NR 38 TC 7 Z9 7 U1 3 U2 57 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 1932-1058 J9 BIOMICROFLUIDICS JI Biomicrofluidics PD JUL PY 2014 VL 8 IS 4 AR 044105 DI 10.1063/1.4890330 PG 12 WC Biochemical Research Methods; Biophysics; Nanoscience & Nanotechnology; Physics, Fluids & Plasmas SC Biochemistry & Molecular Biology; Biophysics; Science & Technology - Other Topics; Physics GA AS4EG UT WOS:000344225400010 PM 25379090 ER PT J AU Theodoroff, SM Schuette, A Griest, S Henry, JA AF Theodoroff, Sarah M. Schuette, Andrew Griest, Susan Henry, James A. TI Individual Patient Factors Associated with Effective Tinnitus Treatment SO JOURNAL OF THE AMERICAN ACADEMY OF AUDIOLOGY LA English DT Article DE Tinnitus; logistic regression; psychoacoustics; treatment ID RETRAINING THERAPY; PSYCHOMETRIC PROPERTIES; CLINICAL-TRIALS; MANAGEMENT; QUESTIONNAIRE; AMPLIFICATION; INVENTORY; DISTRESS; MASKING AB Background: Little is known about patient factors that might influence outcomes of tinnitus interventions. Determining such factors would offer insights into why some individuals benefit from tinnitus intervention whereas others do not. Purpose: The purpose of this study was to evaluate selected patient factors that may be associated with outcomes of tinnitus intervention. Factors studied include demographics, tinnitus characteristics, psychoacoustic tinnitus measures, audiometric data, and overall physical/emotional health status. Research Design: A retrospective analysis was performed on data obtained from a controlled clinical study that compared factors associated with tinnitus relief after tinnitus masking and tinnitus retraining therapy. Study Sample: A total of 126 military veterans participated in this controlled clinical study. Of these, 89 completed outcome measures at both baseline and 12 mo and were included in the present analysis. Data Collection and Analysis: A "responder" to intervention was identified as having a decrease (improvement) of 20 or more points on the Tinnitus Handicap Inventory between baseline and 12 mo. A "nonresponder" did not achieve a 20-point improvement on the Tinnitus Handicap Inventory. Individual patient factors were examined using independent t-tests or chi(2) analysis. A logistic regression model was used to determine how well each factor predicted treatment outcome (responder or nonresponder) while controlling for each of the other factors. Results: Five patient factors were significantly different (p <= 0.05) between responders and nonresponders. Responders tended to (1) be younger in age; (2) have better low-frequency hearing sensitivity; (3) have greater problems with overall hearing; (4) be more likely to have tinnitus for shorter durations; and (5) perceive their tinnitus to be located "in the head" versus "in the ears." A logistic regression was then performed to determine how well each factor predicted the treatment outcome (responder versus nonresponder) while controlling for each of the other factors. Results from the logistic regression revealed two of the five factors, localization of tinnitus and self-report of hearing problems, to be statistically significant. Conclusions: Examining the association of individual patient factors to a specific tinnitus intervention yielded several significant findings. Although these findings are not definitive, they reveal the capability that exists to perform these kinds of analyses to investigate relationships between individual patient characteristics and outcomes of intervention for tinnitus. Prospective research using systematic approaches is needed to identify these relationships that would contribute toward the ability to differentially predict outcomes of various tinnitus interventions. Obtaining this information would lead to more targeted therapy and ultimately more effective intervention. C1 [Theodoroff, Sarah M.; Griest, Susan; Henry, James A.] Natl Ctr Rehabilitat Auditory Res, VA Med Ctr, Vet Affairs VA Rehabil Res & Dev Serv, Portland, OR 97207 USA. [Theodoroff, Sarah M.; Griest, Susan; Henry, James A.] Oregon Hlth & Sci Univ, Dept Otolaryngol Head & Neck Surg, Portland, OR 97201 USA. [Schuette, Andrew] Washington Univ, Div Audiol, St Louis, MO USA. RP Theodoroff, SM (reprint author), Natl Ctr Rehabilitat Auditory Res, Portland VA Med Ctr, 3710 SW US Vet Hosp Rd, Portland, OR 97207 USA. EM sarah.theodoroff@va.gov FU National Institutes of Health National Institute on Deafness and Other Communication Disorders T35 Research Training Grant [DC008764]; VA Rehabilitation Research and Development Service [C2887R, C3214R, F7070S]; National Center for Rehabilitative Auditory Research at the Portland VA Medical Center FX Support for this project was provided by the National Institutes of Health National Institute on Deafness and Other Communication Disorders T35 Research Training Grant (DC008764), and VA Rehabilitation Research and Development Service (C2887R, C3214R, and F7070S). Additional support was provided by the National Center for Rehabilitative Auditory Research at the Portland VA Medical Center. NR 56 TC 0 Z9 0 U1 1 U2 5 PU AMER ACAD AUDIOLOGY PI RESTON PA 11730 PLAZA DR, STE 300, RESTON, VA 20190 USA SN 1050-0545 EI 2157-3107 J9 J AM ACAD AUDIOL JI J. Am. Acad. Audiol. PD JUL-AUG PY 2014 VL 25 IS 7 BP 631 EP 643 DI 10.3766/jaaa.25.7.2 PG 13 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA AS0DY UT WOS:000343949700002 PM 25365366 ER PT J AU Williams, BR Blizard, TI Goode, PS Harada, CN Woodby, LL Burgio, KL Sims, RV AF Williams, Beverly R. Blizard, Tracie I. Goode, Patricia S. Harada, Caroline N. Woodby, Lesa L. Burgio, Kathryn L. Sims, Richard V. TI Exploring the affective dimension of the life review process: Facilitators' interactional strategies for fostering personhood and social value among older adults with early dementia SO DEMENTIA-INTERNATIONAL JOURNAL OF SOCIAL RESEARCH AND PRACTICE LA English DT Article DE dementia; emotions; identity; life review; older adults ID EARLY-STAGE DEMENTIA; OF-THE-LITERATURE; ALZHEIMERS-DISEASE; COMMUNICATION STRATEGIES; PSYCHOSOCIAL INTERVENTIONS; SUBJECTIVE EXPERIENCES; PEOPLE; CARE; SELF; IDENTITY AB We employed an auto-ethnography approach to explore the affective dimension of life review sessions with community-dwelling older military veterans with minor cognitive impairment (MCI) and early dementia. Using researchers' analytic memos, we identified facilitators' interactional strategies that fostered the participant's sense of personal identity, dignity and social self-worth. Interaction among participant, caregiver, and facilitators evoked a range of emotional responses, offering a window into the affective world of MCI and early dementia. Positive emotional responses outnumbered negative emotional responses by a ratio of two-to-one in the life review sessions; however, negative emotions were more revelatory of current struggles with declines in health and function. Facilitators utilized two interactional strategies, in particular, to foster personhood and social value of participants: focusing on the participant and creating an empathic connection with the participant. Further work is needed to understand the role of emotions in research interactions and to examine the psychosocial mechanisms through which positive affect functions in promoting identity, personhood and social value among persons with MCI and early dementia. C1 [Williams, Beverly R.; Goode, Patricia S.; Harada, Caroline N.; Woodby, Lesa L.; Burgio, Kathryn L.; Sims, Richard V.] Birmingham Atlanta Geriatr Res Clin & Educ Ctr, Birmingham, AL USA. [Williams, Beverly R.; Blizard, Tracie I.; Goode, Patricia S.; Harada, Caroline N.; Woodby, Lesa L.; Burgio, Kathryn L.; Sims, Richard V.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Williams, Beverly R.; Woodby, Lesa L.; Sims, Richard V.] Univ Alabama Birmingham, Div Gerontol Geriatr & Palliat Care, Birmingham, AL 35294 USA. [Williams, Beverly R.; Goode, Patricia S.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Harada, Caroline N.; Burgio, Kathryn L.] Univ Alabama Birmingham, Birmingham, AL 35294 USA. RP Williams, BR (reprint author), Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. EM Bwilliams@aging.uab.edu NR 117 TC 1 Z9 1 U1 6 U2 26 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1471-3012 EI 1741-2684 J9 DEMENTIA-LONDON JI Dement.-Int. J. soc. Res. Pract. PD JUL PY 2014 VL 13 IS 4 BP 498 EP 524 DI 10.1177/1471301213478811 PG 27 WC Gerontology SC Geriatrics & Gerontology GA AR7MP UT WOS:000343764200005 PM 24339069 ER PT J AU Gaddikeri, S McNeeley, MF Wang, CL Bhargava, P Dighe, MK Yeh, MMC Dubinsky, TJ Kolokythas, O Lalwani, N AF Gaddikeri, Santhosh McNeeley, Michael F. Wang, Carolyn L. Bhargava, Puneet Dighe, Manjiri K. Yeh, Matthew M. C. Dubinsky, Theodore Jay Kolokythas, Orpheus Lalwani, Neeraj TI Hepatocellular Carcinoma in the Noncirrhotic Liver SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE cirrhosis; CT; hepatocellular carcinoma; MRI; noncirrhotic liver; risk factors ID RADIOLOGIC-PATHOLOGICAL CORRELATION; C VIRUS-INFECTION; MALIGNANT-TRANSFORMATION; FIBROLAMELLAR CARCINOMA; AFLATOXIN EXPOSURE; CENTRAL SCARS; DISEASE; HEPATITIS; CIRRHOSIS; RESECTION AB OBJECTIVE. Hepatocellular carcinomas (HCCs) that arise in noncirrhotic livers have several histologic and biochemical features that distinguish them from HCCs occurring in the setting of cirrhosis. Because the presentation, management, and prognosis of these entities are distinct, the accurate preoperative characterization of these lesions is of great clinical significance. We review the pathogenesis, imaging appearance, and clinical implications of noncirrhotic HCCs as they pertain to the clinical radiologist. CONCLUSION. HCCs that develop in noncirrhotic patients have distinct etiologic, cytogenetic, histopathologic, and clinical features. Despite a larger tumor burden at the time of HCC diagnosis, noncirrhotic patients with HCC have better overall survival and disease-free survival than cirrhotic patients with HCC. Knowledge of the precise clinical and imaging features of this entity and of other diagnostic considerations for the noncirrhotic liver is essential for improved patient care. C1 [Gaddikeri, Santhosh; McNeeley, Michael F.; Wang, Carolyn L.; Dighe, Manjiri K.; Dubinsky, Theodore Jay; Lalwani, Neeraj] Univ Washington, Dept Radiol, Seattle, WA 98195 USA. [Bhargava, Puneet] VA Puget Sound Hlth Care Syst, Dept Radiol, Seattle, WA USA. [Yeh, Matthew M. C.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Kolokythas, Orpheus] Kantonsspital Winterthur, Inst Radiol, Winterthur, Switzerland. RP Lalwani, N (reprint author), Univ Washington, Dept Radiol, 1959 NE Pacific St, Seattle, WA 98195 USA. EM neerajl@uw.edu OI Bhargava, Puneet/0000-0002-3849-9666 NR 62 TC 5 Z9 6 U1 2 U2 5 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUL PY 2014 VL 203 IS 1 BP W34 EP W47 DI 10.2214/AJR.13.11511 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AR2GD UT WOS:000343400900005 PM 24951228 ER PT J AU Shin, DS Ingraham, CR Dighe, MK Wang, C Vaidya, S Moshiri, M Lall, C Park, JO Bhargava, P AF Shin, David S. Ingraham, Christopher R. Dighe, Manjiri K. Wang, Carolyn Vaidya, Sandeep Moshiri, Mariam Lall, Chandana Park, James O. Bhargava, Puneet TI Surgical Resection of a Malignant Liver Lesion: What the Surgeon Wants the Radiologist to Know SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE hepatic malignancy; hepatocellular carcinoma; liver resection; surgical planning ID PORTAL-VEIN EMBOLIZATION; EARLY HEPATOCELLULAR-CARCINOMA; GD-EOB-DTPA; HEPATIC RESECTION; CLINICAL-EVALUATION; METASTASES; SURVIVAL; CHOLANGIOCARCINOMA; TRANSPLANTATION; MANAGEMENT AB OBJECTIVE. Hepatic malignancy is a common and lethal disease, whether due to a primary tumor or metastasis. There are numerous treatment options available depending on the stage of the disease and medical condition of the patient, including systemic chemotherapy, transcatheter embolization, thermal ablation, and surgical resection. In a subset of patients with liver malignancy, surgical resection can offer the best chance of long-term survival and potentially even cure. This article reviews the major indications and contraindications for resection, basic surgical techniques and terminology, key clinical and imaging preoperative workup, and pertinent interventional oncology procedures in the management of hepatic malignancy. CONCLUSION. Diagnostic and interventional radiology plays an important role in the assessment and treatment of malignant hepatic lesions. Radiologists should be familiar with how surgeons select, work up, and treat candidates for liver resection to provide the most clinically valuable service. C1 [Shin, David S.; Ingraham, Christopher R.; Dighe, Manjiri K.; Wang, Carolyn; Vaidya, Sandeep; Moshiri, Mariam] Univ Washington, Dept Radiol, Sch Med, Seattle, WA 98108 USA. [Lall, Chandana] Univ Calif Irvine, Dept Radiol, Orange, CA 92668 USA. [Park, James O.] Univ Washington, Dept Surg, Sch Med, Seattle, WA 98108 USA. [Bhargava, Puneet] Univ Washington, Dept Radiol, Seattle, WA 98108 USA. [Bhargava, Puneet] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Bhargava, P (reprint author), Univ Washington, Dept Radiol, Mail Box 358280,S-114 Radiol,1660 S Columbian Way, Seattle, WA 98108 USA. EM bhargp@uw.edu OI Bhargava, Puneet/0000-0002-3849-9666 NR 47 TC 6 Z9 6 U1 0 U2 5 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUL PY 2014 VL 203 IS 1 BP W21 EP W33 DI 10.2214/AJR.13.11701 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AR2GD UT WOS:000343400900004 PM 24951226 ER PT J AU Wentzel, JL Mulligan, JK Soler, ZM White, DR Schlosser, RJ AF Wentzel, Jennifer L. Mulligan, Jennifer K. Soler, Zachary M. White, David R. Schlosser, Rodney J. TI Passive smoke exposure in chronic rhinosinusitis as assessed by hair nicotine SO AMERICAN JOURNAL OF RHINOLOGY & ALLERGY LA English DT Article ID SECONDHAND SMOKE; CIGARETTE-SMOKE; TOBACCO-SMOKE; EPITHELIAL-CELLS; NASAL POLYPOSIS; CHILDREN; PREVALENCE; OUTCOMES; ASTHMA; IMPACT AB Background: Prevalence of passive smoke exposure is relatively unknown in chronic rhinosinusitis (CRS). Previous studies have attempted to establish this relationship using subjective, questionnaire-based methodologies to assess smoke exposure, thus introducing the potential for error bias. The purpose of this study was to accurately determine the prevalence of passive smoke exposure in CRS and control patients using hair nicotine levels as a quantitative measure of cigarette smoke exposure. Methods: Hair samples were obtained at time of surgery from 569 patients: 404 undergoing surgery for CRS and 165 controls undergoing surgery for repair of cerebrospinal fluid leak, removal of pituitary tumors, or adenoidectomy from 2007 to 2013. Patient charts were reviewed for reported smoking status. Hair nicotine was quantified using reversed-phase high-performance liquid chromatography. Nonsmoking patients were classified as passive smoke exposed or smoke naive according to the hair nicotine results. Statistical analysis was performed to test for differences in demographic information and smoke exposure prevalence between CRS, CRS subtypes, and controls. Results: The prevalence of passive smoke exposure in CRS as documented by hair nicotine was lower than previously reported subjective estimates. Passive smoke exposure rates were equivalent between those with CRS versus controls and significantly higher in children. Severity of passive smoke exposure was also equivalent between CRS subsets and controls. Annual passive smoke exposure prevalence did not change over time. Conclusion: There is no clear evidence of avoidance of passive smoke exposure in the CRS population compared with controls. Passive smoke exposure also remained stable over time despite recent regional implementation of smoking bans. Given the constancy of exposure, it is critical that the impact of passive smoke on CRS exacerbation, outcomes, and pathophysiology be evaluated in large-scale clinical studies. C1 [Wentzel, Jennifer L.; Mulligan, Jennifer K.; Soler, Zachary M.; White, David R.; Schlosser, Rodney J.] Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, Charleston, SC 29425 USA. [Mulligan, Jennifer K.] Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. [Mulligan, Jennifer K.; Schlosser, Rodney J.] Ralph H Johnson VA Med Ctr, Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Mulligan, JK (reprint author), 135 Rutledge Ave,MSC 550, Charleston, SC 29425 USA. EM konopa@musc.edu FU Flight Attendant Medical Research Institute [092401, 113042, 113039]; Department of Veterans Affairs [1 I01 CX000377] FX Funded by grants from the Flight Attendant Medical Research Institute to JK Mulligan (092401), Z Solar (113042), and RJ Schlosser (113039), as well as a Merit-Review Award from the Clinical Sciences Research and Development Program of the Department of Veterans Affairs (1 I01 CX000377). NR 37 TC 6 Z9 6 U1 0 U2 5 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1945-8924 EI 1945-8932 J9 AM J RHINOL ALLERGY JI Am. J. Rhinol. Allergy PD JUL-AUG PY 2014 VL 28 IS 4 BP 297 EP 301 DI 10.2500/ajra.2014.28.4058 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA AQ4FF UT WOS:000342748000010 PM 25197916 ER PT J AU Skovrlj, B Haghighi, M Smethurst, ME Caridi, J Bederson, JB AF Skovrlj, Branko Haghighi, Maryam Smethurst, Mark E. Caridi, John Bederson, Joshua B. TI Curvularia Abscess of the Brainstem SO WORLD NEUROSURGERY LA English DT Article DE Brainstem; Curvularia abscess; Fungal central nervous system infection; Phaeohyphomycosis ID CENTRAL-NERVOUS-SYSTEM; INVASIVE PULMONARY ASPERGILLOSIS; WANGIELLA-DERMATITIDIS; CONTAMINATED MARIJUANA; TRANSPLANT RECIPIENT; FUNGAL-INFECTIONS; MELANIN; PHEOHYPHOMYCOSIS; VIRULENCE; SMOKING AB OBJECTIVE: To present a unique case of a brainstem Curvularia fungal infection and review the diagnosis and management of this rare phenomenon. METHODS: A 33-year-old immunocompetent African American male presented with 2 weeks of headache, nausea, and vomiting in a setting of a recent 20-lb weight loss. Neurological examination was positive for multiple cranial nerve palsies, hemisensory loss, and gait instability. Magnetic resonance imaging demonstrated an enhancing medullary lesion. RESULTS: Metastatic and infectious workup revealed a left lung lesion, which on subsequent biopsy was positive for a granuloma yielding no further clues to the etiology of the brainstem lesion. On surgical exploration of the cranial lesion, a puss-filed, encapsulated lesion was encountered that was tightly adherent to the brainstem. Intraoperative biopsy of the lesion capsule was initially negative but on postoperative day 9, fungal hyphae were encountered identified on morphology as Curvularia species. The patient was started on triple antifungal therapy but necessitated a second surgery for lesion debulking and drainage. The patient was discharged home 10 weeks after initial presentation. At the 13-months follow-up the patient is doing very well and his neurological examination continues to improve. CONCLUSIONS: This is the first reported case of a brainstem Curvularia infection. This case highlights the importance of an aggressive surgical and antibiotic therapy in the treatment of central nervous system Curvularia infections. There appears to be a strong relationship between heavy marijuana use and Curvularia infection, producing lung granulomas that may extend to other organs such as the central nervous system of immunocompetent patients. C1 [Skovrlj, Branko; Caridi, John; Bederson, Joshua B.] Mt Sinai Sch Med, Dept Neurosurg, New York, NY 10029 USA. [Haghighi, Maryam] Karolinska Inst, Sch Med, Hagalund, Sweden. [Smethurst, Mark E.] James J Peters VA Med Ctr, Dept Pathol, Bronx, NY USA. RP Skovrlj, B (reprint author), Mt Sinai Sch Med, Dept Neurosurg, New York, NY 10029 USA. EM skovrlj.branko@gmail.com NR 32 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1878-8750 EI 1878-8769 J9 WORLD NEUROSURG JI World Neurosurg. PD JUL-AUG PY 2014 VL 82 IS 1-2 AR UNSP 241.e9 DI 10.1016/j.wneu.2013.07.014 PG 5 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA AQ6HM UT WOS:000342911400154 PM 23891581 ER PT J AU Brown, RS Lombardi, A Hasham, A Greenberg, DA Gordon, J Concepcion, E Hammerstad, SS Lotay, V Zhang, W Tomer, Y AF Brown, Rosalind S. Lombardi, Angela Hasham, Alia Greenberg, David A. Gordon, Joshua Concepcion, Erlinda Hammerstad, Sara S. Lotay, Vaneet Zhang, Weijia Tomer, Yaron TI Genetic Analysis in Young-Age-of-Onset Graves' Disease Reveals New Susceptibility Loci SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID THYROID AUTOIMMUNITY; ASSOCIATION; BTNL2; POLYMORPHISMS; PTPN22; FOXP3; MHC AB Context: Genetic and environmental factors play an essential role in the pathogenesis of Graves' Disease (GD). Children with GD have less exposure time to environmental factors and therefore are believed to harbor stronger genetic susceptibility than adults. Objective: The aim of the study was to identify susceptibility loci that predispose to GD in patients with young-age-of-onset (YAO) GD. Setting and Design: One hundred six patients with YAO GD (onset <30 y) and 855 healthy subjects were studied. Cases and controls were genotyped using the Illumina Infinium Immunochip, designed to genotype 196,524 polymorphisms. Case control association analyses were performed using the PLINK computer package. Ingenuity Pathway Analysis program (QIAGEN) was used to carry out pathway analyses. Results: Immunochip genetic association analysis identified 30 single-nucleotide polymorphisms in several genes that were significantly associated with YAO GD, including major histocompatibility complex class I and class II genes, BTNL2, NOTCH4, TNFAIP3, and CXCR4. Candidate gene analysis revealed that most of the genes previously shown to be associated with adult-onset GD were also associated with YAO GD. Pathway analysis demonstrated that antigen presentation, T-helper cell differentiation, and B cell development were the major pathways contributing to the pathogenesis of YAO GD. Conclusions: Genetic analysis identified novel susceptibility loci in YAO GD adding a new dimension to the understanding of GD etiology. C1 [Brown, Rosalind S.; Gordon, Joshua] Childrens Hosp Boston, Div Endocrinol, Boston, MA 02115 USA. [Lombardi, Angela; Hasham, Alia; Concepcion, Erlinda; Hammerstad, Sara S.; Tomer, Yaron] Icahn Sch Med Mt Sinai, Div Endocrinol, New York, NY 10029 USA. [Greenberg, David A.] Nationwide Childrens Hosp, Battelle Ctr Math Med, Columbus, OH 43210 USA. [Lotay, Vaneet; Zhang, Weijia] Mt Sinai Sch Med, Dept Med Bioinformat Core, New York, NY 10029 USA. [Tomer, Yaron] James J Peters VA Med Ctr, Bronx, NY 10468 USA. RP Tomer, Y (reprint author), Icahn Sch Med Mt Sinai, Div Endocrinol, Box 1055,One Gustave L Levy Pl, New York, NY 10029 USA. EM Yaron.Tomer@mssm.edu FU NIDDK [DK061659, DK067555, DK073681]; Department of Veterans Affairs FX This work was supported in part by Grants DK061659, DK067555, and DK073681 from NIDDK. In addition, this material is based upon work supported in part by the Department of Veterans Affairs. NR 20 TC 6 Z9 6 U1 0 U2 2 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 2014 VL 99 IS 7 BP E1387 EP E1391 DI 10.1210/jc.2013-4358 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AP8PM UT WOS:000342341000031 PM 24684463 ER PT J AU Jude, CM Nayak, NB Patel, MK Deshmukh, M Batra, P AF Jude, Cecilia M. Nayak, Nita B. Patel, Maitraya K. Deshmukh, Monica Batra, Poonam TI Pulmonary Coccidioidomycosis: Pictorial Review of Chest Radiographic and CT Findings SO RADIOGRAPHICS LA English DT Article ID PLEURAL EFFUSION; FUNGAL PNEUMONIAS; NEEDLE-BIOPSY; CALIFORNIA; DIAGNOSIS; IMMUNOCOMPETENT; EXPERIENCE; INFECTION; SPHERULES; SPECTRUM AB Pulmonary coccidioidomycosis is a fungal disease endemic to the desert regions of the southwestern United States, Mexico, Central America, and South America. The incidence of reported disease increased substantially between 1998 and 2011, and the infection is encountered beyond the endemic areas because of a mobile society. The disease is caused by inhalation of spores of Coccidioides species. Individuals at high risk are those exposed to frequent soil aerosolization. The diagnosis is established by direct visualization of mature spherules by using special stains or cultures from biologic specimens. Serologic testing of anticoccidioidal antibodies is used for diagnosis and treatment monitoring. The infection is self-limited in 60% of cases. When the disease is symptomatic, the lung is the primary site of involvement. On the basis of clinical presentation and imaging abnormalities, pulmonary involvement is categorized into acute, disseminated, and chronic forms, each with a spectrum of imaging findings. In patients with acute disease, the most common findings are lobar or segmental consolidation, multifocal consolidation, and nodules. Adenopathy and pleural effusions are also seen, usually in association with parenchymal disease. Disseminated disease is rare and occurs in less than 1% of patients. Pulmonary findings are miliary nodules and confluent parenchymal opacities. Acute respiratory distress syndrome is an infrequent complication of disseminated disease. The acute findings resolve in most patients, with chronic changes developing in approximately 5% of patients. Manifestations of chronic disease include residual nodules, chronic cavities, persistent pneumonia with or without adenopathy, pleural effusion, and regressive changes. Unusual complications of chronic disease are mycetoma, abscess formation, and bronchopleural fistula. Patients in an immunocompromised state, those with diabetes mellitus, pregnant women, and those belonging to certain ethnic groups may show severe, progressive, or disseminated disease. (C) RSNA, 2014 C1 [Jude, Cecilia M.; Patel, Maitraya K.; Deshmukh, Monica] Olive View UCLA Med Ctr, Dept Radiol, Sylmar, CA 91342 USA. [Jude, Cecilia M.; Batra, Poonam] W Los Angeles Vet Affairs Med Ctr, Imaging Serv, Los Angeles, CA USA. [Jude, Cecilia M.; Nayak, Nita B.; Patel, Maitraya K.; Deshmukh, Monica; Batra, Poonam] Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiol Sci, Los Angeles, CA 90095 USA. RP Jude, CM (reprint author), Olive View UCLA Med Ctr, Dept Radiol, 14445 Olive View Dr,2D115, Sylmar, CA 91342 USA. EM mjude@outlook.com NR 50 TC 3 Z9 3 U1 0 U2 2 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD JUL-AUG PY 2014 VL 34 IS 4 BP 912 EP 925 DI 10.1148/rg.344130134 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AP2QA UT WOS:000341917400008 PM 25019431 ER PT J AU Keyhani, S Cheng, EM Ofner, S Williams, LS Halm, EA Bravata, DM AF Keyhani, Salomeh Cheng, Eric M. Ofner, Susan Williams, Linda S. Halm, Ethan A. Bravata, Dawn M. TI The Underuse of Interventions in Veterans With Symptomatic Carotid Stenosis SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID MEDICARE BENEFICIARIES; ARTERY STENOSIS; STROKE CARE; ENDARTERECTOMY; APPROPRIATENESS; TRIAL; OUTCOMES; QUALITY; MULTICENTER; PREVENTION AB Objectives To examine the receipt of carotid intervention among eligible patients post stroke in the Veterans Health Administration (VA). Methods We examined whether veterans admitted to OVA medical center in 2007 with a diagnosis of stroke and who were eligible for intervention, received carotid intervention in a period up to 6 months after their index hospitalization. We also examined whether demographics, comorbid conditions, stroke severity and availability of vascular intervention services were independently associated with receipt of intervention. Results Among the 5721 patients admitted, 253 ischemic stroke patients had evidence of some carotid stenosis and had data on side of stroke available. Among the 200 patients who had at least 50% to 99% stenosis of the carotid artery, 34 (17%) received intervention (95% confidence interval [CI], 11.79%-22.21%). In a multivariable model, black race and past history of diabetes were significantly associated with carotid intervention: An eligible black patient was 6 times more likely to NOT receive intervention compared to patients of other races (adjusted odds ratio [OR] = 6.54; 95% CI, 1.34-31.9), and a patient with diabetes was 3 times more likely to NOT receive intervention (adjusted OR = 3.38; 95% CI, 1.24-9.24) compared to nondiabetics. Stroke severity and availability of vascular surgery services was not associated with receipt of intervention. Conclusions Few patients with symptomatic carotid stenosis who were admitted with stroke to the VA received carotid intervention. Future research should be directed at improving access to this procedure among eligible patients in the VA. C1 [Keyhani, Salomeh] San Francisco VA Med Ctr, HSR&D REAP, San Francisco, CA 94121 USA. [Keyhani, Salomeh] UCSF, Div Gen Internal Med, San Francisco, CA USA. [Cheng, Eric M.] VA Greater Los Angeles Healthcare Syst, Dept Neurol, Los Angeles, CA USA. [Cheng, Eric M.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Williams, Linda S.] Richard L Roudebush VA Med Ctr, VHA HSR&D Ctr Excellence Implementing Evidence Ba, Indianapolis, IN USA. [Williams, Linda S.] Indiana Univ Sch Med, Indiana Univ Ctr Aging Res, Indianapolis, IN 46202 USA. [Williams, Linda S.] Regenstrief Inst Hlth Care, Indianapolis, IN 46202 USA. [Ofner, Susan] Indiana Univ Sch Med, Dept Biostat, Indianapolis, IN 46202 USA. [Keyhani, Salomeh; Cheng, Eric M.; Ofner, Susan; Williams, Linda S.; Bravata, Dawn M.] VHA HSR&D Stroke Qual Enhancement Res Initiat Pro, Indianapolis, IN USA. [Williams, Linda S.; Bravata, Dawn M.] Indiana Univ Sch Med, Dept Neurol, Indianapolis, IN 46202 USA. [Bravata, Dawn M.] Indiana Univ Sch Med, Dept Internal Med, Indianapolis, IN 46202 USA. [Halm, Ethan A.] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA. [Halm, Ethan A.] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75390 USA. RP Keyhani, S (reprint author), San Francisco VA Med Ctr, 4150 Clement St,111A1, San Francisco, CA 94121 USA. EM salomeh.keyhani@ucsf.edu FU Department of Veterans Affairs, Veterans Health Administration (VHA), Office of Quality and Performance and Health Services Research and Development Service Quality Enhancement Research Initiative [RRP 09484]; VA HSR&D Career Development Award; Career Development Award from NIH/NINDS [K23NS058571] FX The project reported here was supported by the Department of Veterans Affairs, Veterans Health Administration (VHA), Office of Quality and Performance and Health Services Research and Development Service Quality Enhancement Research Initiative (RRP 09484). SK is also supported by a VA HSR&D Career Development Award. EMC is supported by a Career Development Award from NIH/NINDS (K23NS058571). NR 29 TC 0 Z9 0 U1 0 U2 0 PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC PI PLAINSBORO PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD JUL PY 2014 VL 20 IS 7 BP E250 EP E256 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AO9MI UT WOS:000341679400008 PM 25295544 ER PT J AU Naarding, MA Fernandez, N Kappes, JC Hayes, P Ahmed, T Icyuz, M Edmonds, TG Bergin, P Anzala, O Hanke, T Clark, L Cox, JH Cormier, E Ochsenbauer, C Gilmour, J AF Naarding, Marloes A. Fernandez, Natalia Kappes, John C. Hayes, Peter Ahmed, Tina Icyuz, Mert Edmonds, Tara G. Bergin, Philip Anzala, Omu Hanke, Tomas Clark, Lorna Cox, Josephine H. Cormier, Emmanuel Ochsenbauer, Christina Gilmour, Jill TI Development of a luciferase based viral inhibition assay to evaluate vaccine induced CD8 T-cell responses SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Review DE HIV; Vaccine Clinical trial; CD8 T cells; Viral inhibition assay; Renilla reniformis luciferase; Infectious molecular clones ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACUTE HIV-1 INFECTION; TYPE-1 INFECTION; MOLECULAR CLONES; REPLICATION; LYMPHOCYTES; SUPPRESSION; BREADTH; ENTRY; NEUTRALIZATION AB Emergence of Sly and HIV specific CD8 T cells has been shown to correlate with control of in vivo replication. Poor correlation between IFNI/ ELISPOT responses and in vivo control of the virus has triggered the development of more relevant assays to assess functional HIV-1 specific CD8 T-cell responses for the evaluation and prioritization of new HIV-1 vaccine candidates. We previously established a viral inhibition assay (VIA) that measures the ability of vaccine-induced CD8 T-cell responses to inhibit viral replication in autologous CD4 T cells. In this assay, viral replication is determined by measuring p24 in the culture supernatant. Here we describe the development of a novel VIA, referred to as IMC LucR VIA that exploits replication-competent HIV-1 infectious molecular clones (IMCs) in which the complete proviral genome is strain-specific and which express the Renilla luciferase (LucR) gene to determine viral growth and inhibition. The introduction of the luciferase readout does provide significant improvement of the read out time. In addition to switching to the LucR read out, changes made to the overall protocol resulted in the miniaturization of the assay from a 48 to a 96-well plate format, which preserved sample and allowed for the introduction of replicates. The overall assay time was reduced from 13 to 8 days. The assay has a high degree of specificity, and the previously observed non-specific background inhibition in cells from HIV-1 negative volunteers has been reduced dramatically. Importantly, we observed an increase in positive responses, indicating an improvement in sensitivity compared to the original VIA. Currently, only a limited number of "whole-genome" IMC-LucR viruses are available and our efforts will focus on expanding the panel to better evaluate anti-viral breadth. Overall, we believe the IMC LucR VIA provides a platform to assess functional CD8 T-cell responses in large-scale clinical trial testing, which will enhance the ability to select the most promising HIV-1 vaccine candidates capable of controlling HIV-1 replication in vivo. (C) 2013 The Authors. Published by Elsevier B.V. C1 [Naarding, Marloes A.; Fernandez, Natalia; Hayes, Peter; Bergin, Philip; Clark, Lorna; Cox, Josephine H.; Cormier, Emmanuel; Gilmour, Jill] Univ London Imperial Coll Sci Technol & Med, Int AIDS Vaccine Initiat, Human Immunol Lab, Chelsea & Westminster Hosp, London SW10 9NH, England. [Kappes, John C.; Icyuz, Mert; Edmonds, Tara G.; Ochsenbauer, Christina] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Kappes, John C.] Birmingham Vet Affairs Med Ctr, Res Serv, Birmingham, AL 35233 USA. [Ahmed, Tina; Hanke, Tomas] Univ Oxford, MRC, Human Immunol Unit, Weatherall Inst Mol Med, Oxford, England. [Ahmed, Tina; Hanke, Tomas] Univ Oxford, Jenner Inst Labs, Oxford OX3 7DQ, England. [Anzala, Omu] Kenya AIDS Vaccine Initiat, Nairobi, Kenya. RP Cox, JH (reprint author), Univ London Imperial Coll Sci Technol & Med, Int AIDS Vaccine Initiat, Human Immunol Lab, Chelsea & Westminster Hosp, London SW10 9NH, England. EM jcox@iavi.org OI Bergin, Philip/0000-0001-5522-8350 FU CAVD [OPP1032325]; NIH Center for HIV/AIDS Vaccine Immunology (CHAVI) [U01-AI067854]; CAVD for the CA-VIMC [OPP1032144, 38619]; UAB Center for AIDS Research Virology and Sequencing Cores [NIH P30 AI 27767]; VA through a Career Scientist Award; Merit Review funding; IAVI FX We would like to thank Prof B Walker (Ragon Institute, Boston, USA) for supplying the PBMCs from HIV-1 positive LTNP, and Dr. G Marrow and Dr. R. Lindsay (Development and Design Laboratory, IAVI, NY, USA) for critically reviewing this manuscript. This study was supported by CAVD funding for the CTVIMC, grant number OPP1032325.; CO, JCK, TGE and MI were supported by the NIH Center for HIV/AIDS Vaccine Immunology (CHAVI, U01-AI067854), a subcontract of CAVD funding for the CA-VIMC (grant numbers OPP1032144 and 38619), and through services by the UAB Center for AIDS Research Virology and Sequencing Cores (NIH P30 AI 27767). JCK also received support from the VA through a Career Scientist Award and Merit Review funding.; The International AIDS Vaccine Initiative (IAVI) is a global non-for-profit organization whose mission is to ensure the development of safe, effective, accessible, preventive HIV vaccines for use throughout the world. Founded in 1996, IAVI works with partners in 25 countries to research, design and develop AIDS vaccine candidates. In addition, IAVI conducts policy analyses and serves as an advocate for the AIDS vaccine field. IAVI supports a comprehensive approach to addressing HIV and AIDS that balances the expansion and strengthening of existing HIV-prevention and treatment programs with targeted investments in the design and development of new tools to prevent HIV. IAVI is dedicated to ensuring that a future AIDS vaccine will be available and accessible to all who need it. IAVI relies on the generous donations from governments, private individuals, corporations and foundations to carry out its mission. For more information, see www.iavi.org. NR 44 TC 8 Z9 8 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 EI 1872-7905 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD JUL PY 2014 VL 409 SI SI BP 161 EP 173 DI 10.1016/j.jim.2013.11.021 PG 13 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA AO7QW UT WOS:000341548700017 PM 24291126 ER PT J AU Chao, SZ Matthews, BR Yokoyama, JS Lai, NB Ong, H Tse, M Yuan, RF Lin, A Kramer, J Yaffe, K Kornak, J Miller, BL Rosen, HJ AF Chao, Steven Z. Matthews, Brandy R. Yokoyama, Jennifer S. Lai, Ngan Betty Ong, Hilary Tse, Marian Yuan, Runfen Frances Lin, Amy Kramer, Joel Yaffe, Kristine Kornak, John Miller, Bruce L. Rosen, Howard J. TI Depressive Symptoms in Chinese-American Subjects with Cognitive Impairment SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE Chinese American; dementia; geriatric depression ID NEUROPSYCHIATRIC SYMPTOMS; ALZHEIMERS-DISEASE; PRIMARY-CARE; ANTIDEPRESSANT USE; OLDER PERSONS; UNITED-STATES; RISK-FACTORS; PREVALENCE; DEMENTIA; SCALE AB Objectives: To compare the prevalence of depressive symptoms and frequency of antidepressant use between a group of elderly Chinese-American subjects with and without cognitive impairment and a group of matched white subjects. A secondary aim was to examine the clinical and demographic predictors of depressive symptoms across these groups. Methods: The study was conducted at an academic neurology subspecialty clinic. This was a caseecontrol study with 140 Chinese-American subjects and 140 demographically and cognitively matched white subjects. In each group, there were 48 cognitively normal and 92 cognitively impaired participants (49 with mild cognitive impairment, 43 with Alzheimer disease). The proportion of individuals with significant depressive symptoms, as indicated by a Geriatric Depression Scale score >= 6 of 15, and frequency of antidepressant use were compared across groups by using c 2 analysis. Factors predicting depressive symptoms, including racial and diagnostic group, age, gender, Mini-Mental State Examination score, level of functional impairment, education level, and medical comorbidities, were assessed by using linear regression analysis. Results: Significant depressive symptoms were more common in cognitively impaired Chinese-American (35%) than cognitively impaired white (15%; chi(2)([1]) = 9.4; p = 0.004) subjects. Chinese-American subjects with cognitive impairment were less likely to be receiving treatment for depression (12%) than white subjects with cognitive impairment (37%; chi(2)([1]) = 15.6; p = 0.002). Racial and diagnostic group, age, level of functional impairment, Mini-Mental State Examination score, and education level were all statistically significant independent predictors of Geriatric Depression Scale score. Conclusions: Elderly Chinese-American subjects with cognitive impairment are at increased risk for unrecognized and untreated depressive symptoms compared with elderly white subjects with cognitive impairment. Education level may contribute to this risk or it may be a surrogate marker for other factors contributing to depressive symptoms in this group. C1 [Chao, Steven Z.] VA Palo Alto Hlth Care Syst, Dept Neurol, Palo Alto, CA USA. [Chao, Steven Z.; Yokoyama, Jennifer S.; Lai, Ngan Betty; Ong, Hilary; Tse, Marian; Yuan, Runfen Frances; Lin, Amy; Kramer, Joel; Miller, Bruce L.; Rosen, Howard J.] Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA 94143 USA. [Matthews, Brandy R.] Indiana Univ, Sch Med, Dept Neurol, Indiana Alzheimer Dis Ctr, Indianapolis, IN 46202 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, Memory Disorders Clin, San Francisco, CA USA. [Kornak, John] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Rosen, HJ (reprint author), 675 Nelson Rising Ln,Box 1207,Ste 190, San Francisco, CA 94158 USA. EM hrosen@memory.ucsf.edu FU National Institutes of Health/National Institute on Aging [AG023501]; Larry L. Hillblom Foundation FX This work was supported by the National Institutes of Health/National Institute on Aging grant AG023501 (The UCSF Alzheimer's Disease Research Center) and the Larry L. Hillblom Foundation. NR 49 TC 6 Z9 6 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1064-7481 EI 1545-7214 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD JUL PY 2014 VL 22 IS 7 BP 642 EP 652 DI 10.1016/j.jagp.2012.10.029 PG 11 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA AN9ZX UT WOS:000340969600002 PM 24021225 ER PT J AU Kociolek, LK Gerding, DN AF Kociolek, Larry K. Gerding, Dale N. TI Is pediatric Clostridium difficile infection associated with prior antibiotic exposure? SO FUTURE MICROBIOLOGY LA English DT Editorial Material DE antibiotics; Clostridium difficile; epidemiology; pediatric; risk factors ID CHANGING EPIDEMIOLOGY; CHILDREN; SURVEILLANCE; PREVENTION; RISK C1 [Kociolek, Larry K.] Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL 60611 USA. [Kociolek, Larry K.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Gerding, Dale N.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. [Gerding, Dale N.] Loyola Univ, Stritch Sch Med, Maywood, IL 60153 USA. RP Kociolek, LK (reprint author), Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL 60611 USA. EM lkociolek@luriechildrens.org OI Kociolek, Larry/0000-0002-8756-3417 NR 20 TC 1 Z9 1 U1 1 U2 1 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1746-0913 EI 1746-0921 J9 FUTURE MICROBIOL JI Future Microbiol. PD JUL PY 2014 VL 9 IS 7 BP 825 EP 828 DI 10.2217/FMB.14.51 PG 4 WC Microbiology SC Microbiology GA AO1TV UT WOS:000341098600001 PM 25156370 ER PT J AU Scales, CD Lai, JC Dick, AW Hanley, JM van Meijgaard, J Setodji, CM Saigal, CS AF Scales, Charles D., Jr. Lai, Julie C. Dick, Andrew W. Hanley, Jan M. van Meijgaard, Jeroen Setodji, Claude M. Saigal, Christopher S. CA Amer Project TI Comparative Effectiveness of Shock Wave Lithotripsy and Ureteroscopy for Treating Patients With Kidney Stones SO JAMA SURGERY LA English DT Article ID DISTAL URETERAL CALCULI; INSTRUMENTAL VARIABLES; METABOLIC SYNDROME; 2007 GUIDELINE; UNITED-STATES; HEALTH-CARE; MANAGEMENT; NEPHROLITHIASIS; TECHNOLOGY; PREVALENCE AB IMPORTANCE Shock wave lithotripsy (SWL) and ureteroscopy (URS) account for more than 90% of procedural interventions for kidney stones, which affect 1 in 11 persons in the United States. Efficacy data for SWL are more than 20 years old. Advances in URS, along with emerging evidence of reduced efficacy of modern lithotripters, have created uncertainty regarding the comparative effectiveness of these 2 treatment options. OBJECTIVE To compare the effectiveness of SWL and URS to fragment or remove urinary stones in a large private payer cohort. DESIGN, SETTING, AND PARTICIPANTS We performed a retrospective cohort study of privately insured beneficiaries who had an emergency department visit for a kidney stone and subsequently underwent SWL or URS. Using an instrumental variable approach to control for observed and unobserved differences between the 2 groups, we created a bivariate probit model to estimate the probability of repeat intervention following an initial procedure. MAIN OUTCOMES AND MEASURES A second procedure (SWL or URS) within 120 days of an initial intervention to fragment or remove or a kidney stone. RESULTS Following an acute care visit for a kidney stone, 21 937 patients (45.8%) underwent SWL and 25 914 patients (54.2%) underwent URS to fragment or remove the stone. After the initial URS, 4852 patients (18.7%) underwent an additional fragmentation or removal procedure compared with 5186 patients (23.6%) after the initial SWL (P <.001). After adjusting for observed and unobserved variables, the estimated probabilities of repeat intervention were 11.0% (95% CI, 10.9-11.1) following SWL and 0.3% (95% CI, 0.325-0.329) following URS. CONCLUSIONS AND RELEVANCE Among privately insured beneficiaries requiring procedural intervention to remove a symptomatic stone, repeat intervention is more likely following SWL. For the marginal patient (as opposed to the average patient), the probability of repeat intervention is substantially higher. C1 [Scales, Charles D., Jr.] Univ Calif Los Angeles, Robert Wood Johnson Fdn Clin Scholars Program, Los Angeles, CA USA. [Scales, Charles D., Jr.] US Dept Vet Affairs, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Scales, Charles D., Jr.; Saigal, Christopher S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90095 USA. [Scales, Charles D., Jr.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Lai, Julie C.; Hanley, Jan M.; Saigal, Christopher S.] RAND Corp, Santa Monica, CA USA. [Dick, Andrew W.] RAND Corp, Boston, MA USA. [van Meijgaard, Jeroen] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA USA. [Setodji, Claude M.] RAND Corp, Pittsburgh, PA USA. RP Scales, CD (reprint author), Duke Univ, Med Ctr, Duke Clin Res Inst, Div Urol Surg, 40 Med Cir,Ste 1570, Durham, NC 27710 USA. EM chuck.scales@duke.edu FU Robert Wood Johnson Foundation Clinical Scholars Program; US Department of Veterans Affairs; National Institute of Diabetes and Digestive and Kidney Diseases [HHSN276201200016C]; National Library of Medicine FX This study was supported by the Robert Wood Johnson Foundation Clinical Scholars Program and the US Department of Veterans Affairs (Dr Scales). The Urologic Diseases in America Project is supported by grant HHSN276201200016C from the National Institute of Diabetes and Digestive and Kidney Diseases and the National Library of Medicine. NR 37 TC 20 Z9 20 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6254 EI 2168-6262 J9 JAMA SURG JI JAMA Surg. PD JUL PY 2014 VL 149 IS 7 BP 648 EP 653 DI 10.1001/jamasurg.2014.336 PG 6 WC Surgery SC Surgery GA AN8DV UT WOS:000340833800007 PM 24839228 ER PT J AU Perron-Burdick, M Calhoun, A Idowu, D Pressman, A Zaritsky, E AF Perron-Burdick, Misa Calhoun, Amanda Idowu, Dennis Pressman, Alice Zaritsky, Eve TI Minilaparotomy vs Laparoscopic Hysterectomy: Comparison of Length of Hospital Stay SO JOURNAL OF MINIMALLY INVASIVE GYNECOLOGY LA English DT Article DE Hospital stay; Hysterectomy; Laparoscopy; Laparotomy; Length of stay; Minilaparotomy ID BENIGN GYNECOLOGIC DISEASE; QUALITY-OF-LIFE; ABDOMINAL HYSTERECTOMY; VAGINAL HYSTERECTOMY; UTERINE MYOMAS; WOMEN AB Study Objective: To compare length of hospital stay for minilaparotomy vs laparoscopic hysterectomy. Design: Retrospective cohort study (Canadian Task Force classification II-2). Setting: Kaiser Permanente Northern California, a large integrated health care delivery system. Patients: Women >18 years of age undergoing laparoscopic or minilaparotomy hysterectomy because of benign indications from June 2009 through January 2010. Intervention: Hysterectomy via minilaparotomy or laparoscopy. Measurements and Main Results: Medical records were reviewed for outcomes of interest including length of stay and surgical and demographic data. Parametric and non-parametric analyses were used to compare the 2 groups. The study was powered to detect a difference of 8 hours in length of stay. Two hundred sixty-three cases were identified as hysterectomy via minilaparotomy (n = 100) or laparoscopy (n = 163). The laparoscopy group demonstrated a significantly shorter mean (SD) length of stay (19 [14] hours vs 42 [20] hours; p < .001) and less blood loss (126 [140] mL vs 241 [238] mL; p < .001). The minilaparotomy group experienced a shorter procedure time (113 [47] minutes vs 197 [124] minutes; p < .001). There was no difference between the groups insofar as patient morbidity including intraoperative and postoperative complications, emergency visits, readmissions, or repeat operations. Conclusion: Compared with minilaparotomy, laparoscopic hysterectomy is associated with shorter length of hospital stay, longer operating time, and no increased patient morbidity. Published by Elsevier Inc. on behalf of AAGL. C1 [Perron-Burdick, Misa] San Francisco VA Med Ctr, Dept Gen Internal Med, San Francisco, CA 94112 USA. [Perron-Burdick, Misa] Univ Calif San Francisco, Sch Med, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA USA. [Calhoun, Amanda; Idowu, Dennis; Zaritsky, Eve] Kaiser Permanente No Calif, Dept Obstet & Gynecol, San Francisco, CA USA. [Pressman, Alice] Kaiser Permanente No Calif, Div Res, San Francisco, CA USA. [Pressman, Alice] Sutter Hlth Res, San Francisco, CA USA. RP Perron-Burdick, M (reprint author), San Francisco VA Med Ctr, Dept Gen Internal Med, 647 Edinburgh, San Francisco, CA 94112 USA. EM Perron-BurdickM@obgyn.ucsf.edu NR 19 TC 2 Z9 2 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1553-4650 EI 1553-4669 J9 J MINIM INVAS GYN JI J. Mimim. Invasive Gynecol. PD JUL-AUG PY 2014 VL 21 IS 4 BP 619 EP 623 DI 10.1016/j.jmig.2013.12.125 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AN6ED UT WOS:000340686800021 PM 24469276 ER PT J AU Fihn, SD Francis, J Clancy, C Nielson, C Nelson, K Rumsfeld, J Cullen, T Bates, J Graham, GL AF Fihn, Stephan D. Francis, Joseph Clancy, Carolyn Nielson, Christopher Nelson, Karin Rumsfeld, John Cullen, Theresa Bates, Jack Graham, Gail L. TI Insights From Advanced Analytics At The Veterans Health Administration SO HEALTH AFFAIRS LA English DT Article ID VA-CLINICAL-ASSESSMENT; CENTERED MEDICAL HOME; NATIONAL-SURVEY; INFORMATION-TECHNOLOGY; CART PROGRAM; SYSTEM; STRATEGIES; QUALITY; MODELS; RISK AB Health care has lagged behind other industries in its use of advanced analytics. The Veterans Health Administration (VHA) has three decades of experience collecting data about the veterans it serves nationwide through locally developed information systems that use a common electronic health record. In 2006 the VHA began to build its Corporate Data Warehouse, a repository for patient-level data aggregated from across the VHA's national health system. This article provides a high-level overview of the VHA's evolution toward "big data," defined as the rapid evolution of applying advanced tools and approaches to large, complex, and rapidly changing data sets. It illustrates how advanced analysis is already supporting the VHA's activities, which range from routine clinical care of individual patients-for example, monitoring medication administration and predicting risk of adverse outcomes-to evaluating a systemwide initiative to bring the principles of the patient-centered medical home to all veterans. The article also shares some of the challenges, concerns, insights, and responses that have emerged along the way, such as the need to smoothly integrate new functions into clinical workflow. While the VHA is unique in many ways, its experience may offer important insights for other health care systems nationwide as they venture into the realm of big data. C1 [Fihn, Stephan D.] Vet Hlth Adm VHA Off Analyt & Business Intelligen, Washington, DC 20422 USA. [Fihn, Stephan D.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Fihn, Stephan D.] Univ Washington, Sch Med, Dept Hlth Serv, Seattle, WA USA. [Fihn, Stephan D.] Univ Washington, Sch Publ Hlth, Dept Med, Seattle, WA 98195 USA. [Fihn, Stephan D.] Univ Washington, Sch Publ Hlth, Dept Hlth Serv, Seattle, WA 98195 USA. [Francis, Joseph] VHA Off Analyt & Business Intelligence, Washington, DC USA. [Clancy, Carolyn] VHA, Washington, DC USA. [Nielson, Christopher] VHA Off Analyt & Business Intelligence, Reno, NV USA. [Nelson, Karin] Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Dept, Seattle, WA USA. [Nelson, Karin] Univ Washington, Seattle, WA 98195 USA. [Rumsfeld, John] VHA, Denver, CO USA. [Rumsfeld, John] Univ Colorado, Denver, CO 80202 USA. [Cullen, Theresa] VHA Off Informat & Analyt, Silver Spring, MD USA. [Bates, Jack] Dept Vet Affairs, Off Informat & Technol, North Little Rock, AR USA. [Graham, Gail L.] VHA Off Informat & Analyt, Washington, DC USA. RP Fihn, SD (reprint author), Vet Hlth Adm VHA Off Analyt & Business Intelligen, Washington, DC 20422 USA. EM Stephan.Fihn@va.gov NR 27 TC 20 Z9 20 U1 5 U2 19 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD JUL PY 2014 VL 33 IS 7 BP 1203 EP 1211 DI 10.1377/hlthaff.2014.0054 PG 9 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA AN3FC UT WOS:000340469700014 PM 25006147 ER PT J AU Honda, JR Connick, E MaWhinney, S Chan, ED Flores, SC AF Honda, Jennifer R. Connick, Elizabeth MaWhinney, Samantha Chan, Edward D. Flores, Sonia C. TI Plasma LL-37 correlates with vitamin D and is reduced in human immunodeficiency virus-1 infected individuals not receiving antiretroviral therapy SO JOURNAL OF MEDICAL MICROBIOLOGY LA English DT Article ID D DEFICIENCY; 25-HYDROXYVITAMIN D; HIV; TUBERCULOSIS; ADULTS; WOMEN AB Low levels of the vitamin D-regulated antimicrobial peptide cathelicidin (LL-37) may negatively impact the immune status of human immunodeficiency virus-1 (HIV-1) infected individuals (HIV+). We compared plasma LL-37 levels in healthy controls (HIV) and HIV+ individuals on or off antiretroviral therapies (ARTs) (ART+ and ART-, respectively), and evaluated the relationship between vitamin D and LL-37 levels. In this cross-sectional study, levels of LL-37, 25-hydroxycholecalciferol [25(OH)D-3] and 1,25-dihydroxycholecalciferol [1,25(OH)(2)D-3] were measured from an initial cohort of 18 healthy controls and 10 HIV+/ART- individuals. Because this cohort lacked HIV +/ART + subjects, LL-37 was also quantified from a second cohort of 10 HIV+/ART- and 13 HIV+/ART+ individuals. LL-37 levels were significantly lower in the HIV+/ART- group compared to the healthy controls (P=0.01). A direct relationship was observed between LL-37 and both 25(OH)D-3 and 1,25(OH)(2)D-3. The level of 25(OH)D-3 was predictive of higher LL-37 (P=0.04) and for any given level of 25(OH)D-3, HIV +/ART- subjects averaged 20% lower LL-37 compared to the healthy controls (P=0.045). For any given level of 1,25(OH)(2)D-3, HIV+/ART- subjects averaged 25% lower LL-37 compared to the healthy controls (P=0.018), although 1,25(OH)(2)D-3 was not predictive of higher LL-37 (P=0.28). Finally, LL-37 levels were significantly lower in the HIV+/ART- group compared to the HIV+/ART+ group from the second cohort (P=0.045). Untreated HIV infection may contribute to lower LL-37 levels, independent of vitamin D levels. ART treatment may potentially mitigate this decrease in LL-37 levels. C1 [Honda, Jennifer R.; Flores, Sonia C.] Univ Colorado, Div Pulm Sci & Crit Care Med, Aurora, CO 80045 USA. [Connick, Elizabeth] Univ Colorado, Div Infect Dis, Aurora, CO 80045 USA. [MaWhinney, Samantha] Univ Colorado, Colorado Sch Publ Hlth Biostat & Informat, Aurora, CO 80045 USA. [Chan, Edward D.] Natl Jewish Hlth, Denver, CO 80220 USA. [Chan, Edward D.] Denver Vet Affairs Med Ctr, Denver, CO 80220 USA. RP Honda, JR (reprint author), Univ Colorado, Div Pulm Sci & Crit Care Med, Anschutz Med Campus, Aurora, CO 80045 USA. EM Jennifer.Honda@ucdenver.edu FU National Center for Advancing Translational Sciences at the National Institutes of Health Colorado (CTSI) [UL1 TR000154]; National Heart, Lung, and Blood Institute at the National Institutes of Health; Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado; Colorado HIV-1 Research Training Program through the NRSA NIH Infectious Disease Training Award [T32-AI007447-19]; Tim Gill Endowment for AIDS Research; Pulmonary and Critical Care Medicine Training Award [T32 HL 7085-83] FX We extend our appreciation to all study participants for their enthusiasm and support. This study was supported, in part, by the National Center for Advancing Translational Sciences at the National Institutes of Health Colorado (CTSI grant number UL1 TR000154), and through the National Heart, Lung, and Blood Institute at the National Institutes of Health and institutional funds (Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado) for Dr Sonia Flores. Jennifer R. Honda PhD is supported by the Colorado HIV-1 Research Training Program through the NRSA NIH Infectious Disease (T32-AI007447-19) Training Award, the Tim Gill Endowment for AIDS Research, and the Pulmonary and Critical Care Medicine (T32 HL 7085-83) Training Award. NR 25 TC 3 Z9 3 U1 0 U2 2 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-2615 EI 1473-5644 J9 J MED MICROBIOL JI J. Med. Microbiol. PD JUL PY 2014 VL 63 BP 997 EP 1003 DI 10.1099/jmm.0.070888-0 PN 7 PG 7 WC Microbiology SC Microbiology GA AN3UO UT WOS:000340514400013 PM 24821067 ER PT J AU Cooper, DC Trivedi, RB Nelson, KM Reiber, GE Eugenio, EC Beaver, KA Fan, VS AF Cooper, Denise C. Trivedi, Ranak B. Nelson, Karin M. Reiber, Gayle E. Eugenio, Evercita C. Beaver, Kristine A. Fan, Vincent S. TI Antidepressant Adherence and Risk of Coronary Artery Disease Hospitalizations in Older and Younger Adults with Depression SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE depression; antidepressants; adherence; coronary artery disease; hospitalizations ID AMERICAN-HEART-ASSOCIATION; MYOCARDIAL-INFARCTION; VETERANS; MEDICATION; CARE; MORTALITY; POPULATION; PREDICTORS; DISORDERS; ILLNESSES AB OBJECTIVES: To assess whether the relationship between antidepressant adherence and coronary artery disease (CAD) hospitalizations varied between older and younger adults with depression. DESIGN: Retrospective cohort study. SETTING: Department of Veterans Affairs outpatient clinics nationwide. PARTICIPANTS: Chronically depressed individuals (n = 50,261; aged 20-97) who had been prescribed an antidepressant were identified from records indicating an outpatient clinic visit for depression (index depression visit) during fiscal years 2009 and 2010. Individuals were considered chronically depressed if they had had prior depression visits and treatment for depression within the previous 4 months. The sample was age-stratified into younger (<65) and older (>= 65) groups. MEASUREMENTS: After the index depression visit, medication possession ratios were calculated from pharmacy refill data to determine whether participants had 80% or greater adherence to antidepressant refills during a 6-month treatment observation period. International Classification of Diseases, Ninth Revision, codes were used to derive CAD-related hospitalizations during the follow-up period. Mean follow-up was 24 months. Data were analyzed using Cox proportional hazard models. RESULTS: Older participants with 80% or greater antidepressant adherence had 26% lower risk of CAD hospitalizations (hazard ratio = 0.74, 95% confidence interval = 0.60-0.93). Antidepressant adherence was not significantly related to CAD hospitalizations in younger adults. CONCLUSION: Older adults with chronic depression with 80% or greater antidepressant adherence had significantly lower risk of CAD hospitalizations at follow-up than those with less than 80% adherence. These preliminary results suggest that older adults with depression may derive cardiovascular benefits from clinical efforts to increase antidepressant adherence. C1 [Cooper, Denise C.; Nelson, Karin M.; Reiber, Gayle E.; Eugenio, Evercita C.; Beaver, Kristine A.; Fan, Vincent S.] Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Ctr Innovat Vet Centered & Value Driven Care, Seattle, WA 98195 USA. [Cooper, Denise C.; Reiber, Gayle E.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Trivedi, Ranak B.] Stanford Univ, Vet Affairs Palo Alto Hlth Care Syst, Ctr Innovat Implementat, Palo Alto, CA 94304 USA. [Trivedi, Ranak B.] Stanford Univ, Dept Psychiat & Behav Sci, Palo Alto, CA 94304 USA. [Nelson, Karin M.; Fan, Vincent S.] Univ Washington, Dept Med, Seattle, WA USA. RP Cooper, DC (reprint author), VA Puget Sound Hlth Care Syst, HSR & D, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM cooped2@uw.edu FU VA Quality Enhancement Research Initiative Rapid Response Project [RRP 10-105] FX This study was supported by the VA Quality Enhancement Research Initiative Rapid Response Project (RRP 10-105) (VSF). The views expressed in this article are solely those of the authors and do not necessarily reflect the position or policy of the VA. NR 41 TC 9 Z9 9 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JUL PY 2014 VL 62 IS 7 BP 1238 EP 1245 DI 10.1111/jgs.12849 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AN3IX UT WOS:000340482000004 PM 24890000 ER PT J AU Lum, HD Mody, L Levy, CR Ginde, AA AF Lum, Hillary D. Mody, Lona Levy, Cari R. Ginde, Adit A. TI Pandemic Influenza Plans in Residential Care Facilities SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE residential facility; assisted living facility; geriatric; pandemic; influenza ID ASSISTED LIVING FACILITIES; INFECTION PREVENTION; NURSING-HOMES; PREPAREDNESS AB OBJECTIVES: To identify characteristics of residential care facilities (RCFs) associated with having a pandemic influenza plan. DESIGN: Nationally representative, cross-sectional survey. SETTING: RCFs in the United States. PARTICIPANTS: Participating facilities in the 2010 National Survey of RCFs (N = 2,294), representing 31,030 assisted living facilities and personal care homes. MEASUREMENTS: Facility-level characteristics associated with a pandemic influenza plan, including general organization descriptors, staffing, resident services, and immunization practices. RESULTS: Forty-five percent (95% confidence interval (CI) = 43-47%) had a pandemic plan, 14% (95% CI = 13-16%) had a plan in preparation, and 41% (95% CI = 38-43%) had no plan. In the multivariable model, organization characteristics, staffing, and immunization practices were independently associated with the presence of a pandemic preparedness plan. Organization characteristics were larger size (extra large, OR = 3.27, 95% CI = 1.96-5.46; large, OR = 2.60, 95% CI = 1.81-3.75; medium, OR = 1.66, 95% CI = 1.21-2.27 vs small), not-for-profit status (OR = 1.65, 95% CI = 1.31-2.09 vs for profit), and chain affiliation (OR = 1.65, 95% CI = 1.31-2.09 vs nonaffiliated). Staffing characteristics included number of registered nurse hours (<15 minutes, OR = 1.36, 95% CI = 1.07-1.74 vs no hours), any licensed practical nurse hours (OR = 1.47, 95% CI = 1.08-1.99 vs no hours), and at least 75 hours of required training for aides (OR = 1.34, 95% CI = 1.05-1.71 vs < 75 hours). RCFs with high staff influenza vaccination rates (81-100%, OR = 2.12, 95% CI = 1.273.53 vs 0% vaccinated) were also more likely to have a pandemic plan. CONCLUSION: A majority of RCFs lacked a pandemic influenza plan. These facilities were smaller, for-profit, non-chain-affiliated RCFs and had lower staff vaccination rates. These characteristics may help target facilities that need to develop plans to handle a pandemic, or other disasters. C1 [Lum, Hillary D.] Univ Colorado, Sch Med, Div Geriatr Med, Aurora, CO 80045 USA. [Lum, Hillary D.; Levy, Cari R.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Mody, Lona] Univ Michigan, Div Geriatr & Palliat Care Med, Ann Arbor, MI 48109 USA. [Mody, Lona] Vet Affairs Ann Arbor Healthcare Syst, Geriatr Res Educ & Clin Ctr, Ann Arbor, MI USA. [Levy, Cari R.] Univ Colorado, Sch Med, Div Hlth Care Policy & Res, Aurora, CO 80045 USA. [Ginde, Adit A.] Univ Colorado, Sch Med, Dept Emergency Med, Aurora, CO 80045 USA. RP Lum, HD (reprint author), Univ Colorado, Sch Med, Div Geriatr Med, 12631 E 17th Ave,B-179, Aurora, CO 80045 USA. EM hillary.lum@ucdenver.edu RI bebarta, vikhyat/K-3476-2015; Siry, Bonnie/D-7189-2017 FU National Institute on Aging [R01 AG032298, R01 AG41780, R18 HS019979, K23 AG040708]; University of Michigan Claude D. Pepper Older Americans Independence Center Grant [P30 AG024824] FX Dr. Mody was supported by National Institute on Aging Grants R01 AG032298, R01 AG41780, and R18 HS019979 and University of Michigan Claude D. Pepper Older Americans Independence Center Grant P30 AG024824. Dr. Ginde was supported by National Institute on Aging Grant K23 AG040708. NR 19 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JUL PY 2014 VL 62 IS 7 BP 1310 EP 1316 DI 10.1111/jgs.12879 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AN3IX UT WOS:000340482000013 PM 24852422 ER PT J AU Burke, RE Jones, CD Levy, C Ginde, AA AF Burke, Robert E. Jones, Christine D. Levy, Cari Ginde, Adit A. TI ELECTRONIC COMMUNICATION CAPABILITIES OF RESIDENTIAL CARE FACILITIES AT TIMES OF TRANSITION SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Letter ID SKILLED NURSING FACILITY; EMERGENCY-DEPARTMENT; NETWORK; HOMES C1 [Burke, Robert E.] Denver VA Med Ctr, Hosp Med Sect, Denver, CO 80220 USA. [Burke, Robert E.; Jones, Christine D.] Univ Colorado, Dept Med, Div Gen Internal Med, Denver, CO USA. [Levy, Cari] Univ Colorado, Div Hlth Care Policy & Res, Denver, CO 80202 USA. [Ginde, Adit A.] Univ Colorado, Dept Emergency Med, Denver, CO 80202 USA. RP Burke, RE (reprint author), Denver VA Med Ctr, Hosp Med Sect, Denver, CO 80220 USA. RI bebarta, vikhyat/K-3476-2015 FU NIA NIH HHS [K23 AG040708, K23AG040708] NR 9 TC 2 Z9 2 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JUL PY 2014 VL 62 IS 7 BP 1381 EP 1383 DI 10.1111/jgs.12905 PG 3 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AN3IX UT WOS:000340482000027 PM 25039508 ER PT J AU Li, H Hsu, HC Wu, Q Yang, P Li, J Luo, B Oukka, M Steele, CH Cua, DJ Grizzle, WE Mountz, JD AF Li, Hao Hsu, Hui-Chen Wu, Qi Yang, PingAr Li, Jun Luo, Bao Oukka, Mohamed Steele, Claude H., III Cua, Daniel J. Grizzle, William E. Mountz, John D. TI IL-23 promotes TCR-mediated negative selection of thymocytes through the upregulation of IL-23 receptor and ROR gamma t SO NATURE COMMUNICATIONS LA English DT Article ID ORPHAN NUCLEAR RECEPTOR; LYMPHOID ORGAN DEVELOPMENT; THYMIC EPITHELIAL-CELLS; BONE-MARROW CHIMERAS; AUTOIMMUNE INFLAMMATION; DENDRITIC CELLS; CUTTING EDGE; ASPERGILLUS-FUMIGATUS; MOLECULE EXPRESSION; CYTOKINE PRODUCTION AB Transient thymic involution is frequently found during inflammation, yet the mode of action of inflammatory cytokines is not well defined. Here we report that interleukin-23 (IL-23) production by the thymic dendritic cells (DCs) promotes apoptosis of the CD4(hi)CD8(hi) double-positive (DP) thymocytes. A deficiency in IL-23 signalling interferes with negative selection in the male D-b/H-Y T-cell receptor (TCR) transgenic mice. IL-23 plus TCR signalling results in significant upregulation of IL-23 receptor (IL-23R) expressed predominantly on CD4(hi)CD8(hi)CD3(+) alpha beta TCR+ DP thymocytes, and leads to ROR gamma t-dependent apoptosis. These results extend the action of IL-23 beyond its peripheral effects to a unique role in TCR-mediated negative selection including elimination of natural T regulatory cells in the thymus. C1 [Li, Hao; Hsu, Hui-Chen; Wu, Qi; Yang, PingAr; Li, Jun; Luo, Bao; Mountz, John D.] Univ Alabama Birmingham, Dept Med, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA. [Li, Hao] Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35294 USA. [Oukka, Mohamed] Univ Washington, Dept Pediat, Seattle, WA 98195 USA. [Steele, Claude H., III] Univ Alabama Birmingham, Dept Med, Div Pulm Allergy & Crit Care, Birmingham, AL 35294 USA. [Cua, Daniel J.] Merck Res Labs, Palo Alto, CA 94304 USA. [Grizzle, William E.] Univ Alabama Birmingham, Birmingham, AL 35294 USA. [Mountz, John D.] Birmingham VA Med Ctr, Birmingham, AL 35233 USA. RP Hsu, HC (reprint author), Univ Alabama Birmingham, Dept Med, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA. EM rheu078@uab.edu; jdmountz@uab.edu RI Li, Hao/N-7406-2015 OI Li, Hao/0000-0002-2171-8826 FU VA Merit Review Grant [1I01BX000600-01]; NIH/NIAID [1AI 071110, ARRA 3RO1AI71110-02S1, 1RO1 AI083705]; Rheumatology Research Foundation; Lupus Research Institute; Arthritis Foundation FX We thank Drs. J. Kolls (Louisiana State University) and Paul Robbins (University of Pittsburgh) for providing AdLacZ and AdIL-23; Dr N. Manley (University of Georgia) for technical support in the TEC sorting; and Dr F. Hunter for review of the manuscript. Flow cytometry and confocal imaging data acquisition were carried out at the UAB Comprehensive Flow Cytometry Core (P30 AR048311 and P30 AI027767) and UAB Analytic Imaging and Immunoreagent Core (P30 AR048311), respectively; BioQuant histomorphometry analysis was carried out at the UAB Center for Metabolic Bone Disease-Histomorphometry and Molecular Analysis Core Laboratory (P30 AR46031). This work is supported by grants from VA Merit Review Grant (1I01BX000600-01), NIH/NIAID (1AI 071110, ARRA 3RO1AI71110-02S1 and 1RO1 AI083705), Rheumatology Research Foundation, Lupus Research Institute, and Arthritis Foundation. NR 65 TC 2 Z9 2 U1 2 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD JUL PY 2014 VL 5 AR 4259 DI 10.1038/ncomms5259 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AN5FE UT WOS:000340615000003 PM 25001511 ER PT J AU Collins, SE Saxon, AJ Duncan, MH Smart, BF Merrill, JO Malone, DK Jackson, TR Clifasefi, SL Joesch, J Ries, RK AF Collins, Susan E. Saxon, Andrew J. Duncan, Mark H. Smart, Brian F. Merrill, Joseph O. Malone, Daniel K. Jackson, T. Ron Clifasefi, Seema L. Joesch, Jutta Ries, Richard K. TI Harm reduction with pharmacotherapy for homeless people with alcohol dependence: Protocol for a randomized controlled trial SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE Alcohol dependence; Extended-release naltrexone; Harm reduction; Homelessness; Alcohol treatment ID SUBSTANCE-ABUSE TREATMENT; HOUSING 1ST; ETHYL GLUCURONIDE; USE DISORDERS; BRIEF INTERVENTIONS; CLINICAL-RESEARCH; BEHAVIOR-THERAPY; VIDEO ASSESSMENT; PROBLEM DRINKING; MENTAL-ILLNESS AB Background: Interventions requiring abstinence from alcohol are neither preferred by nor shown to be highly effective with many homeless individuals with alcohol dependence. It is therefore important to develop lower-threshold, patient-centered interventions for this multimorbid and high-utilizing population. Harm-reduction counseling requires neither abstinence nor use reduction and pairs a compassionate style with patient-driven goal-setting. Extended-release naltrexone (XR-NTX), a monthly injectable formulation of an opioid receptor antagonist, reduces craving and may support achievement of harm-reduction goals. Together, harm-reduction counseling and XR-NTX may support alcohol harm reduction and quality-of-life improvement Aims: Study aims include testing: a) the relative efficacy of XR-NTX and harm-reduction counseling compared to a community-based, supportive-services-as-usual control, b) theory-based mediators of treatment effects, and c) treatment effects on publicly funded service costs. Methods: This RCT involves four arms: a) XR-NTX + harm-reduction counseling, b) placebo + harm-reduction counseling, c) harm-reduction counseling only, and d) community-based, supportive-services-as-usual control conditions. Participants are currently/formerly homeless, alcohol dependent individuals (N = 300). Outcomes include alcohol variables (i.e., craving, quantity/frequency, problems and biomarkers), health-related quality of life, and publicly funded service utilization and associated costs. Mediators include 10-point motivation rulers and the Penn Alcohol Craving Scale. XR-NTX and harm-reduction counseling are administered every 4 weeks over the 12-week treatment course. Follow-up assessments are conducted at weeks 24 and 36. Discussion: If found efficacious, XR-NTX and harm-reduction counseling will be well-positioned to support reductions in alcohol-related harm, decreases in costs associated with publicly funded service utilization, and increases in quality of life among homeless, alcohol-dependent individuals. (C) 2014 Elsevier Inc. All rights reserved. C1 [Collins, Susan E.; Duncan, Mark H.; Smart, Brian F.; Joesch, Jutta; Ries, Richard K.] Univ Washington, Harborview Med Ctr, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Saxon, Andrew J.] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Saxon, Andrew J.; Clifasefi, Seema L.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Merrill, Joseph O.] Univ Washington, Harborview Med Ctr, Dept Med, Seattle, WA 98195 USA. [Malone, Daniel K.] Downtown Emergency Serv Ctr, Seattle, WA 98104 USA. [Jackson, T. Ron] Evergreen Treatment Serv REACH, Seattle, WA 98134 USA. RP Collins, SE (reprint author), Univ Washington, Harborview Med Ctr, 325 Ninth Ave,Box 359911, Seattle, WA 98195 USA. EM collinss@uw.edu; andrew.saxon@va.gov; mhduncan@uw.edu; smartb@uw.edu; joem@uw.edu; dmalone@desc.org; ronjack@uw.edu; seemac@uw.edu; Jutta.Joesch@kingcounty.gov; rries@uw.edu FU National Institute on Alcohol Abuse and Alcoholism [1R01AA022309-01] FX This research is supported by a research program grant from the National Institute on Alcohol Abuse and Alcoholism (1R01AA022309-01; PI: Collins), and is registered with clinicaltrials.gov (NCT01932801). The active medication and placebo injections are being provided by Alkermes, Inc. Neither NIAAA nor Alkermes, Inc. had a role in the study design; collection, analysis and interpretation of data; writing of the manuscript; or decision to submit this manuscript for publication. NR 102 TC 0 Z9 0 U1 2 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 EI 1559-2030 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD JUL PY 2014 VL 38 IS 2 BP 221 EP 234 DI 10.1016/j.cct.2014.05.008 PG 14 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA AN0VF UT WOS:000340301400009 PM 24846619 ER PT J AU Van Houtven, CH Oddone, EZ Hastings, SN Hendrix, C Olsen, M Neelon, B Lindquist, J Weidenbacher, H Boles, J Chapman, J Weinberger, M AF Van Houtven, Courtney Harold Oddone, Eugene Z. Hastings, Susan N. Hendrix, Cristina Olsen, Maren Neelon, Brian Lindquist, Jennifer Weidenbacher, Hollis Boles, Jillian Chapman, Jennifer Weinberger, Morris TI Helping Invested Families Improve Veterans' Experiences Study (HI-FIVES): Study design and methodology SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE Informal care; Skills training; Randomized control trial; Days at home; Health care costs; Depressive symptoms ID RANDOMIZED CONTROLLED-TRIAL; COMMUNITY-BASED SERVICES; QUALITY-OF-LIFE; CARE; CAREGIVERS; DEMENTIA; HOME; INTERVENTION; PROGRAM; METAANALYSIS AB Within the Veterans Health Administration (VHA), the largest integrated health care system in the US, approximately 8.5 million Veteran patients receive informal care. Despite a need for training, half of VHA caregivers report that they have not received training that they deemed necessary. Rigorous study is needed to identify effective ways of providing caregivers with the skills they need. This paper describes the Helping Invested Families Improve Veterans' Experience Study (HI-FIVES), an ongoing randomized controlled trial that is evaluating a skills training program designed to support caregivers of cognitively and/or functionally impaired, community-dwelling Veterans who have been referred to receive additional formal home care services. This two-arm randomized controlled trial will enroll a total of 240 caregiver-patient dyads. For caregivers in the HI-FIVES group, weekly individual phone training occurs for 3 weeks, followed by 4 weekly group training sessions, and two additional individual phone training calls. Caregivers in usual care receive information about the VA Caregiver Support Services Program services, including a hotline number. The primary outcome is the number of days a Veteran patient spends at home in the 12 months following randomization (e.g. not in the emergency department, inpatient or nursing home setting). Secondary outcomes include patient VHA health care costs, patient and caregiver satisfaction with VHA health care, and caregiver depressive symptoms. Outcomes from HI-FIVES have the potential to improve our knowledge of how to maximize the ability to maintain patients safely at home for caregivers while preventing poor mental health outcomes among caregivers. (C) 2014 Published by Elsevier Inc. C1 [Van Houtven, Courtney Harold; Oddone, Eugene Z.; Hastings, Susan N.; Hendrix, Cristina; Olsen, Maren; Neelon, Brian; Lindquist, Jennifer; Weidenbacher, Hollis; Chapman, Jennifer; Weinberger, Morris] Durham VA Med Ctr, Ctr Hlth Serv Res Primary Care, US Dept Vet Affairs, Durham, NC 27705 USA. [Van Houtven, Courtney Harold; Oddone, Eugene Z.; Boles, Jillian] Duke Univ, Dept Med, Med Ctr, Div Gen Internal Med, Durham, NC 27710 USA. [Hastings, Susan N.] Duke Univ, Dept Med, Med Ctr, Div Geriatr, Durham, NC 27710 USA. [Hendrix, Cristina] Duke Univ, Med Ctr, Sch Nursing, Durham, NC 27710 USA. [Olsen, Maren; Neelon, Brian] Duke Univ, Med Ctr, Dept Biostat, Durham, NC 27710 USA. [Weinberger, Morris] Univ N Carolina, Dept Hlth Policy & Management, Gillings Sch Global Publ Hlth, Chapel Hill, NC 27599 USA. [Hastings, Susan N.] Geriatr Res Educ & Clin Ctr, Durham, NC 27705 USA. [Hastings, Susan N.; Hendrix, Cristina] Ctr Study Aging & Human Dev, Durham, NC 27710 USA. RP Van Houtven, CH (reprint author), Durham VA Med Ctr, Ctr Hlth Serv Res Primary Care, 508 Fulton St, Durham, NC 27705 USA. EM courtney.vanhoutven@duke.edu; eugene.oddone@dm.duke.edu; susan.hastings@dm.duke.edu; cristina.hendrix@dm.duke.edu; maren.olsen@dm.duke.edu; brian.neelon@duke.edu; jennifer.lindquist@va.gov; hollis.weidenbacher@va.gov; jillian.boles@dm.duke.edu; jennifer.chapman2@va.gov; mweinber@email.unc.edu FU U.S. Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development Service [IIR 11-345]; U.S. Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Research Career Scientist Program [RCS 91-408] FX This project is supported by, the U.S. Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development Service (IIR 11-345). Dr. Weinberger is supported by the the U.S. Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Research Career Scientist Program (RCS 91-408). We thank the members of the study's advisory board, for excellent input and expertise on the study: Peggy Becker, Thomas Edes, Margaret Kabat, Christy Knight, Jennifer Martindale-Adams, Linda Nichols, Kenneth Shay, Scott Trudeau, and Laura Wray. NR 34 TC 0 Z9 0 U1 2 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 EI 1559-2030 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD JUL PY 2014 VL 38 IS 2 BP 260 EP 269 DI 10.1016/j.cct.2014.05.003 PG 10 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA AN0VF UT WOS:000340301400013 PM 24837544 ER PT J AU Nelson, K Drain, N Robinson, J Kapp, J Hebert, P Taylor, L Silverman, J Kiefer, M Lessler, D Krieger, J AF Nelson, Karin Drain, Nathan Robinson, June Kapp, Janet Hebert, Paul Taylor, Leslie Silverman, Julie Kiefer, Meghan Lessler, Dan Krieger, James TI Peer Support for Achieving Independence in Diabetes (Peer-AID): Design, methods and baseline characteristics of a randomized controlled trial of community health worker assisted diabetes self-management support SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE Diabetes self-management; Community health workers ID AFRICAN-AMERICAN WOMEN; QUALITY-OF-LIFE; MEDICATION ADHERENCE; PREDICTIVE-VALIDITY; PHYSICAL-ACTIVITY; CARE UTILIZATION; GLYCEMIC CONTROL; LOW-INCOME; INTERVENTION; ADULTS AB Background & objectives: Community health workers (CHWs) may be an important mechanism to provide diabetes self-management to disadvantaged populations. We describe the design and baseline results of a trial evaluating a home-based CHW intervention. Methods & research design: Peer Support for Achieving Independence in Diabetes (Peer-AID) is a randomized, controlled trial evaluating a home-based CHW-delivered diabetes self-management intervention versus usual care. The study recruited participants from 3 health systems. Change in Al c measured at 12 months is the primary outcome. Changes in blood pressure, lipids, health care utilization, health-related quality of life, self-efficacy and diabetes self-management behaviors at 12 months are secondary outcomes. Results: A total of 1438 patients were identified by a medical record review as potentially eligible, 445 patients were screened by telephone for eligibility and 287 were randomized. Groups were comparable at baseline on socio-demographic and clinical characteristics. All participants were low-income and were from diverse racial and ethnic backgrounds. The mean Al c was 8.9%, mean BMI was above the obese range, and non-adherence to diabetes medications was high. The cohort had high rates of co-morbid disease and low self-reported health status. Although one-third reported no health insurance, the mean number of visits to a physician in the past year was 5.7. Trial results are pending. Conclusions: Peer-AID recruited and enrolled a diverse group of low income participants with poorly controlled type 2 diabetes and delivered a home-based diabetes self-management program. If effective, replication of the Peer-AID intervention in community based settings could contribute to improved control of diabetes in vulnerable populations. Published by Elsevier Inc. C1 [Nelson, Karin; Hebert, Paul; Taylor, Leslie; Silverman, Julie; Kiefer, Meghan] VA Puget Sound Healthcare Syst, Northwest HSR&D Ctr Excellence, Seattle, WA USA. [Nelson, Karin; Silverman, Julie; Kiefer, Meghan] VA Puget Sound Healthcare Syst, Gen Internal Med Serv, Seattle, WA USA. [Nelson, Karin; Hebert, Paul; Silverman, Julie; Kiefer, Meghan; Lessler, Dan; Krieger, James] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Nelson, Karin; Krieger, James] Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA. [Drain, Nathan; Robinson, June; Kapp, Janet; Krieger, James] Publ Hlth Seattle & King Cty, Seattle, WA USA. RP Nelson, K (reprint author), VA Puget Sound Healthcare Syst HSR&D, 1100 Olive Way,Suite 1400, Seattle, WA 98108 USA. EM Karin.Nelson@va.gov FU National Institutes of Health. National Institute of Diabetes and Digestive and Kidney Diseases [5R18DK088072]; Veterans Health Administration (VHA) Diabetes Quality Enhancement Research Initiative [QUERI QLP 92-007] FX National Institutes of Health. National Institute of Diabetes and Digestive and Kidney Diseases. Grant Number 5R18DK088072. Supplemental funding was provided by the Veterans Health Administration (VHA) Diabetes Quality Enhancement Research Initiative (QUERI QLP 92-007) to support Veteran recruitment efforts. NR 56 TC 6 Z9 6 U1 5 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 EI 1559-2030 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD JUL PY 2014 VL 38 IS 2 BP 361 EP 369 DI 10.1016/j.cct.2014.06.011 PG 9 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA AN0VF UT WOS:000340301400026 PM 24956324 ER PT J AU Dishion, TJ Kim, H Stormshak, EA O'Neill, M AF Dishion, Thomas J. Kim, Hanjoe Stormshak, Elizabeth A. O'Neill, Maya TI A Brief Measure of Peer Affiliation and Social Acceptance (PASA): Validity in an Ethnically Diverse Sample of Early Adolescents SO JOURNAL OF CLINICAL CHILD AND ADOLESCENT PSYCHOLOGY LA English DT Article ID CONFIRMATORY FACTOR-ANALYSES; MULTITRAIT-MULTIMETHOD DATA; FAMILY CHECK-UP; PROBLEM BEHAVIOR; ANTECEDENTS; CHILDHOOD; CHILDREN; SCHOOL; TESTS; BOYS AB The purpose of this study was to conduct a multiagent-multimethod analysis of the validity of a brief measure of deviant peer affiliations and social acceptance (PASA) in young adolescents. Peer relationships are critical to child and adolescent social and emotional development, but currently available measures are tedious and time consuming. The PASA consists of a youth, parent, and teacher report that can be collected longitudinally to study development and intervention effectiveness. This longitudinal study included 998 middle school students and their families. We collected the PASA and peer sociometrics data in Grade 7 and a multiagent-multimethod construct of deviant peer clustering in Grade 8. Confirmatory factor analyses of the multiagent-multimethod data revealed that the constructs of deviant peer affiliations and social acceptance and rejection were distinguishable as unique but correlated constructs within the PASA. Convergent, discriminant, concurrent, and predictive validity of the PASA was satisfactory, although the acceptance and rejection constructs were highly correlated and showed similar patterns of concurrent validity. Factor invariance was established for mother reports and for father reports. Results suggest that the PASA is a valid and reliable measure of peer affiliation and of social acceptance among peers during the middle school years and provides a comprehensive yet brief assessment of peer affiliations and social acceptance. C1 [Dishion, Thomas J.; Kim, Hanjoe] Arizona State Univ, Dept Psychol, Tempe, AZ 85287 USA. [Dishion, Thomas J.; Stormshak, Elizabeth A.; O'Neill, Maya] Univ Oregon, Child & Family Ctr, Eugene, OR 97403 USA. [O'Neill, Maya] Portland VA Med Ctr, Portland, OR USA. RP Dishion, TJ (reprint author), Arizona State Univ, Dept Psychol, Tempe, AZ 85287 USA. EM dishion@asu.edu FU NIDA NIH HHS [DA07031, DA016110, R01 DA007031, R01 DA016110, R37 DA007031]; NIMH NIH HHS [T32 MH020012, T32MH20012] NR 55 TC 5 Z9 5 U1 19 U2 33 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1537-4416 EI 1537-4424 J9 J CLIN CHILD ADOLESC JI J. Clin. Child Adolesc. Psychol. PD JUL-AUG PY 2014 VL 43 IS 4 BP 601 EP 612 DI 10.1080/15374416.2013.876641 PG 12 WC Psychology, Clinical; Psychology, Developmental SC Psychology GA AM8JM UT WOS:000340120200006 PM 24611623 ER PT J AU Pedersen, ER Myers, US Browne, KC Norman, SB AF Pedersen, Eric R. Myers, Ursula S. Browne, Kendall C. Norman, Sonya B. TI The Role of Alcohol Expectancies in Drinking Behavior among Women with Alcohol Use Disorder and Comorbid Posttraumatic Stress Disorder SO JOURNAL OF PSYCHOACTIVE DRUGS LA English DT Article DE alcohol; expectancies; intimate partner violence; PTSD ID ADDICTION SEVERITY INDEX; SUBSTANCE USE DISORDERS; COLLEGE-STUDENTS; PARTNER VIOLENCE; PTSD CHECKLIST; TRAUMA; SYMPTOMS; QUESTIONNAIRE; ASSOCIATIONS; CHALLENGE AB Understanding how alcohol expectancies relate to alcohol use among individuals with concurrent alcohol use disorder (AUD) and Posttraumatic Stress Disorder (PTSD) is important to understanding and treating this comorbidity. This study examined the role of positive and negative alcohol expectancies and PTSD symptoms in drinking behavior in a comorbid female sample. Participants were women (n = 33; 56% Caucasian) seeking AUD and PTSD treatment in an outpatient community co-occurring disorders program. Hypotheses related to drinking days and alcohol problems outcomes were evaluated using negative binomial hierarchical regression. PTSD symptoms were associated with fewer reported days of alcohol-related problems. Negative expectancies related to negative changes in social behavior associated with drinking days and cognitive and motor impairment associated with problems. Both the general positive expectancies score and specific global positive change subscale were uniquely associated with drinking and alcohol-related problems days after controlling for PTSD symptom severity and negative expectancies scores. Results suggest that both negative and positive expectancies about alcohol's effects are important correlates of drinking behavior among women with AUD and PTSD, with positive expectancies playing a potentially more salient role on use and consequences than symptom severity and negative expectancies. C1 [Pedersen, Eric R.] RAND Corp, Santa Monica, CA USA. [Myers, Ursula S.] SDSU UCSD Joint Doctoral Program Clin Psychol, San Diego, CA USA. [Browne, Kendall C.] VA Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA USA. [Browne, Kendall C.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Norman, Sonya B.] Natl Ctr PTSD, PTSD Consultat Program, White River Jct, VT USA. [Norman, Sonya B.] VA Ctr Excellence Stress & Mental Hlth, San Diego, CA USA. [Norman, Sonya B.] UCSD Sch Med, San Diego, CA USA. RP Norman, SB (reprint author), VA San Diego Healthcare Syst, 3350 La Jolla Village Dr,MC116B, La Jolla, CA 92161 USA. EM snorman@ucsd.edu FU NIAAA NIH HHS [K23 AA015707] NR 53 TC 2 Z9 2 U1 4 U2 13 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0279-1072 EI 2159-9777 J9 J PSYCHOACTIVE DRUGS JI J. Psychoact. Drugs PD JUL-AUG PY 2014 VL 46 IS 3 BP 178 EP 187 DI 10.1080/02791072.2014.917750 PG 10 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA AM8JW UT WOS:000340121400002 PM 25052876 ER PT J AU Leentjens, AFG Dujardin, K Pontone, GM Starkstein, SE Weintraub, D Martinez-Martin, P AF Leentjens, Albert F. G. Dujardin, Kathy Pontone, Gregory M. Starkstein, Sergio E. Weintraub, Daniel Martinez-Martin, Pablo TI The Parkinson Anxiety Scale (PAS): Development and Validation of a New Anxiety Scale SO MOVEMENT DISORDERS LA English DT Article DE Parkinson's disease; anxiety; rating scale; depression; 'non-motor' symptoms ID HEALTH-STATUS; RATING-SCALES; DISEASE; DEPRESSION; QUALITY; CRITERIA; RELIABILITY; PREVALENCE; DISORDERS; INVENTORY AB Existing anxiety rating scales have limited construct validity in patients with Parkinson's disease (PD). This study was undertaken to develop and validate a new anxiety rating scale, the Parkinson Anxiety Scale (PAS), that would overcome the limitations of existing scales. The general structure of the PAS was based on the outcome of a Delphi procedure. Item selection was based on a canonical correlation analysis and a Rasch analysis of items of the Hamilton Anxiety Rating Scale (HARS) and the Beck Anxiety Inventory (BAI) from a previously published study. Validation was done in a cross-sectional international multicenter study involving 362 patients with idiopathic PD. Patients underwent a single screening session in which the PAS was administered, along with the Hamilton Depression Rating Scale, the HARS, and the BAI. The Mini International Neuropsychiatric Interview was administered to establish Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnoses of anxiety and depressive disorders. The PAS is a 12-item observer or patient-rated scale with three subscales, for persistent, episodic anxiety and avoidance behavior. Properties for acceptability and reliability met predetermined criteria. The convergent and known groups validity was good. The scale has a satisfactory factorial structure. The area under the receiver operating characteristics curve and Youden index of the PAS are higher than that of existing anxiety rating scales. The PAS is a reliable and valid anxiety measure for use in PD patients. It is easy and brief to administer, and has better clinimetric properties than existing anxiety rating scales. The sensitivity to change of the PAS remains to be assessed. (C) 2014 International Parkinson and Movement Disorder Society C1 [Leentjens, Albert F. G.] Maastricht Univ, Med Ctr, Dept Psychiat, NL-6202 AZ Maastricht, Netherlands. [Dujardin, Kathy] Univ Lille, Neurol & Movement Disorders Unit, Med Ctr, Lille, France. [Pontone, Gregory M.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [Starkstein, Sergio E.] Univ Western Australia, Sch Psychiat, Fremantle, WA, Australia. [Starkstein, Sergio E.] Fremantle Hosp, Fremantle, WA, Australia. [Weintraub, Daniel] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Univ Penn, Dept Neurol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Philadelphia Vet Affairs Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA USA. [Martinez-Martin, Pablo] Alzheimer Ctr Reina Sofia Fdn, Alzheimer Dis Res Unit, Madrid, Spain. [Martinez-Martin, Pablo] Alzheimer Ctr Reina Sofia Fdn, CIBERNED, CIEN Fdn, Carlos Inst Hlth 3, Madrid, Spain. RP Leentjens, AFG (reprint author), Maastricht Univ, Med Ctr, Dept Psychiat, POB 5800, NL-6202 AZ Maastricht, Netherlands. EM a.leentjens@np.unimaas.nl FU Michael J. Fox Foundation; Stichting International Parkinson Fonds; France Parkinson; NIH; National Institute on Aging; Acadia Pharmaceuticals; National Health Medical and Research Centre (Australia); Novartis Pharmaceuticals; Department of Veterans Affairs; Alzheimer's Disease Cooperative Study; Parkinson UK; Spanish Official Agency FIS; Spanish Official Agency IMSERSO FX A.F.G.L. has received research grants from the Michael J. Fox Foundation and the Stichting International Parkinson Fonds. K.D. received research support from the Michael J. Fox Foundation and from France Parkinson. G.P. is funded by grants from the NIH and National Institute on Aging, Acadia Pharmaceuticals, and the Michael J. Fox Foundation. S.E.S. is funded by grants from the National Health Medical and Research Centre (Australia) and the Michael J. Fox Foundation. D.W. has received funding from the Michael J. Fox Foundation, NIH, Novartis Pharmaceuticals, Department of Veterans Affairs, and Alzheimer's Disease Cooperative Study. P.M.-M. received grants from the Michael J. Fox Foundation, Parkinson UK, and the Spanish Official Agencies FIS and IMSERSO. NR 33 TC 17 Z9 17 U1 4 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 EI 1531-8257 J9 MOVEMENT DISORD JI Mov. Disord. PD JUL PY 2014 VL 29 IS 8 BP 1035 EP 1043 DI 10.1002/mds.25919 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA AM8AA UT WOS:000340089300013 PM 24862344 ER PT J AU Darsie, B Shlipak, MG Sarnak, MJ Katz, R Fitzpatrick, AL Odden, MC AF Darsie, Brendan Shlipak, Michael G. Sarnak, Mark J. Katz, Ronit Fitzpatrick, Annette L. Odden, Michelle C. TI Kidney Function and Cognitive Health in Older Adults: The Cardiovascular Health Study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE aging; chronic kidney disease; cognitive function; congestive heart failure; myocardial infarction; prospective study; stroke; successful aging ID SERUM CYSTATIN-C; BODY-COMPOSITION; ELDERLY PERSONS; DISEASE; DECLINE; IMPAIRMENT; CREATININE; RISK; DEMENTIA; PEOPLE AB Recent evidence has demonstrated the importance of kidney function in healthy aging. We examined the association between kidney function and change in cognitive function in 3,907 participants in the Cardiovascular Health Study who were recruited from 4 US communities and studied from 1992 to 1999. Kidney function was measured by cystatin C-based estimated glomerular filtration rate (eGFR(cys)). Cognitive function was assessed using the Modified Mini-Mental State Examination and the Digit Symbol Substitution Test, which were administered up to 7 times during annual visits. There was an association between eGFR(cys) and change in cognitive function after adjustment for confounders; persons with an eGFR(cys) of less than 60 mL/minute/1.73 m(2) had a 0.64 (95% confidence interval: 0.51, 0.77) points/year faster decline in Modified Mini-Mental State Examination score and a 0.42 (95% confidence interval: 0.28, 0.56) points/year faster decline in Digit Symbol Substitution Test score compared with persons with an eGFR(cys) of 90 or more mL/minute/1.73 m(2). Additional adjustment for intermediate cardiovascular events modestly affected these associations. Participants with an eGFR(cys) of less than 60 mL/minute/1.73 m(2) had fewer cognitive impairment-free life-years on average compared with those with eGFR(cys) of 90 or more mL/minute/1.73 m(2), independent of confounders and mediating cardiovascular events (mean difference = -0.44, 95% confidence interval: -0.62, -0.26). Older adults with lower kidney function are at higher risk of worsening cognitive function. C1 [Darsie, Brendan; Odden, Michelle C.] Oregon State Univ, Sch Biol & Populat Hlth Sci, Corvallis, OR 97331 USA. [Shlipak, Michael G.] San Francisco VA Med Ctr, Div Gen Internal Med, San Francisco, CA USA. [Shlipak, Michael G.] Univ Calif San Francisco, Dept Med, Div Gen Internal Med, San Francisco, CA USA. [Shlipak, Michael G.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Sarnak, Mark J.] Tufts Med Ctr, Dept Med, Div Nephrol, Boston, MA USA. [Katz, Ronit] Univ Washington, Kidney Res Grp, Seattle, WA 98195 USA. [Fitzpatrick, Annette L.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Fitzpatrick, Annette L.] Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA. RP Darsie, B (reprint author), Oregon State Univ, 141B Milam Hall, Corvallis, OR 97331 USA. EM brendan.darsie@gmail.com FU National Heart, Lung, and Blood Institute [HHSN268201200036C, HHSN 268200800007C, N01HC55222, N01HC85079, N01HC 85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, HL080295]; National Institute on Aging [R01AG023629, R01AG027002, K01AG039387]; American Heart Association Western States Affiliate [11CRP7210088] FX This research was supported by the National Heart, Lung, and Blood Institute (contracts HHSN268201200036C, HHSN 268200800007C, N01HC55222, N01HC85079, N01HC 85080, N01HC85081, N01HC85082, N01HC85083, and N01HC85086, and grant HL080295), with additional contribution from the National Institute of Neurological Disorders and Stroke. Additional support was provided by the National Institute on Aging (grants R01AG023629 and R01AG027002). A full list of principal Cardiovascular Health Study investigators and institutions can be found at http://www.chs-nhlbi.org/PI.htm. M.C.O. is supported by the American Heart Association Western States Affiliate (grant 11CRP7210088) and the National Institute on Aging (grant K01AG039387). NR 36 TC 12 Z9 13 U1 1 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUL 1 PY 2014 VL 180 IS 1 BP 68 EP 75 DI 10.1093/aje/kwu102 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AM4FI UT WOS:000339808200010 PM 24844846 ER PT J AU Rosell, DR Futterman, SE McMaster, A Siever, LJ AF Rosell, Daniel R. Futterman, Shira E. McMaster, Antonia Siever, Larry J. TI Schizotypal Personality Disorder: A Current Review SO CURRENT PSYCHIATRY REPORTS LA English DT Review DE Schizotypal; Schizophrenia; Personality disorder; Frontal lobe; Temporal lobe; Dopamine; Working memory; Cognition; Social cognition; Affect processing; Magical thinking; Perceptual aberration; Suspiciousness; Paranoia; Social anhedonia ID INDUCED DOPAMINE RELEASE; HIGH-ACTIVITY ALLELE; FOLLOW-UP MRI; CAUDATE-NUCLEUS; WORKING-MEMORY; SCHIZOPHRENIA SPECTRUM; EMPATHIC ACCURACY; LARGE POPULATION; CINGULATE GYRUS; NAIVE PATIENTS AB The study of schizotypal personality disorder (SPD) is important clinically, as it is understudied, challenging to treat, often under-recognized or misdiagnosed, and associated with significant functional impairment. SPD also represents an intermediate schizophrenia-spectrum phenotype, and therefore, can provide a better understanding of the genetics, pathogenesis, and treatment of related psychotic illnesses. In this review we discuss recent findings of SPD related to epidemiology and functional impairment, heritability and genetics, working memory and cognitive impairments, social-affective disturbances, and neurobiology. Additionally, we examine the challenges associated with treating patients with SPD, as well as clinical recommendations. Finally, we address future directions and areas in need of further exploration. C1 [Rosell, Daniel R.; Futterman, Shira E.; McMaster, Antonia; Siever, Larry J.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Rosell, Daniel R.; Futterman, Shira E.; McMaster, Antonia; Siever, Larry J.] James J Peters Vet Affairs Med Ctr, Bronx, NY 10468 USA. RP Siever, LJ (reprint author), James J Peters Vet Affairs Med Ctr, 130 West Kingsbridge Rd,Room 6A-44, Bronx, NY 10468 USA. EM larry.siever@va.gov FU Department of Veterans Affairs; National Institute of Mental Health; Mental Illness Research, Education and Clinical Centers; Mount Sinai FX Daniel R. Rosell has received support for travel and payment from writing or reviewing manuscript from the Department of Veterans Affairs.; Shira E. Futterman has received support from a grant from the National Institute of Mental Health awarded to LJS.; Antonia McMaster has received a support from a grant from the National Institute of Mental Health awarded to LJS.; Larry J. Siever has received grants and travel support from the National Institute of Mental Health and the Department of Veterans Affairs. He also received travel support from the Mental Illness Research, Education and Clinical Centers. Dr. Siever also has receive payment for writing or reviewing manuscripts from the Department of Veterans Affairs, the Mental Illness Research, Education and Clinical Centers, and Mount Sinai. NR 82 TC 14 Z9 14 U1 6 U2 38 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1523-3812 EI 1535-1645 J9 CURR PSYCHIAT REP JI Curr. Psychiatry Rep. PD JUL PY 2014 VL 16 IS 7 AR 452 DI 10.1007/s11920-014-0452-1 PG 12 WC Psychiatry SC Psychiatry GA AM4CZ UT WOS:000339801400001 PM 24828284 ER PT J AU Lehavot, K Simpson, TL AF Lehavot, Keren Simpson, Tracy L. TI Trauma, Posttraumatic Stress Disorder, and Depression Among Sexual Minority and Heterosexual Women Veterans SO JOURNAL OF COUNSELING PSYCHOLOGY LA English DT Article DE women veterans; lesbian and bisexual; PTSD; depression; trauma ID MENTAL-HEALTH; FEMALE VETERANS; BISEXUAL ADULTS; CIVILIAN WOMEN; LIFE-SPAN; GULF-WAR; GAY MEN; MILITARY; VICTIMIZATION; ABUSE AB This study examined the impact of various traumas across the life span on screening positive for current posttraumatic stress disorder (PTSD) and depression among heterosexual and sexual minority women veterans. Women veterans were recruited over the Internet (N = 706, 37% lesbian or bisexual) to participate in an anonymous, online survey. We assessed childhood trauma; adult sexual assault and adult physical victimization before, during, and after the military; combat exposure; perceived sexist discrimination during military service; sexual minority military stressors; past-year sexist events; and whether participants screened positive for PTSD or depression. Binary logistic regressions were used to generate odds ratios and 95% confidence intervals for PTSD and depression, stratified by sexual orientation and controlling for demographic characteristics. Lesbian and bisexual women reported higher rates of trauma across the life span, although in some instances (e. g., sexual assault during and after military service, combat exposure), they did not differ from their heterosexual counterparts. Childhood trauma and traumas that occurred during military service added the most variance to both PTSD and depression models. Sexual assault during military service appeared to be especially harmful with respect to screening positive for PTSD for both sexual orientation groups. Results revealed a number of other predictors of mental health status for women veterans, some of which differed by sexual orientation. Findings indicate a significant burden of interpersonal trauma for both heterosexual and lesbian/bisexual women veterans and provide information on the distinct association of various traumas with current PTSD and depression by sexual orientation. C1 [Lehavot, Keren; Simpson, Tracy L.] VA Puget Sound Hlth Care Syst, MIRECC, Seattle, WA USA. [Lehavot, Keren; Simpson, Tracy L.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Simpson, Tracy L.] VA Puget Sound Hlth Care Syst, CESATE, Seattle, WA USA. RP Lehavot, K (reprint author), 1660 South Columbian Way S-116 POC, Seattle, WA 98108 USA. EM klehavot@uw.edu NR 65 TC 9 Z9 9 U1 4 U2 15 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-0167 EI 1939-2168 J9 J COUNS PSYCHOL JI J. Couns. Psychol. PD JUL PY 2014 VL 61 IS 3 BP 392 EP 403 DI 10.1037/cou0000019 PG 12 WC Psychology, Educational; Psychology, Applied SC Psychology GA AM2ER UT WOS:000339662800009 PM 25019543 ER PT J AU Koo, KH Nguyen, HV Gilmore, AK Blayney, JA Kaysen, DL AF Koo, Kelly H. Nguyen, Hong V. Gilmore, Amanda K. Blayney, Jessica A. Kaysen, Debra L. TI Posttraumatic Cognitions, Somatization, and PTSD Severity Among Asian American and White College Women With Sexual Trauma Histories SO PSYCHOLOGICAL TRAUMA-THEORY RESEARCH PRACTICE AND POLICY LA English DT Article DE race; Asian Americans; posttraumatic cognitions; somatization; PTSD ID STRESS-DISORDER; PROCESSING THERAPY; PROLONGED EXPOSURE; EXPERIENCES SURVEY; PROTECTIVE FACTORS; ASSAULT SURVIVORS; INVENTORY PTCI; FEMALE VICTIMS; STUDENTS; HEALTH AB The need for trauma research with monoracial groups such as Asian Americans (AAs) has recently been emphasized to better understand trauma experiences and inform interventions across populations. Given AA cultural contexts, posttraumatic cognitions and somatization may be key in understanding trauma experiences for this group. AA and White American (WA) trauma-exposed college women completed a survey on sexual trauma history, posttraumatic cognitions, somatic symptoms, and PTSD severity. For the overall sample, higher negative cognitions were associated with higher somatization. Asian race was associated with higher negative cognitions, which then predicted higher PTSD. Unexpectedly, WAs more strongly endorsed somatization than AAs. These findings indicate that posttraumatic cognitions may be helpful in understanding relationships between somatization and PTSD severity among those of Asian backgrounds and that the relationship between somatization and PTSD symptoms is culturally complex. C1 [Koo, Kelly H.; Nguyen, Hong V.; Gilmore, Amanda K.] Univ Washington, Dept Psychol, Seattle, WA 98195 USA. [Blayney, Jessica A.; Kaysen, Debra L.] Univ Washington, Seattle, WA 98195 USA. RP Koo, KH (reprint author), San Francisco VA Med Ctr, 4150 Clement St, San Francisco, CA 94121 USA. EM kelly.koo@va.gov FU NIAAA NIH HHS [R21 AA016211] NR 54 TC 4 Z9 4 U1 2 U2 12 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1942-9681 EI 1942-969X J9 PSYCHOL TRAUMA-US JI Psychol. Trauma PD JUL PY 2014 VL 6 IS 4 BP 337 EP 344 DI 10.1037/a0033830 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AM2FD UT WOS:000339664100006 PM 25419439 ER PT J AU McGeary, CA Garcia, HA McGeary, DD Finley, EP Peterson, AL AF McGeary, Cindy A. Garcia, Hector A. McGeary, Donald D. Finley, Erin P. Peterson, Alan L. TI Burnout and Coping: Veterans Health Administration Posttraumatic Stress Disorder Mental Health Providers SO PSYCHOLOGICAL TRAUMA-THEORY RESEARCH PRACTICE AND POLICY LA English DT Article DE burnout; caffeine use; absenteeism; health behaviors; Veterans Health Administration ID OCCUPATIONAL STRESS; GENERAL SURVEY; ABSENTEEISM; EMPLOYEES; NURSES; IRAQ; SATISFACTION; AFGHANISTAN; PERFORMANCE; INVENTORY AB Mental health providers employed specifically by the Veterans Health Administration to treat posttraumatic stress disorder (PTSD) may be at increased risk for burnout due to both organizational and patient care stressors. Usage of caffeine, alcohol, and tobacco products may increase as a means to cope with burnout and stress. This cross-sectional study measured concurrent changes in burnout levels and caffeine, alcohol, and tobacco use as a means to cope with work stressors among a population of Veterans Health Administration mental health providers working within a PTSD specialty clinic. This study consisted of 138 participants, and the sample was mostly female (67%), Caucasian (non-Hispanic; 81%), and married (70%), with a mean age of 44.3 years (SD = 11.2). Participants completed an electronic survey that assessed demographics, absenteeism, and coping behaviors, as well as burnout as measured through the Maslach Burnout Inventory-General Survey (Maslach, Jackson, & Leiter, 1996). The study results revealed a minor predictive relationship between some dimensions of burnout and the use of some negative health behaviors (drinking and caffeine use) to cope with work stress. Burnout scores (i. e., exhaustion) significantly predicted concurrent missed time from work for both physical and emotional health reasons (sick days/mental health days), but tobacco and caffeine use contributed little, and alcohol was not related to burnout at all. In the future, it would be useful to obtain information regarding in-depth health behaviors that include baseline data as well as prospective systematic fluctuations in these behaviors due to work stressors. C1 [McGeary, Cindy A.; McGeary, Donald D.; Peterson, Alan L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychol, San Antonio, TX 78229 USA. [Garcia, Hector A.] South Texas Vet Hlth Care Syst, PTSD Clin Team, San Antonio, TX USA. [Garcia, Hector A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Finley, Erin P.] South Texas Vet Hlth Care Syst, Res Serv, San Antonio, TX USA. [Finley, Erin P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. RP McGeary, CA (reprint author), STRONG STAR, 7550 IH-10 West,Suite 1325, San Antonio, TX 78229 USA. EM mcgearyc@uthscsa.edu OI Finley, Erin/0000-0003-4497-7721 NR 37 TC 1 Z9 1 U1 0 U2 14 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1942-9681 EI 1942-969X J9 PSYCHOL TRAUMA-US JI Psychol. Trauma PD JUL PY 2014 VL 6 IS 4 BP 390 EP 397 DI 10.1037/a0036144 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AM2FD UT WOS:000339664100013 ER PT J AU Axon, RN Coleman, EA AF Axon, R. Neal Coleman, Eric A. TI What Will It Take to Move the Needle on Hospital Readmissions? SO AMERICAN JOURNAL OF MEDICAL QUALITY LA English DT Editorial Material ID CARE TRANSITIONS; QUALITY C1 [Axon, R. Neal] Ralph H Johnson VAMC, Charleston, SC 29401 USA. [Axon, R. Neal] Med Univ S Carolina, Charleston, SC 29425 USA. [Coleman, Eric A.] Univ Colorado Anschutz Med Campus, Aurora, CO USA. RP Axon, RN (reprint author), Ralph H Johnson VAMC, 109 Bee St,Mail Stop 111, Charleston, SC 29401 USA. EM axon@musc.edu NR 10 TC 1 Z9 1 U1 1 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1062-8606 EI 1555-824X J9 AM J MED QUAL JI Am. J. Med. Qual. PD JUL-AUG PY 2014 VL 29 IS 4 BP 357 EP 359 DI 10.1177/1062860613505196 PG 3 WC Health Care Sciences & Services SC Health Care Sciences & Services GA AL9KT UT WOS:000339460700012 PM 24101682 ER PT J AU Burgess, DJ Taylor, BC Phelan, S Spoont, M van Ryn, M Hausmann, LRM Do, T Gordon, HS AF Burgess, Diana J. Taylor, Brent C. Phelan, Sean Spoont, Michele van Ryn, Michelle Hausmann, Leslie R. M. Do, Tam Gordon, Howard S. TI A Brief Self-Affirmation Study to Improve the Experience of Minority Patients SO APPLIED PSYCHOLOGY-HEALTH AND WELL BEING LA English DT Article DE communication; minority; racial disparities; self-affirmation; stereotype threat ID RANDOMIZED CONTROLLED-TRIAL; HEALTH-CARE PROVIDERS; STEREOTYPE THREAT; POSITIVE-AFFECT; PERCEIVED DISCRIMINATION; VALUES AFFIRMATION; AFRICAN-AMERICANS; ACHIEVEMENT GAP; ETHNIC DISPARITIES; PHYSICAL-ACTIVITY AB Background: There is evidence that Black patients may experience stereotype threat-apprehension about being negatively stereotyped-in healthcare settings, which might adversely affect their behavior in clinical encounters. Recent studies conducted outside of healthcare have shown that a brief self-affirmation intervention, in which individuals are asked to focus on and affirm their valued characteristics and sources of personal pride, can reduce the negative effects of stereotype threat on academic performance and on interpersonal communication. Methods: This randomised controlled trial examined whether a self-affirmation (SA) intervention would decrease the negative effects of stereotype threat (negative mood, lower state self-esteem, greater perceptions of racial discrimination) and increase communication self-efficacy among Black primary care patients. Self-affirmation was induced by having patients complete a 32-item values affirmation questionnaire. Results: Patients in the SA condition had lower levels of performance self-esteem and social self-esteem than patients in the control. There were no differences between the SA and the control groups on negative mood, communication self-efficacy, and perceptions of discrimination. Conclusions: Our SA intervention lowered state self-esteem among Black patients. Future research is needed to determine the type of SA task that is most effective for this population. C1 [Burgess, Diana J.; Taylor, Brent C.; Spoont, Michele; Do, Tam] Minneapolis Vet Affairs Healthcare Syst, Ctr Chron Dis Outcomes Res CCDOR, Minneapolis, MN USA. [Burgess, Diana J.; Taylor, Brent C.; Spoont, Michele] Univ Minnesota, Minneapolis, MN 55455 USA. [Phelan, Sean; van Ryn, Michelle] Mayo Div Hlth Care Policy & Res, Rochester, MN 55904 USA. [Hausmann, Leslie R. M.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot CHERP, Pittsburgh, PA USA. [Hausmann, Leslie R. M.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Gordon, Howard S.] Jesse Brown Vet Affairs Med Ctr, Chicago, IL 60612 USA. [Gordon, Howard S.] VA Ctr Innovat Complex Chron Healthcare, Hines, IL USA. [Gordon, Howard S.] Univ Illinois, Chicago Coll Med, Chicago, IL 60680 USA. RP Burgess, DJ (reprint author), VA Med Ctr, Ctr Chron Dis Outcomes Res, One Vet Dr 152-2E, Minneapolis, MN 55417 USA. EM diana.burgess@va.gov RI Gordon, Howard/E-4420-2010; Taylor, Brent/A-8069-2009; Burgess, Diana/A-1946-2016 OI Gordon, Howard/0000-0002-6712-5954; Taylor, Brent/0000-0002-2140-8377; NR 49 TC 2 Z9 2 U1 3 U2 18 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1758-0846 EI 1758-0854 J9 APPL PSYCHOL-HLTH WE JI Appl. Psychol.-Health Well Being PD JUL PY 2014 VL 6 IS 2 BP 135 EP 150 DI 10.1111/aphw.12015 PG 16 WC Psychology, Applied SC Psychology GA AL9BF UT WOS:000339433800001 PM 24124121 ER PT J AU Dhaliwal, G AF Dhaliwal, Gurpreet TI Bringing High-Value Care to the Inpatient Teaching Service SO JAMA INTERNAL MEDICINE LA English DT Editorial Material ID CURRICULUM C1 [Dhaliwal, Gurpreet] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Dhaliwal, Gurpreet] San Francisco VA Med Ctr, Med Serv, San Francisco, CA USA. RP Dhaliwal, G (reprint author), San Francisco VA Med Ctr, Med Serv, 4150 Clement St,111, San Francisco, CA 94121 USA. EM gurpreet.dhaliwal@ucsf.edu NR 7 TC 1 Z9 1 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD JUL PY 2014 VL 174 IS 7 BP 1021 EP 1022 DI 10.1001/jamainternmed.2014.2012 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA AL9VS UT WOS:000339491700001 PM 24862304 ER PT J AU Moin, T Mangione, CM AF Moin, Tannaz Mangione, Carol M. TI Live vs Electronically Delivered Weight-Loss Interventions Paying for Feasible Interventions SO JAMA INTERNAL MEDICINE LA English DT Editorial Material ID METAANALYSIS C1 [Moin, Tannaz] Vet Affairs Greater Los Angeles Healthcare Syst, Hlth Serv Res & Dev Ctr Study Healthcare Innovat, Los Angeles, CA USA. [Moin, Tannaz; Mangione, Carol M.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Mangione, Carol M.] Univ Calif Los Angeles, Jonathan & Karin Fielding Sch Publ Hlth, Los Angeles, CA 90095 USA. RP Moin, T (reprint author), Care of Gonzalez V, Univ Calif Los Angeles, 911 Broxton Ave,Off 302, Los Angeles, CA 90024 USA. EM tmoin@mednet.ucla.edu FU NCATS NIH HHS [UL1TR000124, UL1 TR000124]; NIA NIH HHS [P30-AG021684, P30 AG021684] NR 7 TC 0 Z9 0 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD JUL PY 2014 VL 174 IS 7 BP 1157 EP 1159 DI 10.1001/jamainternmed.2014.414 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA AL9VS UT WOS:000339491700030 PM 24861172 ER PT J AU Greysen, SR Garcia, CC Sudore, RL Cenzer, IS Covinsky, KE AF Greysen, S. Ryan Garcia, Carie Chin Sudore, Rebecca L. Cenzer, Irena Stijacic Covinsky, Kenneth E. TI Functional Impairment and Internet Use Among Older Adults: Implications for Meaningful Use of Patient Portals SO JAMA INTERNAL MEDICINE LA English DT Letter ID CARE C1 [Greysen, S. Ryan] Univ Calif San Francisco, Div Hosp Med, San Francisco, CA 94113 USA. [Garcia, Carie Chin] Calif Pacific Med Ctr, Dept Med, San Francisco, CA USA. [Sudore, Rebecca L.; Cenzer, Irena Stijacic; Covinsky, Kenneth E.] San Francisco VA Med Ctr, San Francisco, CA USA. [Sudore, Rebecca L.; Cenzer, Irena Stijacic; Covinsky, Kenneth E.] Univ Calif San Francisco, Div Geriatr Med, San Francisco, CA 94113 USA. RP Greysen, SR (reprint author), Univ Calif San Francisco, Div Hosp Med, 533 Parnassus Ave,POB 0131, San Francisco, CA 94113 USA. EM ryan.greysen@ucsf.edu FU NIA NIH HHS [R01 AG045043, 1K23AG045338-01, 1R01AG045043-01, K23 AG045338, K24 AG029812, P30 AG044281] NR 6 TC 11 Z9 11 U1 1 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD JUL PY 2014 VL 174 IS 7 BP 1188 EP 1190 DI 10.1001/jamainternmed.2014.1864 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA AL9VS UT WOS:000339491700039 PM 24839165 ER PT J AU Kisiel, CL Fehrenbach, T Torgersen, E Stolbach, B McClelland, G Griffin, G Burkman, K AF Kisiel, Cassandra L. Fehrenbach, Tracy Torgersen, Elizabeth Stolbach, Brad McClelland, Gary Griffin, Gene Burkman, Kristine TI Constellations of Interpersonal Trauma and Symptoms in Child Welfare: Implications for a Developmental Trauma Framework (vol 29, pg 1, 2014) SO JOURNAL OF FAMILY VIOLENCE LA English DT Correction C1 [Kisiel, Cassandra L.; Fehrenbach, Tracy; Torgersen, Elizabeth; McClelland, Gary; Griffin, Gene] Northwestern Univ, Sch Med, Dept Psychiat & Behav Sci, Chicago, IL 60611 USA. [Stolbach, Brad] Univ Chicago, Dept Pediat, Priztker Sch Med, Chicago, IL 60637 USA. [Burkman, Kristine] San Francisco VA Med Ctr, Dept Psychol, San Francisco, CA USA. RP Kisiel, CL (reprint author), Northwestern Univ, Sch Med, Dept Psychiat & Behav Sci, 710 N Lake Shore Dr,12th Floor, Chicago, IL 60611 USA. EM c-kisiel@northwestern.edu NR 1 TC 0 Z9 0 U1 3 U2 4 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0885-7482 EI 1573-2851 J9 J FAM VIOLENCE JI J. Fam. Violence PD JUL PY 2014 VL 29 IS 5 BP 579 EP 579 DI 10.1007/s10896-014-9603-8 PG 1 WC Psychology, Clinical; Family Studies SC Psychology; Family Studies GA AL8FL UT WOS:000339373300011 ER PT J AU Boyers, L Karimkhani, C Crane, LA Asdigian, N Hollonds, A Dellavalle, RP AF Boyers, Lindsay Karimkhani, Chante Crane, Lori A. Asdigian, Nancy Hollonds, Adrienn Dellavalle, Robert P. TI Buying indoor tanning with university debit cards SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Letter C1 [Boyers, Lindsay] Georgetown Univ, Sch Med, Washington, DC USA. [Karimkhani, Chante] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. [Crane, Lori A.; Asdigian, Nancy; Hollonds, Adrienn; Dellavalle, Robert P.] Univ Colorado, Colorado Sch Publ Hlth, Dept Community & Behav Hlth, Aurora, CO USA. [Dellavalle, Robert P.] Univ Colorado, Dept Dermatol, Aurora, CO USA. [Dellavalle, Robert P.] US Dept Vet Affairs, Eastern Colorado Hlth Care Syst, Dermatol Serv, Denver, CO USA. RP Dellavalle, RP (reprint author), Dept Vet Affairs Med Ctr, Dermatol Serv, 1055 Clermont St,Box 165, Denver, CO 80220 USA. EM robert.dellavalle@ucdenver.edu FU NCCDPHP CDC HHS [3U48DP001938-04S1] NR 4 TC 8 Z9 8 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD JUL PY 2014 VL 71 IS 1 BP 199 EP 201 DI 10.1016/j.jaad.2014.02.041 PG 4 WC Dermatology SC Dermatology GA AL7QQ UT WOS:000339330200049 PM 24947697 ER PT J AU Goldstein, G Allen, DN Thaler, NS Luther, JF Panchalingam, K Pettegrew, JW AF Goldstein, Gerald Allen, Daniel N. Thaler, Nicholas S. Luther, James F. Panchalingam, Kanagasabai Pettegrew, Jay W. TI Developmental Aspects and Neurobiological Correlates of Working and Associative Memory SO NEUROPSYCHOLOGY LA English DT Article DE working memory; MR spectroscopy; Loess curves ID MAGNETIC-RESONANCE SPECTROSCOPY; HUMAN CEREBRAL-CORTEX; IN-VIVO; PREFRONTAL CORTEX; METABOLITE CONCENTRATIONS; CORTICAL DEVELOPMENT; ENERGY-METABOLISM; NERVOUS-SYSTEM; TEMPORAL-LOBE; HUMAN BRAIN AB Objective: It has been shown that verbal working and associative memory have different developmental trajectories with working memory, taking a linear course from early childhood to adolescence, whereas associative memory takes a curvilinear course asymptoting at about age 12. This study made a determination of whether these trajectories tracked with 2 magnetic resonance spectroscopy imaging (MRSI) variables: phosphocreatine level (PCr) and gray matter percentage (GM%). Method: In a cross-sectional study, 94 children ranging in age from 6-14 years were administered tests of verbal working and associative memory and underwent an MRSI procedure evaluating 6 major brain regions. The study considered PCr levels and GM% in the 6 regions. Loess curves were constructed plotting the memory tests and MRSI variables across age, and trajectories were evaluated. Results: PCr showed a linear increase with age, particularly in the left superior temporal lobe with this increase closely tracking improvement in working memory but not associative memory scores. GM% did not increase with age in any brain region, and there was no tracking with either of the memory tests. Conclusion: Verbal working memory and verbal associative memory have differing age trajectories, with working memory showing close tracking with PCr level, mainly in the left superior temporal lobe. No such tracking was found for the associative memory tests. GM% curves were flat across regions, showing no association with age. C1 [Goldstein, Gerald; Luther, James F.] VA Pittsburgh Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr 4, Pittsburgh, PA USA. [Allen, Daniel N.] Univ Nevada, Dept Psychol, Las Vegas, NV 89154 USA. [Thaler, Nicholas S.] Univ Oklahoma Hlth Sci, Dept Psychiat & Behav Sci, Oklahoma City, OK USA. [Panchalingam, Kanagasabai] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15260 USA. [Pettegrew, Jay W.] Univ Pittsburgh, Sch Med, Dept Behav & Community Hlth Serv, Dept Neurol,Dept Psychiat, Pittsburgh, PA 15238 USA. [Pettegrew, Jay W.] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15238 USA. [Thaler, Nicholas S.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Dept Psychiat & Behav Sci, Los Angeles, CA 90024 USA. RP Pettegrew, JW (reprint author), Univ Pittsburgh, Sch Med, Dept Psychiat, RIDC Pk,2600 Kappa Dr, Pittsburgh, PA 15238 USA. EM pettegrew@phfrinc.com FU NIHCD/NIH [HD-39799] FX This work was supported in part by an NIHCD/NIH HD-39799 grant (JWP). Indebtedness is expressed to the Medical Research Service and the VA VISN-IV Mental Illness Research, Education and Clinical Center (MIRECC) Depertment of Veterans Affairs. NR 79 TC 0 Z9 0 U1 0 U2 6 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0894-4105 EI 1931-1559 J9 NEUROPSYCHOLOGY JI Neuropsychology PD JUL PY 2014 VL 28 IS 4 BP 496 EP 505 DI 10.1037/neu0000053 PG 10 WC Psychology, Clinical; Neurosciences; Psychology SC Psychology; Neurosciences & Neurology GA AL8OF UT WOS:000339398000002 PM 24564282 ER PT J AU Wollin, DA Makarov, D AF Wollin, Daniel A. Makarov, Danil TI Extended Pelvic Lymph Node Dissection for Prostate Cancer: Do More Nodes Mean Better Survival? SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID RADICAL PROSTATECTOMY; LYMPHADENECTOMY C1 [Wollin, Daniel A.; Makarov, Danil] NYU, Sch Med, Dept Urol, New York, NY 10003 USA. [Makarov, Danil] US Dept Vet Affairs, New York, NY USA. [Makarov, Danil] NYU, Inst Canc, New York, NY 10003 USA. RP Wollin, DA (reprint author), NYU, Sch Med, Dept Urol, New York, NY 10003 USA. FU HSRD VA [IK2 HX000851] NR 7 TC 0 Z9 0 U1 0 U2 0 PU UBM MEDICA PI NORWALK PA 535 CONNECTICUT AVE, STE 300, NORWALK, CT 06854 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD JUL PY 2014 VL 28 IS 7 BP 601 EP 602 PG 2 WC Oncology SC Oncology GA AM1ZK UT WOS:000339647600007 PM 25144281 ER PT J AU Goetz, MB Hoang, T Kan, VL Rimland, D Rodriguez-Barradas, M AF Goetz, Matthew Bidwell Hoang, Tuyen Kan, Virginia L. Rimland, David Rodriguez-Barradas, Maria TI Development and Validation of an Algorithm to Identify Patients Newly Diagnosed with HIV Infection from Electronic Health Records SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID OF-VETERANS-AFFAIRS; UNITED-STATES; CARE SETTINGS; STRATEGIES; ENGAGEMENT; RETENTION AB An algorithm was developed that identifies patients with new diagnoses of HIV infection by the use of electronic health records. It was based on the sequence of HIV diagnostic tests, entry of ICD-9-CM diagnostic codes, and measurement of HIV-1 plasma RNA levels in persons undergoing HIV testing from 2006 to 2012 at four large urban Veterans Health Administration (VHA) facilities. Source data were obtained from the VHA National Corporate Data Warehouse. Chart review was done by a single trained abstractor to validate site-level data regarding new diagnoses. We identified 1,153 patients as having a positive HIV diagnostic test within the VHA. Of these, 57% were determined to have prior knowledge of their HIV status from testing at non-VHA facilities. An algorithm based on the sequence and results of available laboratory tests and ICD-9-CM entries identified new HIV diagnoses with a sensitivity of 83%, specificity of 86%, positive predictive value of 85%, and negative predictive value of 90%. There were no meaningful demographic or clinical differences between newly diagnosed patients who were correctly or incorrectly classified by the algorithm. We have validated a method to identify cases of new diagnosis of HIV infection in large administrative datasets. This method, which has a sensitivity of 83%, specificity of 86%, positive predictive value of 85%, and negative predictive value of 90% can be used in analyses of the epidemiology of newly diagnosed HIV infection. C1 [Goetz, Matthew Bidwell; Hoang, Tuyen] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Goetz, Matthew Bidwell; Hoang, Tuyen] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Kan, Virginia L.] Washington DC VA Med Ctr, Washington, DC USA. [Kan, Virginia L.] George Washington Univ, Sch Med, Washington, DC USA. [Rimland, David] Atlanta VA Med Ctr, Atlanta, GA USA. [Rimland, David] Emory Univ, Sch Med, Atlanta, GA USA. [Rodriguez-Barradas, Maria] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Rodriguez-Barradas, Maria] Baylor Univ, Sch Med, Houston, TX 77030 USA. RP Goetz, MB (reprint author), VA Greater Los Angeles Healthcare Syst, Infect Dis Sect 111 F, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM matthew.goetz@va.gov OI Goetz, Matthew/0000-0003-4542-992X FU Veterans Health Administration, Health Services Research & Development Service [RRP 12-220] FX This study was funded by the Veterans Health Administration, Health Services Research & Development Service (RRP 12-220). NR 20 TC 6 Z9 6 U1 2 U2 5 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JUL PY 2014 VL 30 IS 7 BP 626 EP 633 DI 10.1089/aid.2013.0287 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA AL1IW UT WOS:000338880100002 PM 24564256 ER PT J AU Driver, TH Katz, R Ix, JH Magnani, JW Peralta, CA Parikh, CR Fried, L Newman, AB Kritchevsky, SB Sarnak, MJ Shlipak, MG AF Driver, Todd H. Katz, Ronit Ix, Joachim H. Magnani, Jared W. Peralta, Carmen A. Parikh, Chirag R. Fried, Linda Newman, Anne B. Kritchevsky, Stephen B. Sarnak, Mark J. Shlipak, Michael G. CA Hlth ABC Study TI Urinary Kidney Injury Molecule 1 (KIM-1) and Interleukin 18 (IL-18) as Risk Markers for Heart Failure in Older Adults: The Health, Aging, and Body Composition (Health ABC) Study SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Interleukin 18 (IL-18); kidney injury molecule 1 (KIM-1); cystatin C; heart failure; chronic kidney disease (CKD); risk marker; cardiovascular disease (CVD); albuminuria; kidney tubular injury ID GLOMERULAR-FILTRATION-RATE; CARDIAC-SURGERY; CYSTATIN-C; TRANSPLANT RECIPIENTS; POOR OUTCOMES; BIOMARKERS; MORTALITY; DISEASE; SERUM; MICROALBUMINURIA AB Background: Kidney damage and reduced kidney function are potent risk factors for heart failure, but existing studies are limited to assessing albuminuria or estimated glomerular filtration rate (eGFR). We evaluated the associations of levels of urinary biomarkers of kidney tubular injury (interleukin 18 [IL-18] and kidney injury molecule 1 [KIM-1]) with future risk of heart failure. Study Design: Retrospective cohort study. Setting & Participants: 2,917 participants without heart failure in the Health, Aging, and Body Composition (Health ABC) cohort. Predictors: Ratios of urine KIM-1, IL-18, and albumin to creatinine (KIM-1: Cr, IL-18: Cr, and ACR, respectively). Outcomes: Incident heart failure over a median follow-up of 12 years. Results: Median values of each marker at baseline were 812 (IQR, 497-1,235) pg/mg for KIM-1: Cr, 31 (IQR, 19-56) pg/mg for IL-18: Cr, and 8 (IQR, 5-19) mg/g for ACR. 596 persons developed heart failure during follow-up. The top quartile of KIM-1: Cr was associated with risk of incident heart failure after adjustment for baseline eGFR, heart failure risk factors, and ACR (HR, 1.32; 95% CI, 1.02-1.70) in adjusted multivariate proportional hazards models. The top quartile of IL-18: Cr also was associated with heart failure in a model adjusted for risk factors and eGFR (HR, 1.35; 95% CI, 1.05-1.73), but was attenuated by adjustment for ACR (HR, 1.15; 95% CI, 0.89-1.48). The top quartile of ACR had a stronger adjusted association with heart failure (HR, 1.96; 95% CI, 1.53-2.51). Limitations: Generalizability to other populations is uncertain. Conclusions: Higher urine KIM-1 concentrations were associated independently with incident heart failure risk, although the associations of higher ACR were of stronger magnitude. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. This is a US Government Work. There are no restrictions on its use. C1 [Driver, Todd H.] Univ Calif San Francisco, Sch Med, San Francisco, CA USA. [Katz, Ronit] Univ Washington, Collaborat Hlth Studies Coordinating Ctr, Seattle, WA 98195 USA. [Ix, Joachim H.] Univ Calif San Diego, Dept Med, Div Nephrol & Hypertens, San Diego, CA 92103 USA. [Ix, Joachim H.] Univ Calif San Diego, Div Prevent Med, Dept Family & Prevent Med, San Diego, CA 92103 USA. [Ix, Joachim H.] Vet Affairs San Diego Healthcare Syst, Nephrol Sect, San Diego, CA USA. [Magnani, Jared W.] Boston Univ, Sch Med, Sect Cardiovasc Med, Boston, MA 02118 USA. [Peralta, Carmen A.; Shlipak, Michael G.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Peralta, Carmen A.; Shlipak, Michael G.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Parikh, Chirag R.] Yale Univ, Dept Med, Sect Nephrol, New Haven, CT 06520 USA. [Parikh, Chirag R.] Yale Univ, Program Appl Translat Res, New Haven, CT USA. [Fried, Linda] Vet Affairs Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA. [Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Kritchevsky, Stephen B.] Wake Forest Sch Med, Sticht Ctr Aging, Winston Salem, NC USA. [Sarnak, Mark J.] Tufts Med Ctr, Div Nephrol, Boston, MA USA. [Shlipak, Michael G.] San Francisco VA Med Ctr, Dept Gen Internal Med, San Francisco, CA 94121 USA. RP Shlipak, MG (reprint author), San Francisco VA Med Ctr, 4150 Clement St,Box 111A1, San Francisco, CA 94121 USA. EM michael.shlipak@ucsf.edu RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU NIA [5R01AG027002-07, N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, R01-AG028050]; UCSF-CTSI [TL1 TR000144]; National Institute of Nursing Research [R01-NR012459] FX Drs Shlipak, Sarnak, Ix, and Katz were supported by NIA grant 5R01AG027002-07. Mr Driver was supported by UCSF-CTSI grant TL1 TR000144. Drs Newman and Kritchevsky were supported by NIA contracts N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106; NIA grant R01-AG028050; and National Institute of Nursing Research grant R01-NR012459. The study sponsors had no role in study design; collection, analysis, and interpretation of the data; writing the report; and the decision to submit the report for publication. NR 36 TC 10 Z9 11 U1 0 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD JUL PY 2014 VL 64 IS 1 BP 49 EP 56 DI 10.1053/j.ajkd.2014.01.432 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA AL2EK UT WOS:000338938500011 PM 24656453 ER PT J AU Rogers, CM Mallinson, T Peppers, D AF Rogers, Carly M. Mallinson, Trudy Peppers, Dominique TI High-Intensity Sports for Posttraumatic Stress Disorder and Depression: Feasibility Study of Ocean Therapy With Veterans of Operation Enduring Freedom and Operation Iraqi Freedom SO AMERICAN JOURNAL OF OCCUPATIONAL THERAPY LA English DT Article DE Afghan campaign 2001-; depression; Iraq war, 2003-2011; social participation; sports; stress disorders, post-traumatic; veterans health ID TRAUMATIC BRAIN-INJURY; MAJOR DEPRESSION; MENTAL-HEALTH; RISK-TAKING; MILITARY PERSONNEL; SENSATION SEEKING; COMBAT; AFGHANISTAN; CARE; INVENTORY AB In this study, we conducted a pretest-posttest investigation of a sports-oriented occupational therapy intervention using surfing in an experiential, skills-based program to support veterans with symptoms of posttraumatic stress disorder (PTSD) in their transition to civilian life. The purpose of this feasibility study was to evaluate the intervention for attendance rates and retention in the program provided in 5 sessions over 5 wk. Fourteen veterans from a specialty postdeployment clinic at a Veterans Affairs hospital were enrolled; 11 completed the study, and 10 attended >= 3 sessions. Participants reported clinically meaningful improvement in PTSD symptom severity (PTSD Checklist-Military Version, Wilcoxon signed rank Z = 2.5, p = .01) and in depressive symptoms (Major Depression Inventory, Wilcoxon signed rank Z = 2.05, p = .04). The results of this small, uncontrolled study suggest that a sports-oriented occupational therapy intervention has potential as a feasible adjunct intervention for veterans seeking mental health treatment for symptoms of PTSD. C1 [Rogers, Carly M.] Jimmy Miller Mem Fdn, Manhattan Beach, CA 90524 USA. [Rogers, Carly M.; Mallinson, Trudy] Univ So Calif, Div Occupat Sci & Occupat Therapy, Los Angeles, CA USA. [Rogers, Carly M.; Peppers, Dominique] VA Greater Los Angeles Healthcare Syst, Phys Med Serv, Los Angeles, CA USA. [Rogers, Carly M.; Peppers, Dominique] VA Greater Los Angeles Healthcare Syst, Phys Rehabil Serv, Los Angeles, CA USA. [Peppers, Dominique] VA Puget Sound Healthcare Syst, Dept Phys Med & Rehabil Serv, Seattle, WA USA. RP Rogers, CM (reprint author), Jimmy Miller Mem Fdn, Manhattan Beach, CA 90524 USA. OI Mallinson, Trudy/0000-0002-4888-5579 NR 53 TC 4 Z9 4 U1 3 U2 42 PU AMER OCCUPATIONAL THERAPY ASSOC, INC PI BETHESDA PA 4720 MONTGOMERY LANE, BETHESDA, MD 20814-3425 USA SN 0272-9490 EI 1943-7676 J9 AM J OCCUP THER JI Am. J. Occup. Ther. PD JUL-AUG PY 2014 VL 68 IS 4 BP 395 EP 404 DI 10.5014/ajot.2014.011221 PG 10 WC Rehabilitation SC Rehabilitation GA AL4FR UT WOS:000339088800004 PM 25005502 ER PT J AU Nagami, GT Plumer, AK Beyda, RM Schachter, O AF Nagami, Glenn T. Plumer, Alexandria K. Beyda, Raymond M. Schachter, Oran TI Effects of acid challenges on type 2 angiotensin II receptor-sensitive ammonia production by the proximal tubule SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE kidney; ammoniagenesis; acidosis ID PERFUSED IN-VITRO; AT(2) RECEPTOR; METABOLIC-ACIDOSIS; RAT-KIDNEY; PRESSURE NATRIURESIS; SECRETION; MICE; EXPRESSION; PROTEIN AB Angiotensin II (ANG II) acting through its type 1 (AT(1)) receptor stimulates total ammonia (tNH(3)) production by the proximal tubule. The present studies explored the role of ANG II type 2 (AT(2)) receptors in modulating the stimulatory effects of ANG II on tNH(3) production. Mouse S2 proximal tubule segments derived from 18-h and 7-day acid-loaded mice, and non-acid-loaded controls were dissected and microperfused in vitro. Adding ANG II to the luminal perfusion solution resulted in different increments in tNH(3) production rates in tubules derived from 18-h vs. 7-day acid-loaded mice such that the increase in tNH(3) production with ANG II was higher in tubules derived from 18-h acid-loaded mice compared with those derived from control and 7-day acid-loaded mice. Adding the AT(2) receptor blocker PD123319 with ANG II increased ANG II-stimulated tNH3 production in S2 segments from control and 7-day acid-loaded mice but not in those from 18-h acid-loaded mice, and this increased effect of PD123319 was associated with higher AT(2) receptor protein levels in brush-border membranes. Studies in cultured proximal tubule cells demonstrated that 2-h exposure to pH 7.0 reduced the modulating effect of PD123319 on ANG II-simulated tNH(3) production and reduced cell surface AT2 receptor levels. We concluded that AT(2) receptors reduce the stimulatory effect of ANG II on proximal tubule tNH(3) production and that the time-dependent impact of AT(2) receptor blockade on the ANG II-stimulated tNH(3) production corresponded to time-dependent changes in AT(2) receptor cell surface expression in the proximal tubule. C1 Vet Affairs Greater Los Angeles Healthcare Syst, Nephrol Sect 111L, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. RP Nagami, GT (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU Department of Veterans Affairs; VA Merit Review Award FX This work was supported by the Department of Veterans Affairs and, in part, by a VA Merit Review Award. NR 26 TC 1 Z9 1 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X EI 1522-1466 J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD JUL 1 PY 2014 VL 307 IS 1 BP F53 EP F57 DI 10.1152/ajprenal.00466.2013 PG 5 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA AL1XR UT WOS:000338920200007 PM 24829505 ER PT J AU Akl, TJ Wilson, MA Ericson, MN Cote, GL AF Akl, Tony J. Wilson, Mark A. Ericson, M. Nance Cote, Gerard L. TI Quantifying tissue mechanical properties using photoplethysmography SO BIOMEDICAL OPTICS EXPRESS LA English DT Article ID HEPATIC PORTAL-VEIN; LIVER-TRANSPLANTATION; CONTOUR ANALYSIS; PULSE-WAVE; DISEASE; SENSOR; COMPLICATIONS; PERFUSION; FIBROSIS; ELASTOGRAPHY AB Photoplethysmography (PPG) is a non-invasive optical method that can be used to detect blood volume changes in the microvascular bed of tissue. The PPG signal comprises two components; a pulsatile waveform (AC) attributed to changes in the interrogated blood volume with each heartbeat, and a slowly varying baseline (DC) combining low frequency fluctuations mainly due to respiration and sympathetic nervous system activity. In this report, we investigate the AC pulsatile waveform of the PPG pulse for ultimate use in extracting information regarding the biomechanical properties of tissue and vasculature. By analyzing the rise time of the pulse in the diastole period, we show that PPG is capable of measuring changes in the Young's Modulus of tissue mimicking phantoms with a resolution of 4 KPa in the range of 12 to 61 KPa. In addition, the shape of the pulse can potentially be used to diagnose vascular complications by differentiating upstream from downstream complications. A Windkessel model was used to model changes in the biomechanical properties of the circulation and to test the proposed concept. The modeling data confirmed the response seen in vitro and showed the same trends in the PPG rise and fall times with changes in compliance and vascular resistance. (C) 2014 Optical Society of America C1 [Akl, Tony J.; Cote, Gerard L.] Texas A&M Univ, Dept Biomed Engn, College Stn, TX 77843 USA. [Wilson, Mark A.] Univ Pittsburgh, Dept Surg, Pittsburgh, PA 15213 USA. [Wilson, Mark A.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. [Ericson, M. Nance] Oak Ridge Natl Lab, Oak Ridge, TN 37831 USA. RP Akl, TJ (reprint author), Texas A&M Univ, Dept Biomed Engn, 5045 Emerging Technol Bldg, College Stn, TX 77843 USA. EM takl@tamu.edu RI Ericson, Milton/H-9880-2016 OI Ericson, Milton/0000-0002-6628-4865 FU bioengineering research partnership (BRP) grant from NIH [5R01-GM077150] FX This research was funded by a bioengineering research partnership (BRP) grant from NIH, (#5R01-GM077150). NR 49 TC 3 Z9 3 U1 3 U2 24 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 2156-7085 J9 BIOMED OPT EXPRESS JI Biomed. Opt. Express PD JUL 1 PY 2014 VL 5 IS 7 BP 2362 EP 2375 DI 10.1364/BOE.5.002362 PG 14 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA AL2AV UT WOS:000338929100028 PM 25071970 ER PT J AU Epstein, AJ Yang, L Yang, FF Groeneveld, PW AF Epstein, Andrew J. Yang, Lin Yang, Feifei Groeneveld, Peter W. TI A Comparison of Clinical Outcomes From Carotid Artery Stenting Among US Hospitals SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE Medicare; outcome assessment (health care) ID ACUTE MYOCARDIAL-INFARCTION; HIGH-RISK PATIENTS; 30-DAY MORTALITY; ENDARTERECTOMY; PERFORMANCE; RATES; REVASCULARIZATION; PHASE; MODEL AB Background-The Centers for Medicare and Medicaid Services require hospitals performing carotid artery stenting (CAS) to recertify the quality of their programs every 2 years, but currently this involves no explicit comparisons of postprocedure mortality across hospitals. Hence, the current recertification process may fail to identify hospitals that are performing poorly in relation to peer institutions. Our objective was to compare risk-standardized procedural outcomes across US hospitals that performed CAS and to identify hospitals with statistically high postprocedure mortality rates. Methods and Results-We conducted a retrospective cohort study of Medicare beneficiaries who underwent CAS from July 2009 to June 2011 at 927 US hospitals. Thirty-day risk-standardized mortality rates were calculated using the Hospital Compare statistical method, a well-validated hierarchical generalized linear model that included both patient-level and hospital-level predictors. Claims were examined from 22 708 patients undergoing CAS, with a crude 30-day mortality rate of 2.0%. Risk-standardized 30-day mortality rates after CAS varied from 1.1% to 5.1% (P<0.001 for the difference). Thirteen hospitals had risk-standardized mortality rates that were statistically (P<0.05) higher than the national mean. Conversely, 5 hospitals had risk-standardized mortality rates that were statistically (P<0.05) lower than the national mean. Conclusions-We used administrative claims to identify several CAS hospitals with excessively high 30-day mortality after carotid stenting. When combined with information currently used by Medicare for CAS recertification, such as clinical registry data and program reports, clinical outcomes comparisons could enhance Medicare's ability to identify hospitals that are questionable candidates for recertification. C1 [Epstein, Andrew J.; Groeneveld, Peter W.] Philadelphia Vet Affairs Med Ctr, Dept Vet Affairs Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Epstein, Andrew J.; Yang, Lin; Yang, Feifei; Groeneveld, Peter W.] Univ Penn, Perelman Sch Med, Div Gen Internal Med, Dept Med, Philadelphia, PA 19104 USA. [Epstein, Andrew J.; Groeneveld, Peter W.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. RP Groeneveld, PW (reprint author), Univ Penn, Perelman Sch Med, Div Gen Internal Med, Dept Med, 1229 Blockley Hall,423 Serv Dr, Philadelphia, PA 19104 USA. EM petergro@upenn.edu FU Agency for Healthcare Research and Quality [1R01HS018403] FX This study was supported by grant 1R01HS018403 from the Agency for Healthcare Research and Quality, which had no role in the design and conduct of the study, in the collection, management, analysis, and interpretation of the data, in the preparation, review, and approval of the manuscript, or in the decision to submit the manuscript for publication. Dr Groeneveld had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. NR 26 TC 3 Z9 3 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7705 EI 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD JUL PY 2014 VL 7 IS 4 BP 574 EP 580 DI 10.1161/CIRCOUTCOMES.113.000819 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AL6OJ UT WOS:000339251900011 PM 24895452 ER PT J AU Lu, LY Krumholz, HM Tu, JV Ross, JS Ko, DT Jackevicius, CA AF Lu, Lingyun Krumholz, Harlan M. Tu, Jack V. Ross, Joseph S. Ko, Dennis T. Jackevicius, Cynthia A. TI Impact of Drug Policy on Regional Trends in Ezetimibe Use SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE drug utilization; ezetimibe; health policy ID UNITED-STATES; CARDIOVASCULAR-DISEASE; BRITISH-COLUMBIA; HEALTH-POLICY; CANADA; OUTCOMES; CHOLESTEROL; SIMVASTATIN; PREVENTION; INHIBITORS AB Background-Ezetimibe use has steadily increased in Canada during the past decade even in the absence of evidence demonstrating a beneficial effect on clinical outcomes. Among the 4 most populated provinces in Canada, there is a gradient in the restrictiveness of ezetimibe in public-funded formularies (most to least strict: British Columbia, Alberta, Quebec, and Ontario). The effect of formulary policy on the use of ezetimibe over time is unknown. Methods and Results-We conducted a population-level cohort study using Intercontinental Marketing Services Health Canada's data from June 2003 to December 2012 to examine ezetimibe use in these 4 provinces to better understand the association between use and formulary restrictiveness. We found regional variations in the patterns of ezetimibe use. From June 2003 to December 2012, British Columbia (most restrictive) had the lowest monthly increasing rate from $261 to $21 926 ($190/100 000 population/mo), whereas Ontario (least restrictive) had the most rapid monthly increase from $223 to $74 030 ($647/100 000 population/mo), and Quebec from $130 to $59 690 ($522/100 000 population/mo) and Alberta from $356 to $37 604 ($327/100 000 population/mo) were intermediate (P<0.001). Conclusions-Ezetimibe use remains common, increasing during the past decade. Use steadily increased in provinces with the most lenient formularies. In contrast, use was lower, plateauing since 2008 in British Columbia and Alberta, which have more restrictive formularies. The gradient in ezetimibe use was related to variability in restrictiveness of the provincial formularies, illustrating the potential of a policy response gradient that may be used to more effectively manage medication use. C1 [Lu, Lingyun; Jackevicius, Cynthia A.] Western Univ Hlth Sci, Coll Pharm, Dept Pharm Practice & Adm, Pomona, CA 91766 USA. [Lu, Lingyun; Jackevicius, Cynthia A.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Krumholz, Harlan M.] Yale Univ, Sch Med, Dept Med, Sect Cardiovasc Med, New Haven, CT 06510 USA. [Krumholz, Harlan M.; Ross, Joseph S.] Yale Univ, Sch Med, Yale New Haven Hosp, Ctr Outcomes Res & Evaluat, New Haven, CT USA. [Krumholz, Harlan M.; Ross, Joseph S.] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, Sect Hlth Policy & Adm, New Haven, CT 06510 USA. [Krumholz, Harlan M.; Ross, Joseph S.] Robert Wood Johnson Clin Scholars Program, New Haven, CT USA. [Tu, Jack V.; Ko, Dennis T.; Jackevicius, Cynthia A.] Inst Clin Evaluat Sci, Toronto, ON, Canada. [Tu, Jack V.; Ko, Dennis T.; Jackevicius, Cynthia A.] Univ Toronto, Fac Med, Dept Hlth Policy Management & Evaluat, Toronto, ON, Canada. [Tu, Jack V.; Ko, Dennis T.] Univ Toronto, Sunnybrook Hlth Sci Ctr, Schulich Heart Ctr, Div Cardiol, Toronto, ON, Canada. [Ross, Joseph S.] Yale Univ, Sch Med, Dept Med, Gen Internal Med Sect, New Haven, CT 06510 USA. [Jackevicius, Cynthia A.] Univ Hlth Network, Toronto, ON, Canada. RP Jackevicius, CA (reprint author), Western Univ Hlth Sci, Coll Pharm, 309 E Second St, Pomona, CA 91766 USA. EM cjackevicius@westernu.edu FU College of Pharmacy of Western University of Health Sciences, Pomona, CA; Institute for Circulatory and Respiratory Health/Canadian Institutes of Health Research Team [TCA 118349] FX This study was funded, in part, by the College of Pharmacy of Western University of Health Sciences, Pomona, CA, and, in part, by an Institute for Circulatory and Respiratory Health/Canadian Institutes of Health Research Team Grant to the Cardiovascular Health in Ambulatory Care Research Team TCA 118349. The funding source did not have any role in the design and conduct of the study, collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the article. The authors are solely responsible for the design and conduct of this study, all study analyses, the drafting and editing of the article, and its final contents. NR 38 TC 3 Z9 3 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7705 EI 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD JUL PY 2014 VL 7 IS 4 BP 589 EP 596 DI 10.1161/CIRCOUTCOMES.114.001023 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AL6OJ UT WOS:000339251900013 PM 24895451 ER PT J AU Sansbury, BE DeMartino, AM Xie, ZZ Brooks, AC Brainard, RE Watson, LJ DeFilippis, AP Cummins, TD Harbeson, MA Brittian, KR Prabhu, SD Bhatnagar, A Jones, SP Hill, BG AF Sansbury, Brian E. DeMartino, Angelica M. Xie, Zhengzhi Brooks, Alan C. Brainard, Robert E. Watson, Lewis J. DeFilippis, Andrew P. Cummins, Timothy D. Harbeson, Matthew A. Brittian, Kenneth R. Prabhu, Sumanth D. Bhatnagar, Aruni Jones, Steven P. Hill, Bradford G. TI Metabolomic Analysis of Pressure-Overloaded and Infarcted Mouse Hearts SO CIRCULATION-HEART FAILURE LA English DT Article DE amino acids; glycolysis; heart failure; hypertrophy; metabolomics; mitochondria; oxidative stress ID MYOCARDIAL LIPID-METABOLISM; INDUCED CARDIAC-HYPERTROPHY; FATTY-ACID OXIDATION; INSULIN-RESISTANCE; FAILING HEART; AMINO-ACID; DILATED CARDIOMYOPATHY; RAT-HEART; FAILURE; MICE AB Background-Cardiac hypertrophy and heart failure are associated with metabolic dysregulation and a state of chronic energy deficiency. Although several disparate changes in individual metabolic pathways have been described, there has been no global assessment of metabolomic changes in hypertrophic and failing hearts in vivo. Hence, we investigated the impact of pressure overload and infarction on myocardial metabolism. Methods and Results-Male C57BL/6J mice were subjected to transverse aortic constriction or permanent coronary occlusion (myocardial infarction [MI]). A combination of LC/MS/MS and GC/MS techniques was used to measure 288 metabolites in these hearts. Both transverse aortic constriction and MI were associated with profound changes in myocardial metabolism affecting up to 40% of all metabolites measured. Prominent changes in branched-chain amino acids were observed after 1 week of transverse aortic constriction and 5 days after MI. Changes in branched-chain amino acids after MI were associated with myocardial insulin resistance. Longer duration of transverse aortic constriction and MI led to a decrease in purines, acylcarnitines, fatty acids, and several lysolipid and sphingolipid species but a marked increase in pyrimidines as well as ascorbate, heme, and other indices of oxidative stress. Cardiac remodeling and contractile dysfunction in hypertrophied hearts were associated with large increases in myocardial, but not plasma, levels of the polyamines putrescine and spermidine as well as the collagen breakdown product prolylhydroxyproline. Conclusions-These findings reveal extensive metabolic remodeling common to both hypertrophic and failing hearts that are indicative of extracellular matrix remodeling, insulin resistance and perturbations in amino acid, and lipid and nucleotide metabolism. C1 [Sansbury, Brian E.; DeMartino, Angelica M.; Xie, Zhengzhi; Brooks, Alan C.; Brainard, Robert E.; Watson, Lewis J.; DeFilippis, Andrew P.; Brittian, Kenneth R.; Bhatnagar, Aruni; Jones, Steven P.; Hill, Bradford G.] Univ Louisville, Dept Med, Inst Mol Cardiol, Div Cardiol, Louisville, KY 40202 USA. [Sansbury, Brian E.; Xie, Zhengzhi; Brooks, Alan C.; Cummins, Timothy D.; Harbeson, Matthew A.; Brittian, Kenneth R.; Bhatnagar, Aruni; Jones, Steven P.; Hill, Bradford G.] Univ Louisville, Dept Med, Diabet & Obes Ctr, Louisville, KY 40202 USA. [Brooks, Alan C.; Bhatnagar, Aruni; Hill, Bradford G.] Univ Louisville, Dept Biochem & Mol Biol, Louisville, KY 40202 USA. [Sansbury, Brian E.; DeMartino, Angelica M.; Brainard, Robert E.; Watson, Lewis J.; Bhatnagar, Aruni; Jones, Steven P.; Hill, Bradford G.] Univ Louisville, Dept Physiol & Biophys, Louisville, KY 40202 USA. [Prabhu, Sumanth D.] Univ Alabama Birmingham, Dept Med, Div Cardiovasc Dis, Birmingham, AL 35294 USA. [Prabhu, Sumanth D.] Birmingham VAMC, Birmingham, AL 35233 USA. [DeFilippis, Andrew P.] Johns Hopkins Univ, Dept Med, Baltimore, MD USA. RP Hill, BG (reprint author), Univ Louisville, Dept Med, Diabet & Obes Ctr, Inst Mol Cardiol, 580 South Preston St,Rm 404A, Louisville, KY 40202 USA. EM bradford.hill@louisville.edu RI Hill, Bradford/I-4154-2013; Watson, Lewis/F-3688-2011; Jones, Steven/D-5092-2009 OI Hill, Bradford/0000-0001-5332-8286; Watson, Lewis/0000-0002-8273-7676; Jones, Steven/0000-0001-5376-8089 FU National Institutes of Health [GM103492, HL78825, HL83320, HL55477, HL59378, HL94419] FX This work was supported in part by National Institutes of Health grants (GM103492, HL78825, HL83320, HL55477, HL59378, and HL94419). NR 61 TC 29 Z9 31 U1 3 U2 18 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3289 EI 1941-3297 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD JUL PY 2014 VL 7 IS 4 BP 634 EP U161 DI 10.1161/CIRCHEARTFAILURE.114.001151 PG 34 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AL5KD UT WOS:000339171600013 PM 24762972 ER PT J AU Bohm, M Perez, AC Jhund, PS Reil, JC Komajda, M Zile, MR McKelvie, RS Anand, IS Massie, BM Carson, PE McMurray, JJV AF Boehm, Michael Perez, Ana-Cristina Jhund, Pardeep S. Reil, Jan C. Komajda, Michel Zile, Michael R. McKelvie, Robert S. Anand, Inder S. Massie, Barry M. Carson, Peter E. McMurray, John J. V. CA I-Preserve Comm Investigators TI Relationship between heart rate and mortality and morbidity in the irbesartan patients with heart failure and preserved systolic function trial (I-Preserve) SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Article DE Heart failure; Heart rate; Irbesartan; Morbidity; Mortality ID VENTRICULAR EJECTION FRACTION; CORONARY-ARTERY-DISEASE; RATE REDUCTION; RISK-FACTOR; OUTCOMES; ASSOCIATION; FORCE; DYSFUNCTION; INHIBITION; IVABRADINE AB Background Higher heart rate is associated with poorer outcomes in patients with heart failure and reduced ejection fraction (HF-REF). Less is known about the association between heart rate and outcomes in patients with heart failure and preserved ejection fraction (HF-PEF). Therefore, we examined the relationship between heart rate and outcomes in the irbesartan in patients with heart failure and preserved systolic function trial (I-Preserve) in patients with an ejection fraction >45% aged >60 years. Methods and results Heart rate was analysed as both a categorical (tertiles) and continuous variable. Patients in sinus rhythm (n = 3271) and atrial fibrillation (n = 696) were analysed separately. The outcomes examined were the primary endpoint of the trial (all-cause death or cardiovascular hospitalization), the composite of cardiovascular death or heart failure hospitalization (and its components) and all-cause death alone. Higher heart rate was associated with a significantly higher risk of all outcomes studied for patients in sinus rhythm, even after adjustment for other prognostic variables, including N-terminal pro-B-type natriuretic peptide. Each standard deviation (12.4 bpm) increase in heart rate was associated with an increase in risk of 13% for cardiovascular death or heart failure hospitalization (P = 0.002). No relationship between heart rate and outcomes was observed for patients in atrial fibrillation. Beta-blocker treatment did not reduce the heart rate-risk relationship. Conclusions In patients with heart failure and preserved ejection fraction, heart rate is in sinus rhythm an independent predictor of adverse clinical outcomes and might be a therapeutic target in this syndrome. Clinical Trial Registration - URL http://www.clinicaltrials.gov. Unique identifier: NCT 0095238 C1 [Boehm, Michael; Reil, Jan C.] Univ Klinikum Saarlandes, DE-66424 Homburg, Germany. [Perez, Ana-Cristina; Jhund, Pardeep S.; McMurray, John J. V.] Univ Glasgow, Inst Cardiovasc & Med Sci, BHF Glasgow Cardiovasc Res Ctr, Glasgow, Lanark, Scotland. [Komajda, Michel] Univ Paris 06, Paris, France. [Komajda, Michel] Hosp Pitie Salpetriere, Paris, France. [Zile, Michael R.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Zile, Michael R.] Med Univ S Carolina, Charleston, SC USA. [McKelvie, Robert S.] McMaster Univ, Hamilton Hlth Sci, Hamilton, ON, Canada. [Anand, Inder S.] Vet Affairs Med Ctr, Minneapolis, MN USA. [Anand, Inder S.] Univ Minnesota, Minneapolis, MN USA. [Massie, Barry M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Massie, Barry M.] San Francisco VA Med Ctr, San Francisco, CA USA. [Carson, Peter E.] Georgetown Univ, Washington, DC USA. [Carson, Peter E.] Washington DC Vet Affairs Med Ctr, Washington, DC USA. RP Bohm, M (reprint author), Univ Klinikum Saarlandes, Innere Med Klin 3, Kirrberger Str 1, DE-66424 Homburg, Germany. EM michael.boehm@uks.eu OI Perez Moreno, Ana Cristina/0000-0001-9265-6880; Jhund, Pardeep/0000-0003-4306-5317; mcmurray, john/0000-0002-6317-3975 FU Consejo Nacional de Ciencia y Tecnologia; Bristol-Myers Squibb; BMS; Amgen; Cyberonics; Novartis; Medtronic FX The authors served as consultants and received honoraria from the following companies: M. B., Boehringer Ingelheim, Bristol-Myers Squibb, Daichi Sankyo, Medtronic, Pfizer, Servier, St Jude; A. C. P., research scholarship from Consejo Nacional de Ciencia y Tecnologia; P.S.J., Bristol-Myers Squibb; M. K., Bristol-Myers Squibb; M.R.Z., BMS; R.S.McK., Bristol-Myers Squibb; I. A., Amgen, Cyberonics, Novartis, Medtronic; B.M., Bristol-Myers Squibb; P. E. C., Bristol-Myers Squibb; J.R. and J.McM. declare no conflict of interest. NR 27 TC 20 Z9 22 U1 1 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1388-9842 EI 1879-0844 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD JUL PY 2014 VL 16 IS 7 BP 778 EP 787 DI 10.1002/ejhf.85 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AL4HS UT WOS:000339094200011 PM 24864045 ER PT J AU Brody, AL Mukhin, AG Mamoun, MS Luu, T Neary, M Liang, L Shieh, J Sugar, CA Rose, JE Mandelkern, MA AF Brody, Arthur L. Mukhin, Alexey G. Mamoun, Michael S. Trinh Luu Neary, Meaghan Liang, Lidia Shieh, Jennifer Sugar, Catherine A. Rose, Jed E. Mandelkern, Mark A. TI Brain Nicotinic Acetylcholine Receptor Availability and Response to Smoking Cessation Treatment A Randomized Trial SO JAMA PSYCHIATRY LA English DT Article ID ECOLOGICAL MOMENTARY ASSESSMENT; SUSTAINED-RELEASE BUPROPION; CEREBRAL-BLOOD-FLOW; TRANSDERMAL NICOTINE; SELF-EFFICACY; QUIT ATTEMPT; TIMELINE FOLLOWBACK; REPLACEMENT THERAPY; CIGARETTE SMOKERS; CLINICAL-TRIALS AB IMPORTANCE Cigarette smoking leads to upregulation of nicotinic acetylcholine receptors (nAChRs) in the human brain, including the common alpha 4 beta 2* nAChR subtype. While subjective aspects of tobacco dependence have been extensively examined as predictors of quitting smoking with treatment, no studies to our knowledge have yet reported the relationship between the extent of pretreatment upregulation of nAChRs and smoking cessation. OBJECTIVE To determine whether the degree of nAChR upregulation in smokers predicts quitting with a standard course of treatment. DESIGN, SETTING, AND PARTICIPANTS Eighty-one tobacco-dependent cigarette smokers (volunteer sample) underwent positron emission tomographic (PET) scanning of the brain with the radiotracer 2-FA followed by 10 weeks of double-blind, placebo-controlled treatment with nicotine patch (random assignment). Pretreatment specific binding volume of distribution (V-S/f(P)) on PET images (a value that is proportional to alpha(4)beta(2)* nAChR availability) was determined for 8 brain regions of interest, and participant-reported ratings of nicotine dependence, craving, and self-efficacy were collected. Relationships between these pretreatment measures, treatment type, and outcome were then determined. The study took place at academic PET and clinical research centers. MAIN OUTCOMES AND MEASURES Posttreatment quit status after treatment, defined as a participant report of 7 or more days of continuous abstinence and an exhaled carbon monoxide level of 3 ppm or less. RESULTS Smokers with lower pretreatment V-S/f(P) values (a potential marker of less severe nAChR upregulation) across all brain regions studied were more likely to quit smoking (multivariate analysis of covariance, F-8.69 = 4.5; P < .001), regardless of treatment group assignment. Furthermore, pretreatment average V-S/f(P) values provided additional predictive power for likelihood of quitting beyond the self-report measures (stepwise binary logistic regression, likelihood ratio chi(2)(1)= 19.8; P < .001). CONCLUSIONS AND RELEVANCE Smokers with less upregulation of available alpha(4)beta(2)* nAChRs have a greater likelihood of quitting with treatment than smokers with more upregulation. In addition, the biological marker studied here provided additional predictive power beyond subjectively rated measures known to be associated with smoking cessation outcome. While the costly, time-consuming PET procedure used here is not likely to be used clinically, simpler methods for examining alpha(4)beta(2)* nAChR upregulation could be tested and applied in the future to help determine which smokers need more intensive and/or lengthier treatment. C1 [Brody, Arthur L.; Mamoun, Michael S.; Trinh Luu; Neary, Meaghan; Liang, Lidia; Shieh, Jennifer; Mandelkern, Mark A.] VA Greater Los Angeles Healthcare Syst, Dept Res, Los Angeles, CA USA. [Brody, Arthur L.; Sugar, Catherine A.] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 90095 USA. [Mukhin, Alexey G.; Rose, Jed E.] Duke Univ, Dept Psychiat, Durham, NC 27706 USA. [Sugar, Catherine A.] Univ Calif Los Angeles, Dept Biostat, Los Angeles, CA 90095 USA. [Mandelkern, Mark A.] Univ Calif Irvine, Dept Phys, Irvine, CA 92717 USA. RP Brody, AL (reprint author), Univ Calif Los Angeles, Dept Psychiat, 300 UCLA Med Plaza,Ste 2200, Los Angeles, CA 90095 USA. EM abrody@ucla.edu FU National Institute on Drug Abuse [R01 DA20872]; Tobacco-Related Disease Research Program [19XT-0135]; Clinical Science Research and Development Merit Review Award from the Office of Research and Development, US Department of Veterans Affairs [I01CX000412] FX This study was supported by grant R01 DA20872 from the National Institute on Drug Abuse (Dr Brody), grant 19XT-0135 from the Tobacco-Related Disease Research Program (Dr Brody), and Clinical Science Research and Development Merit Review Award I01CX000412 from the Office of Research and Development, US Department of Veterans Affairs (Dr Brody). NR 94 TC 13 Z9 13 U1 3 U2 10 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-622X EI 2168-6238 J9 JAMA PSYCHIAT JI JAMA Psychiatry PD JUL PY 2014 VL 71 IS 7 BP 797 EP 805 DI 10.1001/jamapsychiatry.2014.138 PG 9 WC Psychiatry SC Psychiatry GA AL5HU UT WOS:000339165200010 PM 24850280 ER PT J AU Inacio, MCS Paxton, EW Fisher, D Li, RA Barber, TC Singh, JA AF Inacio, Maria C. S. Paxton, Elizabeth W. Fisher, David Li, Robert A. Barber, Thomas C. Singh, Jasvinder A. TI Bariatric Surgery Prior to Total Joint Arthroplasty May Not Provide Dramatic Improvements in Post-Arthroplasty Surgical Outcomes SO JOURNAL OF ARTHROPLASTY LA English DT Article DE bariatric surgery; joint arthroplasty; obesity; revision; surgical site infection; complications ID TOTAL KNEE ARTHROPLASTY; TOTAL HIP-ARTHROPLASTY; RISK-FACTORS; NUTRITIONAL DEFICIENCIES; MEDICARE PATIENTS; EARLY REVISION; OBESITY; METAANALYSIS; TRENDS; INFECTION AB This study compared the total joint arthroplasty (TJA) surgical outcomes of patients who had bariatric surgery prior to TJA to TJA patients who were candidates but did not have bariatric surgery. Patients were retrospectively grouped into: Group 1 (n = 69), those with bariatric surgery >2 years prior to TJA, Group 2 (n = 102), those with surgery within 2 years of TJA, and Group 3 (n = 11,032), those without bariatric surgery. In Group 1, 2.9% (95% CI 0.0-6.9%) had complications within 1 year compared to 5.9% (95% CI 1.3%-10.4%) in Group 2, and 4.1% (95% CI 3.8%-4.5%) in Group 3. Ninety-day readmission (7.2%, 95% CI 1.1%-13.4%) and revision density (3.4/100 years of observation) was highest in Group 1. Bariatric surgery prior to TJA may not provide dramatic improvements in post-operative TJA surgical outcomes. (C) 2014 Elsevier Inc. All rights reserved. C1 [Inacio, Maria C. S.; Paxton, Elizabeth W.] Kaiser Permanente, Surg Outcomes & Anal Dept, San Diego, CA 92108 USA. [Fisher, David] Kaiser Permanente, Dept Surg, Richmond, CA USA. [Li, Robert A.] Kaiser Permanente, Dept Bariatr Surg, San Francisco, CA USA. [Barber, Thomas C.] Kaiser Permanente, Dept Orthoped Surg, Oakland, CA USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL USA. [Singh, Jasvinder A.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Inacio, MCS (reprint author), Kaiser Permanente, Surg Outcomes & Anal Dept, San Diego, CA 92108 USA. OI Inacio, Maria/0000-0001-8261-2665 FU AHRQ HHS [HS013852, HS013852-07]; None [HS013852, HS013852-07] NR 37 TC 18 Z9 18 U1 0 U2 3 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 EI 1532-8406 J9 J ARTHROPLASTY JI J. Arthroplast. PD JUL PY 2014 VL 29 IS 7 BP 1359 EP 1364 DI 10.1016/j.arth.2014.02.021 PG 6 WC Orthopedics SC Orthopedics GA AL2FP UT WOS:000338941600007 PM 24674730 ER PT J AU Oh, CC Ko, HCH Lee, HY Safdar, N Maki, DG Chlebicki, MP AF Oh, Choon Chiat Ko, Henry Chung Hung Lee, Haur Yueh Safdar, Nasia Maki, Dennis G. Chlebicki, Maciej Piotr TI Antibiotic prophylaxis for preventing recurrent cellulitis: A systematic review and meta-analysis SO JOURNAL OF INFECTION LA English DT Review DE Cellulitis; Prophylaxis; Prevention; Recurrence ID SOFT-TISSUE INFECTIONS; LOWER-LIMB CELLULITIS; RISK-FACTORS; BACTERIAL CELLULITIS; LEG CELLULITIS; ERYSIPELAS; PENICILLIN; DISEASE; TRIAL; SKIN AB Importance: A significant proportion of patients who have had a first episode of erysipelas or uncomplicated cellulitis will subsequently develop a recurrence. There is disagreement about how effective antibiotic prophylaxis is for preventing recurrent cellulitis. Objective: To determine if antibiotic prophylaxis is effective in preventing recurrent cellulitis compared to no prophylaxis using a systematic review and meta-analysis. Data sources: Studies in any language identified by searching Medline, EMBASE, Cochrane Library, CINAHL, TRIP database, clinical practice guidelines websites, and ongoing trials databases up to 31st August 2012. Search terms included cellulitis, erysipelas, controlled clinical trial, randomized, placebo, clinical trials, randomly, and trial. Study selection: Only controlled trials comparing antibiotic prophylaxis to no antibiotic prophylaxis in patients age 16 years and above, and after 1 or more episodes of cellulitis, were included. Data extraction and synthesis: Independent extraction of articles was done by 2 investigators using predefined data extraction templates, including study quality indicators. PROSPERO registration number: CRD42012002528. Meta-analyses were done using random-effects models. Main outcomes and measures: The primary outcome was the number of patients with a recurrence of cellulitis. Secondary outcomes were (1) the time to next episode of recurrence, (2) quality of life measures, and (3) adverse events (e.g. allergic reactions, nausea). Results: Five randomized controlled trials (n = 535), with 260 patients in the intervention arm and 275 in the comparator group met our inclusion criteria. 44 patients (8%) in the antibiotic prophylaxis group and 97 patients (18%) in the comparator group had an episode of cellulitis. Antibiotic prophylaxis significantly reduced the number of patients having recurrent cellulitis, with a risk ratio (RR) of 0.46 (95% CI 0.26-0.79). None of the studies reported severe adverse effects to antibiotics. There was methodological heterogeneity amongst the studies in terms of types of antibiotic used, delivery modes, number of recurrences of cellulitis at study entry, and study quality. Conclusion and relevance: Antibiotic prophylaxis can prevent recurrent cellulitis. Future research should aim to identify the ideal type, dosage, and duration of antibiotics for prophylaxis, as well as to identify the group of patients who will benefit most from antibiotic prophylaxis. (C) 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved. C1 [Oh, Choon Chiat; Lee, Haur Yueh] Singapore Gen Hosp, Dept Dermatol, Singapore, Singapore. [Ko, Henry Chung Hung] SingHealth Corp, Ctr Hlth Serv Res, Res Off, Singapore, Singapore. [Ko, Henry Chung Hung] Duke NUS Grad Med Sch, Singapore, Singapore. [Ko, Henry Chung Hung] SingHlth Acad Med Res Inst, Singapore, Singapore. [Chlebicki, Maciej Piotr] Singapore Gen Hosp, Dept Infect Dis, Singapore, Singapore. [Safdar, Nasia] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Safdar, Nasia; Maki, Dennis G.] Univ Wisconsin, Sch Med, Dept Med, Infect Dis Sect, Madison, WI 53706 USA. RP Oh, CC (reprint author), Singapore Gen Hosp, Dept Dermatol, Singapore, Singapore. EM oh.choon.chiat@sgh.com.sg; henry.ko@ctc.usyd.edu.au; lee.haur.yueh@sgh.com.sg; ns2@medicine.wisc.edu; maki.dennis@yahoo.com; piotr.chlebicki@sgh.com.sg OI lee, haur yueh/0000-0003-1432-5810 FU MERIT award from the Department of Veterans Affairs FX Nasia Safdar is supported by a MERIT award from the Department of Veterans Affairs. The views in this paper do not necessarily represent the views of the authors' employers, nor the Department of Veterans Affairs. NR 38 TC 7 Z9 8 U1 1 U2 12 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0163-4453 EI 1532-2742 J9 J INFECTION JI J. Infect. PD JUL PY 2014 VL 69 IS 1 BP 26 EP 34 DI 10.1016/j.jinf.2014.02.011 PG 9 WC Infectious Diseases SC Infectious Diseases GA AL7YD UT WOS:000339352100003 PM 24576824 ER PT J AU Rankin, BL Buffo, SK Dean, JC AF Rankin, Bradford L. Buffo, Stephanie K. Dean, Jesse C. TI A neuromechanical strategy for mediolateral foot placement in walking humans SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article DE biomechanics; locomotion; muscle activity; stability ID FRONTAL PLANE; DYNAMIC STABILITY; LATERAL BALANCE; CORRECTIVE REACTIONS; TREADMILL WALKING; MUSCLE-ACTIVITY; HEALTHY-ADULTS; FALL-PRONE; LOWER-LIMB; GAIT AB Stability is an important concern during human walking and can limit mobility in clinical populations. Mediolateral stability can be efficiently controlled through appropriate foot placement, although the underlying neuromechanical strategy is unclear. We hypothesized that humans control mediolateral foot placement through swing leg muscle activity, basing this control on the mechanical state of the contralateral stance leg. Participants walked under Unperturbed and Perturbed conditions, in which foot placement was intermittently perturbed by moving the right leg medially or laterally during the swing phase (by similar to 50-100 mm). We quantified mediolateral foot placement, electromyographic activity of frontal-plane hip muscles, and stance leg mechanical state. During Unperturbed walking, greater swing-phase gluteus medius (GM) activity was associated with more lateral foot placement. Increases in GM activity were most strongly predicted by increased mediolateral displacement between the center of mass (CoM) and the contralateral stance foot. The Perturbed walking results indicated a causal relationship between stance leg mechanics and swing-phase GM activity. Perturbations that reduced the mediolateral CoM displacement from the stance foot caused reductions in swing-phase GM activity and more medial foot placement. Conversely, increases in mediolateral CoM displacement caused increased swing-phase GM activity and more lateral foot placement. Under both Unperturbed and Perturbed conditions, humans controlled their mediolateral foot placement by modulating swing-phase muscle activity in response to the mechanical state of the contralateral leg. This strategy may be disrupted in clinical populations with a reduced ability to modulate muscle activity or sense their body's mechanical state. C1 [Rankin, Bradford L.; Buffo, Stephanie K.; Dean, Jesse C.] Med Univ S Carolina, Coll Hlth Profess, Div Phys Therapy, Charleston, SC 29425 USA. [Dean, Jesse C.] Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC USA. RP Dean, JC (reprint author), 77 President St,MSC700, Charleston, SC 29425 USA. EM deaje@musc.edu OI Dean, Jesse/0000-0003-2034-4217 FU Department of Veterans Affairs, Office of Research and Development, Rehabilitation Research and Development Service [1IK2RX000750-01A1]; National Institute of Child Health and Human Development [1R21 HD-064964-01A1] FX This study was partially supported by the Department of Veterans Affairs, Office of Research and Development, Rehabilitation Research and Development Service through Grant 1IK2RX000750-01A1. This study was also partially supported by the National Institute of Child Health and Human Development through Grant 1R21 HD-064964-01A1. NR 66 TC 8 Z9 8 U1 4 U2 14 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 EI 1522-1598 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JUL PY 2014 VL 112 IS 2 BP 374 EP 383 DI 10.1152/jn.00138.2014 PG 10 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA AL5KM UT WOS:000339172500015 PM 24790168 ER PT J AU Gelfman, LP Kalman, J Goldstein, NE AF Gelfman, Laura P. Kalman, Jill Goldstein, Nathan E. TI Engaging Heart Failure Clinicians To Increase Palliative Care Referrals: Overcoming Barriers, Improving Techniques SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID ASSOCIATION TASK-FORCE; QUALITY-OF-LIFE; MEDICARE BENEFICIARIES; CONSENSUS STATEMENT; PRACTICE GUIDELINES; LUNG-CANCER; END; MANAGEMENT; CAREGIVERS; MORTALITY AB Background: Heart failure (HF) is the most common cause of hospitalization among adults over the age of 65. Hospital readmission rates, mortality rates, and Medicare costs for patients with this disease are high. Furthermore, patients with HF experience a number of symptoms that worsen as the disease progresses. However, a small minority of patients with HF receives hospice or palliative care. One possible reason for this may be that the HF and palliative care clinicians have differing perspectives on the role of palliative care for these patients. Aim: The goal of the article is to offer palliative care clinicians a roadmap for collaborating with HF clinicians by reviewing the needs of patients with HF. Conclusions: This article reviews the needs of patients with HF and their families, the barriers to referral to palliative care for patients with HF, and provides suggestions for improving collaboration between palliative care and HF clinicians. C1 [Gelfman, Laura P.; Goldstein, Nathan E.] Icahn Sch Med Mt Sinai, Brookdale Dept Geriatr & Palliat Med, New York, NY 10029 USA. [Kalman, Jill] Icahn Sch Med Mt Sinai, Dept Cardiol, New York, NY 10029 USA. [Gelfman, Laura P.; Goldstein, Nathan E.] James J Peters VA Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. RP Gelfman, LP (reprint author), Icahn Sch Med Mt Sinai, Brookdale Dept Geriatr & Palliat Med, 1 Gustave L Levy Pl,Box 1070, New York, NY 10029 USA. EM Laura.Gelfman@mssm.edu FU National Palliative Care Research Center (NPCRC) Junior Faculty Career Development Award; Mount Sinai School of Medicine's Older American Independence Center, Research Career Development Core support [5P30AG28741-04]; National Heart Lung and Blood Institute [R01 (5R01HL102084-03)]; [T32 (T32HP10262)]; [R03 (5R03AG042344-02)] FX The authors have no financial disclosures to present. Dr. Gelfman was supported by a T32 (T32HP10262) and is supported a National Palliative Care Research Center (NPCRC) Junior Faculty Career Development Award, an R03 (5R03AG042344-02), and Mount Sinai School of Medicine's Older American Independence Center (5P30AG28741-04) Research Career Development Core support. Dr. Kalman is supported by an R01 (5R01HL102084-03) from the National Heart Lung and Blood Institute. Dr. Goldstein is supported by an R01 (5R01HL102084-03) from the National Heart Lung and Blood Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Department of Veterans Affairs. NR 43 TC 10 Z9 10 U1 5 U2 9 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 EI 1557-7740 J9 J PALLIAT MED JI J. Palliat. Med. PD JUL PY 2014 VL 17 IS 7 BP 753 EP 760 DI 10.1089/jpm.2013.0675 PG 8 WC Health Care Sciences & Services SC Health Care Sciences & Services GA AL2HK UT WOS:000338946400005 PM 24901674 ER PT J AU Mehraei, G Gallun, FJ Leek, MR Bernstein, JGW AF Mehraei, Golbarg Gallun, Frederick J. Leek, Marjorie R. Bernstein, Joshua G. W. TI Spectrotemporal modulation sensitivity for hearing-impaired listeners: Dependence on carrier center frequency and the relationship to speech intelligibility SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID TEMPORAL FINE-STRUCTURE; AUDITORY FILTER SHAPES; MASKING RELEASE; RECEPTION THRESHOLD; NOTCHED-NOISE; AGE; SELECTIVITY; PERCEPTION; DISCRIMINATION; INDIVIDUALS AB Poor speech understanding in noise by hearing-impaired (HI) listeners is only partly explained by elevated audiometric thresholds. Suprathreshold-processing impairments such as reduced temporal or spectral resolution or temporal fine-structure (TFS) processing ability might also contribute. Although speech contains dynamic combinations of temporal and spectral modulation and TFS content, these capabilities are often treated separately. Modulation-depth detection thresholds for spectrotemporal modulation (STM) applied to octave-band noise were measured for normal-hearing and HI listeners as a function of temporal modulation rate (4-32 Hz), spectral ripple density [0.5-4 cycles/octave (c/o)] and carrier center frequency (500-4000Hz). STM sensitivity was worse than normal for HI listeners only for a low-frequency carrier (1000 Hz) at low temporal modulation rates (4-12 Hz) and a spectral ripple density of 2 c/o, and for a high-frequency carrier (4000Hz) at a high spectral ripple density (4 c/o). STM sensitivity for the 4-Hz, 4-c/o condition for a 4000-Hz carrier and for the 4-Hz, 2-c/o condition for a 1000-Hz carrier were correlated with speech-recognition performance in noise after partialling out the audiogram-based speech-intelligibility index. Poor speech-reception and STM-detection performance for HI listeners may be related to a combination of reduced frequency selectivity and a TFS-processing deficit limiting the ability to track spectral-peak movements. C1 [Mehraei, Golbarg] Harvard Univ, MIT, Program Speech & Hearing Bioscience & Technol, Cambridge, MA 02139 USA. [Gallun, Frederick J.; Leek, Marjorie R.] Portland VA Med Ctr, VA RR&D Natl Ctr Rehabilitat Auditory Res, Portland, OR 97239 USA. [Bernstein, Joshua G. W.] Walter Reed Natl Mil Med Ctr, Natl Mil Audiol & Speech Pathol Ctr, Bethesda, MD 20889 USA. RP Bernstein, JGW (reprint author), Walter Reed Natl Mil Med Ctr, Natl Mil Audiol & Speech Pathol Ctr, Bethesda, MD 20889 USA. EM joshua.g.bernstein.civ@health.mil FU NIDCD NIH HHS [R01 DC011828, T32 DC000038] NR 48 TC 7 Z9 7 U1 2 U2 15 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 EI 1520-8524 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD JUL PY 2014 VL 136 IS 1 BP 301 EP 316 DI 10.1121/1.4881918 PG 16 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA AL5HH UT WOS:000339163800037 PM 24993215 ER PT J AU Bourdette, D AF Bourdette, Dennis TI Alemtuzumab and multiple sclerosis Is it safe? SO NEUROLOGY LA English DT Editorial Material ID CONTROLLED PHASE-3 TRIAL; DISEASE C1 [Bourdette, Dennis] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Bourdette, Dennis] Portland VA Med Ctr, Multiple Sclerosis Ctr Excellence West, Portland, OR USA. RP Bourdette, D (reprint author), Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. EM bourdett@ohsu.edu NR 7 TC 2 Z9 2 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD JUL 1 PY 2014 VL 83 IS 1 BP 17 EP 18 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA AL2VB UT WOS:000338982500007 PM 24920853 ER PT J AU Smith, LJ Gorth, DJ Showalter, BL Chiaro, JA Beattie, EE Elliott, DM Mauck, RL Chen, W Malhotra, NR AF Smith, Lachlan J. Gorth, Deborah J. Showalter, Brent L. Chiaro, Joseph A. Beattie, Elizabeth E. Elliott, Dawn M. Mauck, Robert L. Chen, Weiliam Malhotra, Neil R. TI In Vitro Characterization of a Stem-Cell-Seeded Triple-Interpenetrating-Network Hydrogel for Functional Regeneration of the Nucleus Pulposus SO TISSUE ENGINEERING PART A LA English DT Article ID LOW-BACK-PAIN; PHOTOCROSSLINKED CARBOXYMETHYLCELLULOSE HYDROGELS; HUMAN INTERVERTEBRAL-DISK; N-CARBOXYETHYL CHITOSAN; OXIDIZED DEXTRAN; CARTILAGE MATRIX; HYALURONIC-ACID; LUMBAR DISC; DIFFERENTIATION; SPINE AB Intervertebral disc degeneration is implicated as a major cause of low-back pain. There is a pressing need for new regenerative therapies for disc degeneration that restore native tissue structure and mechanical function. To that end we investigated the therapeutic potential of an injectable, triple-interpenetrating-network hydrogel comprised of dextran, chitosan, and teleostean, for functional regeneration of the nucleus pulposus (NP) of the intervertebral disc in a series of biomechanical, cytotoxicity, and tissue engineering studies. Biomechanical properties were evaluated as a function of gelation time, with the hydrogel reaching similar to 90% of steady-state aggregate modulus within 10 h. Hydrogel mechanical properties evaluated in confined and unconfined compression were comparable to native human NP properties. To confirm containment within the disc under physiological loading, toluidine-blue-labeled hydrogel was injected into human cadaveric spine segments after creation of a nucleotomy defect, and the segments were subjected to 10,000 cycles of loading. Gross analysis demonstrated no implant extrusion, and further, that the hydrogel interdigitated well with native NP. Constructs were next surface-seeded with NP cells and cultured for 14 days, confirming lack of hydrogel cytotoxicity, with the hydrogel maintaining NP cell viability and promoting proliferation. Next, to evaluate the potential of the hydrogel to support cell-mediated matrix production, constructs were seeded with mesenchymal stem cells (MSCs) and cultured under prochondrogenic conditions for up to 42 days. Importantly, the hydrogel maintained MSC viability and promoted proliferation, as evidenced by increasing DNA content with culture duration. MSCs differentiated along a chondrogenic lineage, evidenced by upregulation of aggrecan and collagen II mRNA, and increased GAG and collagen content, and mechanical properties with increasing culture duration. Collectively, these results establish the therapeutic potential of this novel hydrogel for functional regeneration of the NP. Future work will confirm the ability of this hydrogel to normalize the mechanical stability of cadaveric human motion segments, and advance the material toward human translation using preclinical large-animal models. C1 [Smith, Lachlan J.; Gorth, Deborah J.; Showalter, Brent L.; Chiaro, Joseph A.; Malhotra, Neil R.] Univ Penn, Dept Neurosurg, Perelman Sch Med, Philadelphia, PA 19104 USA. [Smith, Lachlan J.; Gorth, Deborah J.; Showalter, Brent L.; Chiaro, Joseph A.; Beattie, Elizabeth E.; Mauck, Robert L.] Univ Penn, Dept Orthoped Surg, Perelman Sch Med, Philadelphia, PA 19104 USA. [Smith, Lachlan J.; Gorth, Deborah J.; Chiaro, Joseph A.; Mauck, Robert L.] Philadelphia Vet Affairs Med Ctr, Translat Musculoskeletal Res Ctr, Philadelphia, PA USA. [Showalter, Brent L.; Elliott, Dawn M.] Univ Delaware, Dept Biomed Engn, Coll Engn, Newark, DE USA. [Chen, Weiliam] NYU, Dept Surg, Sch Med, New York, NY 10016 USA. RP Malhotra, NR (reprint author), Univ Penn, Dept Neurosurg, 3 Silverstein Pavil,3400 Spruce St, Philadelphia, PA 19104 USA. EM neil.malhotra@uphs.upenn.edu FU Neurosurgery Research and Education Foundation; Department of Veterans Affairs [IO1RX000211]; Histology and Biomechanics cores of the Penn Center for Musculoskeletal Disorders [NIH P30 AR050950] FX This project was funded by grants from the Neurosurgery Research and Education Foundation and the Department of Veterans Affairs (IO1RX000211), and was supported by the Histology and Biomechanics cores of the Penn Center for Musculoskeletal Disorders (NIH P30 AR050950). NR 46 TC 13 Z9 15 U1 7 U2 32 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1937-3341 EI 1937-335X J9 TISSUE ENG PT A JI Tissue Eng. Part A PD JUL PY 2014 VL 20 IS 13-14 BP 1841 EP 1849 DI 10.1089/ten.tea.2013.0516 PG 9 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA AL5KG UT WOS:000339171900007 PM 24410394 ER PT J AU Sher, L AF Sher, Leo TI Alcohol, testosterone and suicide SO AUSTRALIAN AND NEW ZEALAND JOURNAL OF PSYCHIATRY LA English DT Letter C1 [Sher, Leo] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Sher, Leo] James J Peters Vet Adm, Med Ctr, Bronx, NY 10468 USA. RP Sher, L (reprint author), James J Peters Vet Adm, Med Ctr, 130 West Kingsbridge Rd, Bronx, NY 10468 USA. EM Leo.Sher@mssm.edu NR 3 TC 0 Z9 0 U1 2 U2 6 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0004-8674 EI 1440-1614 J9 AUST NZ J PSYCHIAT JI Aust. N. Z. J. Psych. PD JUL PY 2014 VL 48 IS 7 BP 688 EP 689 DI 10.1177/0004867414525845 PG 2 WC Psychiatry SC Psychiatry GA AL0JE UT WOS:000338812400018 PM 24567539 ER PT J AU Senders, A Hanes, D Bourdette, D Whitham, R Shinto, L AF Senders, Angela Hanes, Douglas Bourdette, Dennis Whitham, Ruth Shinto, Lynne TI Reducing survey burden: feasibility and validity of PROM IS measures in multiple sclerosis SO MULTIPLE SCLEROSIS JOURNAL LA English DT Article DE Computerized Adaptive Test; multiple sclerosis; outcome measurement; PROMIS; self-reporting; survey design; validation ID SHORT-FORM; DEPRESSION; OUTCOMES; INSTRUMENTS; VALIDATION; SYMPTOMS; SF-36 AB Background: Patient-reported outcomes are important for clinical research and care, yet administering and scoring the questionnaires requires considerable effort and time. The Patient Reported Outcomes Measurement Information System (PROMIS) could considerably reduce administrative obstacles and lessen survey burden for participants. Objective: Assess the feasibility and validity of PROMIS, compared to commonly-used legacy measures for multiple sclerosis (MS). Methods: In this cross-sectional survey, 133 participants with confirmed MS completed legacy surveys and PROMIS Computerized Adaptive Tests (CATs) for depression, anxiety, pain, fatigue and physical function. We conducted a multi-trait, multi-method analysis and verified results with confirmatory factor analysis. Results: The correlations between PROMIS and the corresponding legacy measures were large (0.67 to 0.87). The multi-trait, multi-method criteria were generally well met, providing good evidence of the validity of PROMIS measures. PROMIS surveys asked fewer questions and required substantially less time to complete than the legacy scales. Conclusions: Our results provide evidence of the construct validity of PROMIS for use with MS patients. Several aspects of the PROMIS CATs made them an important resource, including: (a) less time was required to complete them; (b) missing data was reduced; and (c) the automatic scoring referenced the general population. Our findings support the use of PROMIS in MS research and may have broader implications for clinical care, as well. C1 [Senders, Angela; Bourdette, Dennis; Whitham, Ruth; Shinto, Lynne] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. [Senders, Angela; Hanes, Douglas] Natl Coll Nat Med, Helfgott Res Inst, Portland, OR USA. [Bourdette, Dennis; Whitham, Ruth] Portland VA Med Ctr, Dept Neurol, Portland, OR USA. RP Senders, A (reprint author), Oregon Hlth & Sci Univ, Dept Neurol, 3181 SW Sam Jackson Pk Rd,Mail Code CR120, Portland, OR 97239 USA. EM senders@ohsu.edu FU Oregon Clinical and Translational Research Institute (National Center for Research Resources) [UL1 RR024140]; Oregon Clinical and Translational Research Institute (National Center for Advancing Translational Sciences of the National Institutes of Health (NIH)); National Center for Complementary and Alternative Medicine of the NIH [2R25AT002878-05A1, AT002688]; Agency for Healthcare Research Quality [5T32HS017582-05]; Medical Research Foundation of Oregon FX This work was supported by the Oregon Clinical and Translational Research Institute (grant number UL1 RR024140 from the National Center for Research Resources and the National Center for Advancing Translational Sciences of the National Institutes of Health (NIH)), the National Center for Complementary and Alternative Medicine of the NIH (grant numbers 2R25AT002878-05A1 and AT002688), the Agency for Healthcare Research Quality (grant number 5T32HS017582-05), and the Medical Research Foundation of Oregon. NR 30 TC 6 Z9 6 U1 13 U2 17 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 EI 1477-0970 J9 MULT SCLER J JI Mult. Scler. J. PD JUL PY 2014 VL 20 IS 8 BP 1102 EP 1111 DI 10.1177/1352458513517279 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AL0LW UT WOS:000338819400013 PM 24402035 ER PT J AU Dauvilliers, Y Siegel, JM Lopez, R Torontali, ZA Peever, JH AF Dauvilliers, Yves Siegel, Jerry M. Lopez, Regis Torontali, Zoltan A. Peever, John H. TI Cataplexy-clinical aspects, pathophysiology and management strategy SO NATURE REVIEWS NEUROLOGY LA English DT Review ID OREXIN KNOCKOUT MICE; SLEEP-WAKING CYCLE; QUALITY-OF-LIFE; REM-SLEEP; HUMAN NARCOLEPSY; SODIUM OXYBATE; CHILDHOOD NARCOLEPSY; CANINE NARCOLEPSY; INTRAVENOUS IMMUNOGLOBULINS; HYPOCRETIN-1 OREXIN AB Cataplexy is the pathognomonic symptom of narcolepsy, and is the sudden uncontrollable onset of skeletal muscle paralysis or weakness during wakefulness. Cataplexy is incapacitating because it leaves the individual awake but temporarily either fully or partially paralyzed. Occurring spontaneously, cataplexy is typically triggered by strong positive emotions such as laughter and is often underdiagnosed owing to a variable disease course in terms of age of onset, presenting symptoms, triggers, frequency and intensity of attacks. This disorder occurs almost exclusively in patients with depletion of hypothalamic orexin neurons. One pathogenetic mechanism that has been hypothesized for cataplexy is the activation, during wakefulness, of brainstem circuitry that normally induces muscle tone suppression in rapid eye movement sleep. Muscle weakness during cataplexy is caused by decreased excitation of noradrenergic neurons and increased inhibition of skeletal motor neurons by gamma-aminobutyric acid-releasing or glycinergic neurons. The amygdala and medial prefrontal cortex contain neural pathways through which positive emotions probably trigger cataplectic attacks. Despite major advances in understanding disease mechanisms in cataplexy, therapeutic management is largely symptomatic, with antidepressants and gamma-hydroxybutyrate being the most effective treatments. This Review describes the clinical and pathophysiological aspects of cataplexy, and outlines optimal therapeutic management strategies. C1 [Dauvilliers, Yves; Lopez, Regis] Univ Montpellier, Dept Neurol, INSERM, U1061, F-34295 Montpellier, France. [Siegel, Jerry M.] Univ Coll Los Angeles, Vet Adm Greater Los Angeles Healthcare Syst, North Hills, CA 91343 USA. [Torontali, Zoltan A.; Peever, John H.] Univ Toronto, Ctr Brain Sci, Dept Cell & Syst Biol, Toronto, ON M4X 1H7, Canada. RP Dauvilliers, Y (reprint author), Univ Montpellier, Dept Neurol, INSERM, U1061, F-34295 Montpellier, France. EM ydauvilliers@yahoo.fr NR 114 TC 29 Z9 29 U1 6 U2 23 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4758 EI 1759-4766 J9 NAT REV NEUROL JI Nat. Rev. Neurol. PD JUL PY 2014 VL 10 IS 7 BP 386 EP 395 DI 10.1038/nrneurol.2014.97 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA AL2HF UT WOS:000338945900005 PM 24890646 ER PT J AU Buman, MP Phillips, BA Youngstedt, SD Kline, CE Hirshkowitz, M AF Buman, Matthew P. Phillips, Barbara A. Youngstedt, Shawn D. Kline, Christopher E. Hirshkowitz, Max TI Does nighttime exercise really disturb sleep? Results from the 2013 National Sleep Foundation Sleep in America Poll SO SLEEP MEDICINE LA English DT Article DE Physical activity; Exercise; Survey; Sleep hygiene; Sleep quality; Sleep onset ID PHYSICAL-ACTIVITY; ADOLESCENTS; INSOMNIA; QUALITY; ADULTS AB Objective: To assess the relationship between sleep, time of exercise, and intensity of exercise in a large American sample. Methods: The 2013 National Sleep Foundation Sleep in America Poll was a cross-sectional study of 1000 adults stratified by age (23-60 years) and US geographical region. Sleep outcomes included self-reported sleep quality, total sleep time, sleep latency, and waking unrefreshed. Exercise timing was characterized as morning (>8 h before bed), afternoon (4-8 h before bed), or evening (<4 h before bed). Exercise intensity was assessed with a modified version of the International Physical Activity Questionnaire. Results: After adjustment for confounders, evening moderate or vigorous exercisers did not differ in any of the reported sleep metrics compared to non-exercisers. Morning vigorous exercisers had the most favorable sleep outcomes, including greater likelihood of reporting good sleep quality (OR = 1.88, p < .001) and lower likelihood of waking unrefreshed (OR = 0.56, p = .03). Most individuals who performed vigorous evening exercise believed that their sleep was of equal or better quality (97%) and duration (98%) on days they exercised. Conclusion: Evening exercise was not associated with worse sleep. These findings add to the growing body of evidence that sleep hygiene recommendations should not discourage evening exercise. (C) 2014 Elsevier B.V. All rights reserved. C1 [Buman, Matthew P.] Arizona State Univ, Sch Nutr & Hlth Promot, Phoenix, AZ 85004 USA. [Youngstedt, Shawn D.] Univ Kentucky, Coll Med, Div Pulm Crit Care & Sleep Med, Lexington, KY 40536 USA. [Youngstedt, Shawn D.] Univ S Carolina, WJB Dorn VA Med Ctr, Dept Exercise Sci, Columbia, SC 29208 USA. [Youngstedt, Shawn D.] Univ S Carolina, WJB Dorn VA Med Ctr, Dept Psychol, Columbia, SC 29208 USA. [Kline, Christopher E.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15213 USA. [Hirshkowitz, Max] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Sleep Ctr, Houston, TX 77030 USA. [Hirshkowitz, Max] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. RP Buman, MP (reprint author), Arizona State Univ, Sch Nutr & Hlth Promot, 500 N 3rd St,Mail Code 3020, Phoenix, AZ 85004 USA. EM matthew.buman@asu.edu RI Kline, Christopher/B-1477-2012 OI Kline, Christopher/0000-0003-1025-9430 NR 36 TC 23 Z9 23 U1 3 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1389-9457 EI 1878-5506 J9 SLEEP MED JI Sleep Med. PD JUL PY 2014 VL 15 IS 7 BP 755 EP 761 DI 10.1016/j.sleep.2014.01.008 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA AK7PT UT WOS:000338620900005 PM 24933083 ER PT J AU Ersek, M Jablonski, A AF Ersek, Mary Jablonski, Anita TI A Mixed-Methods Approach to Investigating the Adoption of Evidence-Based Pain Practices in Nursing Homes SO JOURNAL OF GERONTOLOGICAL NURSING LA English DT Article ID OLDER PERSONS; PERSISTENT PAIN; CARE; MANAGEMENT; IMPLEMENTATION; INTERVENTIONS; RESIDENTS; STAFF; ASSISTANTS; DEPRESSION AB This mixed methods study examined perceived facilitators and obstacles to adopting evidence-based pain management protocols vis-a-vis documented practice changes that were measured using a chart audit tool. This analysis used data from a subgroup of four nursing homes that participated in a clinical trial. Focus group interviews with staff yielded qualitative data about perceived factors that affected their willingness and ability to use the protocols. Chart audits determined whether pain assessment and management practices changed over time in light of these reported facilitators and barriers. Reported facilitators included administrative support, staff consistency, and policy and procedure changes. Barriers were staff attitudes, regulatory issues, and provider mistrust of nurses' judgment. Overall, staff reported improvements in pain practices. These reports were corroborated by modest but significant increases in adherence to recommended practices. Change in clinical practice is complex and requires attention to both structural and process aspects of care. C1 [Ersek, Mary] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Ersek, Mary] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. [Jablonski, Anita] Seattle Univ, Coll Nursing, Seattle, WA 98122 USA. RP Ersek, M (reprint author), Univ Penn, Sch Nursing, 418 Curie Blvd,Room 329, Philadelphia, PA 19104 USA. EM ersekm@nursing.upenn.edu FU NINR NIH HHS [R01 NR009100, R01NR009100] NR 39 TC 4 Z9 4 U1 0 U2 3 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0098-9134 EI 1938-243X J9 J GERONTOL NURS JI J. Gerontol. Nurs. PD JUL PY 2014 VL 40 IS 7 BP 52 EP 60 PG 9 WC Geriatrics & Gerontology; Gerontology; Nursing SC Geriatrics & Gerontology; Nursing GA AK9RC UT WOS:000338763400007 PM 24640959 ER PT J AU Horny, M Burgess, JF Horwitt, J Cohen, AB AF Horny, Michal Burgess, James F., Jr. Horwitt, Jedediah Cohen, Alan B. TI Advanced Diagnostic Imaging in Privately Insured Patients: Recent Trends in Utilization and Payments SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Diagnostic imaging; utilization; payments; commercial insurance AB Recent studies have reported that the rate of growth in utilization of noninvasive diagnostic imaging has slowed, with a concomitant reduction in total payments to providers in the Medicare Part B fee-for-service population. Utilization and payment growth trends in commercially insured populations, however, are not as well understood. We used the Truven Health Analytics MarketScan (R) Commercial Claims and Encounters database containing more than 29 million individuals to investigate commercially insured population trends in utilization of and payments for CT, MRI, PET, and ultrasound procedures in the years 2007-2011. We found that imaging use-after a brief downturn in 2010 rose again in 2011, coupled with substantial increases in adjusted payments for all four imaging modalities, raising concerns about future efforts to stem growth in imaging use and associated spending. C1 [Horny, Michal; Burgess, James F., Jr.] Boston Univ, Sch Publ Hlth, Boston, MA 02118 USA. [Burgess, James F., Jr.] US Dept Vet Affairs, Boston, MA USA. [Horwitt, Jedediah; Cohen, Alan B.] Boston Univ, Sch Management, Boston, MA 02215 USA. RP Horny, M (reprint author), Boston Univ, Sch Publ Hlth, Talbot Bldg T251W,715 Albany St, Boston, MA 02118 USA. EM mhorny@bu.edu OI Cohen, Alan B./0000-0002-5232-8927; Horny, Michal/0000-0003-3624-6398 NR 12 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD JUL PY 2014 VL 11 IS 7 BP 692 EP 697 DI 10.1016/j.jacr.2014.01.019 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AL0EP UT WOS:000338800500013 PM 24813748 ER PT J AU Morley, JF Pawlowski, SM Kesari, A Maina, I Pantelyat, A Duda, JE AF Morley, James F. Pawlowski, Stephanie M. Kesari, Adhithi Maina, Ivy Pantelyat, Alexander Duda, John E. TI Motor and non-motor features of Parkinson's disease that predict persistent drug-induced Parkinsonism SO PARKINSONISM & RELATED DISORDERS LA English DT Article DE Drug-induced Parkinsonism; Parkinson's disease; Non-motor symptoms; Olfactory dysfunction ID NEUROLEPTIC-INDUCED PARKINSONISM; SMELL IDENTIFICATION TEST; SLEEP BEHAVIOR DISORDER; OLFACTORY FUNCTION; QUESTIONNAIRE; BIOMARKER; SYMPTOMS AB Background: Drug-induced Parkinsonism is common, causes significant morbidity, and can be clinically indistinguishable from idiopathic Parkinson's disease. Additionally, drug-induced Parkinsonism may, in some cases, represent "unmasking" of incipient Parkinson's disease. Clinical features or tests that distinguish degenerative from pharmacologic Parkinsonism are needed. Methods: We performed a retrospective case-control study of 97 drug-induced Parkinsonism subjects and 97 age-matched patients with Parkinson's disease. We compared the frequency of subjective motor and non-motor complaints, objective motor findings (Unified Parkinson's Disease Rating Scale Part III) and, where available, objective olfactory tests. We also performed a nested case-control study wherein we compared these same features between drug-induced Parkinsonism patients based on whether or not they recovered after changing the offending agent. Results: Non-motor symptoms including constipation and sexual dysfunction were more common in Parkinson's disease than in drug-induced Parkinsonism. While total motor scores were similar between groups, Postural Instability-Gait Difficulty scores were also higher in Parkinson's disease. Features that were significantly different or showed a trend towards significance in both comparisons included subjective loss of facial expression, dream-enactment behavior, autonomic complaints and Postural Instability-Gait Difficulty scores. Hyposmia was more common in Parkinson's disease and was strongly predictive of persistent drug-induced Parkinsonism after therapy change (odds ratio 30.3, 95% confidence interval: 1.5-500, p = 0.03). Conclusions: A constellation of motor and non-motor features may differentiate unmasked Parkinson's disease from drug-induced Parkinsonism. In particular, olfactory testing may offer a simple and inexpensive method to help predict outcomes in drug-induced Parkinsonism and, potentially, identify a cohort of pre-motor Parkinson's disease. Published by Elsevier Ltd. C1 [Morley, James F.; Pawlowski, Stephanie M.; Kesari, Adhithi; Maina, Ivy; Pantelyat, Alexander; Duda, John E.] Philadelphia VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA 19104 USA. [Morley, James F.; Pantelyat, Alexander; Duda, John E.] Univ Penn, Perelman Sch Med, Dept Neurol, Philadelphia, PA 19104 USA. RP Morley, JF (reprint author), 3900 Woodland Ave,Mail Stop 127, Philadelphia, PA 19104 USA. EM James.morley@va.gov NR 29 TC 5 Z9 5 U1 0 U2 11 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1353-8020 EI 1873-5126 J9 PARKINSONISM RELAT D JI Parkinsonism Relat. Disord. PD JUL PY 2014 VL 20 IS 7 BP 738 EP 742 DI 10.1016/j.parkreldis.2014.03.024 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA AL0GL UT WOS:000338805300008 PM 24742370 ER PT J AU Chahine, LM Kauta, SR Daley, JT Cantor, CR Dahodwala, N AF Chahine, Lama M. Kauta, Shilpa R. Daley, Joseph T. Cantor, Charles R. Dahodwala, Nabila TI Surface EMG activity during REM sleep in Parkinson's disease correlates with disease severity SO PARKINSONISM & RELATED DISORDERS LA English DT Article DE Parkinson's disease; REM sleep behavior disorder; REM sleep without atonia; Surface EMG activity ID BEHAVIOR DISORDER; MOTOR FEATURES; DIAGNOSIS; DEMENTIA; QUESTIONNAIRE; PROGRESSION; ATONIA AB Objectives: Over 40% of individuals with Parkinson's disease (PD) have rapid eye movement sleep behavior disorder (RBD). This is associated with excessive sustained (tonic) or intermittent (phasic) muscle activity instead of the muscle atonia normally seen during REM sleep. We examined characteristics of manually-quantitated surface EMG activity in PD to ascertain whether the extent of muscle activity during REM sleep is associated with specific clinical features and measures of disease severity. Methods: In a convenience sample of outpatients with idiopathic PD, REM sleep behavior disorder was diagnosed based on clinical history and polysomnogram, and severity was measured using the RBD sleep questionnaire. Surface EMG activity in the mentalis, extensor muscle group of the forearms, and anterior tibialis was manually quantitated. Percentage of REM time with excessive tonic or phasic muscle activity was calculated and compared across PD and RBD characteristics. Results: Among 65 patients, 31 had confirmed RBD. In univariate analyses, higher amounts of surface EMG activity were associated with longer PD disease duration (srho = 0.34; p = 0.006) and greater disease severity (p < 0.001). In a multivariate regression model, surface EMG activity was significantly associated with RBD severity (p < 0.001) after adjustment for age, PD disease duration, PD severity and co-morbid sleep abnormalities. Conclusion: Surface EMG activity during REM sleep was associated with severity of both PD and RBD. This measure may be useful as a PD biomarker and, if confirmed, may aid in determining which PD patients warrant treatment for their dream enactment to reduce risk of injury. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Chahine, Lama M.; Cantor, Charles R.; Dahodwala, Nabila] Univ Penn, Perelman Sch Med, Dept Neurol, Philadelphia, PA 19104 USA. [Chahine, Lama M.; Kauta, Shilpa R.; Cantor, Charles R.] Univ Penn, Perelman Sch Med, Div Sleep Med, Philadelphia, PA 19104 USA. [Daley, Joseph T.] Univ Alabama Birmingham, Sch Med, Birmingham VA Med Ctr, Birmingham, AL USA. [Daley, Joseph T.] Univ Alabama Birmingham, Sch Med, Dept Neurol, Birmingham, AL USA. RP Chahine, LM (reprint author), 330 S 9th St, Philadelphia, PA 19107 USA. EM lamachahine@hotmail.com FU Vandrevala family; [K23 AG034236] FX We thank the patients whose participation made this work possible. We also thank the staff at the Hospital of the University of Pennsylvania Clinical Research Center for Sleep. This work was supported through the generosity of the Vandrevala family. Dr. Dahodwala was supported by K23 AG034236 during this project. NR 30 TC 9 Z9 9 U1 0 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1353-8020 EI 1873-5126 J9 PARKINSONISM RELAT D JI Parkinsonism Relat. Disord. PD JUL PY 2014 VL 20 IS 7 BP 766 EP 771 DI 10.1016/j.parkreldis.2014.04.011 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA AL0GL UT WOS:000338805300013 PM 24787758 ER PT J AU Jacobs, JV Nutt, JG Carlson-Kuhta, P Allen, R Horak, FB AF Jacobs, Jesse V. Nutt, John G. Carlson-Kuhta, Patricia Allen, Rebecca Horak, Fay B. TI Dual tasking during postural stepping responses increases falls but not freezing in people with Parkinson's disease SO PARKINSONISM & RELATED DISORDERS LA English DT Article DE Parkinson's disease; Dual task; Attention; Freezing of gait; Balance; Falls ID GAIT AB Purpose: Although falls in people with Parkinson's disease (PD) associate with dual tasking and freezing of gait (FoG), it is not known whether falls during dual tasking are due to FoG. This study investigated the effects of a cognitive task on the occurrence of falls and FoG when subjects with PD step in response to a postural perturbation. Methods: Ten subjects with PD and a history of FoG as well as 10 age-matched subjects without PD stepped in response to large, backward displacements of the support surface, with and without performing a fluency task of listing items in a category. Subjects with PD performed the task in the "off" and "on" dopaminergic medication states. We recorded the percentage of trials with FoG (a lack of step in response to the perturbation), foot-lift latencies, and trials with falls into a safety harness. Results: Dual tasking significantly increased the incidence of falls in people with PD, but subjects without PD did not fall in any condition. Dual tasking did not significantly increase trials without steps or foot-lift latencies. Falls were often coincident with a lack of step (FOG) in the single-task condition, but the increased falls with dual tasking occurred on trials with steps. Levodopa tended to decrease FOG and falls with or without dual tasking. However, medication did not significantly alter the effects of dual tasking on FoG or falls. Conclusions: For people with PD and FoG, forward falls may not always be caused by FoG, particularly under attention-distracting conditions. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Nutt, John G.; Carlson-Kuhta, Patricia; Allen, Rebecca; Horak, Fay B.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Nutt, John G.; Horak, Fay B.] Portland VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Portland, OR USA. [Jacobs, Jesse V.] Univ Vermont, Dept Rehabil & Movement Sci, Burlington, VT USA. RP Jacobs, JV (reprint author), 305 Rowell Bldg,106 Carrigan Dr, Burlington, VT 05405 USA. EM jjacobs@uvm.edu FU National Institutes of Health [AG006457] FX We thank the subjects who participated in the protocol. We are grateful for help with data analysis from Edward King, Michael Amos, and Christine Ryciewcz, and for technical assistance from Dr. Charles Russell and Edward King. The National Institutes of Health funded this study: grant AG006457. NR 7 TC 4 Z9 4 U1 0 U2 13 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1353-8020 EI 1873-5126 J9 PARKINSONISM RELAT D JI Parkinsonism Relat. Disord. PD JUL PY 2014 VL 20 IS 7 BP 779 EP 781 DI 10.1016/j.parkreldis.2014.04.001 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA AL0GL UT WOS:000338805300016 PM 24768615 ER PT J AU Bear, UR Anderson, H Manson, SM Shore, JH Prochazka, AV Novins, DK AF Bear, Ursula Running Anderson, Heather Manson, Spero M. Shore, Jay H. Prochazka, Allan V. Novins, Douglas K. TI Impact of adaptive functioning on readmission to alcohol detoxification among Alaska Native People SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Readmission; Detoxification; Substance abuse treatment; Alaska Native People; American Indian ID IV AXIS V; FOLLOW-UP; INPATIENT DETOXIFICATION; HOSPITAL READMISSION; GLOBAL ASSESSMENT; HEALTH-CARE; PREDICTION; MANAGEMENT; WITHDRAWAL; SERVICES AB Background: This study examined predictors associated with readmission to detoxification in a sample of adult Alaska Native patients admitted to inpatient alcohol detoxification. Even though Alaska Native people diagnosed with alcoholism have been identified as frequent utilizers of the health care system and at elevated risk of death, little is known about factors associated with readmission to detoxification for this group. Methods: We sought to predict readmission using a retrospective cohort study. The sample included 383 adult Alaska Native patients admitted to an inpatient detoxification unit and diagnosed with alcohol withdrawal during 2006 and 2007. Cox proportional hazard modeling was used to estimate unadjusted and adjusted associations with time to readmission within one year. Results: Forty-two percent of the patients were readmitted within one year. Global Assessment Functioning (GAF; Axis V in the multi-axial diagnostic system of the Diagnostic and Statistical Manual of Mental Disorders [DSM IV]) score measured at the time of intake was associated with readmission. A one point increase in the GAF score (HR=.96,95% CL=.94,.99, P=.002) was associated with a four percent decrease in readmission. The results also indicated that the GAF mediated the relationship between readmission and: employment and housing status. Conclusions: The GAF measures both illness severity and adaptive functioning, is part of standard behavioral health assessments, and is easy to score. Readmission rates potentially could be decreased by creating clinical protocols that account for differences in adaptive functioning and illness severity during detoxification treatment and aftercare. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Bear, Ursula Running; Manson, Spero M.; Shore, Jay H.; Novins, Douglas K.] Univ Colorado, Colorado Sch Publ Hlth, Ctr Amer Indian Hlth, Aurora, CO 80045 USA. [Bear, Ursula Running; Manson, Spero M.; Shore, Jay H.; Novins, Douglas K.] Univ Colorado, Colorado Sch Publ Hlth, Ctr Alaska Native Hlth, Aurora, CO 80045 USA. [Anderson, Heather] Univ Colorado, Skaggs Sch Pharm & Pharmaceut Sci, Dept Clin Pharm, Aurora, CO 80045 USA. [Shore, Jay H.; Novins, Douglas K.] Univ Colorado, Dept Psychiat, Aurora, CO 80045 USA. [Prochazka, Allan V.] Univ Colorado, Dept Med, Acad Off One, Aurora, CO 80045 USA. [Prochazka, Allan V.] Denver VA Med Ctr, Denver, CO 80220 USA. RP Bear, UR (reprint author), Univ Colorado, Colorado Sch Publ Hlth, Ctr Amer Indian Hlth, Anschutz Med Campus,13055 East 17th Ave, Aurora, CO 80045 USA. EM Ursula.RunningBear@ucdenver.edu FU National Institute for Minority Health and Health Disparities [P60 MD000507]; NIH/NCATS Colorado CTSI [UL1 TR000154] FX There was no funding source for the conduct of this research. Dr. Manson's efforts in the development and contributions of this manuscript were support by the National Institute for Minority Health and Health Disparities, P60 MD000507 (SM Manson, PI). Dr. Prochazka's efforts in the development and contributions of this manuscript were supported by NIH/NCATS Colorado CTSI Grant Number UL1 TR000154. NIMHD and NIH/NCATS had no further role in the study; design, analysis, interpretation of the data, writing of the manuscript or decision to submit the paper for publication NR 45 TC 3 Z9 3 U1 1 U2 6 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 EI 1879-0046 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD JUL 1 PY 2014 VL 140 BP 168 EP 174 DI 10.1016/j.drugalcdep.2014.04.018 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA AK7PD UT WOS:000338619300023 ER PT J AU Restrepo, MI Anzueto, A AF Restrepo, Marcos I. Anzueto, Antonio TI Macrolide Antibiotics for Prevention of Chronic Obstructive Pulmonary Disease Exacerbations: Are We There Yet? SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Editorial Material ID CONTROLLED-TRIAL; AZITHROMYCIN; COPD; THERAPY; RISK C1 [Restrepo, Marcos I.] Univ Texas Hlth Sci Ctr San Antonio, Div Pulm Dis & Crit Care Med, San Antonio, TX 78229 USA. South Texas Vet Hlth Care Syst, Audie L Murphy Mem Vet Affairs Hosp Div, San Antonio, TX USA. RP Restrepo, MI (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Div Pulm Dis & Crit Care Med, San Antonio, TX 78229 USA. FU NCATS NIH HHS [UL1 TR001120, KL2 TR001118]; NHLBI NIH HHS [K23 HL096054, K23HL096054] NR 17 TC 4 Z9 4 U1 1 U2 7 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JUL 1 PY 2014 VL 190 IS 1 BP 1 EP 2 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA AK3KX UT WOS:000338323900003 PM 24983214 ER PT J AU Wells, JM O'Reilly, PJ Szul, T Sullivan, DI Handley, G Garrett, C McNicholas, CM Roda, MA Miller, BE Tal-Singer, R Gaggar, A Rennard, SI Jackson, PL Blalock, JE AF Wells, J. Michael O'Reilly, Philip J. Szul, Tomasz Sullivan, Daniel I. Handley, Guy Garrett, Chris McNicholas, Carmel M. Roda, Mojtaba Abdul Miller, Bruce E. Tal-Singer, Ruth Gaggar, Amit Rennard, Stephen I. Jackson, Patricia L. Blalock, J. Edwin TI An Aberrant Leukotriene A(4) Hydrolase-Proline-Glycine-Proline Pathway in the Pathogenesis of Chronic Obstructive Pulmonary Disease SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE COPD; inflammation; PGP; leukotriene A(4) hydrolase; acrolein ID EXHALED BREATH CONDENSATE; CIGARETTE-SMOKE; ALPHA,BETA-UNSATURATED ALDEHYDES; NEUTROPHILIC INFLAMMATION; AIRWAY INFLAMMATION; COPD; EMPHYSEMA; ACROLEIN; MICE; CHEMOATTRACTANT AB Rationale: Chronic neutrophilic inflammation is a hallmark in the pathogenesis of chronic obstructive pulmonary disease (COPD) and persists after cigarette smoking has stopped. Mechanisms involved in this ongoing inflammatory response have not been delineated. Objectives: We investigated changes to the leukotriene A(4) hydrolase (LTA(4)H)-proline-glycine-proline (PGP) pathway and chronic inflammation in the development of COPD. Methods: A/J mice were exposed to air or cigarette smoke for 22 weeks followed by bronchoalveolar lavage and lung and cardiac tissue analysis. Two human cohorts were used to analyze changes to the LTA(4)H-PGP pathway in never smokers, control smokers, COPD smokers, and COPD former smokers. PGP/AcPGP and LTA(4)H aminopeptidase activity were detected by mass spectroscopy, LTA(4)H amounts were detected by ELISA, and acrolein was detected by Western blot. Measurements and Main Results: Mice exposed to cigarette smoke developed emphysema with increased PGP, neutrophilic inflammation, and selective inhibition of LTA(4)H aminopeptidase, which ordinarily degrades PGP. We recapitulated these findings in smokers with and without COPD. PGP and AcPGP are closely associated with cigarette smoke use. Once chronic inflammation is established, changes to LTA(4)H aminopeptidase remain, even in the absence of ongoing cigarette use. Acrolein modifies LTA(4)H and inhibits aminopeptidase activity to the same extent as cigarette smoke. Conclusions: These results demonstrate a novel pathway of aberrant regulation of PGP/AcPGP, suggesting this inflammatory pathway may be intimately involved in disease progression in the absence of ongoing cigarette smoke exposure. We highlight a mechanism by which acrolein potentiates neutrophilic inflammation through selective inhibition of LTA(4)H aminopeptidase activity. C1 [Wells, J. Michael; O'Reilly, Philip J.; Szul, Tomasz; Roda, Mojtaba Abdul; Gaggar, Amit; Jackson, Patricia L.; Blalock, J. Edwin] Univ Alabama Birmingham, Div Pulm Allergy & Crit Care Med, Birmingham, AL USA. [Wells, J. Michael; Jackson, Patricia L.; Blalock, J. Edwin] Univ Alabama Birmingham, Lung Hlth Ctr, Birmingham, AL USA. [Wells, J. Michael; O'Reilly, Philip J.; Szul, Tomasz; Sullivan, Daniel I.; Handley, Guy; Gaggar, Amit; Jackson, Patricia L.; Blalock, J. Edwin] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Garrett, Chris] Univ Alabama Birmingham, Dept Chem, Birmingham, AL 35294 USA. [McNicholas, Carmel M.] Univ Alabama Birmingham, Dept Cell Dev & Integrat Biol, Birmingham, AL USA. [Wells, J. Michael; Gaggar, Amit] Birmingham VA Med Ctr, Birmingham, AL USA. [Roda, Mojtaba Abdul] Univ Utrecht, Utrecht Inst Pharmaceut Sci, Fac Sci, Div Pharmacol, Utrecht, Netherlands. [Miller, Bruce E.] GlaxoSmithKline, King Of Prussia, PA USA. [Rennard, Stephen I.] Univ Nebraska Med Ctr, Div Pulm Crit Care Sleep & Allergy, Omaha, NE USA. RP Wells, JM (reprint author), 1900 Univ Blvd,THT 422, Birmingham, AL 35294 USA. EM jmwells@uab.edu FU Walter B. Frommeyer Jr. Fellowship in Investigational Medicine, University of Alabama; NHLBI [HL110950, HL114439, HL07783, HL092296]; Netherlands Organization for Scientific Research (Nederlandse Organisatie voor Wetenschappelijk Onderzoek, The Hague, The Netherlands) [017.008.029]; GlaxoSmithKline; University of Alabama O'Brien Acute Kidney Injury Center [P30 DK079337]; University of Alabama Skin Disease Research Center [P30 AR50948]; University of Alabama Lung Health Center; University of Alabama Center for Free Radical Biology FX Supported by a Walter B. Frommeyer Jr. Fellowship in Investigational Medicine, University of Alabama (J.M.W.); NHLBI grants HL110950, HL114439, and HL07783 (J.E.B.); NHLBI grant HL092296 (P.J.O'R.); Mosaic grant from the Netherlands Organization for Scientific Research (Nederlandse Organisatie voor Wetenschappelijk Onderzoek, The Hague, The Netherlands; grant 017.008.029 (M.A.R.). ECLIPSE was funded by GlaxoSmithKline. Funds for the operation of the Targeted Metabolomics and Proteomics Laboratory come in part from the University of Alabama O'Brien Acute Kidney Injury Center (P30 DK079337), the University of Alabama Skin Disease Research Center (P30 AR50948), the University of Alabama Lung Health Center, and the University of Alabama Center for Free Radical Biology. NR 38 TC 16 Z9 16 U1 0 U2 5 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JUL 1 PY 2014 VL 190 IS 1 BP 51 EP 61 DI 10.1164/rccm.201401-0145OC PG 11 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA AK3KX UT WOS:000338323900012 PM 24874071 ER PT J AU McDonell, M McPherson, S Vilardaga, R Srebnik, D Angelo, FN Leickly, E Saxon, AJ Roll, J Ries, R AF McDonell, Michael McPherson, Sterling Vilardaga, Roger Srebnik, Debra Angelo, Frank N. Leickly, Emily Saxon, Andrew J. Roll, John Ries, Richard TI Preliminary Findings: Contingency Management Targeting Psycho-Stimulant Use Results in Secondary Decreases in Smoking for Severely Mentally Ill Adults SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID CIGARETTE-SMOKING; ILLNESS; SERVICES AB Background: Treatments for drug addiction and smoking in severely mentally ill (SMI) adults are needed. Objectives: To investigate the effect of a contingency management (CM) intervention targeting psycho-stimulant on cigarette smoking. Methods: 126 stimulant dependent SMI smokers were assigned to CM or a non-contingent control condition. Rates of smoking-negative (<3 ppm) carbon monoxide breath-samples were compared. Results: Individuals who received CM targeting psycho-stimulants were 79% more likely to submit a smoking-negative breath-sample relative to controls. Conclusions and Scientific Significance: This study provides initial evidence that a behavioral treatment for drug use results in reductions in cigarette smoking in SMI adults. C1 [McDonell, Michael; Vilardaga, Roger; Srebnik, Debra; Angelo, Frank N.; Leickly, Emily; Saxon, Andrew J.; Ries, Richard] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98104 USA. [McDonell, Michael; Vilardaga, Roger; Srebnik, Debra; Angelo, Frank N.; Leickly, Emily; Ries, Richard] Univ Washington, Harborview Med Ctr, Seattle, WA 98104 USA. [McPherson, Sterling; Roll, John] Washington State Univ, Coll Nursing, Pullman, WA 99164 USA. [Saxon, Andrew J.] VA Puget Sound Hlth Care Syst, Ctr Excellence Substance Abuse Treatment & Educ, Seattle, WA USA. RP McDonell, M (reprint author), Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Harborview Med Ctr, Box 359911,325 9th Ave, Seattle, WA 98104 USA. EM mikemcd@uw.edu FU NIAAA NIH HHS [R01 AA020248, R01AA020248‐01A1]; NIDA NIH HHS [5R01DA022476‐04, R01 DA022476, L30 DA038339]; NIMH NIH HHS [T32 MH082709] NR 10 TC 2 Z9 2 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1055-0496 EI 1521-0391 J9 AM J ADDICTION JI Am. J. Addict. PD JUL-AUG PY 2014 VL 23 IS 4 BP 407 EP 410 DI 10.1111/j.1521-0391.2014.12114.x PG 4 WC Substance Abuse SC Substance Abuse GA AK0PM UT WOS:000338116600013 PM 24961363 ER PT J AU Huisinga, JM St George, RJ Spain, R Overs, S Horak, FB AF Huisinga, Jessie M. St George, Rebecca J. Spain, Rebecca Overs, Shannon Horak, Fay B. TI Postural Response Latencies Are Related to Balance Control During Standing and Walking in Patients With Multiple Sclerosis SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Electromyography; Evoked potentials; somatosensory; Multiple sclerosis; Rehabilitation; Walking ID DISABILITY STATUS SCALE; TIMED 25-FOOT WALK; OLDER-ADULTS; CENTRAL SET; GAIT; ACCELEROMETRY; IMPAIRMENT; FAMPRIDINE; CONDUCTION; DEFICITS AB Objective: To understand and examine the relation between postural response latencies obtained during postural perturbations and representative measures of balance during standing (sway variables) and walking (trunk motion). Design: Cross-sectional. Setting: University medical center. Participants: Persons with multiple sclerosis (MS) (n=40) were compared with similar aged control subjects (n=20). There were 20 subjects with MS in the normal walking velocity group and 20 subjects with MS who had slow walking velocity based on a timed 25-foot walk (T25FW) of <5 seconds. Interventions: None. Main Outcome Measures: Postural response latency, sway variables, trunk motion variables. Results: We found that subjects with MS with both slow or normal walking velocities had significantly longer postural response latencies than the healthy control group. Postural response latency was not correlated with the T25FW. Postural response latency was significantly correlated with center of pressure sway variables during quiet standing (root mean square: rho=.334, P=.04; range: rho=.385, P=.017; mean velocity: rho=.337, P=.038; total sway area: rho=.393, P=.015). Postural response latency was also significantly correlated with motion of the trunk during walking (sagittal plane range of motion: rho=.316, P=.05; SD of transverse plane range of motion: rho=-.43, P=.006). Conclusions: These findings clearly indicate that slow postural responses to external perturbations in patients with MS contribute to disturbances in balance control during both standing and walking. (C) 2014 by the American Congress of Rehabilitation Medicine C1 [Huisinga, Jessie M.] Univ Kansas, Landon Ctr Aging, Med Ctr, Kansas City, KS 66160 USA. [St George, Rebecca J.; Spain, Rebecca; Overs, Shannon; Horak, Fay B.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Spain, Rebecca] Portland VA Med Ctr, Dept Neurol, Portland, OR USA. RP Huisinga, JM (reprint author), Univ Kansas, Landon Ctr Aging, Med Ctr, 3901 Rainbow Blvd,MS1005, Kansas City, KS 66160 USA. EM jhuisinga@kumc.edu FU National Multiple Sclerosis Society [MB 0011]; National Institutes of Health [AG006457] FX Supported by the National Multiple Sclerosis Society (grant no. MB 0011) and the National Institutes of Health (grant no. AG006457). NR 40 TC 13 Z9 13 U1 2 U2 11 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 EI 1532-821X J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD JUL PY 2014 VL 95 IS 7 BP 1390 EP 1397 DI 10.1016/j.apmr.2014.01.004 PG 8 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA AK5QA UT WOS:000338479700023 PM 24445088 ER PT J AU Gelernter, J Kranzler, HR Sherva, R Koesterer, R Almasy, L Zhao, HY Farrer, LA AF Gelernter, Joel Kranzler, Henry R. Sherva, Richard Koesterer, Ryan Almasy, Laura Zhao, Hongyu Farrer, Lindsay A. TI Genome-Wide Association Study of Opioid Dependence: Multiple Associations Mapped to Calcium and Potassium Pathways SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Calcium signaling; complex traits; convergence; genome-wide association; opioid dependence; potassium ID NICOTINE DEPENDENCE; LINKAGE SCAN; DISEASE; SCHIZOPHRENIA; ALCOHOLISM; AFRICAN; TRAITS; FAMILY; GENES AB Background: We report a genome-wide association study (GWAS) of two populations, African-American and European-American (AA, EA) for opioid dependence (OD) in three sets of subjects, to identify pathways, genes, and alleles important in OD risk. Methods: The design employed three phases (on the basis of separate sample collections). Phase 1 included our discovery GWAS dataset consisting of 5697 subjects (58% AA) diagnosed with opioid and/or other substance dependence and control subjects. Subjects were genotyped with the Illumina OmniQuad microarray, yielding 890,000 single nucleotide polymorphisms (SNPs) suitable for analysis. Additional genotypes were imputed with the 1000 Genomes reference panel. Top-ranked findings were further evaluated in Phase 2 by incorporating information from the publicly available Study of Addiction: Genetics and Environment dataset, with GWAS data from 4063 subjects (32% AA). In Phase 3, the most significant SNPs from Phase 2 were genotyped in 2549 independent subjects (32% AA). Analyses were performed with case-control and ordinal trait designs. Results: Most significant results emerged from the AA subgroup. Genome-wide-significant associations (p < 5.0 x 10(-8)) were observed with SNPs from multiple loci-KCNG2*rs62103177 was most significant after combining results from datasets in every phase of the study. The most compelling results were obtained with genes involved in potassium signaling pathways (e.g., KCNC1 and KCNG2). Pathway analysis also implicated genes involved in calcium signaling and long-term potentiation. Conclusions: This is the first study to identify risk variants for OD with GWAS. Our results strongly implicate risk pathways and provide insights into novel therapeutic and prevention strategies and might biologically bridge OD and other non-substance dependence psychiatric traits where similar pathways have been implicated. C1 [Gelernter, Joel] Yale Univ, Sch Med, Dept Psychiat, West Haven, CT 06516 USA. [Gelernter, Joel] Yale Univ, Sch Med, Dept Genet, Div Human Genet, West Haven, CT 06516 USA. [Gelernter, Joel] Yale Univ, Sch Med, Dept Neurobiol, West Haven, CT 06516 USA. [Gelernter, Joel] VA Connecticut Healthcare Ctr, West Haven, CT USA. [Zhao, Hongyu] Yale Univ, Sch Publ Hlth, Dept Biostat, New Haven, CT USA. [Zhao, Hongyu] Yale Univ, Sch Publ Hlth, Dept Genet, New Haven, CT USA. [Kranzler, Henry R.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Kranzler, Henry R.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Sherva, Richard; Koesterer, Ryan; Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Med Biomed Genet, Boston, MA 02118 USA. [Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Neurol Ophthalmol Genet & Genom, Dept Epidemiol & Biostat, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Boston, MA USA. [Almasy, Laura] Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA. RP Gelernter, J (reprint author), Yale Univ, Sch Med, Dept Psychiat, Div Human Genet, VA CT 116A2,950 Campbell Ave, West Haven, CT 06516 USA. EM joel.gelernter@yale.edu OI Farrer, Lindsay/0000-0001-5533-4225 FU NIH Genes; Environment and Health Initiative (GEI) [U01 HG004422]; Gene Environment Association Studies (GENEVA) under GEI; GENEVA Coordinating Center [U01 HG004446]; Collaborative Study on the Genetics of Alcoholism (COGA) [U10 AA008401]; Collaborative Genetic Study of Nicotine Dependence (COGEND) [P01 CA089392]; Family Study of Cocaine Dependence (FSCD) [R01 DA013423]; NIH GEI [U01HG004438]; National Institute on Alcohol Abuse and Alcoholism; National Institute on Drug Abuse; NIH contract "High throughput genotyping for studying the genetic contributions to human disease" [HHSN268200782096C]; Genetics and Environment (SAGE) FX Funding support for the Study of Addiction: Genetics and Environment (SAGE) was provided through the NIH Genes, Environment and Health Initiative (GEI) (U01 HG004422). SAGE is one of the genome-wide association studies funded as part of the Gene Environment Association Studies (GENEVA) under GEI. Assistance with phenotype harmonization and genotype cleaning, as well as with general study coordination, was provided by the GENEVA Coordinating Center (U01 HG004446).; Assistance with data cleaning was provided by the National Center for Biotechnology Information. Support for collection of datasets and samples was provided by the Collaborative Study on the Genetics of Alcoholism (COGA; U10 AA008401), the Collaborative Genetic Study of Nicotine Dependence (COGEND; P01 CA089392), and the Family Study of Cocaine Dependence (FSCD; R01 DA013423). Funding for genotyping, which was performed at the Johns Hopkins University Center for Inherited Disease Research, was provided by the NIH GEI (U01HG004438), the National Institute on Alcohol Abuse and Alcoholism, the National Institute on Drug Abuse, and the NIH contract "High throughput genotyping for studying the genetic contributions to human disease" (HHSN268200782096C). NR 38 TC 36 Z9 36 U1 2 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUL 1 PY 2014 VL 76 IS 1 BP 66 EP 74 DI 10.1016/j.biopsych.2013.08.034 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AK2WD UT WOS:000338279500011 PM 24143882 ER PT J AU Myers, B Dolgas, CM Kasckow, J Cullinan, WE Herman, JP AF Myers, Brent Dolgas, C. Mark Kasckow, John Cullinan, William E. Herman, James P. TI Central stress-integrative circuits: forebrain glutamatergic and GABAergic projections to the dorsomedial hypothalamus, medial preoptic area, and bed nucleus of the stria terminalis SO BRAIN STRUCTURE & FUNCTION LA English DT Article DE Retrograde tracing; Amygdala; Prefrontal cortex; Vesicular glutamate transporter; Glutamic acid decarboxylase; Hypothalamo-pituitary-adrenal axis ID CORTICOTROPIN-RELEASING-FACTOR; CEREBRAL HEMISPHERE INTEGRATION; CENTRAL AMYGDALOID NUCLEUS; MESSENGER-RNA EXPRESSION; SEPTAL RAGE SYNDROME; ELEVATED PLUS-MAZE; PARAVENTRICULAR NUCLEUS; RAT-BRAIN; CARDIOVASCULAR-RESPONSE; EFFERENT PROJECTIONS AB Central regulation of hypothalamo-pituitary-adrenocortical (HPA) axis stress responses is mediated by a relatively circumscribed group of projections to the paraventricular hypothalamus (PVN). The dorsomedial hypothalamus (DMH), medial preoptic area (mPOA), and bed nucleus of the stria terminalis (BST) provide direct, predominantly inhibitory, innervation of the PVN. These PVN-projecting neurons are controlled by descending information from limbic forebrain structures, including the prefrontal cortex, amygdala, hippocampus, and septum. The neurochemical phenotype of limbic circuits targeting PVN relays has not been systematically analyzed. The current study combined retrograde tracing and immunohistochemistry/in situ hybridization to identify the specific sites of glutamatergic and GABAergic inputs to the DMH, mPOA, and BST. Following Fluoro-gold (FG) injections in the DMH, retrogradely labeled cells co-localized with vesicular glutamate transporter mRNA in the prefrontal cortex, ventral hippocampus, and paraventricular thalamus. Co-localization of FG and glutamic acid decarboxylase mRNA was present throughout the central and medial amygdaloid nuclei and septal area. In addition, the mPOA received predominantly GABAergic input from the septum, amygdala, and BST. The BST received glutamatergic projections from the hippocampus and basomedial amygdala, whereas, GABAergic inputs arose from central and medial amygdaloid nuclei. Thus, discrete sets of neurons in the hypothalamus and BST are positioned to summate limbic inputs into PVN regulation and may play a role in HPA dysfunction and stress-related illness. C1 [Myers, Brent; Herman, James P.] Univ Cincinnati, Metab Dis Inst, Dept Psychiat & Behav Neurosci, Cincinnati, OH 45237 USA. [Kasckow, John] Univ Pittsburgh, Western Psychiat Inst & Clin, VA Pittsburgh Hlth Care Syst, Med Ctr, Pittsburgh, PA 15213 USA. [Cullinan, William E.] Marquette Univ, Dept Biomed Sci, Milwaukee, WI 53233 USA. RP Myers, B (reprint author), Univ Cincinnati, Metab Dis Inst, Dept Psychiat & Behav Neurosci, 2170 E Galbraith Rd, Cincinnati, OH 45237 USA. EM brent.myers@uc.edu RI Herman, James/D-4960-2015 OI Herman, James/0000-0003-3571-2406 FU NIH [MH049698, MH069725, MH069860, MH090574] FX This work was supported by NIH grants MH049698, MH069725, MH069860, and MH090574 to JPH. The authors wish to thank Chun Xiao and Dana Ziegler for technical assistance. NR 71 TC 24 Z9 25 U1 2 U2 15 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1863-2653 EI 1863-2661 J9 BRAIN STRUCT FUNCT JI Brain Struct. Funct. PD JUL PY 2014 VL 219 IS 4 BP 1287 EP 1303 DI 10.1007/s00429-013-0566-y PG 17 WC Anatomy & Morphology; Neurosciences SC Anatomy & Morphology; Neurosciences & Neurology GA AK6DD UT WOS:000338517400010 PM 23661182 ER PT J AU Cohen, E Spiegel, B AF Cohen, Erica Spiegel, Brennan TI Why Do Symptoms Persist After Acute Diverticulitis? Reply SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Letter ID DISEASE; COLON C1 [Cohen, Erica] Cedars Sinai Med Ctr, VA Greater Los Angeles Healthcare Syst, Dept Gastroenterol, Los Angeles, CA 90048 USA. Cedars Sinai Med Ctr, VA Greater Los Angeles Healthcare Syst, Dept Hlth Serv, Los Angeles, CA 90048 USA. RP Cohen, E (reprint author), Cedars Sinai Med Ctr, VA Greater Los Angeles Healthcare Syst, Dept Gastroenterol, Los Angeles, CA 90048 USA. NR 10 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 EI 1542-7714 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD JUL PY 2014 VL 12 IS 7 BP 1200 EP 1200 DI 10.1016/j.cgh.2014.05.009 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AK4WX UT WOS:000338426100027 PM 24842668 ER PT J AU Williams, JLS Lynch, CP Winchester, R Thomas, L Keith, B Egede, LE AF Williams, Joni L. Strom Lynch, Cheryl P. Winchester, Rhonda Thomas, Leslie Keith, Brad Egede, Leonard E. TI Gender Differences in Composite Control of Cardiovascular Risk Factors Among Patients with Type 2 Diabetes SO DIABETES TECHNOLOGY & THERAPEUTICS LA English DT Article ID CORONARY-HEART-DISEASE; SEX DISPARITIES; MYOCARDIAL-INFARCTION; ARTERY-DISEASE; US ADULTS; MORTALITY; WOMEN; MEN; METAANALYSIS; ASSOCIATION AB Objective: Disparities in outcomes for cardiovascular disease (CVD) exist between men and women with type 2 diabetes mellitus (T2DM). We examined gender differences in composite control of cardiovascular risk factors in a sample of adults with T2DM. Subjects and Methods: This was a cross-sectional study of 680 people recruited from three primary care settings. Primary outcomes were individual and composite control of CVD risk factors. Control of individual risk outcomes was defined as glycosylated hemoglobin A1c (HbA1c) level of < 7%, blood pressure (BP) of < 130/80mm Hg, and low-density lipoprotein (LDL) cholesterol level of < 100 mg/dL. Composite control was defined as having all three outcomes under control simultaneously. Linear and logistic regression models were used to assess differences in individual means and individual and composite outcomes control between men and women, while adjusting for relevant covariates. Results: Men made up 56% of the sample, approximately 67% were non-Hispanic black, and 78% made less than $35,000 annually. Unadjusted mean systolic BP (134mm Hg vs. 130mm Hg, P = 0.005) and LDL cholesterol (99.7 mg/dL vs. 87.6 mg/dL, P < 0.001) levels were significantly higher in women than in men. Adjusted linear regression showed mean diastolic BP (beta = 3.09; 95% confidence interval 0.56, 5.63) was significantly higher in women. Overall, 12.4% of the sample had composite control, and women had poorer composite control compared with men (5.9% vs. 17.3%). Adjusted logistic models showed that men were significantly more likely to have composite risk factor control (odds ratio 2.90; 95% confidence interval 1.37, 6.13) compared with women. Conclusions: In this sample of adults with T2DM, women had significantly lower composite control compared with men, when adjusting for relevant confounders. It is imperative that women are informed about CVD risk factors, educated on how to reduce them, and aggressively treated to avoid adverse outcomes. Additional research involving women is needed to explore and reduce disparities in CVD risk between men and women with T2DM. C1 [Williams, Joni L. Strom; Lynch, Cheryl P.; Egede, Leonard E.] Med Univ S Carolina, Ctr Hlth Dispar Res, Dept Med, Charleston, SC 29425 USA. [Williams, Joni L. Strom; Lynch, Cheryl P.; Thomas, Leslie; Keith, Brad; Egede, Leonard E.] Med Univ S Carolina, Div Gen Internal Med & Geriatr, Dept Med, Charleston, SC 29425 USA. [Lynch, Cheryl P.; Egede, Leonard E.] Ralph H Johnson VA Med Ctr, HEROIC, Charleston, SC USA. [Winchester, Rhonda] Med Univ S Carolina, Coll Med, Charleston, SC 29425 USA. RP Egede, LE (reprint author), Med Univ S Carolina, Ctr Hlth Dispar Res, 135 Rutledge Ave,Room 280G,POB 250593, Charleston, SC 29425 USA. EM egedel@musc.edu FU Agency for Health Care Research and Quality [5K08HS11418] FX This work was funded by the Agency for Health Care Research and Quality (Grant #5K08HS11418). NR 33 TC 7 Z9 7 U1 1 U2 5 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1520-9156 EI 1557-8593 J9 DIABETES TECHNOL THE JI Diabetes Technol. Ther. PD JUL PY 2014 VL 16 IS 7 BP 421 EP 427 DI 10.1089/dia.2013.0329 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AK1PD UT WOS:000338186100003 ER PT J AU Kaunitz, JD AF Kaunitz, Jonathan D. TI Priming the (Proton) Pump SO DIGESTIVE DISEASES AND SCIENCES LA English DT Editorial Material ID SECRETION; MUCOSA C1 [Kaunitz, Jonathan D.] W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. [Kaunitz, Jonathan D.] Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90073 USA. [Kaunitz, Jonathan D.] Univ Calif Los Angeles, Sch Med, Dept Surg, Los Angeles, CA 90073 USA. RP Kaunitz, JD (reprint author), W Los Angeles Vet Affairs Med Ctr, 11301 Wilshire Blvd,Bldg 114,Room 217E, Los Angeles, CA 90073 USA. EM jake@ucla.edu FU NIDDK NIH HHS [R01 DK054221] NR 9 TC 1 Z9 1 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 EI 1573-2568 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD JUL PY 2014 VL 59 IS 7 BP 1356 EP 1357 DI 10.1007/s10620-014-3105-7 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AK3SH UT WOS:000338344500006 PM 24627261 ER PT J AU Sachs, G Shin, JM Munson, K Scott, DR AF Sachs, George Shin, Jai Moo Munson, Keith Scott, David R. TI Gastric Acid-Dependent Diseases: A Twentieth-Century Revolution SO DIGESTIVE DISEASES AND SCIENCES LA English DT Editorial Material ID PROTON PUMP INHIBITOR; HELICOBACTER-PYLORI; PARIETAL-CELLS; MONOFUMARATE TAK-438; MEMBRANE-VESICLES; INTRAGASTRIC PH; GENE-EXPRESSION; DUODENAL-ULCER; ATPASE; OMEPRAZOLE C1 [Sachs, George] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Sachs, George; Munson, Keith; Scott, David R.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Shin, Jai Moo] Jai Sci, Chatsworth, CA USA. RP Sachs, G (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Vet Adm Greater Los Angeles Healthcare Syst, Bldg 113,Rm 324 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM gsachs@ucla.edu NR 65 TC 9 Z9 9 U1 0 U2 12 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 EI 1573-2568 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD JUL PY 2014 VL 59 IS 7 BP 1358 EP 1369 DI 10.1007/s10620-014-3104-8 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AK3SH UT WOS:000338344500007 PM 24852882 ER PT J AU Arney, J Hinojosa-Lindsey, M Street, RL Hou, JS El-Serag, HB Naik, AD AF Arney, Jennifer Hinojosa-Lindsey, Marilyn Street, Richard L., Jr. Hou, Jason El-Serag, Hashem B. Naik, Aanand D. TI Patient Experiences with Surveillance Endoscopy: A Qualitative Study SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Qualitative research; Endoscopy; Barrett's esophagus screening; Patient experience; Adherence ID BARRETTS-ESOPHAGUS; ADENOCARCINOMA; COMMUNICATION; PERCEPTIONS; GUIDELINES; DIAGNOSIS; MEMORIES; PAIN AB Prior studies examining patterns of esophagogastroduodenoscopy (EGD) surveillance in patients with Barrett's esophagus (BE) demonstrate variable adherence to practice guidelines. In prior studies, memories of endoscopic experiences shaped overall perceptions and subsequent adherence behaviors, but the specific elements of that experience are unclear. We sought to identify specific elements of the EGD experience that frame overall perceptions of surveillance. We conducted structured in-depth, qualitative interviews with BE patients with a range of severity (non-dysplastic, low-grade and high-grade dysplasia) who recently completed an EGD. Data collection continued until we reached thematic saturation (n = 20). We applied principles of framework analysis to identify emerging themes regarding patients' salient EGD experiences. We validated our coding scheme through multidisciplinary consensus meetings comprised of clinician (gastroenterologist and internist) and non-clinician investigators (sociologist and public health expert). Patient experiences can be conceptualized within a temporal model: prior to, during, and after endoscopy. The most memorable aspects of the EGD experience include physician-patient communication prior to EGD, wait time at the endoscopy center, interpersonal interactions at the time of the EGD, level of pain or discomfort with the procedure, level of trust in the physician following EGD, and gaining a sense of control over BE. We identified six salient memories before, during, and after the procedure that shape patients' perceptions of the EGD experience. We offer recommendations for measuring patient experiences using a composite of validated survey items. Future studies should test the relation of patient experience measures and adherence to surveillance EGD. C1 [Arney, Jennifer] Univ Houston Clear Lake, Dept Sociol, Houston, TX USA. [Arney, Jennifer; Hinojosa-Lindsey, Marilyn; Street, Richard L., Jr.; Hou, Jason; El-Serag, Hashem B.; Naik, Aanand D.] Michael E DeBakey VA Med Ctr 152, Hlth Serv Res & Dev Ctr Innovat Qual Effectivenes, Houston, TX 77030 USA. [Arney, Jennifer; Hinojosa-Lindsey, Marilyn; Street, Richard L., Jr.; Hou, Jason; El-Serag, Hashem B.; Naik, Aanand D.] Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA. [Street, Richard L., Jr.] Texas A&M Univ, Dept Commun, College Stn, TX USA. RP El-Serag, HB (reprint author), Michael E DeBakey VA Med Ctr 152, Hlth Serv Res & Dev Ctr Innovat Qual Effectivenes, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM hasheme@bcm.edu FU NIH [RC4CA155844]; Texas Digestive Disease Center NIH [DK58338]; Houston VA Health Services Research & Development Center of Innovation [CIN 13-413]; American College of Gastroenterology Junior Faculty Development Award; VA Office of Academic Affiliations Post-Doctoral Fellowship in Health Services Research FX This work was supported by NIH grant RC4CA155844 awarded to Dr. El-Serag and the Texas Digestive Disease Center NIH DK58338. Additional resources and support was provided by the Houston VA Health Services Research & Development Center of Innovation (CIN 13-413) and American College of Gastroenterology Junior Faculty Development Award (J.K. Hou). The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs or National Institutes of Health. Dr. Arney received support from the VA Office of Academic Affiliations Post-Doctoral Fellowship in Health Services Research. NR 35 TC 1 Z9 1 U1 0 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 EI 1573-2568 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD JUL PY 2014 VL 59 IS 7 BP 1378 EP 1385 DI 10.1007/s10620-014-3035-4 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AK3SH UT WOS:000338344500010 PM 24500449 ER PT J AU Kramer, BJ Creekmur, B Mitchell, MN Rose, DJ Pynoos, J Rubenstein, LZ AF Kramer, B. Josea Creekmur, Beth Mitchell, Michael N. Rose, Debra J. Pynoos, Jon Rubenstein, Laurence Z. TI Community Fall Prevention Programs: Comparing Three InSTEP Models by Level of Intensity SO JOURNAL OF AGING AND PHYSICAL ACTIVITY LA English DT Article DE injury; risk reduction; older adults ID OLDER-ADULTS; GERIATRIC SYNDROMES; SCALE; INTERVENTION; METAANALYSIS; EXERCISE; SENIORS; BALANCE; CARE AB The Fall Prevention Center of Excellence designed three progressive-intensity fall prevention program models, Increasing Stability Through Evaluation and Practice (InS1EP), to reduce risk in community-dwelling older adults. Each model included physical activity, medical risk, and home safety components and was implemented as a 12-week program for small class sizes (12-15 people) in community and senior centers. Change in fall rates and fall risk factors was assessed using a battery of performance tests, self-reports of function, and fall diaries in a 3-group within-subjects (N = 200) design measured at baseline, immediately postintervention, and at 3 and 9 months postintervention. Overall, participants experienced a reduction in falls, improved self-perception of gait and balance, and improved dynamic gait function. The medium-intensity InSTEP model significantly (p = .003) reduced self-reported falls in comparison with the other models. InSTEP is a feasible model for addressing fall risk reduction in community-dwelling older adults. C1 [Kramer, B. Josea; Creekmur, Beth] VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ Clin Ctr, Los Angeles, CA 90073 USA. [Mitchell, Michael N.] Michael Mitchell Consulting, Simi Valley, CA USA. [Rose, Debra J.] Calif State Univ Fullerton, Dept Kinesiol, Fullerton, CA 92634 USA. [Pynoos, Jon] Univ So Calif, Andrus Gerontol Ctr, Los Angeles, CA USA. [Rubenstein, Laurence Z.] Univ Oklahoma, Coll Med, Dept Geriatr Med, Oklahoma City, OK 73190 USA. RP Kramer, BJ (reprint author), VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ Clin Ctr, Los Angeles, CA 90073 USA. EM josea.kramer@va.gov OI Creekmur, Beth/0000-0001-7802-1125 FU Archstone Foundation; University of Southern California; California State University at Fullerton; Sepulveda Research Corporation at the VA Greater Los Angeles Healthcare System FX This study was funded by grants from the Archstone Foundation to the University of California, the University of Southern California, California State University at Fullerton, and the Sepulveda Research Corporation at the VA Greater Los Angeles Healthcare System. We would also like to acknowledge the contributions of Karen R. Josephson, MPH, in conceptualizing key issues related to the background, variable selection, and discussion and of Judith O. Harker, PhD, in data management and repeated-measures analyses. NR 30 TC 1 Z9 1 U1 2 U2 8 PU HUMAN KINETICS PUBL INC PI CHAMPAIGN PA 1607 N MARKET ST, PO BOX 5076, CHAMPAIGN, IL 61820-2200 USA SN 1063-8652 EI 1543-267X J9 J AGING PHYS ACTIV JI J. Aging Phys. Act. PD JUL PY 2014 VL 22 IS 3 BP 372 EP 379 DI 10.1123/JAPA.2012-0344 PG 8 WC Geriatrics & Gerontology; Gerontology; Sport Sciences SC Geriatrics & Gerontology; Sport Sciences GA AJ9AI UT WOS:000337998800010 PM 23945593 ER PT J AU Hood, JE Hogben, M Chartier, M Bolan, G Bauer, H AF Hood, Julia E. Hogben, Matthew Chartier, Maggie Bolan, Gail Bauer, Heidi TI Dual contraceptive use among adolescents and young adults: correlates and implications for condom use and sexually transmitted infection outcomes SO JOURNAL OF FAMILY PLANNING AND REPRODUCTIVE HEALTH CARE LA English DT Article ID HORMONAL CONTRACEPTION; WOMEN; PREGNANCY; RISK; PROTECTION; BARRIERS AB Background Simultaneous condom and hormonal contraception usage ('dual method use') maximises protection against pregnancy and sexually transmitted infection (STI), although there is concern that promotion of this strategy could result in diminished condom use and inadvertently increase STI risk. In this study, we (1) assessed how the use of dual methods, versus condoms alone, related to STI and consistency of condom use and (2) described the correlates of dual use. Methods A sample of 1450 young people aged 12-25 years were surveyed and screened for chlamydia and gonorrhoea at non-clinical sites in two high morbidity Californian counties in 2002-2003. Differences in STI prevalence and reported consistency of condom use were assessed for 'condom only' and 'dual method' users. Correlates of dual use were analysed via multivariate polytomous logistic regression. Results Condom only and dual method users did not significantly differ in terms of STI prevalence or reported consistency of condom use. Sex, age, race and relationship tenure were significant correlates of dual use. Discussion In these observational data, dual method use did not detrimentally affect STI risk. If interpreted alongside each subgroups' risk patterns for STI and unplanned pregnancy, the correlates of dual use can inform STI and pregnancy prevention interventions. C1 [Hood, Julia E.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Hogben, Matthew] Ctr Dis Control & Prevent, Social & Behav Res & Evaluat Branch, Div STD Prevent, Atlanta, GA USA. [Chartier, Maggie] San Francisco VA Med Ctr, Dept Veteran Affairs, San Francisco, CA USA. [Bolan, Gail] Ctr Dis Control & Prevent, Div STD Prevent, Atlanta, GA USA. [Bauer, Heidi] Calif Dept Publ Hlth, STD Control Branch, Richmond, CA USA. RP Hood, JE (reprint author), Univ Washington, Dept Epidemiol, F263 Hlth Sci Bldg,1959 NE Pacific St, Seattle, WA 98195 USA. EM juliahehood@gmail.com FU Centers for Disease Control and Prevention (Comprehensive STD Prevention Systems and Infertility Prevention Project) [H25/CCH904362]; California Department of Public Health FX Centers for Disease Control and Prevention (Comprehensive STD Prevention Systems and Infertility Prevention Project Grant Number H25/CCH904362) and California Department of Public Health. NR 32 TC 0 Z9 0 U1 1 U2 9 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1471-1893 EI 2045-2098 J9 J FAM PLAN REPROD H JI J. Fam. Plan. Reprod. Health Care PD JUL PY 2014 VL 40 IS 3 BP 200 EP 207 DI 10.1136/jfprhc-2012-100295 PG 8 WC Family Studies; Obstetrics & Gynecology; Social Sciences, Biomedical SC Family Studies; Obstetrics & Gynecology; Biomedical Social Sciences GA AK1PI UT WOS:000338186800009 PM 24293508 ER PT J AU Yano, EM Bair, MJ Carrasquillo, O Krein, SL Rubenstein, LV AF Yano, Elizabeth M. Bair, Matthew J. Carrasquillo, Olveen Krein, Sarah L. Rubenstein, Lisa V. TI Patient Aligned Care Teams (PACT): VA's Journey to Implement Patient-Centered Medical Homes SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material C1 [Yano, Elizabeth M.; Rubenstein, Lisa V.] VA Greater Los Angeles Healthcare Syst, VA HSR & D Ctr Study Healthcare Innovat Implement, Sepulveda, CA 91343 USA. [Yano, Elizabeth M.; Rubenstein, Lisa V.] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA USA. [Bair, Matthew J.] VA Ctr Hlth Informat & Commun, Roudebush VA Med Ctr, Indianapolis, IN USA. [Bair, Matthew J.] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [Carrasquillo, Olveen] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [Krein, Sarah L.] VA Ann Arbor Hlth Care Syst, Ann Arbor, MI USA. [Krein, Sarah L.] Univ Michigan, Sch Med, Ann Arbor, MI USA. [Rubenstein, Lisa V.] VA Greater Los Angeles Healthcare Syst, VA QUERI Ctr Implementat Practice & Res Support, Sepulveda, CA USA. [Rubenstein, Lisa V.] VA Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA USA. [Rubenstein, Lisa V.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Rubenstein, Lisa V.] RAND Corp, RAND Hlth, Santa Monica, CA USA. RP Yano, EM (reprint author), VA Greater Los Angeles Healthcare Syst, VA HSR & D Ctr Study Healthcare Innovat Implement, Sepulveda, CA 91343 USA. RI Krein, Sarah/E-2742-2014 OI Krein, Sarah/0000-0003-2111-8131 NR 0 TC 6 Z9 6 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2014 VL 29 SU 2 BP 547 EP 549 DI 10.1007/s11606-014-2835-8 PG 3 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AK3OS UT WOS:000338334700001 ER PT J AU Farmer, MM Rose, DE Rubenstein, LV Canelo, IA Schectman, G Stark, R Yano, EM AF Farmer, Melissa M. Rose, Danielle E. Rubenstein, Lisa V. Canelo, Ismelda A. Schectman, Gordon Stark, Richard Yano, Elizabeth M. TI Challenges Facing Primary Care Practices Aiming to Implement Patient-Centered Medical Homes SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE primary care; patient-centered medical home; Veterans; VA healthcare system; health care management ID HEALTH INFORMATION-TECHNOLOGY; COST SAVINGS; CHRONIC PAIN; QUALITY; TRANSFORMATION; INNOVATION; FUTURE; PROVIDERS; SYSTEM AB While the potential of patient-centered medical homes (PCMH) is promising, little is known empirically about the frontline challenges that primary care (PC) leaders face before making the decision to implement PCMH, let alone in making it a reality. Prior to the design and implementation of the Veterans Health Administration's (VA) national PCMH model-Patient Aligned Care Teams (PACT)-we identified the top challenges faced by PC directors and examined the organizational and area level factors that influenced those challenges. A national cross-sectional key informant organizational survey was fielded to the census of PC directors at VA medical centers and large community-based outpatient clinics (final sample n = 229 sites). PC directors were asked to rate the degree to which they faced 48 management challenges in eight PCMH-related domains (access, preventive care, chronic diseases requiring care in PC, challenging medical conditions, mental health/substance abuse, special populations, PC coordination of care, and clinical informatics). Responses were dichotomized as moderately-to-extremely challenging versus somewhat-slightly-not at all challenging. Items were rank ordered; chi square or regression techniques were used to examine variations in facility size, type, urban/rural location, and region. On average, VA PC directors reported 16 moderate-to-extreme challenges, and the top 20 challenges spanned all eight PCMH domains. Four of the top 20 challenges, including the top two challenges, were from the clinical informatics domain. Management of chronic non-malignant pain requiring opiate therapy was the third most reported challenge nationwide. Significant organizational and area level variations in reported challenges were found especially for care coordination. Better understanding of PC challenges ahead of PCMH implementation provides important context for strategic planning and redesign efforts. As a national healthcare system, the VA provides a unique opportunity to examine organizational and area determinants relevant to other PCMH models. C1 [Farmer, Melissa M.; Rose, Danielle E.; Rubenstein, Lisa V.; Canelo, Ismelda A.; Yano, Elizabeth M.] VA Greater Los Angeles Healthcare Syst, VA HSR & D Ctr Study Healthcare Innovat Implement, Sepulveda, CA 91343 USA. [Rubenstein, Lisa V.] David Geffen UCLA Sch Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA USA. [Rubenstein, Lisa V.] RAND Hlth, Santa Monica, CA USA. [Rubenstein, Lisa V.] VA Greater Los Angeles Healthcare Syst, Ctr Implementat Practice & Res Support, Sepulveda, CA 91343 USA. [Schectman, Gordon] Vet Hlth Adm, Off Patient Care Serv, Washington, DC USA. [Stark, Richard] Vet Hlth Adm, Off Primary Care Clin Operat, Washington, DC USA. [Yano, Elizabeth M.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA 90024 USA. RP Farmer, MM (reprint author), VA Greater Los Angeles Healthcare Syst, VA HSR & D Ctr Study Healthcare Innovat Implement, Sepulveda Campus,Mailcode 152,16111 Plummer St, Sepulveda, CA 91343 USA. EM Melissa.Farmer@va.gov FU VA Office of Patient Care Services [XVA 65-011]; VA HSR&D project examining implementation and impact of VA patient-centered medical homes [IIR 09-082]; VA HSR&D Service through a Senior Research Career Scientist award [RCS 05-195] FX We would like to acknowledge funding from the VA Office of Patient Care Services for this operations project in support of VA primary care planning for patient-centered medical home implementation (Project # XVA 65-011). Additional analysis of these data was also supported by a VA HSR&D project examining implementation and impact of VA patient-centered medical homes (Project # IIR 09-082). Dr. Yano's effort was funded by VA HSR&D Service through a Senior Research Career Scientist award (Project # RCS 05-195). We would also like to acknowledge Britney Chow, MPH for administrative support. NR 39 TC 2 Z9 2 U1 1 U2 16 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2014 VL 29 SU 2 BP 555 EP 562 DI 10.1007/s11606-013-2691-y PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AK3OS UT WOS:000338334700004 ER PT J AU Luck, J Bowman, C York, L Midboe, A Taylor, T Gale, R Asch, S AF Luck, Jeff Bowman, Candice York, Laura Midboe, Amanda Taylor, Thomas Gale, Randall Asch, Steven TI Multimethod Evaluation of the VA's Peer-to-Peer Toolkit for Patient-Centered Medical Home Implementation SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE primary care redesign; patient-centered care; evaluation; implementation research; quality improvement ID HEALTH AB Effective implementation of the patient-centered medical home (PCMH) in primary care practices requires training and other resources, such as online toolkits, to share strategies and materials. The Veterans Health Administration (VA) developed an online Toolkit of user-sourced tools to support teams implementing its Patient Aligned Care Team (PACT) medical home model. To present findings from an evaluation of the PACT Toolkit, including use, variation across facilities, effect of social marketing, and factors influencing use. The Toolkit is an online repository of ready-to-use tools created by VA clinic staff that physicians, nurses, and other team members may share, download, and adopt in order to more effectively implement PCMH principles and improve local performance on VA metrics. Multimethod evaluation using: (1) website usage analytics, (2) an online survey of the PACT community of practice's use of the Toolkit, and (3) key informant interviews. Survey respondents were PACT team members and coaches (n = 544) at 136 VA facilities. Interview respondents were Toolkit users and non-users (n = 32). For survey data, multivariable logistic models were used to predict Toolkit awareness and use. Interviews and open-text survey comments were coded using a "common themes" framework. The Consolidated Framework for Implementation Research (CFIR) guided data collection and analyses. The Toolkit was used by 6,745 staff in the first 19 months of availability. Among members of the target audience, 80 % had heard of the Toolkit, and of those, 70 % had visited the website. Tools had been implemented at 65 % of facilities. Qualitative findings revealed a range of user perspectives from enthusiastic support to lack of sufficient time to browse the Toolkit. An online Toolkit to support PCMH implementation was used at VA facilities nationwide. Other complex health care organizations may benefit from adopting similar online peer-to-peer resource libraries. C1 [Luck, Jeff] Oregon State Univ, Coll Publ Hlth & Human Sci, Corvallis, OR 97331 USA. [Luck, Jeff; Bowman, Candice; York, Laura] VA Greater Los Angeles Healthcare Syst, Ctr Study Healthcare Provider Behav, Los Angeles, CA USA. [Midboe, Amanda; Taylor, Thomas; Gale, Randall; Asch, Steven] VA Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, Menlo Pk, CA USA. [Asch, Steven] Stanford Univ, Div Gen Med Disciplines, Palo Alto, CA 94304 USA. RP Luck, J (reprint author), Oregon State Univ, Coll Publ Hlth & Human Sci, 401 Waldo Hall, Corvallis, OR 97331 USA. EM Jeff.luck@oregonstate.edu FU VA Office of Systems Redesign FX Funding: This study was funded by a grant from the VA Office of Systems Redesign with additional in-kind support from the VA Center for Applied Systems Engineering (VA-CASE). NR 23 TC 5 Z9 5 U1 1 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2014 VL 29 SU 2 BP 572 EP 578 DI 10.1007/s11606-013-2738-0 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AK3OS UT WOS:000338334700006 ER PT J AU Butler, A Canamucio, A Macpherson, D Skoko, J True, G AF Butler, Anneliese Canamucio, Anne Macpherson, David Skoko, Jennifer True, Gala TI Primary Care Staff Perspectives on a Virtual Learning Collaborative to Support Medical Home Implementation SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE primary care redesign; medical education-computer/web-based learning; survey research; qualitative research; quality improvement; curriculum/program evaluation ID QUALITY IMPROVEMENT COLLABORATIVES; BLACK-BOX; LESSONS; TRANSFORMATION; INTERVENTIONS; PROJECT AB Many organizations rely on quality improvement collaboratives (QICs) to facilitate Patient-Centered Medical Home (PCMH) implementation, and there is a trend toward conducting QIC activities virtually to reduce costs and expand their reach. However, the evidence base for QICs is limited; questions remain about how QICs operate, why they succeed or fail, and how they are experienced by participants. We surveyed participants in an innovative Virtual Collaborative (VC) designed to support PCMH implementation within one Veterans Integrated Service Network, to understand why and for whom the VC was more/less effective and identify opportunities for improvement. This anonymous online survey was designed to assess participants' views on the VC's usefulness, impact, and acceptability, and to explore variations by role, practice setting, prior training, and overall engagement in VC activities. Respondents were 353 primary care staff, including providers, nurses, and support staff. The survey comprised 32 structured and three free-response items. Structured items assessed participation in and perceived usefulness of VC activities; perceived acceptability of the training format; overall perceived impact; and basic demographics. Responses were dichotomized and compared using Chi-square tests. Free-response items inviting constructive criticism of the VC were coded and summarized to identify themes and illustrative quotes. The VC most benefited respondents with prior PCMH training and those who fully participated in VC activities. Respondents especially valued the opportunity to share experiences with other teams. Non-providers and those new to PCMH felt learning content did not meet their needs. Reported barriers to full participation included staffing constraints, insufficient and/or unprotected time, and inadequate leadership support. Our study offers practical lessons for others considering a virtual collaborative model for PCMH spread. Findings contribute to the evidence base for QICs overall and virtual QICs in particular, highlighting the value of seeking input from "the trenches.". C1 [Butler, Anneliese; Canamucio, Anne; True, Gala] Philadelphia Vet Affairs Med Ctr, Ctr Evaluat Patient Aligned Care Teams CEPACT, Philadelphia, PA 19104 USA. [Macpherson, David; Skoko, Jennifer] 4th Vet Integrated Serv Network, Pittsburgh, PA USA. [Macpherson, David] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [True, Gala] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Butler, A (reprint author), Philadelphia Vet Affairs Med Ctr, Ctr Evaluat Patient Aligned Care Teams CEPACT, 3900 Woodland Ave,Bldg 4100, Philadelphia, PA 19104 USA. EM Anneliese.Butler@va.gov FU VA Office of Patient Care Services FX Funders: This work was undertaken as part of the Veterans Administration's PACT Demonstration Laboratory initiative, supporting and evaluating VA's transition to a patient-centered medical home. Funding for the PACT Demonstration Laboratory initiative is provided by the VA Office of Patient Care Services. NR 25 TC 5 Z9 5 U1 1 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2014 VL 29 SU 2 BP 579 EP 588 DI 10.1007/s11606-013-2668-x PG 10 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AK3OS UT WOS:000338334700007 ER PT J AU Rubenstein, LV Stockdale, SE Sapir, N Altman, L Dresselhaus, T Salem-Schatz, S Vivell, S Ovretveit, J Hamilton, AB Yano, EM AF Rubenstein, Lisa V. Stockdale, Susan E. Sapir, Negar Altman, Lisa Dresselhaus, Timothy Salem-Schatz, Susanne Vivell, Susan Ovretveit, John Hamilton, Alison B. Yano, Elizabeth M. TI A Patient-Centered Primary Care Practice Approach Using Evidence-Based Quality Improvement: Rationale, Methods, and Early Assessment of Implementation SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE quality improvement; primary care; patient-centered medical home; logic model; interdisciplinary leadership ID NATIONAL DEMONSTRATION PROJECT; MEDICAL HOME; COLLABORATIVE CARE; SERVICE ORGANIZATIONS; HEALTH; MODEL; DEPRESSION; LESSONS; SUCCESS; CONTEXT AB Healthcare systems and their primary care practices are redesigning to achieve goals identified in Patient-Centered Medical Home (PCMH) models such as Veterans Affairs (VA)'s Patient Aligned Care Teams (PACT). Implementation of these models, however, requires major transformation. Evidence-Based Quality Improvement (EBQI) is a multi-level approach for supporting organizational change and innovation spread. To describe EBQI as an approach for promoting VA's PACT and to assess initial implementation of planned EBQI elements. Descriptive. Regional and local interdisciplinary clinical leaders, patient representatives, Quality Council Coordinators, practicing primary care clinicians and staff, and researchers from six demonstration site practices in three local healthcare systems in one VA region. EBQI promotes bottom-up local innovation and spread within top-down organizational priorities. EBQI innovations are supported by a research-clinical partnership, use continuous quality improvement methods, and are developed in regional demonstration sites. We developed a logic model for EBQI for PACT (EBQI-PACT) with inputs, outputs, and expected outcomes. We describe implementation of logic model outputs over 18 months, using qualitative data from 84 key stakeholders (104 interviews from two waves) and review of study documents. Nearly all implementation elements of the EBQI-PACT logic model were fully or partially implemented. Elements not fully achieved included patient engagement in Quality Councils (4/6) and consistent local primary care practice interdisciplinary leadership (4/6). Fourteen of 15 regionally approved innovation projects have been completed, three have undergone initial spread, five are prepared to spread, and two have completed toolkits that have been pretested in two to three sites and are now ready for external spread. EBQI-PACT has been feasible to implement in three participating healthcare systems in one VA region. Further development of methods for engaging patients in care design and for promoting interdisciplinary leadership is needed. C1 [Rubenstein, Lisa V.; Stockdale, Susan E.; Sapir, Negar; Altman, Lisa; Vivell, Susan; Hamilton, Alison B.; Yano, Elizabeth M.] VA Greater Los Angeles Healthcare Syst, VA HSR & D Ctr Study Healthcare Innovat Implement, North Hills, CA USA. [Rubenstein, Lisa V.; Stockdale, Susan E.; Altman, Lisa; Hamilton, Alison B.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Rubenstein, Lisa V.] RAND Corp, Santa Monica, CA USA. [Rubenstein, Lisa V.; Altman, Lisa] VA Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA USA. [Dresselhaus, Timothy] VA San Diego Healthcare Syst, San Diego, CA USA. [Dresselhaus, Timothy] Univ Calif San Diego, Dept Med, San Diego, CA USA. [Salem-Schatz, Susanne] Hlth Care Qual Initiat, Newton, MA USA. [Ovretveit, John] Karolinska Inst, Stockholm, Sweden. [Rubenstein, Lisa V.; Yano, Elizabeth M.] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA USA. [Rubenstein, Lisa V.] VA QUERI Ctr Implementat Practice & Res Support, Los Angeles, CA USA. RP Rubenstein, LV (reprint author), VA Greater Los Angeles, VA HSR & D Ctr Study Healthcare Innovat Implement, VA Greater Los Angeles Healthcare Syst, 16111 Plummer St, North Hills, CA 91343 USA. EM lisa.rubenstein@va.gov FU VA Office of Patient Care Services [XVA 65-018]; VA HSR&D Senior Research Career Scientist award [05-195]; VA HSR&D Center for the Study of Healthcare Innovation, Implementation and Policy; VA HSR&D Center of Innovation; VA Quality Enhancement Research Initiative's Center for Implementation Practice and Research Support at the VA Greater Los Angeles Healthcare System FX Funders: This work was undertaken as part of the Veterans Affairs PACT Demonstration Laboratory initiative, supporting and evaluating VA's transition to a patient-centered medical home. Funding for the PACT Demonstration Laboratory (XVA 65-018) initiative is provided by the VA Office of Patient Care Services. Dr. Yano's time was supported by a VA HSR&D Senior Research Career Scientist award (Project #05-195). VAIL is also supported, in part, by the VA HSR&D Center for the Study of Healthcare Innovation, Implementation and Policy, a VA HSR&D Center of Innovation (formerly Center of Excellence), and the VA Quality Enhancement Research Initiative's Center for Implementation Practice and Research Support at the VA Greater Los Angeles Healthcare System. NR 52 TC 10 Z9 10 U1 2 U2 21 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2014 VL 29 SU 2 BP 589 EP 597 DI 10.1007/s11606-013-2703-y PG 9 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AK3OS UT WOS:000338334700008 ER PT J AU Tuepker, A Kansagara, D Skaperdas, E Nicolaidis, C Joos, S Alperin, M Hickam, D AF Tuepker, Anais Kansagara, Devan Skaperdas, Eleni Nicolaidis, Christina Joos, Sandra Alperin, Michael Hickam, David TI "We've Not Gotten Even Close to What We Want to Do": a Qualitative Study of Early Patient-Centered Medical Home Implementation SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE primary care redesign; patient-centered medical home; team-based care; Veterans; health services research; qualitative research ID SAFETY NET CLINICS; PRIMARY-CARE; PRACTICE TRANSFORMATION; LESSONS; FEATURES; TEAMS AB The Veterans Health Administration (VA) Patient Aligned Care Teams (PACT) initiative is designed to deliver a medical home model of care associated with better patient outcomes, but success will depend in part on the model's acceptability and sustainability among clinic employees. We sought to identify key themes in the experience of primary care providers, nurse care managers, clerical and clinical associates, and clinic administrators implementing PACT, with the aim of informing recommendations for continued development of the model and its components. Observational qualitative study; data collection from 2010 to 2013, using role-stratified and team focus groups and semi-structured interviews. 241 of 337 (72 %) identified primary care clinic employees in PACT team or administrative roles, from 15 VA clinics in Oregon and Washington. Data coded and analyzed using conventional content analysis techniques. Overall, participants were enthusiastic about the PACT concept, but felt necessary resources for success were not yet in place. Well-functioning teams were perceived as key to successful implementation. Development of such teams depended on adequate staffing, training, and dedicated time for team development. Changes within the broader VA system were also seen as necessary, including devolving greater control to the clinic level and improving system alignment with the PACT model. PACT advocates from among clinic and institutional level leadership were identified as a final key ingredient for success. These themes were consistent despite differences in clinic settings and characteristics. PACT implementation faced significant challenges in its early years. Realizing PACT's transformative potential will require acting on the needs identified by clinic workers in this study: ensuring adequate staffing in all team roles, devoting resources to in-depth training for all employees in communication and other skills needed to maximize team success, and aligning the broader VA hospital system with PACT's decentralized, team-based approach. C1 [Tuepker, Anais; Kansagara, Devan; Skaperdas, Eleni; Joos, Sandra; Alperin, Michael; Hickam, David] Vet Hlth Adm, Portland VA Med Ctr, Hlth Serv Res Dev VISN PACT Demonstrat Lab 20, Portland, OR 97239 USA. [Tuepker, Anais; Kansagara, Devan; Nicolaidis, Christina; Joos, Sandra; Hickam, David] Oregon Hlth & Sci Univ, Sch Med, Div Gen Internal Med & Geriatr, Portland, OR 97201 USA. [Nicolaidis, Christina] Portland State Univ, Sch Social Work, Portland, OR 97207 USA. [Nicolaidis, Christina] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA. [Hickam, David] Patient Ctr Outcomes Res Inst PCORI, Washington, DC USA. RP Tuepker, A (reprint author), Vet Hlth Adm, Portland VA Med Ctr, Hlth Serv Res Dev VISN PACT Demonstrat Lab 20, Mail Code RD63,POB 1034, Portland, OR 97239 USA. EM anais.tuepker@va.gov FU VA Office of Patient Care Services FX We gratefully acknowledge the contribution of all members of the VISN 20 PACT Demonstration Lab, as well as the employees in participating clinics, who generously shared their experiences. Funding for the PACT Demonstration Laboratory initiative is provided by the VA Office of Patient Care Services. Dr. Tuepker is a Health Science Specialist at the Portland VA Medical Center. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. NR 27 TC 8 Z9 8 U1 1 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2014 VL 29 SU 2 BP 614 EP 622 DI 10.1007/s11606-013-2690-z PG 9 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AK3OS UT WOS:000338334700011 ER PT J AU Rodriguez, HP Giannitrapani, KF Stockdale, S Hamilton, AB Yano, EM Rubenstein, LV AF Rodriguez, Hector P. Giannitrapani, Karleen F. Stockdale, Susan Hamilton, Alison B. Yano, Elizabeth M. Rubenstein, Lisa V. TI Teamlet Structure and Early Experiences of Medical Home Implementation for Veterans SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE team structure; patient-centered medical home; practice redesign; primary care teams; veterans ID PRIMARY-CARE; RELATIONAL COORDINATION; QUALITY; IMPACT; SATISFACTION; PROVIDERS; JOB AB High functioning interdisciplinary primary care teams are a critical component of the patient-centered medical home. In 2010, the Veterans Administration (VA) implemented a medical home model termed the Patient Aligned Care Teams (PACT), with reorganization of staff into small teams ("teamlets") as a core feature. To examine the early experiences of primary care personnel as they assumed new roles through reorganization into teamlets. Convergent mixed methods study design involving semi-structured interviews and a survey; data were collected in 2011 and 2012. We interviewed 41 frontline teamlet members (i.e., primary care physicians and staff) from three practices that were part of a PACT demonstration laboratory and examined clinician and staff survey data from 22 practices. Semi-structured interview guide and clinician and staff survey questions covering the following domains: teamlet formation and structure, within-teamlet communication, cross-coverage, role changes, teamlet training, impact on Veterans, and leadership facilitation and support. Respondents had limited input into teamlet structure and indicated limited training on the PACT initiative. Guidelines delineating each teamlet member's roles and responsibilities were emphasized as important needs. Chronic understaffing also contributed to implementation challenges and territorial attitudes surfaced when cross-coverage was not clear. In addition, several core features of VA's medical home transformation were not fully implemented by teamlet members. Most also reported limited guidance and feedback from leadership. Despite these challenges, teamlet-based care was perceived to have a positive impact on Veterans' experiences of primary care and also resulted in improved communication among staff. The PACT teamlet model holds much promise for improving primary care at the VA. However, more comprehensive training, improving the stability of teamlets, developing clear cross-coverage policies, and better defined teamlet member responsibilities are important areas in need of attention by VA leadership. C1 [Rodriguez, Hector P.; Giannitrapani, Karleen F.; Yano, Elizabeth M.; Rubenstein, Lisa V.] Univ Calif Los Angeles, Dept Hlth Policy & Management, Fielding Sch Publ Hlth, Los Angeles, CA 90095 USA. [Rodriguez, Hector P.; Giannitrapani, Karleen F.; Stockdale, Susan; Hamilton, Alison B.; Yano, Elizabeth M.; Rubenstein, Lisa V.] VA Greater Los Angeles Hlth Care Syst, HSR & D Ctr Study Healthcare Innovat Implementat, Los Angeles, CA USA. [Stockdale, Susan; Hamilton, Alison B.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Rubenstein, Lisa V.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Rubenstein, Lisa V.] RAND Hlth, Santa Monica, CA USA. RP Rodriguez, HP (reprint author), Univ Calif Los Angeles, Dept Hlth Policy & Management, Fielding Sch Publ Hlth, 650 Charles E Young Dr South, Los Angeles, CA 90095 USA. EM hrod@berkeley.edu FU VA Office of Patient Care Services; VA HSR&D Service Senior Research Career Scientist award [05-195] FX Funders: This work was undertaken as part of the Veterans Health Administration's PACT Demonstration Laboratory initiative, supporting and evaluating VA's transition to a patient-centered medical home. Funding for the PACT Demonstration Laboratory initiative is provided by the VA Office of Patient Care Services. Dr. Yano's effort was funded by a VA HSR&D Service Senior Research Career Scientist award (Project #05-195). The views expressed within are solely those of the authors, and do not necessarily represent the views of the Department of Veterans Affairs or the United States government. NR 20 TC 10 Z9 10 U1 1 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2014 VL 29 SU 2 BP 623 EP 631 DI 10.1007/s11606-013-2680-1 PG 9 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AK3OS UT WOS:000338334700012 ER PT J AU True, G Stewart, GL Lampman, M Pelak, M Solimeo, SL AF True, Gala Stewart, Greg L. Lampman, Michelle Pelak, Mary Solimeo, Samantha L. TI Teamwork and Delegation in Medical Homes: Primary Care Staff Perspectives in the Veterans Health Administration SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE patient-centered medical home; teams; implementation; Veteran's health; qualitative evaluation; primary care; Department of Veterans Affairs ID PRACTICE TRANSFORMATION; LESSONS; TEAMS; CULTURE; QUALITY; PILOT AB The patient-centered medical home (PCMH) relies on a team approach to patient care. For organizations engaged in transitioning to a PCMH model, identifying and providing the resources needed to promote team functioning is essential. To describe team-level resources required to support PCMH team functioning within the Veterans Health Administration (VHA), and provide insight into how the presence or absence of these resources facilitates or impedes within-team delegation. Semi-structured interviews with members of pilot teams engaged in PCMH implementation in 77 primary care clinics serving over 300,000 patients across two VHA regions covering the Mid-Atlantic and Midwest United States. A purposive sample of 101 core members of pilot teams, including 32 primary care providers, 42 registered nurse care managers, 15 clinical associates, and 12 clerical associates. Investigators from two evaluation sites interviewed frontline primary care staff separately, and then collaborated on joint analysis of parallel data to develop a broad, comprehensive understanding of global themes impacting team functioning and within-team delegation. We describe four themes key to understanding how resources at the team level supported ability of primary care staff to work as effective, engaged teams. Team-based task delegation was facilitated by demarcated boundaries and collective identity; shared goals and sense of purpose; mature and open communication characterized by psychological safety; and ongoing, intentional role negotiation. Our findings provide a framework for organizations to identify assets already in place to support team functioning, as well as areas in need of improvement. For teams struggling to make practice changes, our results indicate key areas where they may benefit from future support. In addition, this research sheds light on how variation in medical home implementation and outcomes may be associated with variation in team-based task delegation. C1 [True, Gala; Pelak, Mary] Philadelphia Vet Affairs Med Ctr, VISN Ctr Evaluat Patient Aligned Care Teams CEPAC, Philadelphia, PA 19104 USA. [True, Gala] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Stewart, Greg L.; Lampman, Michelle; Solimeo, Samantha L.] Iowa City VA Hlth Care Syst, Dept Vet Affairs, Patient Aligned Care Team Demonstrat Lab VISN23, Iowa City, IA USA. [Stewart, Greg L.] Univ Iowa, Tippie Coll Business, Iowa City, IA USA. [Lampman, Michelle; Solimeo, Samantha L.] Iowa City VA Hlth Care Syst, Dept Vet Affairs, Ctr Comprehens Access & Delivery Res & Evaluat CA, Iowa City, IA USA. RP True, G (reprint author), Philadelphia Vet Affairs Med Ctr, VISN Ctr Evaluat Patient Aligned Care Teams CEPAC, Bldg 4100,Univ & Woodland Aves, Philadelphia, PA 19104 USA. EM Jennifer.True2@va.gov FU VA Office of Patient Care Services FX Funders: The VISN 4 and VISN 23 Demonstration Laboratories are funded by the VA Office of Patient Care Services. NR 36 TC 6 Z9 6 U1 4 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2014 VL 29 SU 2 BP 632 EP 639 DI 10.1007/s11606-013-2666-z PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AK3OS UT WOS:000338334700013 ER PT J AU Wang, ES Conde, MV Simon, B Leykum, LK AF Wang, Emily S. Conde, Michelle V. Simon, Bret Leykum, Luci K. TI Exploring End-of-Residency Transitions in a VA Patient Aligned Care Team SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE veterans; patient-centered care; transitions of care; medical education; complexity theory ID CONTINUITY PRACTICE; SIGN-OUT; SATISFACTION; PROGRAM; TRIAL AB End-of-residency transitions create disruptions in primary care continuity. The national implementation of Patient Aligned Care Teams (PACT) in Veterans Health Administration (VA) primary care clinics creates an opportunity to mitigate this discontinuity through the provision of team-based care. To identify team-based solutions to end-of-residency transitions in a resident PACT continuity clinic by assessing the knowledge, attitudes, and perceptions of non-physician PACT members and resident PACT physicians. Cross-sectional survey of 27 resident physicians and 24 non-physician PACT members in the Internal Medicine Clinic at the Audie L. Murphy VA Hospital in the South Texas Veterans Health Care System. Twenty-seven residents and 24 non-physician PACT members completed the survey, with response rates of 90 % and 100 %, respectively. All residents and 96 % of non-physician PACT members agreed or strongly agreed that the residents were responsible for informing patients about end-of-residency transitions. Only 38 % of non-physician PACT members versus 52 % of residents indicated that non-physician PACT members should be responsible for this transition. Approximately 80 % of resident physicians and non-physician PACT members agreed there should be a formalized approach to these transitions; 67 % of non-physician PACT members were willing to support this transition. Potential barriers to team-based care transitions were identified. Major themes of write-in suggestions for improving the transition focused on communication and relationships between the patient and PACT and among the PACT members. PACT implementation changes the roles and relationship structures among all team members. While end-of-residency transitions create a disruption in the relationship system, the remainder of the PACT may bridge this transition. Our results demonstrate the importance of a team-based solution that engages all PACT members by improving communication and fostering effective team relationships. C1 [Wang, Emily S.; Conde, Michelle V.; Leykum, Luci K.] South Texas Vet Hlth Care Syst, Audie L Murphy Hosp Div, San Antonio, TX 78229 USA. [Wang, Emily S.; Conde, Michelle V.; Simon, Bret; Leykum, Luci K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. RP Wang, ES (reprint author), South Texas Vet Hlth Care Syst, Audie L Murphy Hosp Div, Med Serv, 7400 Merton Minter,Mail Code 111, San Antonio, TX 78229 USA. EM wange@uthscsa.edu FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service [REA 05-129, CDA 07-022]; South Texas Veterans Health Care System FX The research supported here was supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service (#REA 05-129, #CDA 07-022). Author salary support is through this funding and through the South Texas Veterans Health Care System. The views expressed in this article are those of the authors and do not necessarily reflect the position of policy of the Department of Veterans Affairs. NR 22 TC 1 Z9 1 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2014 VL 29 SU 2 BP 649 EP 658 DI 10.1007/s11606-013-2726-4 PG 10 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AK3OS UT WOS:000338334700015 ER PT J AU Helfrich, CD Dolan, ED Simonetti, J Reid, RJ Joos, S Wakefield, BJ Schectman, G Stark, R Fihn, SD Harvey, HB Nelson, K AF Helfrich, Christian D. Dolan, Emily D. Simonetti, Joseph Reid, Robert J. Joos, Sandra Wakefield, Bonnie J. Schectman, Gordon Stark, Richard Fihn, Stephan D. Harvey, Henry B. Nelson, Karin TI Elements of Team-Based Care in a Patient-Centered Medical Home Are Associated with Lower Burnout Among VA Primary Care Employees SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE patient-centered medical home; burnout; team-based care; organizational change ID PHYSICIAN BURNOUT; SAFETY OUTCOMES; NURSE BURNOUT; STAFF MORALE; HEALTH; SATISFACTION; DISSATISFACTION; SURGEONS; QUALITY; ERRORS AB A high proportion of the US primary care workforce reports burnout, which is associated with negative consequences for clinicians and patients. Many protective factors from burnout are characteristics of patient-centered medical home (PCMH) models, though even positive organizational transformation is often stressful. The existing literature on the effects of PCMH on burnout is limited, with most findings based on small-scale demonstration projects with data collected only among physicians, and the results are mixed. To determine if components of PCMH related to team-based care were associated with lower burnout among primary care team members participating in a national medical home transformation, the VA Patient Aligned Care Team (PACT). Web-based, cross-sectional survey and administrative data from May 2012. A total of 4,539 VA primary care personnel from 588 VA primary care clinics. The dependent variable was burnout, and the independent variables were measures of team-based care: team functioning, time spent in huddles, team staffing, delegation of clinical responsibilities, working to top of competency, and collective self-efficacy. We also included administrative measures of workload and patient comorbidity. Overall, 39 % of respondents reported burnout. Participatory decision making (OR 0.65, 95 % CI 0.57, 0.74) and having a fully staffed PACT (OR 0.79, 95 % CI 0.68, 0.93) were associated with lower burnout, while being assigned to a PACT (OR 1.46, 95 % CI 1.11, 1.93), spending time on work someone with less training could do (OR 1.29, 95 % CI 1.07, 1.57) and a stressful, fast-moving work environment (OR 4.33, 95 % CI 3.78, 4.96) were associated with higher burnout. Longer tenure and occupation were also correlated with burnout. Lower burnout may be achieved by medical home models that are appropriately staffed, emphasize participatory decision making, and increase the proportion of time team members spend working to the top of their competency level. C1 [Helfrich, Christian D.; Dolan, Emily D.; Simonetti, Joseph; Nelson, Karin] US Dept Vet Affairs, VA Puget Sound Hlth Serv Res & Dev Ctr Excellence, Seattle, WA USA. [Helfrich, Christian D.; Simonetti, Joseph] Univ Washington, Sch Publ Hlth, Dept Hlth Serv, Seattle, WA 98195 USA. [Reid, Robert J.] Grp Hlth Res Inst, Seattle, WA USA. [Joos, Sandra] US Dept Vet Affairs, Portland VA Med Ctr, VISN PACT Demonstrat Lab 20, Seattle, WA USA. [Wakefield, Bonnie J.] VA Iowa City Hlth Serv Res & Dev, Ctr Comprehens Access & Delivery Res & Evaluat, Iowa City, IA USA. [Schectman, Gordon] VA Off Patient Care Serv, Washington, DC USA. [Schectman, Gordon] Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA. [Stark, Richard] VA Off Clin Operat, Washington, DC USA. [Fihn, Stephan D.; Harvey, Henry B.] US Dept Vet Affairs, Off Analyt & Business Intelligence, Seattle, WA USA. [Fihn, Stephan D.; Nelson, Karin] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. RP Helfrich, CD (reprint author), US Dept Vet Affairs, VA Puget Sound Hlth Serv Res Dev Ctr Excellence, Seattle, WA 98174 USA. EM christian.helfrich@va.gov RI ; Helfrich, Christian/D-2382-2016 OI simonetti, joseph/0000-0002-1092-160X; Helfrich, Christian/0000-0002-9827-4768 FU VA Office of Patient Care Services FX This work was undertaken as part of the VA's PACT Demonstration Laboratory initiative, supporting and evaluating VA's transition to a patient-centered medical home. Funding for the PACT Demonstration Laboratory initiative is provided by the VA Office of Patient Care Services. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs. NR 51 TC 20 Z9 20 U1 1 U2 13 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2014 VL 29 SU 2 BP 659 EP 666 DI 10.1007/s11606-013-2702-z PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AK3OS UT WOS:000338334700016 ER PT J AU Fix, GM Asch, SM Saifu, HN Fletcher, MD Gifford, AL Bokhour, BG AF Fix, Gemmae M. Asch, Steven M. Saifu, Hemen N. Fletcher, Michael D. Gifford, Allen L. Bokhour, Barbara G. TI Delivering PACT-Principled Care: Are Specialty Care Patients Being Left Behind? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE patient-centered medical home; specialty care; HIV; qualitative research ID CENTERED MEDICAL HOME; NATIONAL DEMONSTRATION PROJECT; HUMAN-IMMUNODEFICIENCY-VIRUS; PHYSICIAN PRACTICES; AGING POPULATION; HEALTH-CARE; RYAN WHITE; HIV; MANAGEMENT; INFECTION AB With the reorganization of primary care into Patient Aligned Care Teams (PACT) teams, the Veteran Affairs Health System (VA) aims to ensure all patients receive care based on patient-centered medical home (PCMH) principles. However, some patients receive the preponderance of care from specialty rather than primary care clinics because of the special nature of their clinical conditions. We examined seven VA (HIV) clinics as a model to test the extent to which such patients receive PCMH-principled care. To examine the extent to which HIV specialty care in VA conforms to PCMH principles. Qualitative study. Forty-one HIV providers from seven HIV clinics and 20 patients from four of these clinics. We conducted semi-structured interviews with HIV clinic providers and patients about care practices and adherence to PCMH principles. Using an iterative approach, data was analyzed using both a content analysis and an a priori, PCMH-principled coding strategy. Patients with HIV receive varying levels of PCMH-principled care across a range of VA HIV clinic structures. The more PCMH-principled HIV clinics largely functioned as PCMHs; patients received integrated, coordinated, comprehensive primary care within a dedicated HIV clinic. In contrast, some clinics were unable to meet the criteria of being a patient's medical home, and instead functioned primarily as a place to receive HIV-related services with limited care coordination. Patients from the less PCMH-principled clinics reported less satisfaction with their care. Even in a large, integrated healthcare system, there is wide variation in patients' receipt of PCMH-principled care in specialty care settings. In order to meet the goal of having all patients receiving PCMH-principled care, there needs to be careful consideration of where primary and specialty care services are delivered and coordinated. The best mechanisms for ensuring that patients with complex medical conditions receive PCMH-principled care may need to be tailored to different specialty care contexts. C1 [Fix, Gemmae M.; Gifford, Allen L.; Bokhour, Barbara G.] ENRM Vet Hosp, Ctr Healthcare Org & Implementat Res CHOIR 152, Bedford, MA 01730 USA. [Fix, Gemmae M.; Gifford, Allen L.; Bokhour, Barbara G.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Fix, Gemmae M.; Asch, Steven M.; Saifu, Hemen N.; Fletcher, Michael D.; Gifford, Allen L.; Bokhour, Barbara G.] Vet Affairs VA Qual Enhancement Res Initiat HIV &, Bedford, MA USA. [Asch, Steven M.] Ctr Innovat Implementat Ci2i, VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Saifu, Hemen N.; Fletcher, Michael D.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Asch, Steven M.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. RP Fix, GM (reprint author), ENRM Vet Hosp, Ctr Healthcare Org & Implementat Res CHOIR 152, 200 Springs Rd, Bedford, MA 01730 USA. EM gemmae.fix@va.gov OI Fix, Gemmae/0000-0001-6055-4177 FU Department of Veteran Affairs, Health Services Research and Development, HIV/Hepatitis QUERI; Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development FX Funders: This study was funded by the Department of Veteran Affairs, Health Services Research and Development, HIV/Hepatitis QUERI. This material is based upon work supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government. NR 41 TC 2 Z9 2 U1 2 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2014 VL 29 SU 2 BP 695 EP 702 DI 10.1007/s11606-013-2677-9 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AK3OS UT WOS:000338334700021 ER PT J AU Yano, EM Haskell, S Hayes, P AF Yano, Elizabeth M. Haskell, Sally Hayes, Patricia TI Delivery of Gender-Sensitive Comprehensive Primary Care to Women Veterans: Implications for VA Patient Aligned Care Teams SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE primary care; women's health; veterans ID HEALTH-CARE; MEDICAL HOME; QUALITY; CLINICS; SATISFACTION; TRANSFORMATION; IMPROVEMENT; ACCESS; SYSTEM; NEED AB The Veterans Health Administration (VA) has undertaken a major initiative to transform primary care delivery through implementation of Patient Aligned Care Teams (PACTs). Based on the patient-centered medical home concept, PACTs aim to improve access, continuity, coordination, and comprehensiveness using team-based care that is patient driven and patient centered. However, how PACT principles should be applied to meet the needs of special populations, including women veterans, is not entirely clear. While historical differences in military participation meant women veterans were rarely seen in VA healthcare settings, they now represent the fastest growing segment of new VA users. They also have complex healthcare needs, adding gender-specific services and other needs to the spectrum of services that the VA must deliver. These trends are changing the VA landscape, introducing challenges to how VA care is organized, how VA providers need to be trained, and how VA considers implementation of new initiatives, such as PACT. We briefly describe the evolution of VA primary care delivery for women veterans, review VA policy for delivering gender-sensitive comprehensive primary care for women, and discuss the challenges that women veterans' needs pose in the context of PACT implementation. We conclude with recommendations for addressing some of these challenges moving forward. C1 [Yano, Elizabeth M.] VA Greater Los Angeles Healthcare Syst, VA HSR & D Ctr Study Healthcare Innovat Implement, Sepulveda, CA 91343 USA. [Yano, Elizabeth M.] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA USA. [Haskell, Sally; Hayes, Patricia] Vet Hlth Adm, Off Patient Care Serv, Womens Hlth Serv, Washington, DC USA. [Haskell, Sally] VA Connecticut Hlth Syst, West Haven, CT USA. [Haskell, Sally] Yale Univ, Sch Med, New Haven, CT USA. RP Yano, EM (reprint author), VA Greater Los Angeles Healthcare Syst, VA HSR & D Ctr Study Healthcare Innovat Implement, Sepulveda Campus,16111 Plummer St,Mail Code 152, Sepulveda, CA 91343 USA. EM Elizabeth.yano@va.gov FU Women's Health Services in the VHA Office of Patient Care Services; VA HSR&D Service (Women's Health CREATE) [CRE 12-026, IAE 07-170]; VA HSR&D Senior Research Career Scientist Award [05-195] FX Funders: This article was supported by funding from Women's Health Services in the VHA Office of Patient Care Services and VA HSR&D Service (Women's Health CREATE Project no. CRE 12-026 and Project no. IAE 07-170). Dr. Yano's effort was funded through a VA HSR&D Senior Research Career Scientist Award (project no. 05-195). NR 40 TC 13 Z9 13 U1 2 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2014 VL 29 SU 2 BP 703 EP 707 DI 10.1007/s11606-013-2699-3 PG 5 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AK3OS UT WOS:000338334700022 ER PT J AU Gopalan, A Tahirovic, E Moss, H Troxel, AB Zhu, JS Loewenstein, G Volpp, KG AF Gopalan, Anjali Tahirovic, Emin Moss, Haley Troxel, Andrea B. Zhu, Jingsan Loewenstein, George Volpp, Kevin G. TI Translating the Hemoglobin A1C with More Easily Understood Feedback: A Randomized Controlled Trial SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE diabetes; hemoglobin A1C; communication; health literacy; diabetes education ID GLYCEMIC CONTROL; FINANCIAL INCENTIVES; ASSOCIATION; NUMERACY; MANAGEMENT; OUTCOMES; CARE AB Previous work has indicated that for patients with diabetes, there is value in understanding glycemic control. Despite these findings, patient understanding of the hemoglobin A1C value (A1C) is notably poor. In this study, we test the effect of two alternative communication formats of the A1C on improving glycemic control among patients with poorly controlled diabetes. 177 patients with poorly controlled diabetes were randomized to one of three study arms that varied in the information they received: (1) a "diabetes report card" containing individualized information about glycemic control for each participant with letter grades ranging from A to F; (2) a "report card" containing a face whose emotion reflected current glycemic control; or (3) a "report card" with glycemic control expressed with the A1C value (standard arm). The primary study outcome was change in A1C at 6 months. Secondary outcomes included changes in participant perceptions of their glycemic control. The average A1C for enrolled participants was 9.9 % (S.D. 1.7) and did not differ significantly among study arms. We noted no significant differences in change in A1C at 6 months between the standard and experimental arms. Using multiple imputation to account for missing A1C values, the changes in A1C for the letter grade, face, and standard arms were -0.55 % (-1.15, 0.05), -0.89 % (-1.49, -0.29), and -0.74 % (-1.51, 0.029), respectively (p = 0.67 for control vs. grade, p = 0.76 for control vs. face). Feedback to patients with poorly controlled diabetes in the form of letter grades and faces did not differentially impact glycemic control at 6 months or participant perceptions of current control. These efforts to improve communication and patient understanding of disease management targets need further refinement to significantly impact diabetes outcomes. NCT01143870. C1 [Gopalan, Anjali; Volpp, Kevin G.] Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. [Gopalan, Anjali] Univ Penn, Robert Wood Johnson Clin Scholars Program, Philadelphia, PA 19104 USA. [Gopalan, Anjali; Tahirovic, Emin; Troxel, Andrea B.; Zhu, Jingsan; Volpp, Kevin G.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Moss, Haley] NYU, Sch Med, New York, NY USA. [Loewenstein, George] Carnegie Mellon Univ, Dietrich Coll Social & Decis Sci, Pittsburgh, PA 15213 USA. RP Gopalan, A (reprint author), Philadelphia VA Med Ctr, 423 Guardian Dr,Blockley Hall,Suite 1303, Philadelphia, PA 19104 USA. EM agopalan@upenn.edu OI Troxel, Andrea/0000-0002-1393-3075 FU Penn CMU Roybal P30 Center [P30AG034546] FX Penn CMU Roybal P30 Center Grant P30AG034546. The funder was not involved in any part of the study design, conducting of the study or the analysis of the results. NR 20 TC 2 Z9 2 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2014 VL 29 IS 7 BP 996 EP 1003 DI 10.1007/s11606-014-2810-4 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AK1VW UT WOS:000338207100009 PM 24567202 ER PT J AU Chang, ET Magnabosco, JL Chaney, E Lanto, A Simon, B Yano, EM Rubenstein, LV AF Chang, Evelyn T. Magnabosco, Jennifer L. Chaney, Edmund Lanto, Andrew Simon, Barbara Yano, Elizabeth M. Rubenstein, Lisa V. TI Predictors of Primary Care Management of Depression in the Veterans Affairs Healthcare System SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE primary care; mental health; depression; care management ID LATE-LIFE DEPRESSION; COMORBIDITY SURVEY REPLICATION; INTEGRATING MENTAL-HEALTH; COLLABORATIVE CARE; QUALITY IMPROVEMENT; UNITED-STATES; TREATMENT PREFERENCES; RANDOMIZED-TRIAL; MEDICAL HOME; DISORDERS AB Primary care providers (PCPs) vary in skills to effectively treat depression. Key features of evidence-based collaborative care models (CCMs) include the availability of depression care managers (DCMs) and mental health specialists (MHSs) in primary care. Little is known, however, about the relationships between PCP characteristics, CCM features, and PCP depression care. To assess relationships between various CCM features, PCP characteristics, and PCP depression management. Cross-sectional analysis of a provider survey. 180 PCPs in eight VA sites nationwide. Independent variables included scales measuring comfort and difficulty with depression care; collaboration with a MHS; self-reported depression caseload; availability of a collocated MHS, and co-management with a DCM or MHS. Covariates included provider type and gender. For outcomes, we assessed PCP self-reported performance of key depression management behaviors in primary care in the past 6 months. Response rate was 52 % overall, with 47 % attending physicians, 34 % residents, and 19 % nurse practitioners and physician assistants. Half (52 %) reported greater than eight veterans with depression in their panels and a MHS collocated in primary care (50 %). Seven of the eight clinics had a DCM. In multivariable analysis, significant predictors for PCP depression management included comfort, difficulty, co-management with MHSs and numbers of veterans with depression in their panels. PCPs who felt greater ease and comfort in managing depression, co-managed with MHSs, and reported higher depression caseloads, were more likely to report performing depression management behaviors. Neither a collocated MHS, collaborating with a MHS, nor co-managing with a DCM independently predicted PCP depression management. Because the success of collaborative care for depression depends on the ability and willingness of PCPs to engage in managing depression themselves, along with other providers, more research is necessary to understand how to engage PCPs in depression management. C1 [Chang, Evelyn T.; Rubenstein, Lisa V.] Vet Affairs VA Los Greater Angeles Healthcare Sys, Dept Gen Internal Med, Los Angeles, CA USA. [Chang, Evelyn T.; Lanto, Andrew; Simon, Barbara; Yano, Elizabeth M.; Rubenstein, Lisa V.] VA Greater Los Angeles Healthcare Syst, VA Ctr Study Healthcare Innovat Implementat & Pol, Sepulveda, CA USA. [Magnabosco, Jennifer L.; Rubenstein, Lisa V.] VA Greater Los Angeles Healthcare Syst, Ctr Implementat Practice & Res Support, Sepulveda, CA USA. [Magnabosco, Jennifer L.] Yo San Univ Tradit Chinese Med, Los Angeles, CA USA. [Chaney, Edmund] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Chaney, Edmund] Vet Affairs Puget Sound Healthcare Syst, Hlth Serv Res & Dev Northwest Ctr Excellence, Seattle, WA USA. [Yano, Elizabeth M.; Rubenstein, Lisa V.] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA USA. [Rubenstein, Lisa V.] Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. [Rubenstein, Lisa V.] RAND Corp, Santa Monica, CA USA. RP Chang, ET (reprint author), VA Greater Los Angeles Healthcare Syst, Dept Gen Internal Med 111G, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM Evelyn.chang@va.gov FU VA HSRD [MNT 03-215]; VA Mental Health Quality Enhancement Research Initiative; VA Office of Academic Affiliations, through the Health Services Research Fellowship Training Program [TMP 65-020]; VA HSR&D Service through a Senior Research Career Scientist Award [RCS 05-195] FX The ReTIDES project "Expanding and Testing VA Collaborative Care Models for Depression" was supported by VA HSR&D (Project #MNT 03-215, PIs Lisa Rubenstein, MD MSHS, and Edmund Chaney, PhD) and VA Mental Health Quality Enhancement Research Initiative. Funding support for preparation of this paper was provided by VA Office of Academic Affiliations, through the Health Services Research Fellowship Training Program (TMP 65-020). Dr. Yano's time was funded by the VA HSR&D Service through a Senior Research Career Scientist Award (Project #RCS 05-195). NR 65 TC 1 Z9 1 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2014 VL 29 IS 7 BP 1017 EP 1025 DI 10.1007/s11606-014-2807-z PG 9 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AK1VW UT WOS:000338207100012 PM 24567200 ER PT J AU Jones, B Brzezinski, WA Estrada, CA Rodriguez, M Kraemer, RR AF Jones, Benjamin Brzezinski, Walter A. Estrada, Carlos A. Rodriguez, Martin Kraemer, Ryan R. TI A 22-Year-Old Woman with Abdominal Pain SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material DE clinical reasoning; illness script; expert clinician; acute intermittent porphyria; abdominal pain ID PORPHYRIAS C1 [Jones, Benjamin] Univ Alabama Birmingham, Tinsley Harrison Internal Med Residency Program, Birmingham, AL 35294 USA. [Brzezinski, Walter A.] Med Univ S Carolina, Charleston, SC 29425 USA. [Estrada, Carlos A.; Kraemer, Ryan R.] Univ Alabama Birmingham, Div Gen Internal Med, Birmingham, AL 35294 USA. [Estrada, Carlos A.; Kraemer, Ryan R.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Estrada, Carlos A.] Vet Affairs Natl Qual Scholars Program, Birmingham, AL USA. [Rodriguez, Martin] Univ Alabama Birmingham, Birmingham, AL 35294 USA. RP Kraemer, RR (reprint author), Univ Alabama Birmingham, Tinsley Harrison Internal Med Residency Program, Div Gen Internal Med, 720 Fac Off Tower 510 20th St South, Birmingham, AL 35294 USA. EM rkraemer@uab.edu NR 10 TC 2 Z9 2 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2014 VL 29 IS 7 BP 1074 EP 1078 DI 10.1007/s11606-013-2747-z PG 5 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AK1VW UT WOS:000338207100026 PM 24420866 ER PT J AU Chiovaro, J AF Chiovaro, Joseph TI The Forgotten War SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material C1 Portland VA Med Ctr, Dept Med, Div Hosp Med, Portland, OR 97239 USA. RP Chiovaro, J (reprint author), Portland VA Med Ctr, Dept Med, Div Hosp Med, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM jchiovaro@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUL PY 2014 VL 29 IS 7 BP 1079 EP 1080 DI 10.1007/s11606-013-2720-x PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA AK1VW UT WOS:000338207100027 PM 24395099 ER PT J AU Hage, FG AF Hage, F. G. TI C-reactive protein and hypertension SO JOURNAL OF HUMAN HYPERTENSION LA English DT Review DE C-reactive protein; cardiovascular; biomarker; vascular stiffness; genetic variation ID CHRONIC KIDNEY-DISEASE; ACUTE MYOCARDIAL-INFARCTION; CARDIOVASCULAR-DISEASE; ISCHEMIC-STROKE; BLOOD-PRESSURE; NEOINTIMA FORMATION; GENE POLYMORPHISMS; TRANSGENIC MICE; HAN CHINESE; CRP LEVELS AB C-reactive protein (CRP), the prototypical acute-phase reactant, is one of the most widely known biomarkers of cardiovascular disease. Circulating levels of CRP are clinically used to predict the occurrence of cardiovascular events and to aide in the selection of therapies based on more accurate risk assessment in individuals who are at intermediate risk. This paper reviews the role of CRP in hypertension. In hypertensive individuals, CRP levels associate with vascular stiffness, atherosclerosis and the development of end-organ damage and cardiovascular events. Data suggest that some anti-hypertensive medications may lower CRP levels in a manner independent of their effect on blood pressure. In individuals who are normotensive at baseline, CRP levels have been shown in multiple cohorts to foretell the development of hypertension on follow-up. Whether genetic variability that influences circulating levels of CRP independent of environmental and behavioral factors can also be used in a similar manner to predict the change in blood pressure and development of hypertension is controversial. In addition to its role as a biomarker, experimental studies have unraveled an active direct participation of CRP in the development of endothelial dysfunction, vascular stiffness and elevated blood pressure. CRP has also been implicated as a mediator of vascular remodeling in response to injury and cardiac remodeling in response to pressure overload. Emerging data may reveal novel vascular inflammatory pathways and identify new targets for treatment of vascular pathology. C1 [Hage, F. G.] Univ Alabama Birmingham, Div Cardiovasc Dis, Birmingham, AL 35294 USA. [Hage, F. G.] Birmingham Vet Affairs Med Ctr, Cardiol Sect, Birmingham, AL USA. RP Hage, FG (reprint author), Univ Alabama Birmingham, Zeigler Res Bldg 1024,703 19th St South, Birmingham, AL 35294 USA. EM fadihage@uab.edu OI Hage, Fadi/0000-0002-1397-4942 FU Veterans Affairs Biomedical Laboratory Research & Development Service Merit Award; American Heart Association NCRP Scientist Development [0930098N]; Novartis Pharmaceuticals FX This work was supported, in part, by a Veterans Affairs Biomedical Laboratory Research & Development Service Merit Award and an American Heart Association NCRP Scientist Development Grant 0930098N. Grant support from Novartis Pharmaceuticals. NR 60 TC 17 Z9 19 U1 4 U2 21 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9240 EI 1476-5527 J9 J HUM HYPERTENS JI J. Hum. Hypertens. PD JUL PY 2014 VL 28 IS 7 BP 410 EP 415 DI 10.1038/jhh.2013.111 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AK3UQ UT WOS:000338350600002 PM 24226100 ER PT J AU Kajiwara, Y Schiff, T Voloudakis, G Sosa, MAG Elder, G Bozdagi, O Buxbaum, JD AF Kajiwara, Yuji Schiff, Tamar Voloudakis, Georgios Sosa, Miguel A. Gama Elder, Gregory Bozdagi, Ozlem Buxbaum, Joseph D. TI A Critical Role for Human Caspase-4 in Endotoxin Sensitivity SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INTERLEUKIN-1-BETA CONVERTING-ENZYME; NONCANONICAL INFLAMMASOME ACTIVATION; SYSTEMIC INFLAMMATION; INSULIN-RESISTANCE; MICE DEFICIENT; SEPTIC SHOCK; DISEASE; NLRP3; IL-1-BETA; MOUSE AB Response to endotoxins is an important part of the organismal reaction to Gram-negative bacteria and plays a critical role in sepsis and septic shock, as well as other conditions such as metabolic endotoxemia. Humans are generally more sensitive to endotoxins when compared with experimental animals such as mice. Inflammatory caspases mediate endotoxin-induced IL-1 beta secretion and lethality in mice, and caspase-4 is an inflammatory caspase that is found in the human, and not mouse, genome. To test whether caspase-4 is involved in endotoxin sensitivity, we developed a transgenic mouse expressing human caspase-4 in its genomic context. Caspase-4 transgenic mice exhibited significantly higher endotoxin sensitivity, as measured by enhanced cytokine secretion and lethality following LPS challenge. Using bone marrow-derived macrophages, we then observed that caspase-4 can support activation of caspase-1 and secretion of IL-1 beta and IL-18 in response to priming signals (LPS or Pam3CSK4) alone, without the need for second signals to stimulate the assembly of the inflammasome. These findings indicate that the regulation of caspase-1 activity by human caspase-4 could represent a unique mechanism in humans, as compared with laboratory rodents, and may partially explain the higher sensitivity to endotoxins observed in humans. Regulation of the expression, activation, or activity of caspase-4 therefore represents targets for systemic inflammatory response syndrome, sepsis, septic shock, and related disorders. C1 [Kajiwara, Yuji; Voloudakis, Georgios; Sosa, Miguel A. Gama; Elder, Gregory; Bozdagi, Ozlem; Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Schiff, Tamar] Baylor Coll Med, Houston, TX 77030 USA. [Sosa, Miguel A. Gama] James J Peters Dept Vet Affairs Med Ctr, Gen Med Res Serv, Bronx, NY 10468 USA. [Elder, Gregory] James J Peters Dept Vet Affairs Med Ctr, Neurol Serv, Bronx, NY 10468 USA. [Elder, Gregory] Icahn Sch Med Mt Sinai, Dept Neurol, New York, NY 10029 USA. [Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY 10029 USA. [Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA. [Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA. [Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA. RP Buxbaum, JD (reprint author), Icahn Sch Med Mt Sinai, One Gustave L Levy Pl,Box 1668,Annenberg 22-24A, New York, NY 10029 USA. EM Joseph.Buxbaum@mssm.edu OI Buxbaum, Joseph/0000-0001-8898-8313 FU Icahn School of Medicine at Mount Sinai Alzheimer Disease Research Center [U01 P50 AG005138-28]; Manasaki Foundation scholarship FX This work was supported by the Icahn School of Medicine at Mount Sinai Alzheimer Disease Research Center (Dr. Mary Sano, principal investigator; O.B. and J.D.B., project leaders; U01 P50 AG005138-28). G.V. was also supported by a Manasaki Foundation scholarship. J.D.B. is the G. Harold and Leila Y. Mathers Professor of Geriatrics and Adult Development. NR 54 TC 31 Z9 32 U1 0 U2 8 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 2014 VL 193 IS 1 BP 335 EP 343 DI 10.4049/jimmunol.1303424 PG 9 WC Immunology SC Immunology GA AK5BN UT WOS:000338438900039 PM 24879791 ER PT J AU Sarnak, MJ Katz, R Newman, A Harris, T Peralta, CA Devarajan, P Bennett, MR Fried, L Ix, JH Satterfield, S Simonsick, EM Parikh, CR Shlipak, MG AF Sarnak, Mark J. Katz, Ronit Newman, Anne Harris, Tamara Peralta, Carmen A. Devarajan, Prasad Bennett, Michael R. Fried, Linda Ix, Joachim H. Satterfield, Suzanne Simonsick, Eleanor M. Parikh, Chirag R. Shlipak, Michael G. CA Hlth ABC Study TI Association of Urinary Injury Biomarkers with Mortality and Cardiovascular Events SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID GELATINASE-ASSOCIATED LIPOCALIN; ACUTE KIDNEY INJURY; GLOMERULAR-FILTRATION-RATE; PROXIMAL TUBULAR CELLS; MOLECULE-1 KIM-1; FUNCTION DECLINE; CARDIAC-SURGERY; RISK; NGAL; INTERLEUKIN-18 AB Kidney damage is a common sequela of several chronic pathologic conditions. Whether biomarkers of kidney damage are prognostic for more severe outcomes is unknown. We measured three urinary bionnarkers (kidney injury molecule-1 [KIM-1], IL-18, and albumin) in 3010 individuals enrolled in the Health, Aging and Body Composition (Health ABC) study and used Cox proportional hazards models to investigate the associations of urinary KIM-1/creatinine (cr), IL-18/cr, and albumin/cr (ACR) with all-cause mortality and cardiovascular disease (CVD). Multivariable models adjusted for demographics, traditional CVD risk factors, and eGFR. Mean age of participants was 74 years, 49% of participants were men, and 41% of participants were black. During the median 12.4 years of follow-up, 1450 deaths and 797 CVD outcomes occurred. Compared with the lowest quartile, successive quartiles had the following adjusted hazard ratios (HRs; 95% confidence intervals [95% as]) for mortality: KIM-1/cr: (1.21; 1.03 to 1.41), (1.13; 0.96 to 1.34), and (1.28; 1.08 to 1.52); IL-18/cr: (1.02; 0.88 to 1.19), (1.16; 0.99 to 1.35), and (1.06; 0.90 to 1.25); ACR: (1.08; 0.91 to 1.27), (1.24; 1.06 to 1.46), and (1.63; 1.39 to 1.91). In similar analyses, only ACR quartiles associated with CVD: (1.19; 0.95 to 1.48), (1.35; 1.08 to 1.67), and (1.54; 1.24 to 1.91). Urinary KIM-1 had a modest association with all-cause mortality but did not associate with CVD, and urinary IL-18 did not associate with either outcome. In contrast, albuminuria strongly associated with all-cause mortality and CVD. Future studies should evaluate reasons for these differences in the prognostic importance of individual kidney injury markers. C1 [Sarnak, Mark J.] Tufts Med Ctr, Div Nephrol, Boston, MA 02111 USA. [Katz, Ronit] Univ Washington, Kidney Res Inst, Seattle, WA 98195 USA. [Newman, Anne] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Harris, Tamara] NIA, Geriatr Epidemiol Sect, NIH, Bethesda, MD 20892 USA. [Peralta, Carmen A.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Peralta, Carmen A.] San Francisco VA Med Ctr, San Francisco, CA USA. [Devarajan, Prasad; Bennett, Michael R.] Cincinnati Childrens Hosp Med Ctr, Div Nephrol & Hypertens, Cincinnati, OH 45229 USA. [Fried, Linda] Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Pittsburgh, PA USA. [Fried, Linda] Univ Pittsburgh, Sch Med, Renal Sect, Pittsburgh, PA USA. [Fried, Linda] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Ix, Joachim H.] Vet Affairs San Diego Healthcare Syst, Nephrol Sect, San Diego, CA USA. [Ix, Joachim H.] Univ Calif San Diego, Div Nephrol, San Diego, CA 92103 USA. [Ix, Joachim H.] Univ Calif San Diego, Div Prevent Med, San Diego, CA 92103 USA. [Satterfield, Suzanne] Univ Tennessee, Dept Prevent Med, Memphis, TN USA. [Simonsick, Eleanor M.] NIA, Intramural Res Program, Baltimore, MD 21224 USA. [Parikh, Chirag R.] Yale Univ, Dept Med, Sect Nephrol, New Haven, CT 06520 USA. [Parikh, Chirag R.] Yale Univ, Program Appl Translat Res, New Haven, CT USA. [Shlipak, Michael G.] Univ Calif San Francisco, Dept Med, Div Gen Internal Med, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. [Shlipak, Michael G.] Univ Calif San Francisco, Dept Epidemiol, Div Gen Internal Med, San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. [Shlipak, Michael G.] Univ Calif San Francisco, Dept Biostat, Div Gen Internal Med, San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. RP Sarnak, MJ (reprint author), Tufts Med Ctr, Div Nephrol, Box 391,800 Washington St, Boston, MA 02111 USA. EM msarnak@tuftsmedicalcenter.org RI Bennett, Maxwell/J-8504-2015 OI Newman, Anne B./0000-0002-0106-1150 FU National Institute on Aging [R01-AG027002, R01-AG028050, N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; National Institute of Nursing Research [R01-NR012459]; Intramural Research Program of the National Institutes of Health, National Institute on Aging FX This research was supported by National Institute on Aging Grants R01-AG027002 and R01-AG028050; National Institute on Aging Contracts N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106; and National Institute of Nursing Research Grant R01-NR012459. This study was also supported, in part, by the Intramural Research Program of the National Institutes of Health, National Institute on Aging. NR 38 TC 13 Z9 13 U1 0 U2 4 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 EI 1533-3450 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JUL PY 2014 VL 25 IS 7 BP 1545 EP 1553 DI 10.1681/ASN.2013070713 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA AK1LL UT WOS:000338176500020 PM 24511130 ER PT J AU Slatore, CG Sullivan, DR Pappas, M Humphrey, LL AF Slatore, Christopher G. Sullivan, Donald R. Pappas, Miranda Humphrey, Linda L. TI Patient-Centered Outcomes among Lung Cancer Screening Recipients with Computed Tomography A Systematic Review SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE Lung cancer; Screening; Patient-centered outcomes ID SERVICES-TASK-FORCE; RANDOMIZED CONTROLLED-TRIAL; QUALITY-OF-LIFE; NELSON TRIAL; PULMONARY NODULES; FOLLOW-UP; RISK; COMMUNICATION; PARTICIPANTS; STATEMENT AB Introduction: Lung cancer screening using low-dose computed tomography (LDCT) is now widely recommended for adults who are current or former heavy smokers. It is important to evaluate the impact of screening on patient-centered outcomes. Among current and former smokers eligible for lung cancer screening, we sought to determine the consequences of screening with LDCT, and subsequent results, on patient-centered outcomes such as quality of life, distress, and anxiety. Methods: We searched the Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews (through the fourth Quarter 2012), MEDLINE (2000 to May 31, 2013), reference lists of articles, and Scopus for relevant English-language studies and systematic reviews. To evaluate the effect of LDCT screening on patient-centered outcomes, we included only randomized controlled trials (RCTs) involving asymptomatic adults. To evaluate the association of particular results and/or recommendations from a screening LDCT with patient-centered outcomes, we included results from RCTs as well as from cohort studies. Results: A total of 8215 abstracts were reviewed. Five publications from two European RCTs and one publication from a cohort study conducted in the United States met inclusion criteria. The process of LDCT lung cancer screening was associated with short-term psychologic discomfort in many people but did not affect distress, worry, or health-related quality of life. False-positive results were associated with short-term increases in distress that returned to levels that were similar to those among people with negative results. Negative results were associated with short-term decreases in distress. Conclusions: As lung cancer screening is implemented in the general population, it will be important to evaluate its association with patient-centered outcomes. People considering lung cancer screening should be aware of the possibility of distress caused by false-positive results. Clinicians may want to consider tailoring communication strategies that can decrease the distress associated with these results. C1 [Slatore, Christopher G.] Portland VA Med Ctr, Portland, OR 97239 USA. [Slatore, Christopher G.] Portland VA Med Ctr, Sect Pulm & Crit Care Med, Portland, OR 97239 USA. [Humphrey, Linda L.] Portland VA Med Ctr, Div Specialty & Hosp Med, Portland, OR 97239 USA. [Slatore, Christopher G.; Sullivan, Donald R.] Oregon Hlth & Sci Univ, Dept Med, Div Pulm & Crit Care Med, Portland, OR 97201 USA. [Slatore, Christopher G.; Pappas, Miranda; Humphrey, Linda L.] Oregon Hlth & Sci Univ, Dept Med Informat & Clin Epidemiol, Pacific Northwest Evidence Based Practice Ctr, Portland, OR 97201 USA. [Humphrey, Linda L.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. RP Slatore, CG (reprint author), Portland VA Med Ctr, 3710 SW US Vet Hosp Rd,R&D 66, Portland, OR 97239 USA. EM slatore@ohsu.edu OI Slatore, Christopher/0000-0003-0958-8122; Sullivan, Donald/0000-0003-3266-3389 FU Agency for Healthcare Research and Quality [HHSA-290-2007-10057-I-EPC3, 13]; Portland VA Medical Center, Portland, Oregon FX This research was supported by the Agency for Healthcare Research and Quality under Contract No. HHSA-290-2007-10057-I-EPC3, Task Order No. 13. The research reported here was also supported by resources from the Portland VA Medical Center, Portland, Oregon. The Department of Veterans Affairs did not have a role in the conduct of the study, in the collection, management, analysis, or interpretation of data, or in the preparation of the article. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs or the U.S. Government. NR 44 TC 23 Z9 23 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD JUL PY 2014 VL 9 IS 7 BP 927 EP 934 DI 10.1097/JTO.0000000000000210 PG 8 WC Oncology; Respiratory System SC Oncology; Respiratory System GA AJ9JK UT WOS:000338025600011 PM 24922011 ER PT J AU Levy, B Spira, A Becker, D Evans, T Schnadig, I Camidge, DR Bauman, JE Hausman, D Walker, L Nemunaitis, J Rudin, CM Halmos, B Bowles, DW AF Levy, Benjamin Spira, Alexander Becker, Daniel Evans, Tracey Schnadig, Ian Camidge, D. Ross Bauman, Julie E. Hausman, Diana Walker, Luke Nemunaitis, John Rudin, Charles M. Halmos, Balazs Bowles, Daniel W. TI A Randomized, Phase 2 Trial of Docetaxel with or without PX-866, an Irreversible Oral Phosphatidylinositol 3-Kinase Inhibitor, in Patients with Relapsed or Metastatic Non-Small-Cell Lung Cancer SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE PIK3CA; Phosphotidylinositol-3 kinase; Docetaxel; Combination therapy; Non-small-cell lung cancer ID ADVANCED SOLID TUMORS; PI3K INHIBITORS; PATHWAY; THERAPY AB Introduction: The phosphotidylinositol-3 kinase/serine-threonine kinase (AKT)/mammalian target of rapamycin signaling pathway is frequently altered in non-small-cell lung cancer (NSCLC). PX-866 is an oral, irreversible, pan-isoform inhibitor of phosphotidylinositol-3 kinase. Preclinical models revealed synergy with docetaxel and a phase 1 trial demonstrated tolerability of this combination. This randomized phase 2 study evaluated PX-866 combined with docetaxel in patients with advanced, refractory NSCLC. Methods: Patients with locally advanced, recurrent, or metastatic NSCLC who had received at least one and no more than two prior systemic treatment regimens were randomized (1:1) to a combination of docetaxel (75 mg/m(2) intravenous every 21 days) with or without PX-866 (8 mg orally daily; arms A and B, respectively). The primary end point was progression-free survival (PFS). Secondary end points included objective response rate, overall survival (OS), toxicity, and correlation of biomarker analyses with efficacy outcomes. Results: A total of 95 patients were enrolled. Median PFS was 2 months in arm A and 2.9 months in arm B (p = 0.65). Objective response rates were 6% and 0% in arms A and B, respectively (p = 0.4). There was no difference in OS between the two arms (7.0 versus 9.2 months; p = 0.9). Grade 3 or higher adverse events were infrequent, but more common in the combination arm with respect to diarrhea (7% versus 2%), nausea (4% versus 0%), and vomiting (7% versus 0%). PIK3CA mutations or PTEN loss were infrequently observed. Conclusion: The addition of PX-866 to docetaxel did not improve PFS, response rate, or OS in patients with advanced, refractory NSCLC without molecular preselection. C1 [Levy, Benjamin; Becker, Daniel] Mt Sinai Hlth Syst, St Lukes Hosp, Beth Israel Hosp, New York, NY 10011 USA. [Spira, Alexander] Virginia Canc Specialists, Fairfax, VA USA. [Spira, Alexander; Schnadig, Ian] US Oncol Res, The Woodlands, TX USA. [Evans, Tracey] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Schnadig, Ian] Northwest Canc Specialists, Portland, OR USA. [Camidge, D. Ross; Bowles, Daniel W.] Univ Colorado, Sch Med, Div Med Oncol, Aurora, CO USA. [Bauman, Julie E.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. [Hausman, Diana; Walker, Luke] Oncothyreon Inc, Seattle, WA USA. [Nemunaitis, John] Mary Crowley Canc Res Ctr, Dallas, TX USA. [Rudin, Charles M.] Johns Hopkins Univ, Baltimore, MD USA. [Rudin, Charles M.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Halmos, Balazs] Columbia Univ, Med Ctr, New York Presbyterian Hosp, New York, NY USA. [Bowles, Daniel W.] Denver Vet Affairs Med Ctr, Sect Hematol Oncol, Denver, CO USA. RP Levy, B (reprint author), Mt Sinai Hlth Syst, Beth Israel Comprehens Canc Ctr, Albert Einstein Coll Med, 325 W 15th St, New York, NY 10011 USA. EM belevy@chpnet.org OI Rudin, Charles/0000-0001-5204-3465; Becker, Daniel/0000-0001-7230-8432 FU Eli Lilly; Genentech; Pfizer; Oncothyreon; Bristol-Myers Squibb; Lilly; Aveo; Daiichi-Sankyo; Merck; Astra-Zeneca; Boehringer-Ingelheim; Astex; Roche; Novartis FX Disclosure: Dr. Levy serves as a paid consultant and receives payments for lectures from Eli Lilly, Genentech, and Pfizer. Dr. Evans serves as a paid consultant for Eli Lilly and Genentech. Dr. Bauman received grant support from Oncothyreon, Bristol-Myers Squibb, Genentech, and Lilly, and is a paid consultant for Aveo. Drs. Walker and Hausman are full time employees of Oncothyreon. Dr. Walker has received travel support to meetings for the study as well as travel unrelated to the study. Dr. Rudin was a past consultant for Celgene. Dr. Halmos has received grant support from Oncothyreon, Pfizer, Daiichi-Sankyo, Eli Lilly, Bristol-Myers Squibb, Merck, Astra-Zeneca, Boehringer-Ingelheim, Astex, Roche, and Novartis. The other authors declare no conflict of interest. NR 14 TC 11 Z9 11 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD JUL PY 2014 VL 9 IS 7 BP 1031 EP 1035 DI 10.1097/JTO.0000000000000183 PG 5 WC Oncology; Respiratory System SC Oncology; Respiratory System GA AJ9JK UT WOS:000338025600024 PM 24926548 ER PT J AU Walker, JP Hiramoto, JS Gasper, WJ Auyang, P Conte, MS Rapp, JH Lovett, DH Owens, CD AF Walker, Joy P. Hiramoto, Jade S. Gasper, Warren J. Auyang, Philip Conte, Michael S. Rapp, Joseph H. Lovett, David H. Owens, Christopher D. TI Vitamin D deficiency is associated with mortality and adverse vascular access outcomes in patients with end-stage renal disease SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT Vascular Annual Meeting of the Society-for-Vascular-Surgery (SVS) CY MAY 29-JUN 01, 2013 CL San Francisco, CA SP Soc Vasc Surg ID CHRONIC KIDNEY-DISEASE; HEMODIALYSIS-PATIENTS; MINERAL METABOLISM; CARDIOVASCULAR-DISEASE; ENDOTHELIAL FUNCTION; UNITED-STATES; DATA SYSTEM; INFLAMMATION; SUPPLEMENTATION; IMPACT AB Background: Plasma 25 hydroxycholecalciferol (vitamin D) deficiency has been associated with adverse cardiovascular outcomes in epidemiologic studies. Chronic kidney disease is associated with loss of 1 alpha-hydroxylase and consequently vitamin D deficiency. We hypothesized that vitamin D deficiency was associated with increased mortality and increased vascular access failure in patients undergoing permanent vascular access for end-stage renal disease. Methods: This retrospective cohort study analyzed 128 patients undergoing permanent vascular access surgery between 2003 and 2012 for whom concurrent plasma vitamin D levels were also available. Levels were considered deficient at < 20 ng/mL. Multivariable analysis was used to determine the association between vitamin D and mortality and vascular access outcomes. Results: The mean age was 66.7 years, 96.8% were male, 32.0% were African American, and 60.9% had diabetes mellitus. In the entire cohort, 55.5% were vitamin D-deficient, despite similar rates of repletion among the vitamin D-deficient and nondeficient groups. During a median follow-up of 2.73 years, there were 40 deaths (31%). Vitamin D-deficient patients tended to be younger (P = .01) and to have higher total cholesterol (P = .001) and lower albumin (P = .017) and calcium (P = .007) levels. Despite their younger age, mortality was significantly higher (P = .026) and vascular access failure was increased (P = .008) in the vitamin D-deficient group. Multivariate logistic regression analysis found vitamin Ddeficiency (odds ratio [OR], 3.64; 95% confidence interval [CI], 1.12-11.79; P = .031), hemodialysis through a central catheter (OR, 3.08; 95% CI, 1.04-9.12; P = .042), coronary artery disease (OR, 3.08; 95% CI, 1.06-8.94; P = .039), increased age (OR, 1.09; 95% CI, 1.03-1.15; P = .001), and albumin (OR, 0.27; 95% CI, 0.09-0.83; P = .023) remained independent predictors of mortality. Vitamin D deficiency (hazard ratio [HR], 2.34; 95% CI, 1.17-4.71; P = .02), a synthetic graft (HR, 3.50; 95% CI, 1.38-8.89; P = .009), and hyperlipidemia (HR, 0.42; 95% CI, 0.22-0.81; P = .01) were independent predictors of vascular access failure in a Cox proportional hazard model. Conclusions: Vitamin D deficiency is highly prevalent in patients undergoing vascular access procedures. Patients who are deficient in vitamin D have worse survival and worse vascular access outcomes. Further study is warranted to assess whether aggressive vitamin D repletion will improve outcomes in this population. C1 [Walker, Joy P.; Hiramoto, Jade S.; Gasper, Warren J.; Conte, Michael S.; Rapp, Joseph H.; Owens, Christopher D.] Univ Calif San Francisco, Dept Vasc & Endovasc Surg, San Francisco, CA 94143 USA. [Auyang, Philip] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Lovett, David H.] San Francisco Vet Adm Med Ctr, Dept Vasc Surg, San Francisco, CA USA. RP Walker, JP (reprint author), 513 Parnassus Ave,S-321, San Francisco, CA 94127 USA. EM joy.walker@ucsfmedctr.org FU NHLBI NIH HHS [K23 HL-92163, K23 HL092163]; NIDDK NIH HHS [T32 DK007219] NR 41 TC 3 Z9 3 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUL PY 2014 VL 60 IS 1 BP 176 EP 183 DI 10.1016/j.jvs.2014.01.037 PG 8 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA AK5FG UT WOS:000338449500031 PM 24582700 ER PT J AU Sandholm, J Tuomela, J Kauppila, JH Harris, KW Graves, D Selander, KS AF Sandholm, Jouko Tuomela, Johanna Kauppila, Joonas H. Harris, Kevin W. Graves, David Selander, Katri S. TI Hypoxia regulates Toll-like receptor-9 expression and invasive function in human brain cancer cells in vitro SO ONCOLOGY LETTERS LA English DT Article DE Toll-like receptor-9; hypoxia; invasion; brain cancer ID PROSTATE-CANCER; BREAST-CANCER; SUBCELLULAR-LOCALIZATION; HELICOBACTER-PYLORI; CELLULAR INVASION; TISSUE INHIBITOR; EPITHELIAL-CELLS; DENDRITIC CELLS; BACTERIAL-DNA; TLR9 AB Toll-like receptor-9 (TLR9) is a cellular DNA sensor of the innate immune system. TLR9 is widely expressed in a number of tumors, including brain cancer; however, little is known regarding its regulation and involvement in cancer pathophysiology. The present study demonstrated that hypoxia upregulates and downregulates TLR9 expression in human brain cancer cells in vitro, in a cell-specific manner. In addition, hypoxia-induced TLR9 upregulation was associated with hypoxia-induced invasion; however, such invasion was not detected in cells where hypoxia had suppressed TLR9 expression. Furthermore, suppression of TLR9 expression through TLR9 siRNA resulted in an upregulation of matrix metalloproteinase (MMP)-2, -9 and -13 and tissue inhibitor of matrix metalloproteinases-3 (TIMP-3) mRNA, and a decreased invasion of cells in normoxia, in a cell-specific manner. In cells where hypoxia induced TLR9 expression, TLR9 expression and invasion were reduced by TLR9 siRNA. The decreased invasion observed in hypoxia was associated with the decreased expression of the MMPs and a concomitant increase in TIMP-3 expression. In conclusion, hypoxia regulates the invasion of brain cancer cells in vitro in a TLR9-dependent manner, which is considered to be associated with a complex expression pattern of TLR9-regulated mediators and inhibitors of invasion. C1 [Sandholm, Jouko; Tuomela, Johanna; Harris, Kevin W.; Selander, Katri S.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Kauppila, Joonas H.] Oulu Univ Hosp, Dept Pathol, Oulu 90029, Finland. [Kauppila, Joonas H.] Oulu Univ Hosp, Dept Surg, Oulu 90029, Finland. [Kauppila, Joonas H.] Univ Oulu, Dept Anat & Cell Biol, FIN-90570 Oulu, Finland. [Harris, Kevin W.] Birmingham Vet Affairs Med Ctr, Birmingham, AL 35233 USA. [Graves, David] Univ Alabama Birmingham, Dept Chem, Birmingham, AL 35294 USA. RP Selander, KS (reprint author), Univ Alabama Birmingham, Dept Med, Div Hematol Oncol, 1825 Univ Blvd, Birmingham, AL 35294 USA. EM katriselander@uabmc.edu RI Kauppila, Joonas/P-1363-2015 OI Kauppila, Joonas/0000-0001-6740-3726; Tuomela, Johanna/0000-0003-4390-4563 FU Oulu University Scholarship Foundation; Cancer Foundation of Northern Finland; Lapland Cultural Foundation; Department of Defense [BC095831] FX The authors would like to thank Ms Christine Pressey for skillful assistance with the qPCR assays. The present study was funded by grants from the Oulu University Scholarship Foundation and Cancer Foundation of Northern Finland (J.H.K), the Lapland Cultural Foundation (K.S.S) and the Department of Defense (K.S.S. and D.G., grant no. BC095831). NR 53 TC 5 Z9 5 U1 3 U2 6 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1792-1074 EI 1792-1082 J9 ONCOL LETT JI Oncol. Lett. PD JUL PY 2014 VL 8 IS 1 BP 266 EP 274 DI 10.3892/ol.2014.2095 PG 9 WC Oncology SC Oncology GA AK1ML UT WOS:000338179100050 ER PT J AU Ford, JM Palzes, VA Roach, BJ Mathalon, DH AF Ford, Judith M. Palzes, Vanessa A. Roach, Brian J. Mathalon, Daniel H. TI Did I Do That? Abnormal Predictive Processes in Schizophrenia When Button Pressing to Deliver a Tone SO SCHIZOPHRENIA BULLETIN LA English DT Article DE predictive coding; efference copy; corollary discharge; ERPs ID SELF-INITIATED SOUNDS; HUMAN AUDITORY-CORTEX; COROLLARY DISCHARGE DYSFUNCTION; RESPONSES; SYMPTOMS; ATTENUATION; SUPPRESSION; ERP; N1; HALLUCINATIONS AB Motor actions are preceded by an efference copy of the motor command, resulting in a corollary discharge of the expected sensation in sensory cortex. These mechanisms allow animals to predict sensations, suppress responses to self-generated sensations, and thereby process sensations efficiently and economically. During talking, patients with schizophrenia show less evidence of pretalking activity and less suppression of the speech sound, consistent with dysfunction of efference copy and corollary discharge, respectively. We asked if patterns seen in talking would generalize to pressing a button to hear a tone, a paradigm translatable to less vocal animals. In 26 patients [23 schizophrenia, 3 schizoaffective (SZ)] and 22 healthy controls (HC), suppression of the N1 component of the auditory event-related potential was estimated by comparing N1 to tones delivered by button presses and N1 to those tones played back. The lateralized readiness potential (LRP) associated with the motor plan preceding presses to deliver tones was estimated by comparing right and left hemispheres' neural activity. The relationship between N1 suppression and LRP amplitude was assessed. LRP preceding button presses to deliver tones was larger in HC than SZ, as was N1 suppression. LRP amplitude and N1 suppression were correlated in both groups, suggesting stronger efference copies are associated with stronger corollary discharges. SZ have reduced N1 suppression, reflecting corollary discharge action, and smaller LRPs preceding button presses to deliver tones, reflecting the efference copy of the motor plan. Effects seen during vocalization largely extend to other motor acts more translatable to lab animals. C1 [Ford, Judith M.; Palzes, Vanessa A.; Roach, Brian J.; Mathalon, Daniel H.] San Francisco VA Med Ctr, Mental Hlth Serv, San Francisco, CA USA. [Ford, Judith M.; Mathalon, Daniel H.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. RP Ford, JM (reprint author), 4150 Clement St, San Francisco, CA 94121 USA. EM Judith.Ford@ucsf.edu OI Roach, Brian/0000-0002-3264-1465 FU Department of Veterans Affairs [I01CX000497]; National Institute of Mental Health [MH-58262] FX Department of Veterans Affairs (I01CX000497); National Institute of Mental Health (MH-58262 to J.M.F.). NR 50 TC 19 Z9 19 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 EI 1745-1701 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD JUL PY 2014 VL 40 IS 4 BP 804 EP 812 DI 10.1093/schbul/sbt072 PG 9 WC Psychiatry SC Psychiatry GA AK0UC UT WOS:000338130300013 PM 23754836 ER PT J AU Smith, MJ Horan, WP Cobia, DJ Karpouzian, TM Fox, JM Reilly, JL Breiter, HC AF Smith, Matthew J. Horan, William P. Cobia, Derin J. Karpouzian, Tatiana M. Fox, Jaclyn M. Reilly, James L. Breiter, Hans C. TI Performance-Based Empathy Mediates the Influence of Working Memory on Social Competence in Schizophrenia SO SCHIZOPHRENIA BULLETIN LA English DT Article DE empathy; functional outcomes; working memory; social cognition ID FACIAL AFFECT RECOGNITION; NEUROCOGNITIVE DEFICITS; FUNCTIONAL-SIGNIFICANCE; COGNITION; ACCURACY; SYMPTOMS; CAPACITY; MATRICS; IMPAIRMENTS; PERCEPTION AB Empathic deficits have been linked to poor functioning in schizophrenia, but this work is mostly limited to self-report data. This study examined whether performance-based empathy measures account for incremental variance in social competence and social attainment above and beyond self-reported empathy, neurocognition, and clinical symptoms. Given the importance of working memory in theoretical models of empathy and in the prediction of functioning in schizophrenia, we also examined whether empathy mediates the relationship between working memory and functioning. Sixty outpatients and 45 healthy controls were compared on performance-based measures of 3 key components of empathic responding, including facial affect perception, emotional empathy (affective responsiveness), and cognitive empathy (emotional perspective-taking). Participants also completed measures of self-reported empathy, neurocognition, clinical symptoms, and social competence and attainment. Patients demonstrated lower accuracy than controls across the 3 performance-based empathy measures. Among patients, these measures showed minimal relations to self-reported empathy but significantly correlated with working memory and other neurocognitive functions as well as symptom levels. Furthermore, cognitive empathy explained significant incremental variance in social competence (Delta R-2 = .07, P < .05) and was found to mediate the relation between working memory and social competence. Performance-based measures of empathy were sensitive to functionally relevant disturbances in schizophrenia. Working memory deficits appear to have an important effect on these disruptions in empathy. Empathy is emerging as a promising new area for social cognitive research and for novel recovery-oriented treatment development. C1 [Smith, Matthew J.; Cobia, Derin J.; Karpouzian, Tatiana M.; Fox, Jaclyn M.; Reilly, James L.; Breiter, Hans C.] Northwestern Univ, Feinberg Sch Med, Dept Psychiat & Behav Sci, Chicago, IL 60611 USA. [Horan, William P.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychait & Biobehav Sci, Los Angeles, CA 90095 USA. [Horan, William P.] VA Greater Los Angeles Healthcare Syst, MIRECC VISN22, Los Angeles, CA USA. [Breiter, Hans C.] Northwestern Univ, Feinberg Sch Med, Warren Wright Adolescent Ctr, Chicago, IL 60611 USA. RP Smith, MJ (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Psychiat & Behav Sci, 446 E Ontario,Suite 7-100, Chicago, IL 60611 USA. EM matthewsmith@northwestern.edu OI Smith, Matthew/0000-0002-0079-1477; Cobia, Derin/0000-0003-2339-958X FU Department of Psychiatry and Behavioral Sciences at Northwestern University Feinberg School of Medicine FX Department of Psychiatry and Behavioral Sciences at Northwestern University Feinberg School of Medicine. NR 102 TC 20 Z9 20 U1 3 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 EI 1745-1701 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD JUL PY 2014 VL 40 IS 4 BP 824 EP 834 DI 10.1093/schbul/sbt084 PG 11 WC Psychiatry SC Psychiatry GA AK0UC UT WOS:000338130300015 PM 23770935 ER PT J AU Ford, JM Morris, SE Hoffman, RE Sommer, I Waters, F McCarthy-Jones, S Thoma, RJ Turner, JA Keedy, SK Badcock, JC Cuthbert, BN AF Ford, Judith M. Morris, Sarah E. Hoffman, Ralph E. Sommer, Iris Waters, Flavie McCarthy-Jones, Simon Thoma, Robert J. Turner, Jessica A. Keedy, Sarah K. Badcock, Johanna C. Cuthbert, Bruce N. TI Studying Hallucinations Within the NIMH RDoC Framework SO SCHIZOPHRENIA BULLETIN LA English DT Article DE Hallucinations; Research Domain Criteria; RDoC ID AUDITORY VERBAL HALLUCINATIONS; INNER SPEECH; COGNITIVE NEUROPSYCHIATRY; COROLLARY DISCHARGE; SCHIZOPHRENIA; THOUGHT; PSYCHOPATHOLOGY; DIRECTIONS; DISORDERS; VOICES AB We explore how hallucinations might be studied within the National Institute of Mental Health (NIMH) Research Domain Criteria (RDoC) framework, which asks investigators to step back from diagnoses based on symptoms and focus on basic dimensions of functioning. We start with a description of the objectives of the RDoC project and its domains and constructs. Because the RDoC initiative asks investigators to study phenomena across the wellness spectrum and different diagnoses, we address whether hallucinations experienced in nonclinical populations are the same as those experienced by people with psychotic diagnoses, and whether hallucinations studied in one clinical group can inform our understanding of the same phenomenon in another. We then discuss the phenomenology of hallucinations and how different RDoC domains might be relevant to their study. We end with a discussion of various challenges and potential next steps to advance the application of the RDoC approach to this area of research. C1 [Ford, Judith M.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Ford, Judith M.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Morris, Sarah E.; Cuthbert, Bruce N.] NIMH, Div Adult Translat Res, Bethesda, MD 20892 USA. [Hoffman, Ralph E.] Yale New Haven Psychiat Hosp, Dept Psychiat, New Haven, CT USA. [Sommer, Iris] Univ Med Ctr, Dept Psychiat, Utrecht, Netherlands. [Waters, Flavie] Univ Western Australia, Ctr Clin Res Neuropsychiat, Sch Psychiat & Clin Neurosci, Perth, WA 6009, Australia. [Waters, Flavie] North Metro Hlth Serv Mental Hlth, Graylands Hosp, Perth, WA, Australia. [McCarthy-Jones, Simon] Macquarie Univ, ARC Ctr Excellence Cognit & Its Disorders, Dept Cognit Sci, Sydney, NSW 2109, Australia. [McCarthy-Jones, Simon] Univ Durham, Dept Psychol, Durham DH1 3LE, England. [Thoma, Robert J.] Univ New Mexico, Dept Psychiat, Albuquerque, NM 87131 USA. [Turner, Jessica A.] Georgia State Univ, Dept Psychol, Atlanta, GA 30303 USA. [Turner, Jessica A.] Georgia State Univ, Inst Neurosci, Atlanta, GA 30303 USA. [Keedy, Sarah K.] Univ Chicago, Dept Psychiat & Behav Neurosci, Chicago, IL 60637 USA. [Badcock, Johanna C.] Univ Western Australia, Sch Psychol, Crawley, WA, Australia. [Badcock, Johanna C.] North Metropolitan Hlth Serv Mental Hlth, Clin Res Ctr, Mt Claremont, WA, Australia. RP Ford, JM (reprint author), San Francisco VA Med Ctr, Psychiat Serv 116D, 4150 Clement St, San Francisco, CA 94121 USA. EM judith.ford@ucsf.edu RI Keedy, Sarah/H-6557-2014; Badcock, Johanna/C-3682-2013; Turner, Jessica/H-7282-2015 OI Keedy, Sarah/0000-0002-2139-9271; Badcock, Johanna/0000-0003-4629-2929; Turner, Jessica/0000-0003-0076-8434 FU National Institute of Mental Health [MH058262, MH067073, MH073673]; Veterans Administration; VIDI from the Netherlands Organization for Scientific Research; National Institutes of Health [2P20GM103472-06]; Wellcome Trust [WT098455]; Macquarie University; [K23MH092702]; [P20RR021938 Phase 1NCRR COBRE] FX National Institute of Mental Health (MH058262 [J.M.F.], MH067073 [R. E. H.], MH073673 [R. E. H.]); Veterans Administration (J.M.F.); VIDI grant from the Netherlands Organization for Scientific Research (I. E. C. S.); K23MH092702 (S. K. K.); National Institutes of Health 2P20GM103472-06 (R.J.T.; J.A.T.); P20RR021938 Phase 1NCRR COBRE (R.J.T.); Wellcome Trust Grant (WT098455 to S.M.-J.); Macquarie University Research Fellowship (S.M.-J.). NR 61 TC 35 Z9 35 U1 5 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 EI 1745-1701 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD JUL PY 2014 VL 40 SU 4 BP S295 EP S304 DI 10.1093/schbul/sbu011 PG 10 WC Psychiatry SC Psychiatry GA AK0US UT WOS:000338132100012 PM 24847862 ER PT J AU Mahmoodi, BK Yatsuya, H Matsushita, K Sang, YY Gottesman, RF Astor, BC Woodward, M Longstreth, WT Psaty, BM Shlipak, MG Folsom, AR Gansevoort, RT Coresh, J AF Mahmoodi, Bakhtawar K. Yatsuya, Hiroshi Matsushita, Kunihiro Sang, Yinying Gottesman, Rebecca F. Astor, Brad C. Woodward, Mark Longstreth, W. T., Jr. Psaty, Bruce M. Shlipak, Michael G. Folsom, Aaron R. Gansevoort, Ron T. Coresh, Josef TI Association of Kidney Disease Measures With Ischemic Versus Hemorrhagic Strokes Pooled Analyses of 4 Prospective Community-Based Cohorts SO STROKE LA English DT Article DE cardiovascular; epidemiology; renal insufficiency; chronic; risk factors; stroke ID GLOMERULAR-FILTRATION-RATE; GENERAL-POPULATION; CYSTATIN C; INTRACEREBRAL HEMORRHAGE; CARDIOVASCULAR-DISEASE; INCIDENT STROKE; BLOOD-PRESSURE; OLDER-ADULTS; ALL-CAUSE; RISK AB Background and purpose-Although low glomerular filtration rate (GFR) and albuminuria are associated with increased risk of stroke, few studies compared their contribution to risk of ischemic versus hemorrhagic stroke separately. We contrasted the association of these kidney measures with ischemic versus hemorrhagic stroke. Methods-We pooled individual participant data from 4 community-based cohorts: 3 from the United States and 1 from The Netherlands. GFR was estimated using both creatinine and cystatin C, and albuminuria was quantified by urinary albumin-to-creatinine ratio (ACR). Associations of estimated GFR and ACR were compared for each stroke type (ischemic versus intraparenchymal hemorrhagic) using study-stratified Cox regression. Results-Among 29 595 participants (mean age, 61 [SD 12.5] years; 46% men; 17% black), 1261 developed stroke (12% hemorrhagic) during 280 549 person-years. Low estimated GFR was significantly associated with increased risk of ischemic stroke, but not hemorrhagic stroke, whereas high ACR was associated with both stroke types. Adjusted hazard ratios for ischemic and hemorrhagic stroke at estimated GFR of 45 (versus 95) mL/min per 1.73 m(2) were 1.30 (95% confidence interval, 1.01-1.68) and 0.92 (0.47-1.81), respectively. In contrast, the corresponding hazard ratios for ACR of 300 (versus 5) mg/g were 1.62 (1.27-2.07) for ischemic and 2.57 (1.37-4.83) for hemorrhagic stroke, with significantly stronger association with hemorrhagic stroke (P=0.04). For hemorrhagic stroke, the association of elevated ACR was of similar magnitude as that of elevated systolic blood pressure. Conclusions-Whereas albuminuria showed significant association with both stroke types, the association of decreased estimated GFR was only significant for ischemic stroke. The strong association of albuminuria with both stroke types warrants clinical attention and further investigations. C1 [Mahmoodi, Bakhtawar K.; Matsushita, Kunihiro; Sang, Yinying; Woodward, Mark; Coresh, Josef] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Mahmoodi, Bakhtawar K.; Gansevoort, Ron T.] Univ Groningen, Univ Med Ctr Groningen, Dept Nephrol, Groningen, Netherlands. [Yatsuya, Hiroshi] Fujita Hlth Univ, Dept Publ Hlth, Toyoake, Aichi, Japan. [Gottesman, Rebecca F.] Johns Hopkins Sch Med, Dept Neurol, Baltimore, MD USA. [Astor, Brad C.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Madison, WI 53706 USA. [Astor, Brad C.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Populat Hlth Sci, Madison, WI 53706 USA. [Woodward, Mark] Univ Sydney, George Inst, Sydney, NSW 2006, Australia. [Longstreth, W. T., Jr.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Longstreth, W. T., Jr.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Psaty, Bruce M.] Univ Washington, Dept Epidemiol & Hlth Serv, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Shlipak, Michael G.] Univ Calif San Francisco, San Francisco VA Med Ctr, Div Gen Internal Med, San Francisco, CA 94143 USA. [Folsom, Aaron R.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. RP Coresh, J (reprint author), 2024 East Monument St,Suite 2-600, Baltimore, MD 21287 USA. EM coresh@jhu.edu RI Woodward, Mark/D-8492-2015 FU National Heart, Lung, and Blood Institute (NHLBI) [HHSN268201100005C, HHSN268201100006C, HHSN26820110 0007C, HHSN268201100008C, HHSN268201100009C, HHSN 268201100010C, HHSN268201100011C, HHSN268201100 012C]; NHLBI [HL080295, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169]; National Institute on Aging [AG023629]; Dutch Kidney Foundation; Dutch Heart Foundation; Dutch Government (NWO); US National Institutes of Health; University Medical Center Groningen; [HHSN268201200036C]; [N01HC85239]; [N01 HC55222]; [N01HC85079]; [N01HC85080]; [N01HC85081]; [N01HC85082]; [N01HC85083]; [N01HC85086] FX Atherosclerosis Risk in Communities Study (ARIC): The Atherosclerosis Risk in Communities Study is performed as a collaborative study supported by National Heart, Lung, and Blood Institute (NHLBI) contracts (HHSN268201100005C, HHSN268201100006C, HHSN26820110 0007C, HHSN268201100008C, HHSN268201100009C, HHSN 268201100010C, HHSN268201100011C, and HHSN268201100 012C). We thank the staff and participants of the ARIC study for their important contributions. Cardiovascular Health Study (CHS): This research was supported by contracts HHSN268201200036C, N01HC85239, N01 HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, and grant HL080295 from the NHLBI, with additional contribution from the National Institute of Neurological Disorders and Stroke. Additional support was provided by AG023629 from the National Institute on Aging. A full list of principal CHS investigators and institutions can be found at http://www.chs-nhlbi.org/PI.htm. We thank the staff and participants of the CHS study for their important contributions. Multi-Ethnic Study of Atherosclerosis (MESA): This research was supported by contracts N01-HC-95159 through N01-HC-95169 from the NHLBI. We thank the other investigators, the staff, and the participants of the MESA study for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org. Prevention of REnal and Vascular ENd-stage Disease (PREVEND): The PREVEND study is supported by several grants from the Dutch Kidney Foundation, and grants from the Dutch Heart Foundation, the Dutch Government (NWO), the US National Institutes of Health, and the University Medical Center Groningen. We thank the staff and participants of the PREVEND study for their important contributions. None of the aforementioned sponsors were involved in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or in the preparation, review, or approval of the article. NR 29 TC 16 Z9 17 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD JUL PY 2014 VL 45 IS 7 BP 1925 EP 1931 DI 10.1161/STROKEAHA.114.004900 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA AK0TV UT WOS:000338129400015 PM 24876078 ER PT J AU Boan, AD Feng, WW Ovbiagele, B Bachman, DL Ellis, C Adams, RJ Kautz, SA Lackland, DT AF Boan, Andrea D. Feng, Wuwei (Wayne) Ovbiagele, Bruce Bachman, David L. Ellis, Charles Adams, Robert J. Kautz, Steven A. Lackland, Daniel T. TI Persistent Racial Disparity in Stroke Hospitalization and Economic Impact in Young Adults in the Buckle of Stroke Belt SO STROKE LA English DT Article DE epidemiology; fees and charges; middle aged; minority health; stroke ID AMERICAN-HEART-ASSOCIATION; UNITED-STATES; BIRACIAL POPULATION; SEEKING TREATMENT; RECURRENT STROKE; TEMPORAL TRENDS; SOUTH-CAROLINA; BLOOD-PRESSURE; RISK; HEALTH AB Background and Purpose-Mounting evidence points to a decline in stroke incidence. However, little is known about recent patterns of stroke hospitalization within the buckle of the stroke belt. This study aims to investigate the age-and race-specific secular trends in stroke hospitalization rates, inpatient stroke mortality rates, and related hospitalization charges during the past decade in South Carolina. Methods-Patients from 2001 to 2010 were identified from the State Inpatient Hospital Discharge Database with a primary discharge diagnosis of stroke (International Classification of Diseases, Ninth Revision codes: 430-434, 436, 437.1). Age- and race-stroke-specific hospitalization rates, hospital charges, charges associated with racial disparity, and 30-day stroke mortality rates were compared between blacks and whites. Results-Of the 84 179 stroke hospitalizations, 31 137 (37.0%) were from patients aged < 65 years and 29 846 (35.5%) were blacks. Stroke hospitalization rates decreased in the older population (aged >= 65 years) for both blacks and whites (P<0.001) but increased among the younger group (aged <65 years; P=0.004); however, this increase was mainly driven by a 17.3% rise among blacks (P=0.001), with no difference seen among whites (P=0.84). Of hospital charges totaling $2.77 billion, $453.2 million (16.4%) are associated with racial disparity (79.6% from patients aged < 65 years). Thirty-day stroke mortality rates decreased in all age-race-stroke-specific groups (P<0.001). Conclusions-The stroke hospitalization rate increased in the young blacks only, which results in a severe and persistent racial disparity. It highlights the urgent need for a racial disparity reduction in the younger population to alleviate the healthcare burden. C1 [Boan, Andrea D.; Feng, Wuwei (Wayne); Ovbiagele, Bruce; Bachman, David L.; Adams, Robert J.; Kautz, Steven A.; Lackland, Daniel T.] Med Univ S Carolina, Stroke Ctr, Dept Neurosci, Charleston, SC 29425 USA. [Feng, Wuwei (Wayne); Ellis, Charles; Kautz, Steven A.] Med Univ S Carolina, Dept Hlth Sci & Res, Charleston, SC 29425 USA. [Ovbiagele, Bruce; Kautz, Steven A.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Feng, WW (reprint author), MUSC Stroke Ctr, Dept Neurosci, 19 Hagood Ave,STE 501, Charleston, SC 29425 USA. EM feng@musc.edu FU Southeastern Virtual Institute for Heath Equality and Wellness; US Army Medical Research and Materiel Command; Telemedicine & Advanced Technology Research Center [W81XWH-10-2-0057]; Stroke Education and Prevention-South Carolina; Health Sciences South Carolina; Consortium for Southeastern Hypertension Control FX This research was supported by Southeastern Virtual Institute for Heath Equality and Wellness, US Army Medical Research and Materiel Command and Telemedicine & Advanced Technology Research Center (W81XWH-10-2-0057); Stroke Education and Prevention-South Carolina, Health Sciences South Carolina; and Consortium for Southeastern Hypertension Control. NR 37 TC 7 Z9 7 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD JUL PY 2014 VL 45 IS 7 BP 1932 EP 1938 DI 10.1161/STROKEAHA.114.004853 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA AK0TV UT WOS:000338129400016 PM 24947293 ER PT J AU Lich, KH Tian, Y Beadles, CA Williams, LS Bravata, DM Cheng, EM Bosworth, HB Homer, JB Matchar, DB AF Lich, Kristen Hassmiller Tian, Yuan Beadles, Christopher A. Williams, Linda S. Bravata, Dawn M. Cheng, Eric M. Bosworth, Hayden B. Homer, Jack B. Matchar, David B. TI Strategic Planning to Reduce the Burden of Stroke Among Veterans Using Simulation Modeling to Inform Decision Making SO STROKE LA English DT Article DE comparative effectiveness research; computer simulation; health planning; stroke; Veterans ID ISCHEMIC-STROKE; ATRIAL-FIBRILLATION; TASK-FORCE; CARE; HEALTH; PREVENTION; OUTCOMES; QUALITY; ORGANIZATION; ASSOCIATION AB Background and Purpose-Reducing the burden of stroke is a priority for the Veterans Affairs Health System, reflected by the creation of the Veterans Affairs Stroke Quality Enhancement Research Initiative. To inform the initiative's strategic planning, we estimated the relative population-level impact and efficiency of distinct approaches to improving stroke care in the US Veteran population to inform policy and practice. Methods-A System Dynamics stroke model of the Veteran population was constructed to evaluate the relative impact of 15 intervention scenarios including both broad and targeted primary and secondary prevention and acute care/rehabilitation on cumulative (20 years) outcomes including quality-adjusted life years (QALYs) gained, strokes prevented, stroke fatalities prevented, and the number-needed-to-treat per QALY gained. Results-At the population level, a broad hypertension control effort yielded the largest increase in QALYs (35 517), followed by targeted prevention addressing hypertension and anticoagulation among Veterans with prior cardiovascular disease (27 856) and hypertension control among diabetics (23 100). Adjusting QALYs gained by the number of Veterans needed to treat, thrombolytic therapy with tissue-type plasminogen activator was most efficient, needing 3.1 Veterans to be treated per QALY gained. This was followed by rehabilitation (3.9) and targeted prevention addressing hypertension and anticoagulation among those with prior cardiovascular disease (5.1). Probabilistic sensitivity analysis showed that the ranking of interventions was robust to uncertainty in input parameter values. Conclusions-Prevention strategies tend to have larger population impacts, though interventions targeting specific high-risk groups tend to be more efficient in terms of number-needed-to-treat per QALY gained. C1 [Lich, Kristen Hassmiller] Univ N Carolina, Dept Hlth Policy & Management, Chapel Hill, NC USA. [Tian, Yuan; Matchar, David B.] Duke NUS Grad Med Sch, Program Hlth Serv & Syst Res, Singapore, Singapore. [Beadles, Christopher A.; Bosworth, Hayden B.] Durham VAMC, Ctr Hlth Serv Res Primary Care, Durham, NC USA. [Williams, Linda S.; Bravata, Dawn M.] VHA Hlth Serv Res & Dev Stroke Qual Enhancement R, Indianapolis, IN USA. [Williams, Linda S.; Bravata, Dawn M.] Richard L Roudebush VHA Med Ctr, VHA Hlth Serv Res & Dev Ctr Excellence Implementi, Indianapolis, IN USA. [Williams, Linda S.; Bravata, Dawn M.] Regenstrief Inst Hlth Care, Indianapolis, IN USA. [Williams, Linda S.] VA Ctr Appl Syst Engn, Vet Engn Resource Ctr, Dept Vet Affairs, Indianapolis, IN USA. [Bravata, Dawn M.] Indiana Univ Sch Med, Dept Internal Med, Indianapolis, IN 46202 USA. [Cheng, Eric M.] VA Greater Los Angeles Healthcare Syst, Dept Neurol, Los Angeles, CA 90073 USA. [Cheng, Eric M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Bosworth, Hayden B.; Matchar, David B.] Duke Univ, Dept Med, Div Gen Internal Med, Durham, NC USA. [Homer, Jack B.] Homer Consulting, Voorhees, NJ USA. [Matchar, David B.] Duke Univ, Duke Clin Res Inst, Durham, NC USA. RP Lich, KH (reprint author), UNC Gillings Sch Global Publ Hlth, Dept Hlth Policy & Management, 135 Dauer Dr,Campus Box 7411, Chapel Hill, NC 27599 USA. EM klich@unc.edu FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service Quality Enhancement Research Initiative [RRP 07-295]; National Center for Research Resources [KL2RR025746]; National Institutes of Health/National Institute of Neurological Disorders and Stroke [K23NS058571]; Singapore Ministry of Health's National Medical Research Council under its STaR Award Grant; VA HSRD [08-027] FX This research was supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service Quality Enhancement Research Initiative (RRP 07-295). Effort by the following authors was also supported by the following grants: K.H.L. by award number KL2RR025746 from the National Center for Research Resources; D.B.M. by award number K23NS058571 from the National Institutes of Health/National Institute of Neurological Disorders and Stroke and the Singapore Ministry of Health's National Medical Research Council under its STaR Award Grant; and H. B. B. by a senior career scientist award from VA HSR&D (08-027). The authors take sole responsibility for the scientific validity and accuracy of the methodology, results, statistical analyses, and conclusions presented. NR 34 TC 2 Z9 2 U1 1 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD JUL PY 2014 VL 45 IS 7 BP 2078 EP 2084 DI 10.1161/STROKEAHA.114.004694 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA AK0TV UT WOS:000338129400039 PM 24923722 ER PT J AU Raskind, MA McCaslin, C Jakupcak, M AF Raskind, Murray A. McCaslin, Creed Jakupcak, Matthew TI Violence in War and Violence Back Home SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Editorial Material ID POSTTRAUMATIC-STRESS-DISORDER; EXPERIENTIAL AVOIDANCE; ALCOHOL-USE; VETERANS; IRAQ; AFGHANISTAN; COMBAT; ANGER; AGGRESSION; BEHAVIOR C1 [Raskind, Murray A.] Northwest Network VISN 20 Mental Illness Res Educ, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Raskind, MA (reprint author), Northwest Network VISN 20 Mental Illness Res Educ, Seattle, WA USA. EM murray.raskind@va.gov NR 15 TC 0 Z9 0 U1 3 U2 3 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X EI 1535-7228 J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JUL PY 2014 VL 171 IS 7 BP 701 EP 704 DI 10.1176/appi.ajp.2014.14040528 PG 4 WC Psychiatry SC Psychiatry GA AJ9AD UT WOS:000337998300001 PM 24980162 ER PT J AU Bowling, MR Xing, DQ Kapadia, A Chen, YF Szalai, AJ Oparil, S Hage, FG AF Bowling, Meaghan R. Xing, Dongqi Kapadia, Akash Chen, Yiu-Fai Szalai, Alexander J. Oparil, Suzanne Hage, Fadi G. TI Estrogen Effects on Vascular Inflammation Are Age Dependent Role of Estrogen Receptors SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE aging; c-reactive protein; estrogen; vascular system injuries ID POSTMENOPAUSAL HORMONE-THERAPY; RANDOMIZED CONTROLLED-TRIAL; C-REACTIVE PROTEIN; SMOOTH-MUSCLE-CELLS; CARDIOVASCULAR-DISEASE; NEOINTIMA FORMATION; REPLACEMENT THERAPY; INJURED ARTERIES; TRANSGENIC MICE; CAROTID-ARTERY AB Objective-17 beta-Estradiol (E2) offers cardiovascular protection in young female animals and postmenopausal women. In contrast, randomized trials of menopausal hormones performed in older women have shown harm or no cardiovascular benefit. We hypothesize that E2 effects on vascular inflammation are age dependent. Approach and Results-Young (10 weeks) and aged (52 weeks) female C57BL/6 mice were used as source for primary cultures of bone marrow-derived macrophages (BMMs) and vascular smooth muscle cells (VSMCs). E2 pretreatment of cells derived from young mice attenuated C-reactive protein (CRP)-induced expression of inflammatory mediators. In contrast, E2 pretreatment of cells from aged mice did not alter (BMMs) or paradoxically exaggerated (VSMCs) inflammatory mediator response to CRP. Using E2 receptor (ER) knockout mice, we demonstrated that E2 regulates inflammatory response to CRP in BMMs via ER alpha and in VSMCs via ER beta. BMMs derived from aged (versus young) mice expressed significantly less ERa mRNA and protein. A selective ligand of the novel ER GPR30 reproduced the E2 effects in BMMs and VSMCs. Unlike in young mice, E2 did not reduce neointima formation in ligated carotid arteries of aged CRP transgenic mice. Conclusions-E2 attenuates inflammatory response to CRP in BMMs and VSMCs derived from young but not aged mice and reduces neointima formation in injured carotid arteries of young but not aged CRP transgenic mice. ER alpha expression in BMMs is greatly diminished with aging. These data suggest that vasoprotective effects of E2 are age dependent and may explain the vasotoxic effects of E2 seen in clinical trials of postmenopausal women. C1 [Bowling, Meaghan R.] Univ Alabama Birmingham, Dept Obstet & Gynecol, Div Reprod Endocrinol & Infertil, Birmingham, AL 35294 USA. [Xing, Dongqi; Chen, Yiu-Fai; Oparil, Suzanne; Hage, Fadi G.] Univ Alabama Birmingham, Div Cardiovasc Dis, Vasc Biol & Hypertens Program, Birmingham, AL 35294 USA. [Szalai, Alexander J.] Univ Alabama Birmingham, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA. [Kapadia, Akash] Univ Alabama Birmingham, Sch Med, Dept Med, Birmingham, AL USA. [Hage, Fadi G.] Birmingham Vet Affairs Med Ctr, Cardiol Sect, Birmingham, AL USA. RP Hage, FG (reprint author), Birmingham Vet Adm Med Ctr, Cardiol Sect, Zeigler Res Bldg 1024,703 19th St South, Birmingham, AL 35294 USA. EM fadihage@uab.edu OI Hage, Fadi/0000-0002-1397-4942 FU Veterans Affairs Biomedical Laboratory Research & Development Service Merit Award; American Heart Association NCRP Scientist Development Grant [0930098]; Greater Southeast Affiliate grant [09BGIA2250367]; National Heart, Lung, and Blood Institute [R01 HL087980, HL080017, HL044195] FX This work was supported, in part, by a Veterans Affairs Biomedical Laboratory Research & Development Service Merit Award (to Dr Hage), American Heart Association NCRP Scientist Development Grant (0930098 N to Dr Hage) and a Greater Southeast Affiliate grant (09BGIA2250367 to Dr Xing), National Heart, Lung, and Blood Institute grants (R01 HL087980 to Dr Oparil) and (HL080017, HL044195 to Dr Chen). NR 48 TC 16 Z9 16 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 EI 1524-4636 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JUL PY 2014 VL 34 IS 7 BP 1477 EP 1485 DI 10.1161/ATVBAHA.114.303629 PG 9 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA AJ5OC UT WOS:000337732900023 PM 24876352 ER PT J AU Bunaciu, L Leen-Feldner, EW Blumenthal, H Knapp, AA Badour, CL Feldner, MT AF Bunaciu, Liviu Leen-Feldner, Ellen W. Blumenthal, Heidemarie Knapp, Ashley A. Badour, Christal L. Feldner, Matthew T. TI An Experimental Test of the Effects of Parental Modeling on Panic-Relevant Escape and Avoidance Among Early Adolescents SO BEHAVIOR THERAPY LA English DT Article DE escape; avoidance; modeling; panic; voluntary hyperventilation ID DIOXIDE-ENRICHED AIR; ANXIETY SENSITIVITY; BEHAVIORAL-INHIBITION; BODILY SENSATIONS; LEARNING HISTORY; VOLUNTARY HYPERVENTILATION; FEAR-ACQUISITION; SOCIAL ANXIETY; CHILD ANXIETY; DISORDER AB Escape and avoidance behaviors play a prominent role in the maintenance and possibly development of panic disorder, yet the literature regarding the etiology of these emotion-regulation strategies is relatively underdeveloped. The current study experimentally tests hypotheses that parental modeling of escape during a well-established panic-relevant biological challenge increases panic-relevant escape and avoidance among offspring. Fifty physically and psychologically healthy early adolescents (28 females; M-age = 11.58; 86% Caucasian), stratified by gender, were randomly assigned to observe one of their parents (39 females; M-age = 40.04): either (a) model completing a 3-min voluntary hyperventilation exercise (no escape modeling group) or (b) model premature termination of a similar procedure (escape modeling group). Offspring in the escape modeling group demonstrated a stronger escape response by discontinuing their own challenge sooner than those in the no-escape modeling group (r = .70). No group differences emerged in terms of avoidance responding, as indexed by nearly identical responding in terms of delay time before initiating the challenge, respiration rate, and self-reported willingness to engage in a second proposed challenge. Results suggest that parental behaviors may play an important role in the development of some forms of panic-relevant responding. These preliminary findings may have important implications for future prevention programs targeting parents and at-risk youth. C1 [Bunaciu, Liviu; Leen-Feldner, Ellen W.; Knapp, Ashley A.; Badour, Christal L.; Feldner, Matthew T.] Univ Arkansas, Fayetteville, AR 72701 USA. [Bunaciu, Liviu] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA. [Blumenthal, Heidemarie] Univ N Texas, Denton, TX 76203 USA. [Badour, Christal L.] Med Univ S Carolina, Charleston, SC USA. [Badour, Christal L.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Feldner, Matthew T.] Laureate Inst Brain Res, Tulsa, OK USA. RP Bunaciu, L (reprint author), Univ Arkansas, Dept Psychol Sci, Intervent Sci Lab, 216 Mem Hall, Fayetteville, AR 72701 USA. EM liviu_bunaciu@brown.edu; mfeldne@uark.edu NR 69 TC 1 Z9 1 U1 5 U2 16 PU ASSOC ADV BEHAVIOR THERAPY PI NEW YORK PA 305 7TH AVE #16A, NEW YORK, NY 10001-6008 USA SN 0005-7894 EI 1878-1888 J9 BEHAV THER JI Behav. Therapy PD JUL PY 2014 VL 45 IS 4 BP 517 EP 529 PG 13 WC Psychology, Clinical SC Psychology GA AJ7EQ UT WOS:000337860400006 PM 24912464 ER PT J AU Giglia, JL White, MJ Hart, AJ Toro, JJ Freytes, CO Holt, CC Cai, Y Williams, SM Brandt, SJ AF Giglia, Jennifer L. White, Marquitta J. Hart, Andrew J. Toro, Juan J. Freytes, Cesar O. Holt, Cherish C. Cai, Ying Williams, Scott M. Brandt, Stephen J. TI A Single Nucleotide Polymorphism in SLC7A5 Is Associated with Gastrointestinal Toxicity after High-Dose Melphalan and Autologous Stem Cell Transplantation for Multiple Myeloma SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Pharmacogenetics; Multiple myeloma; High-dose melphalan; Autologous hematopoietic stem; cell transplantation; Gastrointestinal toxicity; Drug transporter ID ACID TRANSPORTER-1 LAT1; ORAL MUCOSITIS; SYSTEM L; AMINO; PHARMACOKINETICS AB Multiple myeloma is the most frequent indication for high-dose melphalan (HDM) chemotherapy with autologous stem cell transplantation (ASCT). Gastrointestinal symptoms represent the most significant nonhematological toxicity of HDM. However, specific, especially genetic, predictors of their incidence or clinical severity are lacking. The amino acid transporters LAT1 and LAT2 encoded by the SLC7A5 and SLC7A8 genes, respectively, are the principal mediators of melphalan uptake into cells. To determine whether genetic variability at these loci contributed to interindividual differences in the development of gastrointestinal complications of HDM, we analyzed single nucleotide polymorphisms (SNPs) in these genes in 135 patients with multiple myeloma treated with HDM and ASCT and correlated these with the need for total parenteral nutrition (TPN). Seven SNPs in SLC7A5 and 20 in SLC7A8 were genotyped. Multiple analyses indicated that 1 SNP in the first intron of SLC7A5, rs4240803, was significantly associated with TPN use (odds ratio = .45, 95% confidence interval, .25 to .79; P = .007). Further, every haplotype that correlated with TPN requirement included this SNP. These results suggest that variability in melphalan transport affects mucosal injury after HDM. This finding could help in individualizing the dose of this effective and widely used chemotherapeutic agent for multiple myeloma. (C) 2014 American Society for Blood and Marrow Transplantation. C1 [Giglia, Jennifer L.; Hart, Andrew J.; Cai, Ying; Brandt, Stephen J.] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN 37232 USA. [White, Marquitta J.; Holt, Cherish C.; Williams, Scott M.] Vanderbilt Univ, Med Ctr, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA. [White, Marquitta J.; Holt, Cherish C.; Williams, Scott M.] Vanderbilt Univ, Med Ctr, Ctr Human Genet Res, Nashville, TN 37232 USA. [Toro, Juan J.; Freytes, Cesar O.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Toro, Juan J.; Freytes, Cesar O.] Audie L Murphy VA Hosp, South Texas Vet Hlth Care Syst, Dept Vet Affairs, San Antonio, TX USA. [Williams, Scott M.] Vanderbilt Univ, Med Ctr, Dept Pediat, Nashville, TN 37232 USA. [Brandt, Stephen J.] Vanderbilt Univ, Med Ctr, Dept Cell & Dev Biol, Nashville, TN 37232 USA. [Brandt, Stephen J.] Vanderbilt Univ, Med Ctr, Dept Canc Biol, Nashville, TN 37232 USA. [Brandt, Stephen J.] Vanderbilt Univ, Med Ctr, Vanderbilt Ingram Canc Ctr, Nashville, TN 37232 USA. [Brandt, Stephen J.] Nashville VA Hosp, Tennessee Valley Healthcare Syst, Dept Vet Affairs, Nashville, TN USA. RP Brandt, SJ (reprint author), Vanderbilt Univ, Med Ctr, Div Hematol Oncol, Room 777,Preston Res Bldg, Nashville, TN 37232 USA. EM stephen.brandt@vanderbilt.edu FU Clinical and Translational Science Award - National Center for Advancing Translational Sciences, National Institutes of Health [UL1TR000445] FX This project was supported in part by a Clinical and Translational Science Award program grant originally designated UL1TR000445 from the National Center for Advancing Translational Sciences, National Institutes of Health. The views expressed in this article do not reflect the official policy or position of the National Institutes of Health. NR 17 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JUL PY 2014 VL 20 IS 7 BP 1014 EP 1020 DI 10.1016/j.bbmt.2014.03.022 PG 7 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA AJ7AX UT WOS:000337850500016 PM 24704384 ER PT J AU Maggard-Gibbons, M AF Maggard-Gibbons, Melinda TI The use of report cards and outcome measurements to improve the safety of surgical care: the American College of Surgeons National Surgical Quality Improvement Program SO BMJ QUALITY & SAFETY LA English DT Review ID RISK ADJUSTMENT; POSTOPERATIVE MORTALITY; BYPASS-SURGERY; PRIVATE-SECTOR; COMPLICATION; FEASIBILITY; HOSPITALS; INFECTION; NSQIP AB Postoperative adverse events occur all too commonly and contribute greatly to our large and increasing healthcare costs. Surgeons, as well as hospitals, need to know their own outcomes in order to recognise areas that need improvement before they can work towards reducing complications. In the USA, the American College of Surgeons National Surgical Quality Improvement Project (ACS NSQIP) collects clinical data that provide benchmarks for providers and hospitals. This review summarises the history of ACS NSQIP and its components, and describes the evidence that feeding outcomes back to providers, along with real-time comparisons with other hospital rates, leads to quality improvement, better patient outcomes, cost savings and overall improved patient safety. The potential harms and limitations of the program are discussed. C1 [Maggard-Gibbons, Melinda] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Maggard-Gibbons, Melinda] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. [Maggard-Gibbons, Melinda] Olive View UCLA Med Ctr, Dept Surg, Sylmar, CA 91342 USA. RP Maggard-Gibbons, M (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, CHS 72-215,10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM mmaggard@mednet.ucla.edu FU Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services [HHSA-290-2007-100621] FX This study was funded by the Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services (contract no. HHSA-290-2007-100621). The Agency for Healthcare Research and Quality reviewed contract deliverables to ensure adherence to contract requirements and quality, and a copyright release was obtained from the Agency for Healthcare Research and Quality before submission of this manuscript. The author of this study is responsible for its content. Statements in the study should not be construed as endorsement by the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services. NR 37 TC 18 Z9 18 U1 2 U2 9 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-5415 EI 2044-5423 J9 BMJ QUAL SAF JI BMJ Qual. Saf. PD JUL PY 2014 VL 23 IS 7 BP 589 EP 599 DI 10.1136/bmjqs-2013-002223 PG 11 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA AJ7ZB UT WOS:000337919700010 PM 24748371 ER PT J AU Donthamsetty, S Brahmbhatt, M Pannu, V Rida, PCG Ramarathinam, S Ogden, A Cheng, A Singh, KK Aneja, R AF Donthamsetty, Shashikiran Brahmbhatt, Meera Pannu, Vaishali Rida, Padmashree C. G. Ramarathinam, Sujatha Ogden, Angela Cheng, Alice Singh, Keshav K. Aneja, Ritu TI Mitochondrial genome regulates mitotic fidelity by maintaining centrosomal homeostasis SO CELL CYCLE LA English DT Article DE mitochondrial genome; centrosome amplification; osteosarcoma; rho0; cybrid ID RENAL-CELL CARCINOMA; HUMAN BREAST-CANCER; DNA MUTATIONS; CHROMOSOMAL INSTABILITY; SPINDLE MULTIPOLARITY; AURORA-A; DEPLETION; AMPLIFICATION; TUMORIGENESIS; P53 AB Centrosomes direct spindle morphogenesis to assemble a bipolar mitotic apparatus to enable error-free chromosome segregation and preclude chromosomal instability (CIN). Amplified centrosomes, a hallmark of cancer cells, set the stage for CIN, which underlies malignant transformation and evolution of aggressive phenotypes. Several studies report CIN and a tumorigenic and/or aggressive transformation in mitochondrial DNA (mtDNA)-depleted cells. Although several nuclear-encoded proteins are implicated in centrosome duplication and spindle organization, the involvement of mtDNA encoded proteins in centrosome amplification (CA) remains elusive. Here we show that disruption of mitochondrial function by depletion of mtDNA induces robust CA and mitotic aberrations in osteosarcoma cells. We found that overexpression of Aurora A, Polo-like kinase 4 (PLK4), and Cyclin E was associated with emergence of amplified centrosomes. Supernumerary centrosomes in rho0 (mtDNA-depleted) cells resulted in multipolar mitoses bearing "real" centrosomes with paired centrioles at the multiple poles. This abnormal phenotype was recapitulated by inhibition of respiratory complex I in parental cells, suggesting a role for electron transport chain (ETETC) in maintaining numeral centrosomal homeostasis. Furthermore, rho0 cells displayed a decreased proliferative capacity owing to a G2/M arrest. Downregulation of nuclear-encoded p53 in rho0 cells underscores the importance of mitochondrial and nuclear genome crosstalk and may perhaps underlie the observed mitotic aberrations. By contrast, repletion of wild-type mtDNA in rho0 cells (cybrid) demonstrated a much lesser extent of CA and spindle multipolarity, suggesting partial restoration of centrosomal homeostasis. Our study provides compelling evidence to implicate the role of mitochondria in regulation of centrosome duplication, spindle architecture, and spindle pole integrity. C1 [Donthamsetty, Shashikiran; Brahmbhatt, Meera; Pannu, Vaishali; Rida, Padmashree C. G.; Ramarathinam, Sujatha; Ogden, Angela; Cheng, Alice; Aneja, Ritu] Georgia State Univ, Dept Biol, Atlanta, GA 30302 USA. [Singh, Keshav K.] Univ Alabama Birmingham, Dept Genet, Birmingham, AL USA. [Singh, Keshav K.] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. [Singh, Keshav K.] Univ Alabama Birmingham, Dept Environm Hlth, Birmingham, AL USA. [Singh, Keshav K.] Univ Alabama Birmingham, Ctr Free Rad Biol, Ctr Aging, Birmingham, AL USA. [Singh, Keshav K.] Univ Alabama Birmingham, UAB Comprehens Canc Ctr, Birmingham, AL USA. [Singh, Keshav K.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Aneja, R (reprint author), Georgia State Univ, Dept Biol, Atlanta, GA 30302 USA. EM kksingh@uab.edu; raneja@gsu.edu FU National Cancer Institute at the National Institutes of Health [R00CA131489, R01 CA169127]; Veterans Administration [1I01BX001716]; National Institute of Health [R01CA121904] FX This study was supported by grants to R. A. from the National Cancer Institute at the National Institutes of Health (R00CA131489, R01 CA169127). Research in K. K. S. laboratory is supported by Veterans Administration grant 1I01BX001716 and National Institute of Health R01CA121904. We thank Dr Bhupendra Singh for helping us with Figure 4F. NR 45 TC 5 Z9 6 U1 0 U2 9 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 EI 1551-4005 J9 CELL CYCLE JI Cell Cycle PD JUL 1 PY 2014 VL 13 IS 13 BP 2056 EP 2063 DI 10.4161/cc.29061 PG 8 WC Cell Biology SC Cell Biology GA AJ9OJ UT WOS:000338041700012 PM 24799670 ER PT J AU Elmets, CA Cala, CM Xu, H AF Elmets, Craig A. Cala, Cather M. Xu, Hui TI Photoimmunology SO DERMATOLOGIC CLINICS LA English DT Article DE Photoimmunology; Nonmelanoma skin cancer; Ultraviolet radiation; Polymorphous light eruption; Chronic actinic dermatitis; Cutaneous lupus erythematosus; Phototherapy; Photosensitivity ID CUTANEOUS LUPUS-ERYTHEMATOSUS; RADIATION-INDUCED IMMUNOSUPPRESSION; POLYMORPHIC LIGHT ERUPTION; CHRONIC ACTINIC DERMATITIS; INDUCED IMMUNE SUPPRESSION; HIGH-DOSE UVA1; ULTRAVIOLET-B PHOTOTHERAPY; NECROSIS-FACTOR-ALPHA; GENE-RELATED PEPTIDE; REGULATORY-T-CELLS AB The discipline that investigates the biologic effects of ultraviolet radiation on the immune system is called photoimmunology. Photoimmunology evolved from an interest in understanding the role of the immune system in skin cancer development and why immunosuppressed organ transplant recipients are at a greatly increased risk for cutaneous neoplasms. In addition to contributing to an understanding of the pathogenesis of nonmelanoma skin cancer, the knowledge acquired about the immunologic effects of ultraviolet radiation exposure has provided an understanding of its role in the pathogenesis of other photodermatologic diseases. C1 [Elmets, Craig A.; Xu, Hui] Univ Alabama Birmingham, Birmingham VA Med Ctr, UAB Comprehens Canc Ctr, Dept Dermatol,UAB Skin Dis Res Ctr, Birmingham, AL 35294 USA. [Cala, Cather M.] Univ Alabama Birmingham, Dept Dermatol, Birmingham, AL 35294 USA. RP Elmets, CA (reprint author), Univ Alabama Birmingham, Birmingham VA Med Ctr, UAB Comprehens Canc Ctr, Dept Dermatol,UAB Skin Dis Res Ctr, EFH 414,1720 2nd Ave South, Birmingham, AL 35294 USA. EM celmets@uab.edu FU NIH [P30 AR050948, P30 CA013148, N01 CN05014-69]; VA Merit Review [18-103-02] FX Funded by NIH grants and contracts: P30 AR050948, P30 CA013148, N01 CN05014-69 and by VA Merit Review 18-103-02. NR 112 TC 5 Z9 5 U1 1 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0733-8635 EI 1558-0520 J9 DERMATOL CLIN JI Dermatol. Clin. PD JUL PY 2014 VL 32 IS 3 BP 277 EP + DI 10.1016/j.det.2014.03.005 PG 15 WC Dermatology SC Dermatology GA AJ7AL UT WOS:000337849300004 PM 24891051 ER PT J AU Taborsky, GJ Mei, Q Bornfeldt, KE Hackney, DJ Mundinger, TO AF Taborsky, Gerald J., Jr. Mei, Qi Bornfeldt, Karin E. Hackney, Daryl J. Mundinger, Thomas O. TI The p75 Neurotrophin Receptor Is Required for the Major Loss of Sympathetic Nerves From Islets Under Autoimmune Attack SO DIABETES LA English DT Article ID DEPENDENT DIABETES-MELLITUS; AUTONOMIC NEUROPATHY; IMPAIRED GLUCAGON; TRANSGENIC MODEL; NERVOUS-SYSTEM; GROWTH-FACTOR; INNERVATION; INSULIN; SECRETION; RAT AB Our goal was to determine the role of the p75 neurotrophin receptor (p75NTR) in the loss of islet sympathetic nerves that occurs during the autoimmune attack of the islet. The islets of transgenic (Tg) mice in which beta-cells express a viral glycoprotein (GP) under the control of the insulin promotor (Ins2) were stained for neuropeptide Y before, during, and after virally induced autoimmune attack of the islet. Ins2-GP(Tg) mice injected with lymphocytic choriomeningitis virus (LCMV) lost islet sympathetic nerves before diabetes development but coincident with the lymphocytic infiltration of the islet. The nerve loss wasmarked and islet-selective. Similar nerve loss, chemically induced, was sufficient to impair sympathetically mediated glucagon secretion. In contrast, LCMV-injected Ins2-GP(Tg) mice lacking the p75NTR retained most of their islet sympathetic nerves, despite both lymphocytic infiltration and development of diabetes indistinguishable from that of p75NTR wild-type mice. We conclude that an nducible autoimmune attack of the islet causes a marked and islet-selective loss of sympathetic nerves that precedes islet collapse and hyperglycemia. The p75NTR mediates this nerve loss but plays no role in mediating the loss of islet b-cells or the subsequent diabetes. p75NTR-mediated nerve loss may contribute to the impaired glucose counterregulation seen in type 1 diabetes. C1 [Taborsky, Gerald J., Jr.] Vet Affairs Puget Sound Hlth Care Syst, Div Endocrinol Metab, Seattle, WA 98108 USA. [Taborsky, Gerald J., Jr.; Mei, Qi; Bornfeldt, Karin E.; Mundinger, Thomas O.] Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. [Bornfeldt, Karin E.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Bornfeldt, Karin E.] Univ Washington, Diabet Obes Ctr Excellence, Seattle, WA 98195 USA. [Hackney, Daryl J.] Seattle Inst Biomed & Clin Res, Seattle, WA USA. RP Taborsky, GJ (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Div Endocrinol Metab, Seattle, WA 98108 USA. EM taborsky@u.washington.edu FU Medical Research Service of the Department of Veterans Affairs; National Institutes of Health [R01-DK-50154, P30-DK-17047, R01-HL-097365, R01-HL-062887, P01-HL-092969] FX This work was supported by the Medical Research Service of the Department of Veterans Affairs (to G.J.T.) and National Institutes of Health grants R01-DK-50154 (to G.J.T.), P30-DK-17047, R01-HL-097365, R01-HL-062887, and P01-HL-092969 (to K.E.B.). NR 38 TC 5 Z9 5 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD JUL PY 2014 VL 63 IS 7 BP 2369 EP 2379 DI 10.2337/db13-0778 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AJ7YO UT WOS:000337918200026 PM 24608438 ER PT J AU Liu, RJ Zhong, YF Li, XZ Chen, HB Jim, B Zhou, MM Chuang, PY He, JC AF Liu, Ruijie Zhong, Yifei Li, Xuezhu Chen, Haibing Jim, Belinda Zhou, Ming-Ming Chuang, Peter Y. He, John Cijiang TI Role of Transcription Factor Acetylation in Diabetic Kidney Disease SO DIABETES LA English DT Article ID GLYCATION END-PRODUCTS; IN-VIVO; SIRT1; NEPHROPATHY; INHIBITION; EXPRESSION; ACTIVATION; RESVERATROL; BROMODOMAIN; PODOCYTES AB Nuclear factor (NF)-kappa B and signal transducer and activator of transcription 3 (STAT3) play a critical role in diabetic nephropathy (DN). Sirtuin-1 (SIRT1) regulates transcriptional activation of target genes through protein deacetylation. Here, we determined the roles of Sirt1 and the effect of NF-kappa B (p65) and STAT3 acetylation in DN. We found that acetylation of p65 and STAT3 was increased in both mouse and human diabetic kidneys. In human podocytes, advanced glycation end products (AGEs) induced p65 and STAT3 acetylation and overexpression of acetylation-incompetent mutants of p65 and STAT3 abrogated AGE-induced expression of NF-kappa B and STAT3 target genes. Inhibition of AGE formation in db/db mice by pyridoxamine treatment attenuated proteinuria and podocyte injury, restored SIRT1 expression, and reduced p65 and STAT3 acetylation. Diabetic db/db mice with conditional deletion of SIRT1 in podocytes developed more proteinuria, kidney injury, and acetylation of p65 and STAT3 compared with db/db mice without SIRT1 deletion. Treatment of db/db mice with a bromodomain and extraterminal (BET)-specific bromodomain inhibitor (MS417) which blocks acetylation-mediated association of p65 and STAT3 with BET proteins, attenuated proteinuria, and kidney injury. Our findings strongly support a critical role for p65 and STAT3 acetylation in DN. Targeting protein acetylation could be a potential new therapy for DN. C1 [Liu, Ruijie; Chuang, Peter Y.; He, John Cijiang] Mt Sinai Sch Med, Dept Med Nephrol, New York, NY 10029 USA. [Zhong, Yifei] Shanghai Univ Tradit Chinese Med, Longhua Hosp, Dept Nephrol, Shanghai, Peoples R China. [Li, Xuezhu] Tongji Univ, Sch Med, Shanghai East Hosp, Dept Nephrol, Shanghai 200092, Peoples R China. [Chen, Haibing] Shanghai Jiao Tong Univ, Affiliated Peoples Hosp 6, Dept Endocrinol, Shanghai 200030, Peoples R China. [Jim, Belinda] Jacobi Med Ctr, Div Nephrol, Bronx, NY USA. [Zhou, Ming-Ming] Mt Sinai Sch Med, Dept Struct & Chem Biol, New York, NY USA. [He, John Cijiang] James J Peters VA Med Ctr, Renal Sect, Bronx, NY USA. RP He, JC (reprint author), Mt Sinai Sch Med, Dept Med Nephrol, New York, NY 10029 USA. EM cijiang.he@mssm.edu FU VA Merit Award [1I01BX000345]; 973 fund [2012CB517601]; National Institutes of Health (NIH) [1R01-DK-078897, 1R01-DK-088541]; NIH [5K08-DK-082760, R01-HG-004508, R01-CA-87658]; National Natural Science Foundation of China for Young Investigators [1999-30901944]; Shanghai Bureau of Health for Young Investigators [2011-XYQ2011059] FX J.C.H. is supported by VA Merit Award (1I01BX000345), 973 fund (2012CB517601), and National Institutes of Health (NIH) grants 1R01-DK-078897 and 1R01-DK-088541. P.Y.C. is supported by NIH grant 5K08-DK-082760. Y.Z. is supported by the National Natural Science Foundation of China for Young Investigators (1999-30901944) and the Shanghai Bureau of Health for Young Investigators (2011-XYQ2011059). M.-M.Z. is supported by NIH grants R01-HG-004508 and R01-CA-87658. NR 54 TC 34 Z9 35 U1 1 U2 12 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD JUL PY 2014 VL 63 IS 7 BP 2440 EP 2453 DI 10.2337/db13-1810 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AJ7YO UT WOS:000337918200032 PM 24608443 ER PT J AU Clancy, CJ Nguyen, MH AF Clancy, Cornelius J. Minh Hong Nguyen TI Undiagnosed invasive candidiasis: incorporating non-culture diagnostics into rational prophylactic and preemptive antifungal strategies SO EXPERT REVIEW OF ANTI-INFECTIVE THERAPY LA English DT Editorial Material DE anti-mannan antibody; Candida; candidemia; candidiasis; deep-seated candidiasis; Fungitell; intra-abdominal candidiasis; mannan; beta-D-glucan ID PLACEBO-CONTROLLED TRIAL; ILL SURGICAL-PATIENTS; D-GLUCAN ASSAY; REAL-TIME PCR; CRITICALLY-ILL; INTRAABDOMINAL CANDIDIASIS; DOUBLE-BLIND; HIGH-RISK; FLUCONAZOLE PROPHYLAXIS; FUNGAL-INFECTIONS AB The insensitivity of blood cultures for diagnosing invasive candidiasis fuels prophylactic and preemptive antifungal treatment. Assays like serum beta-D-glucan or mannan/anti-mannan detection can identify blood culture-negative invasive candidiasis, but their roles in guiding antifungal therapy are undefined. We propose that non-culture tests can be incorporated into rational management strategies, based on clinical setting. As an example, beta-D-glucan sensitivity/specificity for blood culture-negative, deep-seated candidiasis is approximately 60/75%. In intensive care units with <1 or 3% invasive candidiasis rates, positive/negative predictive values are <2/>99% and 6/98%, respectively. With pre-test likelihoods of 10 and 33%, positive/negative predictive values are 20/94% and 54/79%, respectively. Based on these data, negative and positive beta-D-glucan results likely will be most useful for discontinuing prophylaxis among low-risk to moderate-risk patients (pre-test likelihoods similar to 3-10%), and triggering preemptive therapy among moderate-risk to high-risk patients (pre-test likelihoods similar to 10-25%), respectively. In extremely high-risk patients, universal prophylaxis is likely to be the best strategy. C1 [Clancy, Cornelius J.] Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Div Infect Dis, Pittsburgh, PA 15261 USA. [Clancy, Cornelius J.; Minh Hong Nguyen] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15261 USA. RP Clancy, CJ (reprint author), Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Div Infect Dis, Scaife 867,3550 Terrace St, Pittsburgh, PA 15261 USA. EM cjc76@pitt.edu NR 23 TC 11 Z9 11 U1 0 U2 1 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1478-7210 EI 1744-8336 J9 EXPERT REV ANTI-INFE JI Expert Rev. Anti-Infect. Ther. PD JUL PY 2014 VL 12 IS 7 BP 731 EP 734 DI 10.1586/14787210.2014.919853 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AJ5VO UT WOS:000337758300003 PM 24850393 ER PT J AU Huik, K Avi, R Uibopuu, H Pauskar, M Margus, T Karki, T Krispin, T Kool, P Ruutel, K Talu, A Abel-Ollo, K Uuskula, A Carrillo, A He, WJ Ahuja, SK Lutsar, I AF Huik, Kristi Avi, Radko Uibopuu, Helen Pauskar, Merit Margus, Tonu Karki, Tonis Krispin, Tonu Kool, Piret Rueuetel, Kristi Talu, Ave Abel-Ollo, Katri Uuskuela, Anneli Carrillo, Andrew He, Weijing Ahuja, Sunil K. Lutsar, Irja TI Association Between HIV-1 Tropism and CCR5 Human Haplotype E in a Caucasian Population SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE CCR5; X4 tropic viruses; intravenous drug users ID HUMAN-IMMUNODEFICIENCY-VIRUS; TREATMENT-NAIVE PATIENTS; INJECTION-DRUG USERS; CELL-SURFACE CCR5; DISEASE PROGRESSION; PROMOTER POLYMORPHISM; TYPE-1 VARIANTS; INFECTION; EXPRESSION; DENSITY AB Background:The influence of the diversity of CCR5 on HIV susceptibility and disease progression has been clearly demonstrated but how the variability of this gene influences the HIV tropism is poorly understood. We investigated whether CCR5 haplotypes are associated with HIV tropism in a Caucasian population.Methods:We evaluated 161 HIV-positive subjects in a cross-sectional study. CCR5 haplotypes were derived after genotyping 9 CCR2-CCR5 polymorphisms. The HIV subtype was determined by phylogenetic analysis using the maximum likelihood method and viral tropism by the genotypic tropism assay (geno2pheno). Associations between CCR5 haplotypes and viral tropism were determined using logistic regression analyses. Samples from 500 blood donors were used to evaluate the representativeness of HIV-positives in terms of CCR5 haplotype distribution.Results:The distribution of CCR5 haplotypes was similar in HIV-positive subjects and blood donors. The majority of viruses (93.8%) belonged to HIV-1 CRF06_cpx; 7.5% were X4, and the remaining were R5 tropic. X4 tropic viruses were over represented among people with CCR5 human haplotype E (HHE) compared with those without this haplotype (13.0% vs 1.4%; P = 0.006). People possessing CCR5 HHE had 11 times increased odds (odds ratio = 11.00; 95% confidence interval: 1.38 to 87.38) of having X4 tropic viruses than those with non-HHE. After adjusting for antiretroviral (ARV) therapy, neither the presence of HHE nor the use of ARV was associated with X4 tropic viruses.Conclusions:Our results suggest that CCR5 HHE and ARV treatment might be associated with the presence of HIV-1 X4 tropic viruses. C1 [Huik, Kristi; Avi, Radko; Pauskar, Merit; Karki, Tonis; Krispin, Tonu; Lutsar, Irja] Univ Tartu, Fac Med, Dept Microbiol, EE-50411 Tartu, Estonia. [Uibopuu, Helen] West Tallinn Hosp Labs, Tallinn, Estonia. [Margus, Tonu] Univ Tartu, Inst Mol & Cell Biol, Dept Bioinformat, EE-50411 Tartu, Estonia. [Margus, Tonu] Estonian Bioctr, Tartu, Estonia. [Kool, Piret] Tartu Prison Hosp, Tartu, Estonia. [Rueuetel, Kristi; Abel-Ollo, Katri] Natl Inst Hlth Dev, Tallinn, Estonia. [Talu, Ave; Uuskuela, Anneli] Univ Tartu, Fac Med, Dept Publ Hlth, EE-50411 Tartu, Estonia. [Carrillo, Andrew; He, Weijing; Ahuja, Sunil K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Carrillo, Andrew; He, Weijing; Ahuja, Sunil K.] South Texas Vet Hlth Care Syst, Vet Adm Res Ctr AIDS & HIV Infect 1, San Antonio, TX USA. [Carrillo, Andrew; He, Weijing; Ahuja, Sunil K.] South Texas Vet Hlth Care Syst, Ctr Personalized Med, San Antonio, TX USA. RP Huik, K (reprint author), Univ Tartu, Dept Microbiol, Ravila 19, EE-50411 Tartu, Estonia. EM kristi.huik@ut.ee RI lutsar, irja/H-3177-2015; Uuskula, Anneli/H-3303-2015 FU European Union through European Regional Development Fund; Estonian Science Foundation [8415, 8856]; Basic Financing and the Target Financing of Estonian Ministry of Education and Research [SF0180004s12, SF0180026s09]; European Commission [2005305]; Global Fund to Fight HIV, Tuberculosis and Malaria Program "Scaling up the response to HIV in Estonia"; National HIV/AIDS Strategy; US Civilian Research Development Foundation [ESX0-2722-TA-06]; US National Institutes of Health, National Institute on Drug Abuse [R01DA03574]; Archimedes Foundation; Norwegian Financial Mechanism/EEA [EE0016]; Veterans Affairs (VA) Center for AIDS and HIV Infection; VA Center for Personalized Medicine of the South Texas Veterans Health Care System, a National Institutes of Health MERIT Grant [R37AI046326]; Doris Duke Distinguished Clinical Scientist Award; VA MERIT award; Elizabeth Glaser Pediatric AIDS Foundation; Burroughs Welcome Clinical Scientist Award in Translational Research; Max and Minnie Tomerlin Voelcker Fund FX Supported by European Union through the European Regional Development Fund, Estonian Science Foundation (Grants 8415 and 8856), Basic Financing and the Target Financing of Estonian Ministry of Education and Research (SF0180004s12 and SF0180026s09), European Commission funded project Expanding Network for Comprehensive and Coordinated Action on HIV/AIDS prevention among IDUs and Bridging Population Nr. 2005305 (ENCAP), Global Fund to Fight HIV, Tuberculosis and Malaria Program "Scaling up the response to HIV in Estonia" for 2003-2007, National HIV/AIDS Strategy for 2006-2015, US Civilian Research Development Foundation (Grant ESX0-2722-TA-06), US National Institutes of Health, National Institute on Drug Abuse (Grant R01DA03574), the Archimedes Foundation and Norwegian Financial Mechanism/EEA (Grant EE0016), the Veterans Affairs (VA) Center for AIDS and HIV Infection and VA Center for Personalized Medicine of the South Texas Veterans Health Care System, a National Institutes of Health MERIT Grant (R37AI046326), and the Doris Duke Distinguished Clinical Scientist Award to S.K.A. S.K.A. is also supported by a VA MERIT award, the Elizabeth Glaser Pediatric AIDS Foundation, the Burroughs Welcome Clinical Scientist Award in Translational Research, and the Senior Scholar Award from the Max and Minnie Tomerlin Voelcker Fund. NR 37 TC 2 Z9 2 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD JUL 1 PY 2014 VL 66 IS 3 BP 239 EP 244 DI 10.1097/QAI.0000000000000127 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AJ9JL UT WOS:000338025800005 PM 24508837 ER PT J AU Woody, GE Bruce, D Korthuis, PT Chhatre, S Poole, S Hillhouse, M Jacobs, P Sorensen, J Saxon, AJ Metzger, D Ling, W AF Woody, George E. Bruce, Douglas Korthuis, P. Todd Chhatre, Sumedha Poole, Sabrina Hillhouse, Maureen Jacobs, Petra Sorensen, James Saxon, Andrew J. Metzger, David Ling, Walter TI HIV Risk Reduction With Buprenorphine-Naloxone or Methadone: Findings From a Randomized Trial SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV; risk reduction; buprenorphine; methadone ID HUMAN-IMMUNODEFICIENCY-VIRUS; SUBSTANCE-ABUSE TREATMENT; INTRAVENOUS-DRUG-USERS; OUT-OF-TREATMENT; OPIOID DEPENDENCE; MAINTENANCE TREATMENT; PRIMARY-CARE; FOLLOW-UP; BEHAVIORS; PREVENTION AB Objectives:Compare HIV injecting and sex risk in patients being treated with methadone (MET) or buprenorphine-naloxone (BUP).Methods:Secondary analysis from a study of liver enzyme changes in patients randomized to MET or BUP who completed 24 weeks of treatment and had 4 or more blood draws. The initial 1:1 randomization was changed to 2:1 (BUP:MET) after 18 months due to higher dropout in BUP. The Risk Behavior Survey measured HIV risk before 30 days at baseline and weeks 12 and 24.Results:Among 529 patients randomized to MET, 391 (74%) were completers; among 740 randomized to BUP, 340 (46%) were completers; 700 completed the Risk Behavior Survey. There were significant reductions in injecting risk (P < 0.0008) with no differences between groups in mean number of times reported injecting heroin, speedball, other opiates, and number of injections; or percent who shared needles; did not clean shared needles with bleach; shared cookers; or engaged in front/back loading of syringes. The percent having multiple sex partners decreased equally in both groups (P < 0.03). For males on BUP, the sex risk composite increased; for males on MET, the sex risk decreased resulting in significant group differences over time (P < 0.03). For females, there was a significant reduction in sex risk (P < 0.02) with no group differences.Conclusions:Among MET and BUP patients who remained in treatment, HIV injecting risk was equally and markedly reduced; however, MET retained more patients. Sex risk was equally and significantly reduced among females in both treatment conditions, but it increased for males on BUP and decreased for males on MET. C1 [Woody, George E.; Chhatre, Sumedha; Poole, Sabrina; Metzger, David] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Woody, George E.; Chhatre, Sumedha; Poole, Sabrina; Metzger, David] Treatment Res Inst, Philadelphia, PA 19106 USA. [Bruce, Douglas] Yale Univ, Sch Med, Dept Med, New Haven, CT 06510 USA. [Korthuis, P. Todd] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. [Hillhouse, Maureen; Ling, Walter] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA. [Jacobs, Petra] NIDA, Bethesda, MD 20892 USA. [Sorensen, James] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Saxon, Andrew J.] Vet Affairs Puget Sound Hlth Care Syst, Dept Psychiat, Seattle, WA USA. RP Woody, GE (reprint author), Treatment Res Inst, 150 South Independence Mall W, Philadelphia, PA 19106 USA. EM woody@tresearch.org FU NIDA [U10-DA 13045, U10-DA013714, U10 DA-13043, KO5 DA-17009] FX Supported by NIDA grants: U10-DA 13045 (W.L.); U10-DA013714 (D.D.); U10 DA-13043, KO5 DA-17009 (G.W.). NR 46 TC 12 Z9 12 U1 2 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD JUL 1 PY 2014 VL 66 IS 3 BP 288 EP 293 DI 10.1097/QAI.0000000000000165 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AJ9JL UT WOS:000338025800011 PM 24751432 ER PT J AU Kaup, AR Simonsick, EM Harris, TB Satterfield, S Metti, AL Ayonayon, HN Rubin, SM Yaffe, K AF Kaup, Allison R. Simonsick, Eleanor M. Harris, Tamara B. Satterfield, Suzanne Metti, Andrea L. Ayonayon, Hilsa N. Rubin, Susan M. Yaffe, Kristine TI Older Adults With Limited Literacy Are at Increased Risk for Likely Dementia SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Cognitive aging; Risk factors; Epidemiology ID ETHNICALLY DIVERSE ELDERS; POPULATION-BASED COHORT; HEALTH LITERACY; COGNITIVE DECLINE; BODY-COMPOSITION; READING-ABILITY; SOCIOECONOMIC-STATUS; ALZHEIMERS-DISEASE; EDUCATION; MORTALITY AB Low literacy is common among the elderly and possibly more reflective of educational attainment than years of school completed. We examined the association between literacy and risk of likely dementia in older adults. Participants were 2,458 black and white elders (aged 71-82) from the Health, Aging and Body Composition study, who completed the Rapid Estimate of Adult Literacy in Medicine and were followed for 8 years. Participants were free of dementia at baseline; incidence of likely dementia was defined by hospital records, prescription for dementia medication, or decline in Modified Mini-Mental State Examination score. We conducted Cox proportional hazard models to evaluate the association between literacy and incidence of likely dementia. Demographics, education, income, comorbidities, lifestyle variables, and apolipoprotein E (APOE) epsilon 4 status were included in adjusted analyses. Twenty-three percent of participants had limited literacy (< 9th-grade level). Limited literacy, as opposed to adequate literacy (a parts per thousand yen9th-grade level), was associated with greater incidence of likely dementia (25.5% vs17.0%; unadjusted hazard ratio [HR] = 1.75, 95% confidence interval 1.44-2.13); this association remained significant after adjustment. There was a trend for an interaction between literacy and APOE epsilon 4 status (p = .07); the association between limited literacy and greater incidence of likely dementia was strong among epsilon 4 noncarriers (unadjusted HR = 1.85) but nonsignificant among epsilon 4 carriers (unadjusted HR = 1.25). Limited literacy is an important risk factor for likely dementia, especially among APOE epsilon 4-negative older adults, and may prove fruitful to target in interventions aimed at reducing dementia risk. C1 [Kaup, Allison R.; Yaffe, Kristine] San Francisco VA Med Ctr, Sierra Pacific Mental Illness Res Educ & Clin Ctr, San Francisco, CA 94121 USA. [Kaup, Allison R.; Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Simonsick, Eleanor M.] Harbor Hosp, Translat Gerontol Branch, NIA, Baltimore, MD USA. [Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Satterfield, Suzanne] Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, Memphis, TN USA. [Metti, Andrea L.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA. [Ayonayon, Hilsa N.; Rubin, Susan M.; Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. RP Kaup, AR (reprint author), San Francisco VA Med Ctr, 4150 Clement St,116H, San Francisco, CA 94121 USA. EM allison.kaup@ucsf.edu FU National Institute on Aging [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, R01-AG028050, K24AG031155]; National Institute of Nursing Research [R01-NR012459]; Intramural Research Program of the National Institutes of Health, National Institute on Aging FX This work was supported by the National Institute on Aging (N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106; R01-AG028050, K24AG031155 to K.Y.) and National Institute of Nursing Research (R01-NR012459). This work was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute on Aging. Writing of this manuscript was supported by Department of Veterans Affairs Office of Academic Affiliations Advanced Fellowship Program in Mental Illness Research and Treatment, the Medical Research Service of the San Francisco Veterans Affairs Medical Center, and the Department of Veterans Affairs Sierra-Pacific Mental Illness Research, Education, and Clinical Center. NR 39 TC 10 Z9 11 U1 2 U2 8 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 EI 1758-535X J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JUL PY 2014 VL 69 IS 7 BP 900 EP 906 DI 10.1093/gerona/glt176 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AJ9DG UT WOS:000338006400015 PM 24158765 ER PT J AU Derose, SF Gabayan, GZ Chiu, VY Yiu, SC Sun, BC AF Derose, Stephen F. Gabayan, Gelareh Z. Chiu, Vicki Y. Yiu, Sau C. Sun, Benjamin C. TI Emergency Department Crowding Predicts Admission Length-of-Stay But Not Mortality in a Large Health System SO MEDICAL CARE LA English DT Article DE emergency medicine; ED crowding; length-of-stay; emergency care; inpatient mortality ID AMBULANCE DIVERSION; INPATIENT LENGTH; ASSOCIATION; SURVIVAL; OUTCOMES AB Background:Emergency department (ED) crowding has been identified as a major threat to public health.Objectives:We assessed patient transit times and ED system crowding measures based on their associations with outcomes.Research Design:Retrospective cohort study.Subjects:We accessed electronic health record data on 136,740 adults with a visit to any of 13 health system EDs from January 2008 to December 2010.Measures:Patient transit times (waiting, evaluation and treatment, boarding) and ED system crowding [nonindex patient length-of-stay (LOS) and boarding, bed occupancy] were determined. Outcomes included individual inpatient mortality and admission LOS. Covariates included demographic characteristics, past comorbidities, severity of illness, arrival time, and admission diagnoses.Results:No patient transit time or ED system crowding measure predicted increased mortality after control for patient characteristics. Index patient boarding time and lower bed occupancy were associated with admission LOS (based on nonoverlapping 95% CI vs. the median value). As boarding time increased from none to 14 hours, admission LOS increased an additional 6 hours. As mean occupancy decreased below the median (80% occupancy), admission LOS decreased as much as 9 hours.Conclusions:Measures indicating crowded ED conditions were not predictive of mortality after case-mix adjustment. The first half-day of boarding added to admission LOS rather than substituted for it. Our findings support the use of boarding time as a measure of ED crowding based on robust prediction of admission LOS. Interpretation of measures based on other patient ED transit times may be limited to the timeliness of care. C1 [Derose, Stephen F.; Chiu, Vicki Y.; Yiu, Sau C.] Kaiser Permanente So Calif, Dept Res & Evaluat, Pasadena, CA 91101 USA. [Gabayan, Gelareh Z.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Gabayan, Gelareh Z.] Greater Los Angeles Vet Affairs Healthcare Syst, Dept Med, Los Angeles, CA USA. [Sun, Benjamin C.] Oregon Hlth & Sci Univ, Dept Emergency Med, Portland, OR 97201 USA. RP Derose, SF (reprint author), Kaiser Permanente So Calif, Dept Res & Evaluat, 100 S Los Robles,Floor 3, Pasadena, CA 91101 USA. EM stephen.f.derose@kp.org FU federal NIH/AHRRQ grant [R03HS018994]; Kaiser Permanente of Southern California; National Center for Advancing Translational Sciences [KL2TR000122] FX Supported by federal NIH/AHRRQ grant #R03HS018994 and Kaiser Permanente of Southern California.; During the time of the study, G.Z. Gabayan received support from the National Center for Advancing Translational Sciences, Grant KL2TR000122. The other authors declare no conflict of interest. NR 38 TC 4 Z9 4 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD JUL PY 2014 VL 52 IS 7 BP 602 EP 611 DI 10.1097/MLR.0000000000000141 PG 10 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AJ5TI UT WOS:000337750800007 PM 24926707 ER PT J AU Auer, R Vittinghoff, E Kiefe, C Reis, JP Rodondi, N Khodneva, YA Kertesz, SG Cornuz, J Pletcher, MJ AF Auer, Reto Vittinghoff, Eric Kiefe, Catarina Reis, Jared P. Rodondi, Nicolas Khodneva, Yulia A. Kertesz, Stefan G. Cornuz, Jacques Pletcher, Mark J. TI Change in physical activity after smoking cessation: the Coronary Artery Risk Development in Young Adults (CARDIA) study SO ADDICTION LA English DT Article DE behavior change; marginal structural model; middle age; mixed longitudinal model; physical activity; smoking cessation; trajectory analysis; young adults ID HEALTH-RELATED BEHAVIORS; CIGARETTE-SMOKING; WEIGHT-GAIN; FOLLOW-UP; SELF-REPORTS; LIFE-STYLE; EXERCISE; WOMEN; DISEASE; MIDDLE AB Aims To estimate physical activity trajectories for people who quit smoking, and compare them to what would have been expected had smoking continued. Design, Setting and Participants A total of 5115 participants in the Coronary Artery Risk Development in Young Adults Study (CARDIA) study, a population-based study of African American and European American people recruited at age 18-30 years in 1985/6 and followed over 25 years. Measurements Physical activity was self-reported during clinical examinations at baseline (1985/6) and at years 2, 5, 7, 10, 15, 20 and 25 (2010/11); smoking status was reported each year (at examinations or by telephone, and imputed where missing). We used mixed linear models to estimate trajectories of physical activity under varying smoking conditions, with adjustment for participant characteristics and secular trends. Findings We found significant interactions by race/sex (P=0.02 for the interaction with cumulative years of smoking), hence we investigated the subgroups separately. Increasing years of smoking were associated with a decline in physical activity in black and white women and black men [e.g. coefficient for 10 years of smoking: -0.14; 95% confidence interval (CI)=-0.20 to -0.07, P<0.001 for white women]. An increase in physical activity was associated with years since smoking cessation in white men (coefficient 0.06; 95% CI=0 to 0.13, P=0.05). The physical activity trajectory for people who quit diverged progressively towards higher physical activity from the expected trajectory had smoking continued. For example, physical activity was 34% higher (95% CI=18 to 52%; P<0.001) for white women 10 years after stopping compared with continuing smoking for those 10 years (P=0.21 for race/sex differences). Conclusions Smokers who quit have progressively higher levels of physical activity in the years after quitting compared with continuing smokers. C1 [Auer, Reto; Vittinghoff, Eric; Pletcher, Mark J.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Kiefe, Catarina] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA USA. [Reis, Jared P.] NHLBI, Bethesda, MD 20892 USA. [Rodondi, Nicolas] Univ Bern, Inselspital, Dept Gen Internal Med, CH-3010 Bern, Switzerland. [Khodneva, Yulia A.; Kertesz, Stefan G.] Univ Alabama Birmingham, Birmingham Sch Publ Hlth, Dept Hlth Behav, Birmingham, AL USA. [Kertesz, Stefan G.] Birmingham VA Med Ctr, Ctr Surg Med & Acute Care Res, Birmingham, AL USA. [Kertesz, Stefan G.] Univ Alabama Birmingham, Div Prevent Med, Med Sch Birmingham, Birmingham, AL USA. [Cornuz, Jacques] Univ Lausanne Hosp, Dept Ambulatory & Community Med, Lausanne, Switzerland. RP Auer, R (reprint author), Univ Calif San Francisco, Dept Epidemiol & Biostat, 185 Berry St,Suite 5700, San Francisco, CA 94143 USA. EM reto.auer@ucsf.edu FU National Heart, Lung, and Blood Institute (NHLBI); University of Alabama at Birmingham [HHSN268201300025C, HHSN268201300026C]; Northwestern University [HHSN268201300027C]; University of Minnesota [HHSN268201300028C]; Kaiser Foundation Research Institute [HHSN268201300029C]; Johns Hopkins University School of Medicine [HHSN268200900041C]; National Institute on Aging (NIA); NIA; NHLBI [AG0005]; Swiss National Science Foundation [PBLAP3-136774]; Societe Academique Vaudoise; SICPA Foundation FX The Coronary Artery Risk Development in Young Adults Study (CARDIA) is conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with the University of Alabama at Birmingham (HHSN268201300025C and HHSN268201300026C), Northwestern University (HHSN268201300027C), University of Minnesota (HHSN268201300028C), Kaiser Foundation Research Institute (HHSN268201300029C) and Johns Hopkins University School of Medicine (HHSN268200900041C). CARDIA is also partially supported by the Intramural Research Program of the National Institute on Aging (NIA) and an intra-agency agreement between NIA and NHLBI (AG0005). This manuscript has been reviewed by CARDIA for scientific content. Dr Auer's research on cardiovascular prevention is supported by a grant from the Swiss National Science Foundation PBLAP3-136774, the Societe Academique Vaudoise and the SICPA Foundation. NR 53 TC 3 Z9 3 U1 1 U2 20 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0965-2140 EI 1360-0443 J9 ADDICTION JI Addiction PD JUL PY 2014 VL 109 IS 7 BP 1172 EP 1183 DI 10.1111/add.12561 PG 12 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA AJ3LY UT WOS:000337569200025 PM 24690003 ER PT J AU Sato, S Zhang, XK AF Sato, S. Zhang, X. K. TI The Friend leukaemia virus integration 1 (Fli-1) transcription factor affects lupus nephritis development by regulating inflammatory cell infiltration into the kidney SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE chemokines; chemotaxis; Fli-1; infiltration; lupus nephritis ID HUMAN CRESCENTIC GLOMERULONEPHRITIS; MONOCYTE CHEMOATTRACTANT PROTEIN-1; REDUCES RENAL-DISEASE; ETS GENE FAMILY; PROLONGS SURVIVAL; MRL-FAS(LPR) MICE; EXPRESSION; ERYTHEMATOSUS; MEMBER; DEFICIENCY AB The transcription factor Friend leukaemia virus integration 1 (Fli-1) is implicated in the pathogenesis of systemic lupus erythematosus in both human patients and murine models of lupus. Murphy Roths large (MRL)/lpr mice and New Zealand mixed (NZM)2410 mice, murine models of lupus, with decreased expression of Fli-1 had significantly prolonged survival and reduced nephritis. Lupus nephritis is a major cause of mortality and morbidity in patients, and inflammatory cell infiltration plays a key role in the development of the disease. To study how the expression of Fli-1 affects the infiltration of inflammatory cells into the kidneys, we generated congenic enhanced green fluorescent protein (GFP) transgenic MRL/lpr mice. A significantly increased number of GFP-expressing inflammatory cells infiltrated the kidneys of wild-type MRL/lpr mice compared to Fli-1 heterozygous (Fli-1+/-) MRL/lpr mice after injection of GFP+ cells. Expression of inflammatory chemokine mRNA, including chemokine (C-C motif) ligand (CCL)2, CCL3, CCL4 and CCL5, was significantly lower in the kidneys from Fli-1+/- MRL/lpr mice compared to wild-type littermates. Numbers of infiltrated cells into the kidneys correlate with expression levels of CCL2, CCL4 and CCL5, but not the titres of anti-dsDNA autoantibodies in these mice. Significantly increased inflammatory cells from wild-type MRL/lpr mice infiltrated into kidneys compared to the cells from Fli-1+/- MRL/lpr mice. The chemotaxis of inflammatory cells from Fli-1+/- MRL/lpr mice towards each chemokine was decreased significantly compared to inflammatory cells from wild-type MRL/lpr mice in the transwell migration assay in vitro. Our results indicate that Fli-1 affects lupus nephritis development by regulating the expression of chemokines in the kidney and the migration of inflammatory cells. C1 [Sato, S.; Zhang, X. K.] Ralph H Johnson Vet Affairs Med Ctr, Dept Med, Div Rheumatol & Immunol, Charleston, SC USA. [Zhang, X. K.] Ralph H Johnson Vet Affairs Med Ctr, Med Res Serv, Charleston, SC USA. RP Zhang, XK (reprint author), Med Univ S Carolina, Div Rheumatol & Immunol, 96 Jonathan Lucas St MSC637, Charleston, SC 29425 USA. EM zhangjo@musc.edu FU National Institutes of Health [AR056670]; Medical Research Service, Department of Veterans Affairs FX This work was supported by grants from the National Institutes of Health (AR056670 to X. Z.) and the Medical Research Service, Department of Veterans Affairs (to X. Z.). We would like to thank Ms Eva Karam and Ms Sarah Williams for their excellent technical support and Dr Mara Lennard Richard for critical review of the manuscript. We thank Dr M. Okabe (Osaka University, Japan) for providing enhanced GFP C57BL/6 mice. NR 38 TC 5 Z9 5 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0009-9104 EI 1365-2249 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD JUL PY 2014 VL 177 IS 1 BP 102 EP 109 DI 10.1111/cei.12310 PG 8 WC Immunology SC Immunology GA AJ3SW UT WOS:000337588700011 PM 24580413 ER PT J AU Callegari, LS Zhao, XH Nelson, KM Lehavot, K Bradley, KA Borrero, S AF Callegari, Lisa S. Zhao, Xinhua Nelson, Karin M. Lehavot, Keren Bradley, Katharine A. Borrero, Sonya TI Associations of mental illness and substance use disorders with prescription contraception use among women veterans SO CONTRACEPTION LA English DT Article DE Contraceptive behavior; Veterans health; Mental disorder; Alcohol-related disorders; Substance-related disorders; Highly effective reversible contraception ID POSTTRAUMATIC-STRESS-DISORDER; UNITED-STATES; MINORITY WOMEN; BIRTH-WEIGHT; CONDOM USE; DRUG-USE; DEPRESSION; PREGNANCY; ALCOHOL; HEALTH AB Objective: To investigate whether mental illness and substance use disorder (SUD) are associated with having a prescription contraceptive method among women veterans. Study design: We conducted a retrospective analysis of National Veterans Administration (VA) administrative and clinical data for women veterans aged 18-45 years who made at least one primary care visit in 2008. We assessed associations between mental illness (depression, posttraumatic stress disorder, anxiety, bipolar disorder, schizophrenia and adjustment disorder) and SUD (drug/alcohol use disorder) with having a prescription contraceptive method from VA (pill, patch, ring, injection, implant and intrauterine device) using multivariable logistic regression with random effects for VA facility, adjusting for confounders. Results: Among 94,115 reproductive aged women, 36.5% had mental illness only, 0.6% had SUD only, 5.3% had both mental illness and SUD and 57.7% had neither diagnosis. In these groups, 22.1%, 14.6%, 18.2% and 17.7% (p<0.001), respectively, had documentation in 2008 of prescription contraception. After adjusting for potential confounders, women with mental illness only were as likely as women with neither diagnosis to have a prescription method and were more likely to use a highly effective prescription method (implant or intrauterine device) if using contraception [adjusted odds ratio (aOR) 1.17, 95% confidence interval (CI) = 1.08-1.27]. Women with SUD (with or without mental illness) were significantly less likely to have a prescription method than women with neither diagnosis (aOR 0.73, 95% CI = 0.57-0.95 and aOR 0.79, 95% CI = 0.73-0.86, respectively). Conclusion: Women veterans with SUD are less likely to have prescription contraception compared to other women, which may increase their risk of unintended pregnancy. Published by Elsevier Inc. C1 [Callegari, Lisa S.; Nelson, Karin M.; Bradley, Katharine A.] Dept Vet Affairs VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. [Callegari, Lisa S.] Univ Washington, Dept Obstet & Gynecol, Seattle, WA 98195 USA. [Zhao, Xinhua; Borrero, Sonya] VA Pittsburgh Hlth Care Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Zhao, Xinhua; Borrero, Sonya] VA Pittsburgh Hlth Care Syst, Ctr Hlth Equ Res & Promot, Seattle, WA USA. [Nelson, Karin M.; Bradley, Katharine A.] Univ Washington, Dept Med, Seattle, WA USA. [Lehavot, Keren] VA Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA USA. [Lehavot, Keren] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Bradley, Katharine A.] Grp Hlth Res Inst, Seattle, WA USA. [Borrero, Sonya] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. RP Callegari, LS (reprint author), Puget Sound Vet Adm Univ Washington, Seattle HSR&D Ctr, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM lcallega@uw.edu FU Department of Veterans Affairs, Veteran Health Administration, Office of Research and Development, VISN 4 CHERP Pilot Project Award; VA Health Services Research and Development Postdoctoral Fellowship [TPM 61-041]; VA Office of Academic Affiliations, Advanced Fellowship Program in Mental Illness Research and Treatment FX This study was supported by the Department of Veterans Affairs, Veteran Health Administration, Office of Research and Development, VISN 4 CHERP Pilot Project Award (PI: Sonya Borrero). L.S.C. was supported by a VA Health Services Research and Development Postdoctoral Fellowship (TPM 61-041). K.L. was supported by the VA Office of Academic Affiliations, Advanced Fellowship Program in Mental Illness Research and Treatment. NR 37 TC 4 Z9 4 U1 2 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0010-7824 EI 1879-0518 J9 CONTRACEPTION JI Contraception PD JUL PY 2014 VL 90 IS 1 BP 97 EP 103 DI 10.1016/j.contraception.2014.02.028 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AJ0HO UT WOS:000337331600017 PM 24731860 ER PT J AU Safdar, N O'Horo, JC Ghufran, A Bearden, A Didier, ME Chateau, D Maki, DG AF Safdar, Nasia O'Horo, John C. Ghufran, Aiman Bearden, Allison Didier, Maria Eugenia Chateau, Dan Maki, Dennis G. TI Chlorhexidine-Impregnated Dressing for Prevention of Catheter-Related Bloodstream Infection: A Meta-Analysis SO CRITICAL CARE MEDICINE LA English DT Article DE catheter-related infection; chlorhexidine; nosocomial infection ID RANDOMIZED CONTROLLED-TRIAL; CRITICALLY-ILL ADULTS; INTENSIVE-CARE-UNIT; RESISTANT STAPHYLOCOCCUS-AUREUS; CENTRAL VENOUS CATHETERS; DISEASES SOCIETY; POVIDONE-IODINE; IN-VITRO; GUIDELINES; COLONIZATION AB Objective: To assess the efficacy of a chlorhexidine-impregnated dressing for prevention of central venous catheter-related colonization and catheter-related bloodstream infection using meta-analysis. Data Sources: Multiple computerized database searches supplemented by manual searches including relevant conference proceedings. Study Selection: Randomized controlled trials evaluating the efficacy of a chlorhexidine-impregnated dressing compared with conventional dressings for prevention of catheter colonization and catheter-related bloodstream infection. Data Extraction: Data were extracted on patient and catheter characteristics and outcomes. Data Synthesis: Nine randomized controlled trials met the inclusion criteria. Use of a chlorhexidine-impregnated dressing resulted in a reduced prevalence of catheter-related bloodstream infection (random effects relative risk, 0.60; 95% CI, 0.41-0.88, p = 0.009). The prevalence of catheter colonization was also markedly reduced in the chlorhexidine-impregnated dressing group (random effects relative risk, 0.52; 95% CI, 0.43-0.64; p < 0.001). There was significant benefit for prevention of catheter colonization and catheter-related bloodstream infection, including arterial catheters used for hemodynamic monitoring. Other than in low birth weight infants, adverse effects were rare and minor. Conclusions: Our analysis shows that a chlorhexidine-impregnated dressing is beneficial in preventing catheter colonization and, more importantly, catheter-related bloodstream infection and warrants routine use in patients at high risk of catheter-related bloodstream infection and central venous catheter or arterial catheter colonization. C1 [Safdar, Nasia] William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. [Safdar, Nasia; Ghufran, Aiman; Bearden, Allison; Didier, Maria Eugenia; Maki, Dennis G.] Univ Wisconsin Sch Med & Publ Hlth, Infect Dis Sect, Dept Med, Madison, WI USA. [O'Horo, John C.] Mayo Clin, Div Pulm & Crit Care Med, Dept Med, Rochester, MN USA. [Chateau, Dan] Univ Manitoba, Dept Community Hlth Sci, Biostat Consulting Unit, Winnipeg, MB R3T 2N2, Canada. RP Safdar, N (reprint author), William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. EM ns2@medicine.wisc.edu RI O'Horo, John/N-8681-2013 OI O'Horo, John/0000-0002-0880-4498; chateau, Dan/0000-0002-2215-820X FU National Institute on Aging, National Institutes of Health [AG40669]; VA MERIT grant FX Dr. Safdar is supported by grant number AG40669 from the National Institute on Aging, National Institutes of Health, and a VA MERIT grant. The remaining authors have disclosed that they do not have any potential conflicts of interest. NR 62 TC 21 Z9 22 U1 1 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD JUL PY 2014 VL 42 IS 7 BP 1703 EP 1713 DI 10.1097/CCM.0000000000000319 PG 11 WC Critical Care Medicine SC General & Internal Medicine GA AJ5DU UT WOS:000337703000035 PM 24674924 ER PT J AU Yan, M Dong, ZM Zhao, F Chauncey, T Deauna-Limayo, D Wang-Rodriguez, J Liu, DY Wang, HY Pilz, R AF Yan, Min Dong, Zhaoming Zhao, Frank Chauncey, Thomas Deauna-Limayo, Delva Wang-Rodriguez, Jessica Liu, Dayu Wang, Huan-You Pilz, Renate TI CD20-positive plasmablastic lymphoma with excellent response to bortezomib combined with rituximab SO EUROPEAN JOURNAL OF HAEMATOLOGY LA English DT Article DE plasmablastic lymphoma; CD20; CD138; bortezomib; rituximab; lymphoma ID CHEMOTHERAPY AB As a distinct type of aggressive mature large B-cell lymphoma, plasmablastic lymphoma (PBL) poses diagnostic and treatment challenges. PBL is distinguished from other B-cell lymphomas by the presence of plasmacytic differentiation markers such as CD38, CD138, and MUM1. Clinically, PBLs from oral and extra-oral sites are rapidly progressive tumors with frequent relapse after treatment with standard diffuse large B-cell lymphoma regimens. Here, we report a near-complete response of one patient with relapsed PBL following treatment with a non-cytotoxic regimen containing bortezomib, rituximab, and dexamethasone. C1 [Yan, Min; Zhao, Frank; Wang-Rodriguez, Jessica; Wang, Huan-You; Pilz, Renate] Univ Calif San Diego Hlth Syst, Moores Canc Ctr, La Jolla, CA 92093 USA. [Dong, Zhaoming; Chauncey, Thomas] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Deauna-Limayo, Delva] VA Hosp Southern Nevada, North Las Vegas, NV USA. [Liu, Dayu] Shandong Univ, Qilu Hosp, Jinan 250100, Peoples R China. RP Yan, M (reprint author), Univ Calif San Diego Hlth Syst, Moores Canc Ctr, 3855 Hlth Sci Dr,Mc 0829, La Jolla, CA 92093 USA. EM M5yan@ucsd.edu; Rpilz@ucsd.edu NR 11 TC 11 Z9 13 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0902-4441 EI 1600-0609 J9 EUR J HAEMATOL JI Eur. J. Haematol. PD JUL PY 2014 VL 93 IS 1 BP 77 EP 80 DI 10.1111/ejh.12286 PG 4 WC Hematology SC Hematology GA AJ4SP UT WOS:000337666400011 PM 24528507 ER PT J AU Deo, R Yang, W Khan, AM Bansal, N Zhang, XM Leonard, MB Keane, MG Soliman, EZ Steigerwalt, S Townsend, RR Shlipak, MG Feldman, HI AF Deo, Rajat Yang, Wei Khan, Abigail M. Bansal, Nisha Zhang, Xiaoming Leonard, Mary B. Keane, Martin G. Soliman, Elsayed Z. Steigerwalt, Susan Townsend, Raymond R. Shlipak, Michael G. Feldman, Harold I. CA CRIC Study Investigators TI Serum Aldosterone and Death, End-Stage Renal Disease, and Cardiovascular Events in Blacks and Whites Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study SO HYPERTENSION LA English DT Article DE aldosterone; death; heart failure; renal insufficiency; chronic ID CHRONIC KIDNEY-DISEASE; HEART-FAILURE; MINERALOCORTICOID RECEPTOR; BLOOD-PRESSURE; MYOCARDIAL-INFARCTION; HEMODIALYSIS-PATIENTS; HYPERTENSION; MORTALITY; RISK; SPIRONOLACTONE AB Prior studies have demonstrated that elevated aldosterone concentrations are an independent risk factor for death in patients with cardiovascular disease. Limited studies, however, have evaluated systematically the association between serum aldosterone and adverse events in the setting of chronic kidney disease. We investigated the association between serum aldosterone and death and end-stage renal disease in 3866 participants from the Chronic Renal Insufficiency Cohort. We also evaluated the association between aldosterone and incident congestive heart failure and atherosclerotic events in participants without baseline cardiovascular disease. Cox proportional hazards models were used to evaluate independent associations between elevated aldosterone concentrations and each outcome. Interactions were hypothesized and explored between aldosterone and sex, race, and the use of loop diuretics and renin-angiotensin-aldosterone system inhibitors. During a median follow-up period of 5.4 years, 587 participants died, 743 developed end-stage renal disease, 187 developed congestive heart failure, and 177 experienced an atherosclerotic event. Aldosterone concentrations (per SD of the log-transformed aldosterone) were not an independent risk factor for death (adjusted hazard ratio, 1.00; 95% confidence interval, 0.93-1.12), end-stage renal disease (adjusted hazard ratio, 1.07; 95% confidence interval, 0.99-1.17), or atherosclerotic events (adjusted hazard ratio, 1.04; 95% confidence interval, 0.85-1.18). Aldosterone was associated with congestive heart failure (adjusted hazard ratio, 1.21; 95% confidence interval, 1.02-1.35). Among participants with chronic kidney disease, higher aldosterone concentrations were independently associated with the development of congestive heart failure but not for death, end-stage renal disease, or atherosclerotic events. Further studies should evaluate whether mineralocorticoid receptor antagonists may reduce adverse events in individuals with chronic kidney disease because elevated cortisol levels may activate the mineralocorticoid receptor. C1 [Deo, Rajat; Khan, Abigail M.] Univ Penn, Dept Med, Div Cardiovasc Med, Perelman Sch Med, Philadelphia, PA 19146 USA. [Townsend, Raymond R.] Univ Penn, Dept Med, Renal Electrolyte & Hypertens Div, Perelman Sch Med, Philadelphia, PA 19146 USA. [Yang, Wei; Zhang, Xiaoming; Leonard, Mary B.; Feldman, Harold I.] Univ Penn, Sch Med, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19146 USA. [Yang, Wei; Zhang, Xiaoming; Leonard, Mary B.; Feldman, Harold I.] Univ Penn, Sch Med, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19146 USA. [Bansal, Nisha] Univ Washington, Dept Med, Div Nephrol, Seattle, WA 98195 USA. [Leonard, Mary B.] Childrens Hosp Philadelphia, Div Nephrol, Philadelphia, PA USA. [Keane, Martin G.] Temple Univ, Div Cardiovasc Med, Philadelphia, PA 19122 USA. [Soliman, Elsayed Z.] Wake Forest Univ, Bowman Gray Sch Med, Epidemiol Cardiol Res Ctr, Winston Salem, NC USA. [Soliman, Elsayed Z.] Wake Forest Univ, Bowman Gray Sch Med, Dept Epidemiol & Prevent, Winston Salem, NC USA. [Soliman, Elsayed Z.] Wake Forest Univ, Bowman Gray Sch Med, Dept Internal Med, Cardiol Sect, Winston Salem, NC USA. [Steigerwalt, Susan] St John Hosp & Med Ctr, Div Nephrol & Hypertens, Detroit, MI USA. [Shlipak, Michael G.] Univ Calif San Francisco, Dept Med Epidemiol & Biostat, San Francisco, CA 94143 USA. [Shlipak, Michael G.] San Francisco VA Med Ctr, Dept Gen Internal Med, San Francisco, CA USA. RP Deo, R (reprint author), Univ Penn, 3400 Spruce St,9 Founders Cardiol, Philadelphia, PA 19146 USA. EM Rajat.Deo@uphs.upenn.edu FU National Institutes of Health (NIH) [K23DK089118]; National Institute of Diabetes and Digestive and Kidney Diseases [U01DK060990, U01DK060984, U01DK061022, U01DK061021, U01DK061028, U01DK060980, U01DK060963, U01DK060902]; Perelman School of Medicine at the University of Pennsylvania Clinical and Translational Science Award NIH/National Center for Advancing Translational Sciences (NCATS) [UL1TR000003]; Johns Hopkins University [UL1 TR-000424]; University of Maryland General Clinical Research Center [M01 RR-16500]; Clinical and Translational Science Collaborative of Cleveland, NCATS component of the National Institutes of Health [UL1TR000439]; NIH roadmap for Medical Research; Michigan Institute for Clinical and Health Research [UL1TR000433]; University of Illinois at Chicago Clinical and Translational Science Award [UL1RR029879]; Tulane University Translational Research in Hypertension and Renal Biology [P30GM103337]; Kaiser Permanente NIH/National Center for Research Resources UCSF-CTSI [UL1 RR-024131] FX This work was supported by National Institutes of Health (NIH) grant K23DK089118 to R. Deo. Funding for the Chronic Renal Insufficiency Cohort (CRIC) Study was obtained under a cooperative agreement from National Institute of Diabetes and Digestive and Kidney Diseases (U01DK060990, U01DK060984, U01DK061022, U01DK061021, U01DK061028, U01DK060980, U01DK060963, and U01DK060902). In addition, this work was supported, in part, by the Perelman School of Medicine at the University of Pennsylvania Clinical and Translational Science Award NIH/National Center for Advancing Translational Sciences (NCATS) UL1TR000003, Johns Hopkins University UL1 TR-000424, University of Maryland General Clinical Research Center M01 RR-16500, Clinical and Translational Science Collaborative of Cleveland, UL1TR000439 from the NCATS component of the National Institutes of Health and NIH roadmap for Medical Research, Michigan Institute for Clinical and Health Research UL1TR000433, University of Illinois at Chicago Clinical and Translational Science Award UL1RR029879, Tulane University Translational Research in Hypertension and Renal Biology P30GM103337, and Kaiser Permanente NIH/National Center for Research Resources UCSF-CTSI UL1 RR-024131. NR 39 TC 8 Z9 8 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X EI 1524-4563 J9 HYPERTENSION JI Hypertension PD JUL PY 2014 VL 64 IS 1 BP 103 EP 110 DI 10.1161/HYPERTENSIONAHA.114.03311 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AJ5CY UT WOS:000337700400018 PM 24752431 ER PT J AU Subhash, SS Cavaiuolo, M Radonovich, LJ Eagan, A Lee, ML Campbell, S Martinello, RA AF Subhash, Shobha S. Cavaiuolo, Maria Radonovich, Lewis J., Jr. Eagan, Aaron Lee, Martin L. Campbell, Sheldon Martinello, Richard A. TI Effectiveness of Common Healthcare Disinfectants against H1N1 Influenza Virus on Reusable Elastomeric Respirators SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID EFFICACY; HANDS AB This study evaluated the efficacy of 3 common hospital disinfectants to inactivate influenza virus on elastomeric respirators. Quaternary ammonium/isopropyl alcohol and bleach detergent wipes eliminated live virus, whereas 70% isopropyl alcohol alone was ineffective. C1 [Subhash, Shobha S.; Radonovich, Lewis J., Jr.; Eagan, Aaron] Vet Hlth Adm, Off Publ Hlth, Natl Ctr Occupat Hlth & Infect Control, Gainesville, FL USA. [Cavaiuolo, Maria; Campbell, Sheldon] Vet Affairs Connecticut Hlth Care Syst, West Haven, CT USA. [Radonovich, Lewis J., Jr.] Univ Florida, Dept Med, Gainesville, FL USA. [Lee, Martin L.] Univ Calif Los Angeles, Sch Publ Hlth, Vet Affairs Greater Los Angeles Healthcare Syst S, Los Angeles, CA 90024 USA. [Lee, Martin L.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90024 USA. [Campbell, Sheldon] Yale Univ, Sch Med, Dept Lab Med, New Haven, CT 06510 USA. [Martinello, Richard A.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. [Martinello, Richard A.] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA. [Martinello, Richard A.] Off Publ Hlth, Dept Vet Affairs, Washington, DC USA. RP Subhash, SS (reprint author), 1601 Southwest Archer Rd 151E, Gainesville, FL 32608 USA. EM shobha.subhash@va.gov FU Veterans Health Administration FX This study was funded by the Veterans Health Administration. NR 10 TC 1 Z9 1 U1 0 U2 5 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X EI 1559-6834 J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD JUL PY 2014 VL 35 IS 7 BP 894 EP 897 DI 10.1086/676863 PG 4 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA AJ5OV UT WOS:000337735400021 PM 24915224 ER PT J AU Paul, LA Walsh, K McCauley, JL Ruggiero, KJ Resnick, HS Kilpatrick, DG AF Paul, Lisa A. Walsh, Kate McCauley, Jenna L. Ruggiero, Kenneth J. Resnick, Heidi S. Kilpatrick, Dean G. TI CHARACTERISTICS AND LIFE EXPERIENCES ASSOCIATED WITH RECEIVING A RAPE DISCLOSURE WITHIN A NATIONAL TELEPHONE HOUSEHOLD PROBABILITY SAMPLE OF WOMEN SO JOURNAL OF COMMUNITY PSYCHOLOGY LA English DT Article ID SEXUAL ASSAULT VICTIMS; SOCIAL REACTIONS; CHILDHOOD RAPE; COLLEGE-WOMEN; SURVIVORS; SUPPORT; VICTIMIZATION; PREDICTORS; FRIENDS; OTHERS AB Disclosure of rape to informal support sources is relatively common, but not well understood. This study expands our limited knowledge of disclosure recipients' experience by examining associations between their sociodemographic and life experiences with receipt of a rape disclosure and encouragement of the victim to formally report her assault. Over 35% of the 3,001 community-residing women in this national sample reported receiving a rape disclosure. Women who had a personal history of sexual assault, met lifetime diagnostic criteria for posttraumatic stress disorder or depression, met past-year diagnostic criteria for substance abuse, engaged in monthly binge drinking and nonexperimental substance use, and sought help for emotional concerns were significantly more likely to be recipients. Approximately two thirds (69%) of disclosure recipients encouraged the victim to formally report the rape, and encouragement was also significantly associated with these characteristics. Implications of these findings for improving the disclosure process are provided. (C) 2014 Wiley Periodicals, Inc. C1 [Paul, Lisa A.] No Illinois Univ, De Kalb, IL 60115 USA. [Walsh, Kate] Columbia Univ, New York, NY 10027 USA. [McCauley, Jenna L.; Ruggiero, Kenneth J.; Resnick, Heidi S.; Kilpatrick, Dean G.] Med Univ S Carolina, Charleston, SC 29425 USA. [Ruggiero, Kenneth J.] Ralph H Johnson VAMC, Charleston, SC USA. RP Kilpatrick, DG (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, Natl Crime Victims Res & Treatment Ctr, 67 President St,MSC 861,2nd Fl,IOP South Bldg, Charleston, SC 29425 USA. EM kilpatdg@musc.edu FU NIDA NIH HHS [K12 DA031794, L30 DA036213, T32 DA031099]; NIMH NIH HHS [T32 MH018869] NR 30 TC 0 Z9 0 U1 2 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0090-4392 EI 1520-6629 J9 J COMMUNITY PSYCHOL JI J. Community Psychol. PD JUL PY 2014 VL 42 IS 5 BP 583 EP 592 DI 10.1002/jcop.21639 PG 10 WC Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Social Work SC Public, Environmental & Occupational Health; Psychology; Social Work GA AJ4IP UT WOS:000337639000007 PM 25382881 ER PT J AU Turvey, C Klein, D Fix, G Hogan, TP Woods, S Simon, SR Charlton, M Vaughan-Sarrazin, M Zulman, DM Dindo, L Wakefield, B Graham, G Nazi, K AF Turvey, Carolyn Klein, Dawn Fix, Gemmae Hogan, Timothy P. Woods, Susan Simon, Steven R. Charlton, Mary Vaughan-Sarrazin, Mary Zulman, Donna M. Dindo, Lilian Wakefield, Bonnie Graham, Gail Nazi, Kim TI Blue Button use by patients to access and share health record information using the Department of Veterans Affairs' online patient portal SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID PRIMARY-CARE PHYSICIANS; DIGITAL DIVIDE; COMMUNICATION; EXCHANGE; ADOPTION; DOCTORS; PERCEPTIONS; EXPERIENCE; INTERNET; SYSTEMS AB Objective The Blue Button feature of online patient portals promotes patient engagement by allowing patients to easily download their personal health information. This study examines the adoption and use of the Blue Button feature in the Department of Veterans Affairs' (VA) personal health record portal, My HealtheVet. Materials and methods An online survey presented to a 4% random sample of My HealtheVet users between March and May 2012. Questions were designed to determine characteristics associated with Blue Button use, perceived value of use, and how Veterans with non-VA providers use the Blue Button to share information with their non-VA providers. Results Of the survey participants (N=18 398), 33% were current Blue Button users. The most highly endorsed benefit was that it helped patients understand their health history better because all the information was in one place (73%). Twenty-one percent of Blue Button users with a non-VA provider shared their VA health information, and 87% reported that the non-VA provider found the information somewhat or very helpful. Veterans' self-rated computer ability was the strongest factor contributing to both Blue Button use and to sharing information with non-VA providers. When comparing Blue Button users and non-users, barriers to adoption were low awareness of the feature and difficulty using the Blue Button. Conclusions This study contributes to the understanding of early Blue Button adoption and use of this feature for patient-initiated sharing of health information. Educational efforts are needed to raise awareness of the Blue Button and to address usability issues that hinder adoption. C1 [Turvey, Carolyn; Klein, Dawn; Charlton, Mary; Vaughan-Sarrazin, Mary; Wakefield, Bonnie] Iowa City VA Hlth Care Syst, Comprehens Access & Delivery Res & Evaluat CADRE, Iowa City, IA USA. [Turvey, Carolyn; Klein, Dawn; Dindo, Lilian] Univ Iowa, Dept Psychiat, Carver Coll Med, Iowa City, IA 52242 USA. [Fix, Gemmae; Hogan, Timothy P.] Edith Nourse Rogers Mem Vet Adm Hosp, CHOIR, A VA HSR&D Ctr Innovat, Bedford, MA 01730 USA. [Fix, Gemmae] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. [Hogan, Timothy P.] Edith Nourse Rogers Mem Vet Adm Hosp, eHlth Qual Enhancement Res Initiat, Natl eHlth QUERI Coordinating Ctr, Bedford, MA 01730 USA. [Hogan, Timothy P.] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Div Hlth Informat & Implementat Sci, Worcester, MA USA. [Woods, Susan] Portland VA Med Ctr, Hlth Serv Res & Dev, Portland, OR USA. [Woods, Susan] Oregon Hlth & Sci Univ, Dept Med Informat & Clin Epidemiol, Portland, OR 97201 USA. [Simon, Steven R.] Vet Affairs Boston Healthcare Syst, Gen Internal Med Sect, Boston, MA USA. [Simon, Steven R.] Brigham & Womens Hosp, Div Gen Med & Primary Care, Boston, MA 02115 USA. [Charlton, Mary] Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA USA. [Vaughan-Sarrazin, Mary] Univ Iowa, Dept Internal Med, Carver Coll Med, Iowa City, IA 52242 USA. [Zulman, Donna M.] Vet Affairs Palo Alto Hlth Care Syst, Ctr Innovat Implementat, Menlo Pk, CA USA. [Zulman, Donna M.] Stanford Univ, Div Gen Med Disciplines, Stanford, CA 94305 USA. [Wakefield, Bonnie] Univ Missouri, Sinclair Sch Nursing, Columbia, MO USA. [Graham, Gail; Nazi, Kim] Vet Hlth Adm, Off Informat & Analyt, Vet & Consumers Hlth Informat Off, Washington, DC USA. RP Turvey, C (reprint author), Iowa City VA Hlth Care Syst 152, 601 Highway West, Iowa City, IA 52246 USA. EM carolyn.turvey@va.gov OI Fix, Gemmae/0000-0001-6055-4177 FU Department of Veterans Affairs, Health Services Research & Development, eHealth Quality Enhancement Research Initiative [RRP 11-407] FX This work was supported by the Department of Veterans Affairs, Health Services Research & Development, eHealth Quality Enhancement Research Initiative (RRP 11-407). The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. NR 45 TC 27 Z9 27 U1 2 U2 23 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1067-5027 EI 1527-974X J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD JUL PY 2014 VL 21 IS 4 SI SI BP 657 EP 663 DI 10.1136/amiajnl-2014-002723 PG 7 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics SC Computer Science; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics GA AJ4QJ UT WOS:000337660600018 PM 24740865 ER PT J AU Giardina, TD Menon, S Parrish, DE Sittig, DF Singh, H AF Giardina, Traber Davis Menon, Shailaja Parrish, Danielle E. Sittig, Dean F. Singh, Hardeep TI Patient access to medical records and healthcare outcomes: a systematic review SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; CANCER-PATIENTS; OWN RECORDS; PATIENTS SATISFACTION; COLLABORATIVE CARE; GENERAL-PRACTICE; SAFETY; INFORMATION; COMMUNICATION; INVOLVEMENT AB Objectives We conducted a systematic review to determine the effect of providing patients access to their medical records (electronic or paper-based) on healthcare quality, as defined by measures of safety, effectiveness, patient-centeredness, timeliness, efficiency, and equity. Methods Articles indexed in PubMed from January 1970 to January 2012 were reviewed. Twenty-seven English-language controlled studies were included. Outcomes were categorized as measures of effectiveness (n=19), patient-centeredness (n=16), and efficiency (n=2); no study addressed safety, timeliness, or equity. Results Outcomes were equivocal with respect to several aspects of effectiveness and patient-centeredness. Efficiency outcomes in terms of frequency of in-person and telephone encounters were mixed. Access to health records appeared to enhance patients' perceptions of control and reduced or had no effect on patient anxiety. Conclusion Although few positive findings generally favored patient access, the literature is unclear on whether providing patients access to their medical records improves quality. C1 [Giardina, Traber Davis; Menon, Shailaja; Singh, Hardeep] Michael E DeBakey VA Med Ctr, Houston VA HSR&D Ctr Innovat Qual Effectiveness &, Houston, TX USA. [Giardina, Traber Davis; Menon, Shailaja; Singh, Hardeep] Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA. [Giardina, Traber Davis; Parrish, Danielle E.] Univ Houston, Grad Coll Social Work, Houston, TX USA. [Sittig, Dean F.] Univ Texas Sch Biomed Informat, Houston, TX USA. [Sittig, Dean F.] UT Mem Hermann Ctr Healthcare Qual & Safety, Houston, TX USA. RP Giardina, TD (reprint author), VA Med Ctr 152, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM Traber.Davis@va.gov FU VA National Center of Patient Safety; Houston VA Center for Innovations in Quality, Effectiveness and Safety [CIN 13-413] FX This work was supported by the VA National Center of Patient Safety and in part by the Houston VA Center for Innovations in Quality, Effectiveness and Safety (CIN 13-413). These sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. NR 64 TC 12 Z9 12 U1 1 U2 16 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1067-5027 EI 1527-974X J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD JUL PY 2014 VL 21 IS 4 SI SI BP 737 EP 741 DI 10.1136/amiajnl-2013-002239 PG 5 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics SC Computer Science; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics GA AJ4QJ UT WOS:000337660600030 ER PT J AU Caverly, TJ Prochazka, AV Binswanger, IA Kutner, JS Matlock, DD AF Caverly, Tanner J. Prochazka, Allan V. Binswanger, Ingrid A. Kutner, Jean S. Matlock, Daniel D. TI Confusing Relative Risk with Absolute Risk Is Associated with More Enthusiastic Beliefs about the Value of Cancer Screening SO MEDICAL DECISION MAKING LA English DT Article DE statistics; medical education; physicians; numeracy; risk communication ID 5-YEAR SURVIVAL RATES; UNITED-STATES; DOCTORS; IMPACT AB Background. Reviews of how data are presented in medical literature document that the benefit from an intervention is often exaggerated relative to the harm (e.g., relative risk for benefit and absolute risk for harm). Such mismatched presentations may create unwarranted enthusiasm, especially among those who misinterpret the statistics presented. The objective was to determine whether misinterpretation of risk data predicts enthusiasm for cancer screening. Methods. The authors administered a survey with 14 items assessing beliefs about cancer screening and 6 items measuring data interpretation ability. Multiple linear regression was used to evaluate the association between data interpretation and enthusiasm for cancer screening, with adjustment for gender and year graduated from medical school. Results. Eighty-eight of 139 physicians at a state-wide professional meeting returned completed surveys (63% response rate). Lower data interpretation scores were associated with higher enthusiasm for cancer screening scores (P = 0.004) in the adjusted primary analysis. Confusing relative risk with absolute risk appeared to drive the overall association. Conclusions. Biased presentations of risk data could affect general beliefs about the value of cancer screening, especially among physicians who uncritically accept mismatched presentations of data. C1 [Caverly, Tanner J.] Ann Arbor VA Hlth Syst, Ann Arbor, MI USA. [Caverly, Tanner J.] Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA. [Prochazka, Allan V.; Binswanger, Ingrid A.; Kutner, Jean S.; Matlock, Daniel D.] Univ Colorado, Div Gen Internal Med, Aurora, CO USA. [Prochazka, Allan V.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Binswanger, Ingrid A.] Denver Hlth Med Ctr Denver, Denver, CO USA. RP Caverly, TJ (reprint author), Univ Michigan, Sch Med, VA Ctr Clin Management Res, Ann Arbor VA Hlth Syst, 2800 Plymouth Rd,Bldg 16,Room 326W, Ann Arbor, MI 48109 USA. EM tcaverly@med.umich.edu OI Binswanger, Ingrid/0000-0001-8862-8078 FU National Research Service Award [T32HP1006]; K23 [AG040696-01] FX Dr. Caverly was supported by a National Research Service Award T32HP1006 grant and Dr. Matlock was supported by a K23 (AG040696-01). This research was presented orally at the 2012 North American Annual Meeting for the Society for Medical Decision Making. Revision accepted for publication 5 February 2014. NR 17 TC 2 Z9 2 U1 0 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-989X EI 1552-681X J9 MED DECIS MAKING JI Med. Decis. Mak. PD JUL PY 2014 VL 34 IS 5 BP 686 EP 692 DI 10.1177/0272989X14526641 PG 7 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA AJ3NB UT WOS:000337572300012 PM 24732049 ER PT J AU McMurtrey, C Harriff, M Liles, LM Swarbrick, G Bardet, W Canfield, ET Jackson, K Lewinsohn, D Lewinsohn, D Hildebrand, W AF McMurtrey, Curtis Harriff, Melanie Liles, Lauren M. Swarbrick, Gwendolyn Bardet, Wilfried Canfield, Elizabeth T. Jackson, Ken Lewinsohn, Deborah Lewinsohn, David Hildebrand, William TI M. TUBERCULOSIS PEPTIDE LIGAND PRESENTATION BY NON-CLASSICAL HLA-E SO TISSUE ANTIGENS LA English DT Meeting Abstract CT 28th EFI European Immunogenetics and Histocompatibility Conference CY JUN 25-28, 2014 CL Stockholm, SWEDEN SP EFI C1 [McMurtrey, Curtis; Liles, Lauren M.; Bardet, Wilfried; Jackson, Ken; Hildebrand, William] Univ Oklahoma HSC, Oklahoma City, OK USA. [Harriff, Melanie; Swarbrick, Gwendolyn; Canfield, Elizabeth T.; Lewinsohn, Deborah; Lewinsohn, David] Portland VA Med Ctr, Portland, OR USA. EM william-hildebrand@ouhsc.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0001-2815 EI 1399-0039 J9 TISSUE ANTIGENS JI Tissue Antigens PD JUL PY 2014 VL 84 IS 1 BP 6 EP 6 PG 1 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA AJ3DN UT WOS:000337546000005 ER PT J AU Morrison, P Nikolajski, C Borrero, S Zickmund, S AF Morrison, Penelope Nikolajski, Cara Borrero, Sonya Zickmund, Susan TI Youth Perspectives on Risk and Resiliency: A Case Study From Juiz de Fora, Brazil SO YOUTH & SOCIETY LA English DT Article DE culture; health; risk behavior; resiliency ID PROTECTIVE FACTORS; SAO-PAULO; FAMILY-STRUCTURE; SEXUAL-BEHAVIOR; DRUG-USE; HEALTH; ADOLESCENTS; CHILDHOOD; ADULTHOOD; ATTITUDES AB The present work seeks to contribute to studies of cross-cultural risk and resiliency by presenting results from qualitative research with adolescents attending programs for at-risk youth in Juiz de Fora, Brazil. In 1990, Brazil introduced the Child and Adolescent Act (ECA), a significant piece of legislation that has had a direct impact on how at-risk youth are conceptualized both nationally and locally, through programs that target them. Little, however, is known about how youth in Brazil understand risk behaviors, what factors they believe contribute to risk taking or what they believe promotes resiliency. Furthermore, virtually no qualitative information exists on adolescents who are engaged in programs that use ECA as a prioritizing principle. By examining adolescent perspectives on risk and resiliency in such a context, we highlight the cultural differences in how youth negotiate their daily lives and the implications that continued exclusion of youth has on Brazilian society. C1 [Morrison, Penelope] Univ Pittsburgh, Hlth Inst, RAND, Pittsburgh, PA 15213 USA. [Nikolajski, Cara] Univ Pittsburgh, Ctr Res Hlth Care, Pittsburgh, PA 15213 USA. [Borrero, Sonya] Univ Pittsburgh, Pittsburgh, PA 15213 USA. [Zickmund, Susan] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Morrison, P (reprint author), Univ Pittsburgh, Hlth Inst, RAND, 230 McKeePl,Suite 600, Pittsburgh, PA 15213 USA. EM morrisonpk@upmc.edu NR 70 TC 0 Z9 0 U1 2 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0044-118X EI 1552-8499 J9 YOUTH SOC JI Youth Soc. PD JUL PY 2014 VL 46 IS 4 BP 505 EP 528 DI 10.1177/0044118X12441614 PG 24 WC Social Issues; Social Sciences, Interdisciplinary; Sociology SC Social Issues; Social Sciences - Other Topics; Sociology GA AJ3ZG UT WOS:000337606900004 ER PT J AU Hanson, RF Gros, KS Davidson, TM Barr, S Cohen, J Deblinger, E Mannarino, AP Ruggiero, KJ AF Hanson, Rochelle F. Gros, Kirstin Stauffacher Davidson, Tatiana M. Barr, Simone Cohen, Judith Deblinger, Esther Mannarino, Anthony P. Ruggiero, Kenneth J. TI National Trainers' Perspectives on Challenges to Implementation of an Empirically-Supported Mental Health Treatment SO ADMINISTRATION AND POLICY IN MENTAL HEALTH AND MENTAL HEALTH SERVICES RESEARCH LA English DT Article DE Treatment fidelity; Implementation of evidence-based treatment; Child mental health ID COGNITIVE-BEHAVIORAL THERAPY; POSTTRAUMATIC-STRESS-DISORDER; RANDOMIZED-CONTROLLED-TRIAL; PSYCHOSOCIAL TREATMENTS; COMMUNITY TREATMENT; TRAUMATIC EVENTS; PTSD SYMPTOMS; CHILDREN; ADOLESCENTS; FIDELITY AB This study examined perceived challenges to implementation of an empirically supported mental health treatment for youth (Trauma-Focused Cognitive Behavioral Therapy; TF-CBT) and explored the potential use of technology-based resources in treatment delivery. Thematic interviews were conducted with 19 approved national TF-CBT trainers to assess their perspectives about challenges to implementation of TF-CBT and to explore their perceptions about the potential value of innovative, technology-based solutions to enhance provider fidelity and improve quality of care. These data offer some important insights and implications for training in evidence-based treatments, provider fidelity and competence, and patient engagement, particularly for those interventions targeting trauma-related symptoms among youth. C1 [Hanson, Rochelle F.; Gros, Kirstin Stauffacher; Davidson, Tatiana M.; Barr, Simone; Ruggiero, Kenneth J.] Med Univ S Carolina, Natl Crime Victims Res & Treatment Ctr, Charleston, SC 29425 USA. [Gros, Kirstin Stauffacher; Ruggiero, Kenneth J.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Cohen, Judith; Mannarino, Anthony P.] Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. [Deblinger, Esther] Univ Med & Dent New Jersey, Newark, NJ 07103 USA. RP Hanson, RF (reprint author), Med Univ S Carolina, Natl Crime Victims Res & Treatment Ctr, MSC 861, Charleston, SC 29425 USA. EM hansonrf@musc.edu FU CMHS SAMHSA HHS [1U79SM061269-01]; NCATS NIH HHS [UL1 TR000062]; NCRR NIH HHS [UL1 RR029882]; NIMH NIH HHS [R25 MH080916-01A2, 1 R34 MH096907-01, R01 MH081056, R25 MH080916, R34 MH096907] NR 50 TC 7 Z9 7 U1 1 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0894-587X EI 1573-3289 J9 ADM POLICY MENT HLTH JI Adm. Policy. Ment. Health PD JUL PY 2014 VL 41 IS 4 BP 522 EP 534 DI 10.1007/s10488-013-0492-6 PG 13 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AI7OS UT WOS:000337083600009 PM 23605292 ER PT J AU Neverova, N Teerlink, JR AF Neverova, Natalia Teerlink, John R. TI Serelaxin: a potential new drug for the treatment of acute heart failure SO EXPERT OPINION ON INVESTIGATIONAL DRUGS LA English DT Article DE acute heart failure; dyspnea; relaxin; serelaxin; vasodilator ID RANDOMIZED CONTROLLED TRIAL; CARDIAC MYOSIN ACTIVATOR; DOUBLE-BLIND; RELAX-AHF; INTRAVENOUS NESIRITIDE; TISSUE DISTRIBUTION; OMECAMTIV MECARBIL; HORMONE RELAXIN; FUTURE-RESEARCH; NITRIC-OXIDE AB Introduction: The incidence and mortality related to acute heart failure (AHF) have increased in the recent decades despite clinical trials of multiple agents and considerable progress in cardiovascular disease overall. Areas covered: This article reviews serelaxin, a new investigational drug in the treatment of AHF. It provides the background of the available treatments and focuses on serelaxin mechanisms, pharmacology, clinical features and its potential role in AHF. Expert opinion: Recent clinical trials of serelaxin (Pre-RELAX-AHF; RELAX-AHF) have provided a new hope in AHF. They have demonstrated significant serelaxin-related improvement in heart failure symptoms, length of hospital stay as well as mortality reduction in AHF patients. These findings were in the context of early administration in the course of AHF presentation in patients with normal or high blood pressures, thus highlighting the drug's strengths based on its molecular mechanisms of action. Overall, serelaxin is a promising therapy, and further studies aimed at reproducibility of prior results, safety and hemodynamic effects of serelaxin, as well as investigation of the molecular reasons for such effects are currently under way. C1 [Neverova, Natalia; Teerlink, John R.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94117 USA. [Teerlink, John R.] San Francisco VA Med Ctr, Cardiol Sect, San Francisco, CA 94131 USA. RP Teerlink, JR (reprint author), Univ Calif San Francisco, Dept Med, San Francisco, CA 94117 USA. EM john.teerlink@ucsf.edu FU Amgen, Inc; Cytokinetics; Novartis; Trevena Inc. FX JR Teerlink has received research grants and consultancy fees from Amgen, Inc, Cytokinetics, Novartis and Trevena Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 66 TC 7 Z9 7 U1 2 U2 17 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1354-3784 EI 1744-7658 J9 EXPERT OPIN INV DRUG JI Expert Opin. Investig. Drugs PD JUL PY 2014 VL 23 IS 7 BP 1017 EP 1026 DI 10.1517/13543784.2014.924504 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AI7QF UT WOS:000337089000011 PM 24865798 ER PT J AU Chiang, S Haneef, Z AF Chiang, Sharon Haneef, Zulfi TI Graph theory findings in the pathophysiology of temporal lobe epilepsy SO CLINICAL NEUROPHYSIOLOGY LA English DT Review DE Graph theory; Temporal lobe epilepsy; Pathophysiology; Functional connectivity; Diffusion tensor imaging; Small-world networks ID SMALL-WORLD NETWORKS; RESTING-STATE FMRI; COMPLEX BRAIN NETWORKS; DEFAULT MODE NETWORK; FUNCTIONAL CONNECTIVITY; THEORETICAL ANALYSIS; STRUCTURAL CONNECTIVITY; HIPPOCAMPAL ATROPHY; COGNITIVE DECLINE; CEREBRAL-CORTEX AB Temporal lobe epilepsy (TLE) is the most common form of adult epilepsy. Accumulating evidence has shown that TLE is a disorder of abnormal epileptogenic networks, rather than focal sources. Graph theory allows for a network-based representation of TLE brain networks, and has potential to illuminate characteristics of brain topology conducive to TLE pathophysiology, including seizure initiation and spread. We review basic concepts which we believe will prove helpful in interpreting results rapidly emerging from graph theory research in TLE. In addition, we summarize the current state of graph theory findings in TLE as they pertain its pathophysiology. Several common findings have emerged from the many modalities which have been used to study TLE using graph theory, including structural MRI, diffusion tensor imaging, surface EEG, intracranial EEG, magnetoencephalography, functional MRI, cell cultures, simulated models, and mouse models, involving increased regularity of the interictal network configuration, altered local segregation and global integration of the TLE network, and network reorganization of temporal lobe and limbic structures. As different modalities provide different views of the same phenomenon, future studies integrating data from multiple modalities are needed to clarify findings and contribute to the formation of a coherent theory on the pathophysiology of TLE. (C) 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. C1 [Chiang, Sharon] Rice Univ, Dept Stat, Houston, TX 77251 USA. [Haneef, Zulfi] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. [Haneef, Zulfi] VA Med Ctr, Houston, TX USA. RP Haneef, Z (reprint author), Baylor Coll Med, Dept Neurol, Peter Kellaway Sect Neurophysiol, One Baylor Plaza,MS NB302, Houston, TX 77030 USA. EM zulfi.haneef@bcm.edu FU Epilepsy Foundation of America; National Library of Medicine Training Fellowship in Biomedical Informatics; Gulf Coast Consortia for Quantitative Biomedical Sciences [2T15LM007093-21]; National Institute of Health [5T32CA09652007]; Epilepsy Foundation of America and the Baylor College of Medicine Computational; Integrative Biomedical Research Center (CIBR) FX Funding for this study was provided by the Epilepsy Foundation of America. Ms. Chiang's contributions to this article include writing of the review and the decision to submit the article for publication. She is funded by the National Library of Medicine Training Fellowship in Biomedical Informatics, Gulf Coast Consortia for Quantitative Biomedical Sciences (Grant # 2T15LM007093-21) and by the National Institute of Health (Grant # 5T32CA09652007). Ms. Chiang reports no disclosures, commercial considerations, or financial conflicts of interest. Dr. Haneef's contributions to this article include writing of the review and the decision to submit the article for publication. He is funded by the Epilepsy Foundation of America and the Baylor College of Medicine Computational and Integrative Biomedical Research Center (CIBR) seed grant awards. Dr. Haneef reports no disclosures, commercial considerations, or financial conflicts of interest. NR 85 TC 28 Z9 29 U1 3 U2 26 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1388-2457 EI 1872-8952 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD JUL PY 2014 VL 125 IS 7 BP 1295 EP 1305 DI 10.1016/j.clinph.2014.04.004 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AI0AC UT WOS:000336507100004 PM 24831083 ER PT J AU Louie, PK Sangeorzan, BJ Fassbind, MJ Ledoux, WR AF Louie, Philip K. Sangeorzan, Bruce J. Fassbind, Michael J. Ledoux, William R. TI Talonavicular Joint Coverage and Bone Morphology between Different Foot Types SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE pes planus; pes cavus; talonavicular joint; talus; navicular ID POSTERIOR TIBIAL TENDON; PES PLANUS; FLAT FOOT; PREVALENCE; RUPTURE; ADULTS; WOLFF; TALAR; LAW AB This study explored three dimensional (3D) talonavicular joint (TNJ) coverage/orientation and bone morphology to reveal parameters that could classify and identify predispositions to cavus and planus feet. 3D models of 65 feet from 40 subjects were generated from computed tomography images classified as pes cavus, neutrally aligned, or asymptomatic/symptomatic pes planus. We calculated the talar and navicular overlap (TNJ coverage). We also measured orientation of the navicular, morphological parameters of the talus and navicular, and angular position of the talar head to body. Pes cavus showed significantly less talonavicular coverage (58 +/- 2% talus and 86 +/- 2% navicular) compared to asymptomatic pes planus (63 +/- 2% and 95 +/- 2%) and neutrally aligned feet (98 +/- 2% navicular), and significantly more navicular dorsiflexion and adduction relative to the talus (p<0.0083). The talar head in cavus feet was inverted relative to the body compared to planus feet (p<0.0083). For symptomatic pes planus, significant abduction was measured for the navicular relative to the talus and the talar head was plantar flexed relative to the body (p<0.0083). The talar head in planus feet was everted relative to the body compared to neutrally aligned feet. Both intrinsic (bone morphology) and extrinsic (bone position) differences exist in groups of feet described as cavus and planus. (c) 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:958-966, 2014. C1 [Louie, Philip K.; Sangeorzan, Bruce J.; Fassbind, Michael J.; Ledoux, William R.] VA Puget Sound, RR&D Ctr Excellence Limb Loss Prevent & Prosthet, Seattle, WA 98108 USA. [Louie, Philip K.] Univ Washington, Sch Med, Seattle, WA 98195 USA. [Sangeorzan, Bruce J.; Ledoux, William R.] Univ Washington, Dept Orthopaed Surg & Sports Med, Seattle, WA 98195 USA. [Ledoux, William R.] Univ Washington, Dept Mech Engn, Seattle, WA 98195 USA. RP Sangeorzan, BJ (reprint author), VA Puget Sound, RR&D Ctr Excellence Limb Loss Prevent & Prosthet, Seattle, WA 98108 USA. EM bsangeor@uw.edu RI Ledoux, William/K-6815-2015 OI Ledoux, William/0000-0003-4982-7714 NR 26 TC 4 Z9 4 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0736-0266 EI 1554-527X J9 J ORTHOP RES JI J. Orthop. Res. PD JUL PY 2014 VL 32 IS 7 BP 958 EP 966 DI 10.1002/jor.22612 PG 9 WC Orthopedics SC Orthopedics GA AG5ST UT WOS:000335479700015 PM 24719271 ER PT J AU Steele, JW Brautigam, H Short, JA Sowa, A Shi, MX Yadav, A Weaver, CM Westaway, D Fraser, PE St George-Hyslop, PH Gandy, S Hof, PR Dickstein, DL AF Steele, John W. Brautigam, Hannah Short, Jennifer A. Sowa, Allison Shi, Mengxi Yadav, Aniruddha Weaver, Christina M. Westaway, David Fraser, Paul E. St George-Hyslop, Peter H. Gandy, Sam Hof, Patrick R. Dickstein, Dara L. TI Early Fear Memory Defects Are Associated With Altered Synaptic Plasticity and Molecular Architecture in the TgCRND8 Alzheimer's Disease Mouse Model SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE amyloid beta; mouse model of dementia; neuronal morphology; dendritic pathology; spine pathology ID AMYLOID PRECURSOR PROTEIN; DENDRITIC SPINE MORPHOLOGY; MEDIAL PREFRONTAL CORTEX; TRANSGENIC MICE; ISOTROPIC FRACTIONATOR; MICROSCOPY IMAGES; PYRAMIDAL NEURONS; BETA OLIGOMERS; VISUAL-CORTEX; A-BETA AB Alzheimer's disease (AD) is a complex and slowly progressing dementing disorder that results in neuronal and synaptic loss, deposition in brain of aberrantly folded proteins, and impairment of spatial and episodic memory. Most studies of mouse models of AD have employed analyses of cognitive status and assessment of amyloid burden, gliosis, and molecular pathology during disease progression. Here we sought to understand the behavioral, cellular, ultrastructural, and molecular changes that occur at a pathological stage equivalent to the early stages of human AD. We studied the TgCRND8 mouse, a model of aggressive AD amyloidosis, at an early stage of plaque pathology (3 months of age) in comparison to their wildtype littermates and assessed changes in cognition, neuron and spine structure, and expression of synaptic glutamate receptor proteins. We found that, at this age, TgCRND8 mice display substantial plaque deposition in the neocortex and hippocampus and impairment on cued and contextual memory tasks. Of particular interest, we also observed a significant decrease in the number of neurons in the hippocampus. Furthermore, analysis of CA1 neurons revealed significant changes in apical and basal dendritic spine types, as well as altered expression of GluN1 and GluA2 receptors. This change in molecular architecture within the hippocampus may reflect a rising representation of inherently less stable thin spine populations, which can cause cognitive decline. These changes, taken together with toxic insults from amyloid- protein, may underlie the observed neuronal loss. J. Comp. Neurol. 522:2319-2335, 2014. (c) 2014 Wiley Periodicals, Inc. C1 [Steele, John W.] Rockefeller Univ, Lab Mol & Cellular Neurosci, New York, NY 10065 USA. [Steele, John W.; Brautigam, Hannah; Short, Jennifer A.; Sowa, Allison; Shi, Mengxi; Yadav, Aniruddha; Hof, Patrick R.; Dickstein, Dara L.] Icahn Sch Med Mt Sinai, Fishberg Dept Neurosci, New York, NY 10029 USA. [Steele, John W.; Brautigam, Hannah; Gandy, Sam] Icahn Sch Med Mt Sinai, Dept Neurol, New York, NY 10029 USA. [Brautigam, Hannah; Short, Jennifer A.; Sowa, Allison; Shi, Mengxi; Yadav, Aniruddha; Hof, Patrick R.; Dickstein, Dara L.] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA. [Weaver, Christina M.] Franklin & Marshall Coll, Dept Math & Comp Sci, Lancaster, PA 17604 USA. [Westaway, David] Univ Alberta, Ctr Prions & Prot Folding Dis, Edmonton, AB T6G 2M8, Canada. [Fraser, Paul E.; St George-Hyslop, Peter H.] Univ Toronto, Tanz Ctr Res Neurodegenerat Dis, Toronto, ON M5S 3H2, Canada. [Fraser, Paul E.; St George-Hyslop, Peter H.] Univ Toronto, Dept Med Biophys, Toronto, ON M5S 3H2, Canada. [St George-Hyslop, Peter H.] Univ Cambridge, Dept Clin Neurosci, Cambridge CB2 0XY, England. [Gandy, Sam] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Gandy, Sam] James J Peters VA Med Ctr, Bronx, NY 10468 USA. RP Dickstein, DL (reprint author), Icahn Sch Med Mt Sinai, Fishberg Dept Neurosci, One Gustave L Levy Pl,Box 1639, New York, NY 10029 USA. EM jsteele@amicusrx.com; dara.dickstein@mssm.edu FU National Institutes of Health [T32 GM062754, F31 AG039890, P50 AG005138, P01 AG010491, R01 AG035071]; Canadian Institutes of Health Research [MOP-115056]; Canada Research Chairs; Alberta Innovatives-Health Solutions; Alberta Prion Research Institute; Wellcome Trust; Medical Research Council; Howard Hughes Medical Institute; Alzheimer Society of Ontario FX Grant sponsor: National Institutes of Health; Grant numbers: T32 GM062754 (to J.W.S.); F31 AG039890 (to H. B.); P50 AG005138 (to D. L. D., S. G., P. R. H.); P01 AG010491 (to S. G.); and R01 AG035071 (to P. R. H., C. M. W.); Grant sponsor: Canadian Institutes of Health Research; Grant number: MOP-115056 (to P. E. F.); Grant sponsors: the Canada Research Chairs, Alberta Innovatives-Health Solutionsand the Alberta Prion Research Institute (to D. W.); Grant sponsors: Wellcome Trust, Medical Research Council, the Howard Hughes Medical Institute, and the Alzheimer Society of Ontario (to P.E.F., P.H.H.). NR 77 TC 7 Z9 7 U1 0 U2 22 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9967 EI 1096-9861 J9 J COMP NEUROL JI J. Comp. Neurol. PD JUL 1 PY 2014 VL 522 IS 10 BP 2319 EP 2335 DI 10.1002/cne.23536 PG 17 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA AF1QR UT WOS:000334488900006 PM 24415002 ER PT J AU Siddesha, JM Valente, AJ Sakamuri, SSVP Gardner, JD Delafontaine, P Noda, M Chandrasekar, B AF Siddesha, Jalahalli M. Valente, Anthony J. Sakamuri, Siva S. V. P. Gardner, Jason D. Delafontaine, Patrice Noda, Makoto Chandrasekar, Bysani TI Acetylsalicylic Acid Inhibits IL-18-Induced Cardiac Fibroblast Migration Through the Induction of RECK SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID NF-KAPPA-B; ALPHA-CONVERTING ENZYME; MUSCLE-CELL MIGRATION; OXIDATIVE STRESS; DOWN-REGULATION; CANCER CELLS; CIKS ACT1; IN-VITRO; EXPRESSION; ASPIRIN AB The pathogenesis of cardiac fibrosis and adverse remodeling is thought to involve the ROS-dependent induction of inflammatory cytokines and matrix metalloproteinases (MMPs), and the activation and migration of cardiac fibroblasts (CF). Here we investigated the role of RECK (reversion-inducing-cysteine-rich protein with Kazal motifs), a unique membrane-anchored MMP regulator, on IL-18-induced CF migration, and the effect of acetylsalicylic acid (ASA) on this response. In a Matrigel invasion assay, IL-18-induced migration of primary mouse CF was dependent on both IKK/NF-B- and JNK/AP-1-mediated MMP9 induction and Sp1-mediated RECK suppression, mechanisms that required Nox4-dependent H2O2 generation. Notably, forced expression of RECK attenuated IL-18-induced MMP9 activation and CF migration. Further, therapeutic concentrations of ASA inhibited IL-18-induced H2O2 generation, MMP9 activation, RECK suppression, and CF migration. The salicylic acid moiety of ASA similarly attenuated IL-18-induced CF migration. Thus, ASA may exert potential beneficial effect in cardiac fibrosis through multiple protective mechanisms. J. Cell. Physiol. 229: 845-855, 2014. (c) 2013 Wiley Periodicals, Inc. C1 [Siddesha, Jalahalli M.; Chandrasekar, Bysani] Southeast Louisiana Vet Hlth Care Syst, Res Serv, New Orleans, LA USA. [Siddesha, Jalahalli M.; Sakamuri, Siva S. V. P.; Delafontaine, Patrice; Chandrasekar, Bysani] Tulane Univ, Sch Med, Inst Heart & Vasc, New Orleans, LA 70112 USA. [Valente, Anthony J.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Valente, Anthony J.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Gardner, Jason D.] Louisiana State Univ, Dept Physiol, Hlth Sci Ctr, New Orleans, LA USA. [Noda, Makoto] Kyoto Univ, Dept Mol Oncol, Grad Sch Med, Sakyo Ku, Kyoto, Japan. RP Chandrasekar, B (reprint author), Tulane Univ, Sch Med, Inst Heart & Vasc, 1430 Tulane Ave,SL 48, New Orleans, LA 70112 USA. EM bchandra@tulane.edu OI Delafontaine, Patrice/0000-0003-3744-3617 FU Veterans Affairs Office of Research and Development-Biomedical Laboratory Research and Development Service Award [1IO1BX000246]; NHLBI [HL-86787, HL-70241, HL-80682] FX Contract grant sponsor: Veterans Affairs Office of Research and Development-Biomedical Laboratory Research and Development Service Award;; Contract grant number: 1IO1BX000246.; Contract grant sponsor: NHLBI;; Contract grant numbers: HL-86787, HL-70241, HL-80682. NR 47 TC 16 Z9 17 U1 2 U2 26 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9541 EI 1097-4652 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD JUL PY 2014 VL 229 IS 7 BP 845 EP 855 DI 10.1002/jcp.24511 PG 11 WC Cell Biology; Physiology SC Cell Biology; Physiology GA AD4DW UT WOS:000333198200003 PM 24265116 ER PT J AU Waters, AM Nazarian, M Mineka, S Zinbarg, RE Griffith, JW Naliboff, B Ornitz, EM Craske, MG AF Waters, Allison M. Nazarian, Maria Mineka, Susan Zinbarg, Richard E. Griffith, James W. Naliboff, Bruce Ornitz, Edward M. Craske, Michelle G. TI Context and explicit threat cue modulation of the startle reflex: Preliminary evidence of distinctions between adolescents with principal fear disorders versus distress disorders SO PSYCHIATRY RESEARCH LA English DT Article DE Fear disorders; Distress disorders; Startle reflexes; Adolescents ID POSTTRAUMATIC-STRESS-DISORDER; GENERALIZED ANXIETY DISORDER; MAJOR DEPRESSIVE DISORDER; PANIC DISORDER; POTENTIATED STARTLE; INTERNALIZING PSYCHOPATHOLOGY; HIERARCHICAL MODEL; TRIPARTITE MODEL; SOCIAL PHOBIA; COMORBIDITY AB Anxiety and depression are prevalent, impairing disorders. High comorbidity has raised questions about how to define and classify them. Structural models emphasise distinctions between "fear" and "distress" disorders while other initiatives propose they be defined by neurobiological indicators that cut across disorders. This study examined startle reflex (SR) modulation in adolescents with principal fear disorders (specific phobia; social phobia) (n=20), distress disorders (unipolar depressive disorders, dysthymia, generalised anxiety disorder; post-traumatic stress disorder) (n=9), and controls (n=29) during (a) baseline conditions, (b) threat context conditions (presence of contraction pads over the biceps muscle), and (c) an explicit threat cue paradigm involving phases that signalled safety from aversive stimuli (early and late stages of safe phases; early stages of danger phases) and phases that signalled immediate danger of an aversive stimulus (late stages of danger phases). Adolescents with principal fear disorders showed larger SRs than other groups throughout safe phases and early stages of danger phases. SRs did not differ between groups during late danger phases. Adolescents with principal distress disorders showed attenuated SRs during baseline and context conditions compared to other groups. Preliminary findings support initiatives to redefine emotional disorders based on neurobiological functioning. (C) 2014 Elsevier Ireland Ltd. All rights resented. C1 [Nazarian, Maria; Craske, Michelle G.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. [Waters, Allison M.] Griffith Univ, Sch Appl Psychol, Brisbane, Qld 4111, Australia. [Mineka, Susan; Zinbarg, Richard E.; Griffith, James W.] Northwestern Univ, Dept Psychol, Evanston, IL USA. [Naliboff, Bruce; Ornitz, Edward M.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA USA. [Zinbarg, Richard E.] Northwestern Univ, Family Inst, Evanston, IL USA. [Naliboff, Bruce] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Ornitz, Edward M.] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA USA. RP Craske, MG (reprint author), Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. EM craske@psych.ucla.edu RI Griffith, James/O-2551-2016 OI Griffith, James/0000-0002-4840-8692; Waters, Allison/0000-0003-2453-793X FU National Institutes of Health [MH065651]; Virginia Friedhofer Charitable Trust [MH065652] FX This work was supported by Grants from the National Institutes of Health to Dr. Craske (MH065651) and Drs. Zinbarg and Mineka (MH065652) and from the Virginia Friedhofer Charitable Trust to Dr. Ornitz. NR 65 TC 6 Z9 6 U1 5 U2 13 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD JUN 30 PY 2014 VL 217 IS 1-2 BP 93 EP 99 DI 10.1016/j.psychres.2014.01.047 PG 7 WC Psychiatry SC Psychiatry GA AI2SR UT WOS:000336708900015 PM 24679992 ER PT J AU Shi, Y Ivannikov, MV Walsh, ME Liu, YH Zhang, YQ Jaramillo, CA Macleod, GT Van Remmen, H AF Shi, Yun Ivannikov, Maxim V. Walsh, Michael E. Liu, Yuhong Zhang, Yiqiang Jaramillo, Carlos A. Macleod, Gregory T. Van Remmen, Holly TI The Lack of CuZnSOD Leads to Impaired Neurotransmitter Release, Neuromuscular Junction Destabilization and Reduced Muscle Strength in Mice SO PLOS ONE LA English DT Article ID SPINAL MUSCULAR-ATROPHY; SKELETAL-MUSCLE; SUPEROXIDE-DISMUTASE; MOUSE MODEL; OXIDATIVE STRESS; KNOCKOUT MICE; MOTOR-NEURONS; ION CHANNELS; SYNAPSE; TRANSMISSION AB Elevated reactive oxygen species (ROS) production and ROS-dependent protein damage is a common observation in the pathogenesis of many muscle wasting disorders, including sarcopenia. However, the contribution of elevated ROS levels to -a breakdown in neuromuscular communication and muscle atrophy remains unknown. In this study, we examined a copper zinc superoxide dismutase [CuZnSOD (Sod1)] knockout mouse (Sod1(-/-)), a mouse model of elevated oxidative stress that exhibits accelerated loss of muscle mass, which recapitulates many phenotypes of sarcopenia as early as 5 months of age. We found that young adult Sod1(-/-) mice display a considerable reduction in hind limb skeletal muscle mass and strength when compared to age-matched wild-type mice. These changes are accompanied by gross alterations in neuromuscular junction (NMJ) morphology, including reduced occupancy of the motor endplates by axons, terminal sprouting and axon thinning and irregular swelling. Surprisingly however, the average density of acetylcholine receptors in endplates is preserved. Using in vivo electromyography and ex vivo electrophysiological studies of hind limb muscles in Sod1(-/-) mice, we found that motor axons innervating the extensor digitorum longus (EDL) and gastrocnemius muscles release fewer synaptic vesicles upon nerve stimulation. Recordings from individually identified EDL NMJs show that reductions in neurotransmitter release are apparent in the Sod1(-/-) mice even when endplates are close to fully innervated. However, electrophysiological properties, such as input resistance, resting membrane potential and spontaneous neurotransmitter release kinetics (but not frequency) are similar between EDL muscles of Sod1(-/-) and wild-type mice. Administration of the potassium channel blocker 3,4-diaminopyridine, which broadens the presynaptic action potential, improves both neurotransmitter release and muscle strength. Together, these results suggest that ROS-associated motor nerve terminal dysfunction is a contributor to the observed muscle changes in Sod1(-/-) mice. C1 [Shi, Yun; Ivannikov, Maxim V.; Walsh, Michael E.; Liu, Yuhong; Zhang, Yiqiang; Van Remmen, Holly] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Shi, Yun; Walsh, Michael E.; Liu, Yuhong; Van Remmen, Holly] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Shi, Yun; Liu, Yuhong; Jaramillo, Carlos A.] South Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX USA. [Ivannikov, Maxim V.; Zhang, Yiqiang; Macleod, Gregory T.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. [Jaramillo, Carlos A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Rehabil Med, San Antonio, TX 78229 USA. [Van Remmen, Holly] Oklahoma City VA Med Ctr, Oklahoma City, OK USA. RP Van Remmen, H (reprint author), Florida Atlantic Univ, Dept Biol Sci, Jupiter, FL 33458 USA. EM holly-vanremmen@omrf.org FU NIH [AG020591, NS061914, T32-AG021890] FX This study was supported by NIH grants AG020591 to HVR, NS061914 to GTM and T32-AG021890 to MVI. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 52 TC 12 Z9 12 U1 3 U2 10 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 27 PY 2014 VL 9 IS 6 AR e100834 DI 10.1371/journal.pone.0100834 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AK6BK UT WOS:000338512200066 PM 24971750 ER PT J AU Boulware, DR Meya, DB Muzoora, C Rolfes, MA Hullsiek, KH Musubire, A Taseera, K Nabeta, HW Schutz, C Williams, DA Rajasingham, R Rhein, J Thienemann, F Lo, MW Nielsen, K Bergemann, TL Kambugu, A Manabe, YC Janoff, EN Bohjanen, PR Meintjes, G AF Boulware, David R. Meya, David B. Muzoora, Conrad Rolfes, Melissa A. Hullsiek, Katherine Huppler Musubire, Abdu Taseera, Kabanda Nabeta, Henry W. Schutz, Charlotte Williams, Darlisha A. Rajasingham, Radha Rhein, Joshua Thienemann, Friedrich Lo, Melanie W. Nielsen, Kirsten Bergemann, Tracy L. Kambugu, Andrew Manabe, Yukari C. Janoff, Edward N. Bohjanen, Paul R. Meintjes, Graeme CA COAT Trial Team TI Timing of Antiretroviral Therapy after Diagnosis of Cryptococcal Meningitis SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID RECONSTITUTION INFLAMMATORY SYNDROME; HIGH-DOSE FLUCONAZOLE; EARLY MORTALITY; TUBERCULOUS MENINGITIS; AMPHOTERICIN-B; HIV; INFECTION; ADULTS; DISEASE; COHORT AB BACKGROUND Cryptococcal meningitis accounts for 20 to 25% of acquired immunodeficiency syndrome-related deaths in Africa. Antiretroviral therapy (ART) is essential for survival; however, the question of when ART should be initiated after diagnosis of cryptococcal meningitis remains unanswered. METHODS We assessed survival at 26 weeks among 177 human immunodeficiency virus-infected adults in Uganda and South Africa who had cryptococcal meningitis and had not previously received ART. We randomly assigned study participants to undergo either earlier ART initiation (1 to 2 weeks after diagnosis) or deferred ART initiation (5 weeks after diagnosis). Participants received amphotericin B (0.7 to 1.0 mg per kilogram of body weight per day) and fluconazole (800 mg per day) for 14 days, followed by consolidation therapy with fluconazole. RESULTS The 26-week mortality with earlier ART initiation was significantly higher than with deferred ART initiation (45% [40 of 88 patients] vs. 30% [27 of 89 patients]; hazard ratio for death, 1.73; 95% confidence interval [CI], 1.06 to 2.82; P = 0.03). The excess deaths associated with earlier ART initiation occurred 2 to 5 weeks after diagnosis (P = 0.007 for the comparison between groups); mortality was similar in the two groups thereafter. Among patients with few white cells in their cerebrospinal fluid (<5 per cubic millimeter) at randomization, mortality was particularly elevated with earlier ART as compared with deferred ART (hazard ratio, 3.87; 95% CI, 1.41 to 10.58; P = 0.008). The incidence of recognized cryptococcal immune reconstitution inflammatory syndrome did not differ significantly between the earlier-ART group and the deferred-ART group (20% and 13%, respectively; P = 0.32). All other clinical, immunologic, virologic, and microbiologic outcomes, as well as adverse events, were similar between the groups. CONCLUSIONS Deferring ART for 5 weeks after the diagnosis of cryptococcal meningitis was associated with significantly improved survival, as compared with initiating ART at 1 to 2 weeks, especially among patients with a paucity of white cells in cerebrospinal fluid. C1 [Boulware, David R.; Meya, David B.; Rolfes, Melissa A.; Hullsiek, Katherine Huppler; Williams, Darlisha A.; Rajasingham, Radha; Rhein, Joshua; Lo, Melanie W.; Nielsen, Kirsten; Bergemann, Tracy L.; Bohjanen, Paul R.] Univ Minnesota, Minneapolis, MN USA. [Meya, David B.; Musubire, Abdu; Nabeta, Henry W.; Williams, Darlisha A.; Rajasingham, Radha; Rhein, Joshua; Lo, Melanie W.; Kambugu, Andrew; Manabe, Yukari C.] Makerere Univ, Infect Dis Inst, Kampala, Uganda. [Meya, David B.] Makerere Univ, Coll Hlth Sci, Sch Med, Kampala, Uganda. [Muzoora, Conrad; Taseera, Kabanda] Mbarara Univ Sci & Technol, Mbarara, Uganda. [Schutz, Charlotte; Thienemann, Friedrich; Meintjes, Graeme] Univ Cape Town, ZA-7925 Cape Town, South Africa. [Manabe, Yukari C.] Johns Hopkins Sch Med, Baltimore, MD USA. [Janoff, Edward N.] Univ Colorado Denver, Mucosal & Vaccine Res Program Colorado MAVRC, Aurora, CO USA. [Janoff, Edward N.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Meintjes, Graeme] Univ London Imperial Coll Sci Technol & Med, London SW7 2AZ, England. RP Boulware, DR (reprint author), MTRF 3-222,2001 6th St SE, Minneapolis, MN 55455 USA. EM boulw001@umn.edu RI Bohjanen, Paul/B-2329-2015; Schutz, Charlotte/G-6864-2016 OI Bohjanen, Paul/0000-0002-2772-3597; Schutz, Charlotte/0000-0001-8329-6158; Bergemann, Tracy/0000-0003-3902-2605; Bahr, Nathan/0000-0002-9431-8938; Boulware, David/0000-0002-4715-0060 FU National Institute of Allergy and Infectious Diseases FX Funded by the National Institute of Allergy and Infectious Diseases and others; COAT ClinicalTrials.gov number, NCT01075152. NR 40 TC 85 Z9 87 U1 0 U2 19 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 26 PY 2014 VL 370 IS 26 BP 2487 EP 2498 DI 10.1056/NEJMoa1312884 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA AJ6KY UT WOS:000337804400006 PM 24963568 ER PT J AU Gallun, FJ McMillan, GP Molis, MR Kampel, SD Dann, SM Konrad-Martin, DL AF Gallun, Frederick J. McMillan, Garnett P. Molis, Michelle R. Kampel, Sean D. Dann, Serena M. Konrad-Martin, Dawn L. TI Relating age and hearing loss to monaural, bilateral, and binaural temporal sensitivity SO FRONTIERS IN NEUROSCIENCE LA English DT Article DE aging; hearing loss; gap discrimination; monaural; binaural ID FINE-STRUCTURE; FREQUENCY-SELECTIVITY; IMPAIRED HEARING; INTERAURAL PHASE; GAP DETECTION; SPEECH RECEPTION; BAND STIMULI; LISTENERS; NOISE; MODULATION AB Older listeners are more likely than younger listeners to have difficulties in making temporal discriminations among auditory stimuli presented to one or both ears. In addition, the performance of older listeners is often observed to be more variable than that of younger listeners. The aim of this work was to relate age and hearing loss to temporal processing ability in a group of younger and older listeners with a range of hearing thresholds. Seventy-eight listeners were tested on a set of three temporal discrimination tasks (monaural gap discrimination, bilateral gap discrimination, and binaural discrimination of interaural differences in time). To examine the role of temporal fine structure in these tasks, four types of brief stimuli were used: tone bursts, broad-frequency chirps with rising or falling frequency contours, and random-phase noise bursts. Between-subject group analyses conducted separately for each task revealed substantial increases in temporal thresholds for the older listeners across all three tasks, regardless of stimulus type, as well as significant correlations among the performance of individual listeners across most combinations of tasks and stimuli. Differences in performance were associated with the stimuli in the monaural and binaural tasks, but not the bilateral task. Temporal fine structure differences among the stimuli had the greatest impact on monaural thresholds. Threshold estimate values across all tasks and stimuli did not show any greater variability for the older listeners as compared to the younger listeners. A linear mixed model applied to the data suggested that age and hearing loss are independent factors responsible for temporal processing ability, thus supporting the increasingly accepted hypothesis that temporal processing can be impaired for older compared to younger listeners with similar hearing and/or amounts of hearing loss. C1 [Gallun, Frederick J.; McMillan, Garnett P.; Molis, Michelle R.; Kampel, Sean D.; Dann, Serena M.; Konrad-Martin, Dawn L.] Portland VA Med Ctr, Natl Ctr Rehabi Auditory Res, Dept Vet Afffairs, Portland, OR 97207 USA. [Gallun, Frederick J.; Molis, Michelle R.; Konrad-Martin, Dawn L.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [McMillan, Garnett P.] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA. RP Gallun, FJ (reprint author), Portland VA Med Ctr, VA RR&D Natl Ctr Rehabi Auditory Res, 3710 SW US Vet Hosp Rd NCRAR, Portland, OR 97207 USA. EM frederick.gallun@va.gov FU Department of Veterans Affairs Rehabilitation Research and Development (VA RRD) Service [C7450R, C4963W, C6116W, C7113N] FX This research was supported by the Department of Veterans Affairs Rehabilitation Research and Development (VA RR&D) Service [Merit Award C7450R, Career Development Awards C4963W (Gallun) and C6116W (Molis), and Career Development Transition Award C7113N (Konrad-Martin)]. The work was supported with resources and the use of facilities at VA RR&D National Center for Rehabilitative Auditory Research, which is located at the Portland VA Medical Center. We are extremely grateful to the many participants who volunteered their time and ears to make this work possible. The code used to create the chirp stimuli was modified from original Matlab functions generously provided by Dr. Torsten Dau. The contents of this article are the private views of the authors and should not be assumed to represent the views of the Department of Veterans Affairs or the United States Government. NR 43 TC 6 Z9 8 U1 2 U2 9 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1662-453X J9 FRONT NEUROSCI-SWITZ JI Front. Neurosci. PD JUN 25 PY 2014 VL 8 AR 172 DI 10.3389/fnins.2014.00172 PG 14 WC Neurosciences SC Neurosciences & Neurology GA AW8EN UT WOS:000346493600001 PM 25009458 ER PT J AU Dunlop, BW Rothbaum, BO Binder, EB Duncan, E Harvey, PD Jovanovic, T Kelley, ME Kinkead, B Kutner, M Iosifescu, DV Mathew, SJ Neylan, TC Kilts, CD Nemeroff, CB Mayberg, HS AF Dunlop, Boadie W. Rothbaum, Barbara O. Binder, Elisabeth B. Duncan, Erica Harvey, Philip D. Jovanovic, Tanja Kelley, Mary E. Kinkead, Becky Kutner, Michael Iosifescu, Dan V. Mathew, Sanjay J. Neylan, Thomas C. Kilts, Clinton D. Nemeroff, Charles B. Mayberg, Helen S. TI Evaluation of a corticotropin releasing hormone type 1 receptor antagonist in women with posttraumatic stress disorder: study protocol for a randomized controlled trial SO TRIALS LA English DT Article DE Clinical Research Protocol; Drugs; Investigational; HPA Axis; Anxiety disorders; Fear-potentiated startle; Fear conditioning; Neuropsychological tests; Placebo; Psychophysiology; CRH ID POTENTIATED STARTLE PARADIGM; CLINICAL-APPLICATIONS; FEAR INHIBITION; DEPRESSION; SCALE; PTSD; ANTIDEPRESSANTS; QUESTIONNAIRE; VALIDATION; ANXIETY AB Background: Pharmacologic treatment options for posttraumatic stress disorder (PTSD) are limited in number and effectiveness. Medications currently in use to treat PTSD were originally approved based on their efficacy in other disorders, such as major depression. Substantial research in PTSD suggests that increased activity of corticotropin releasing hormone (CRH)-containing circuits are involved in the pathophysiology of the disease. This Phase II trial aims to evaluate the efficacy of a CRH type 1 receptor (CRHR1) antagonist in the treatment of PTSD. Methods/design: Currently untreated adult women, ages 18 to 65 years, with a primary psychiatric diagnosis of PTSD of at least 3 months' duration, are being enrolled in a parallel-group, double-blind, placebo-controlled, randomized clinical trial evaluating the efficacy and safety of GSK561679, a novel CRHR1 receptor antagonist. GSK561679 (or matching placebo) is prescribed at a fixed dose of 350 mg nightly for six weeks. The primary trial hypothesis is that GSK561679 will reduce symptoms of PTSD, as measured by the Clinician-Administered PTSD Scale (CAPS), significantly more than placebo after six weeks of treatment. Putative biological markers of PTSD which may influence treatment response are measured prior to randomization and after five weeks' exposure to the study medication, including: fear conditioning and extinction using psychophysiological measures; variants of stress-related genes and gene expression profiles; and indices of HPA axis reactivity. In addition, the impact of PTSD and treatment on neuropsychological performance and functional capacity are assessed at baseline and after the fifth week of study medication. After completion of the six-week double blind treatment period, subjects enter a one-month follow-up period to monitor for sustained response and resolution of any adverse effects. Discussion: Considerable preclinical and human research supports the hypothesis that alterations in central nervous system CRH neuronal activity are a potential mediator of PTSD symptoms. This study is the first to assess the efficacy of a specific antagonist of a CRH receptor in the treatment of PTSD. Furthermore, the biological and neuropsychological measures included in this trial will substantially inform our understanding of the mechanisms of PTSD. C1 [Dunlop, Boadie W.; Rothbaum, Barbara O.; Binder, Elisabeth B.; Duncan, Erica; Jovanovic, Tanja; Kinkead, Becky; Mayberg, Helen S.] Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA. [Binder, Elisabeth B.] Max Planck Inst Psychiat, D-80804 Munich, Germany. [Duncan, Erica] Atlanta Vet Affairs Med Ctr, Decatur, GA USA. [Harvey, Philip D.; Nemeroff, Charles B.] Univ Miami, Miller Sch Med, Dept Psychiat & Behav Sci, Miami, FL 33136 USA. [Kelley, Mary E.; Kutner, Michael] Emory Univ, Dept Biostat & Bioinformat, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. [Iosifescu, Dan V.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Mathew, Sanjay J.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Michael Debakey VA Med Ctr, Houston, TX 77030 USA. [Neylan, Thomas C.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Neylan, Thomas C.] San Francisco VA Med Ctr, San Francisco, CA USA. [Kilts, Clinton D.] Univ Arkansas Med Sci, Inst Psychiat Res, Little Rock, AR 72205 USA. RP Dunlop, BW (reprint author), Emory Univ, Sch Med, Dept Psychiat & Behav Sci, 12 Execut Pk Dr NE,3rd Floor, Atlanta, GA 30322 USA. EM bdunlop@emory.edu RI Binder, Elisabeth/K-8905-2014; Duncan, Erica/B-1671-2016 FU National Institute of Mental Health [U19 MH069056]; CSRD [09S-NIMH-002]; [K23 MH086690] FX Funding for the study is provided from a grant from the National Institute of Mental Health, U19 MH069056 (BWD, HM). Additional support was received from K23 MH086690 (BWD) and VA CSRD Project ID 09S-NIMH-002 (TCN). GlaxoSmithKline contributed the study medication and matching placebo, as well as funds to support subject recruitment and laboratory testing. GSK is uninvolved in the data collection, data analysis (excepting some pharmacokinetic analysis), or interpretation of findings. The GSK561679 compound is currently licensed by Neurocrine Biosciences, which will also perform pharmacokinetic analyses.; This work was supported with resources and the use of facilities at the Michael E DeBakey VA Medical Center, Houston, TX. Disclaimer: the views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government. NR 49 TC 8 Z9 8 U1 4 U2 10 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1745-6215 J9 TRIALS JI Trials PD JUN 21 PY 2014 VL 15 AR 240 DI 10.1186/1745-6215-15-240 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AK5KG UT WOS:000338462800001 PM 24950747 ER PT J AU Hamilton, AB Mittman, BS Williams, JK Liu, HHH Eccles, AM Hutchinson, CS Wyatt, GE AF Hamilton, Alison B. Mittman, Brian S. Williams, John K. Liu, Honghu H. Eccles, Alicia M. Hutchinson, Craig S. Wyatt, Gail E. TI Community-based implementation and effectiveness in a randomized trial of a risk reduction intervention for HIV-serodiscordant couples: study protocol SO IMPLEMENTATION SCIENCE LA English DT Article DE Implementation science; Hybrid design; HIV prevention; Serodiscordance; Couples; African Americans; Behavioral intervention; Sustainability ID SEXUALLY-TRANSMITTED DISEASES; MENTAL-HEALTH-SERVICES; CONDOM-USE; ORGANIZATIONAL READINESS; PREVENTION INTERVENTION; FUTURE-RESEARCH; UNITED-STATES; QUERI SERIES; WOMEN; AIDS AB Background: The HIV/AIDS epidemic continues to disproportionately affect African American communities in the US, particularly those located in urban areas. Despite the fact that HIV is often transmitted from one sexual partner to another, most HIV prevention interventions have focused only on individuals, rather than couples. This five-year study investigates community-based implementation, effectiveness, and sustainability of 'Eban II,' an evidence-based risk reduction intervention for African-American heterosexual, serodiscordant couples. Methods/design: This hybrid implementation/effectiveness implementation study is guided by organizational change theory as conceptualized in the Texas Christian University Program Change Model (PCM), a model of phased organizational change from exposure to adoption, implementation, and sustainability. The primary implementation aims are to assist 10 community-based organizations (CBOs) to implement and sustain Eban II; specifically, to partner with CBOs to expose providers to the intervention; facilitate its adoption, implementation and sustainment; and to evaluate processes and determinants of implementation, effectiveness, fidelity, and sustainment. The primary effectiveness aim is to evaluate the effect of Eban II on participant (n = 200 couples) outcomes, specifically incidents of protected sex and proportion of condom use. We will also determine the cost-effectiveness of implementation, as measured by implementation costs and potential cost savings. A mixed methods evaluation will examine implementation at the agency level; staff members from the CBOs will complete baseline measures of organizational context and climate, while key stakeholders will be interviewed periodically throughout implementation. Effectiveness of Eban II will be assessed using a randomized delayed enrollment (waitlist) control design to evaluate the impact of treatment on outcomes at posttest and three month follow up. Multi level hierarchical modeling with a multi-level nested structure will be used to evaluate the effects of agency- and couples-level characteristics on couples-level outcomes (e.g., condom use). Discussion: This study will produce important information regarding the value of the Eban II program and a theory-guided implementation process and tools designed for use in Eban II and other evidence-based programs in demographically diverse, resource-constrained treatment settings. C1 [Hamilton, Alison B.; Williams, John K.; Eccles, Alicia M.; Hutchinson, Craig S.; Wyatt, Gail E.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Hamilton, Alison B.; Mittman, Brian S.] VA Greater Angeles Healthcare Syst, Sepulveda, CA 91343 USA. [Liu, Honghu H.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. RP Hamilton, AB (reprint author), Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, 760 Westwood Plaza,38-240 NPI,Box 175919, Los Angeles, CA 90024 USA. EM alisonh@ucla.edu FU National Institutes of Mental Health [NIMH R01 MH093230] FX Funding provided by National Institutes of Mental Health (NIMH R01 MH093230). We wish to acknowledge the generous participation of the community-based organizations. We also wish to thank Ms. Louise Datu and Ms. Elizabeth Aguilar for their administrative support. NR 76 TC 1 Z9 1 U1 4 U2 13 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1748-5908 J9 IMPLEMENT SCI JI Implement. Sci. PD JUN 20 PY 2014 VL 9 AR 79 DI 10.1186/1748-5908-9-79 PG 12 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA AK8MJ UT WOS:000338681600001 PM 24950708 ER PT J AU Weathington, NM Snavely, CA Chen, BB Zhao, J Zhao, YT Mallampalli, RK AF Weathington, Nathaniel M. Snavely, Courtney A. Chen, Bill B. Zhao, Jing Zhao, Yutong Mallampalli, Rama K. TI Glycogen Synthase Kinase-3 beta Stabilizes the Interleukin (IL)-22 Receptor from Proteasomal Degradation in Murine Lung Epithelia SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INNATE LYMPHOID-CELLS; MUCOSAL HOST-DEFENSE; ACTIN POLYMERIZATION; TH17 CELLS; PROTEIN; IL-22; UBIQUITINATION; INFLAMMATION; CORTACTIN; PHOSPHORYLATES AB Signaling through the interleukin (IL)-22 cytokine axis provides essential immune protection in the setting of extracellular infection as part of type 17 immunity. Molecular regulation of IL-22 receptor (IL-22R) protein levels is unknown. In murine lung epithelia, IL-22R is a relatively short-lived protein (t(1/2) similar to 1.5 h) degraded by the ubiquitin proteasome under normal unstimulated conditions, but its degradation is accelerated by IL-22 treatment. Lys(449) within the intracellular C-terminal domain of the IL-22R serves as a ubiquitin acceptor site as disruption of this site by deletion or site-directed mutagenesis creates an IL-22R variant that, when expressed in cells, is degradation-resistant and not ubiquitinated. Glycogen synthase kinase (GSK)-3 beta phosphorylates the IL-22R within a consensus phosphorylation signature at Ser(410) and Ser(414), and IL-22 treatment of cells triggers GSK-3 beta inactivation. GSK-3 beta overexpression results in accumulation of IL-22R protein, whereas GSK-3 beta depletion in cells reduces levels of the receptor. Mutagenesis of IL-22R at Ser(410) and Ser(414) results in receptor variants that display reduced phosphorylation levels and are more labile as compared with wild-type IL-22R when expressed in cells. Further, the cytoskeletal protein cortactin, which is important for epithelial spreading and barrier formation, is phosphorylated and activated at the epithelial cell leading edge after treatment with IL-22, but this effect is reduced after GSK-3 beta knockdown. These findings reveal the ability of GSK-3 beta to modulate IL-22R protein stability that might have significant implications for cyto-protective functions and therapeutic targeting of the IL-22 signaling axis. C1 [Weathington, Nathaniel M.; Snavely, Courtney A.; Chen, Bill B.; Zhao, Jing; Zhao, Yutong; Mallampalli, Rama K.] Univ Pittsburgh, Dept Med, Acute Lung Injury Ctr Excellence, Pittsburgh, PA 15213 USA. [Zhao, Yutong; Mallampalli, Rama K.] Univ Pittsburgh, Dept Cell Biol & Physiol, Pittsburgh, PA 15213 USA. [Mallampalli, Rama K.] Vet Affairs Pittsburgh Healthcare Syst, Med Specialty Serv Line, Pittsburgh, PA 15240 USA. RP Mallampalli, RK (reprint author), Univ Pittsburgh, UPMC Montefiore, Dept Med, Div Pulm Allergy & Crit Care Med, NW 628, Pittsburgh, PA 15213 USA. EM mallampallirk@upmc.edu FU United States Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development; United States Department of Veterans Affairs; National Institutes of Health R01 [HL096376, HL097376, HL098174, HL081784, UH2 HL123502, P01 HL114453, HL116472, HL01916]; American Heart Association [12SDG9050005] FX This work was supported in part by the United States Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development, and a Merit Review Award from the United States Department of Veterans Affairs (to R. K. M. and N.M.W.). This work was also supported, in part, by National Institutes of Health R01 Grants HL096376, HL097376, HL098174, HL081784, UH2 HL123502, and P01 HL114453 (to R. K. M.), HL116472 (to B. B. C.), and HL01916 (to Y.Z.), and an American Heart Association Award 12SDG9050005 (to J.Z.). NR 31 TC 8 Z9 8 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 20 PY 2014 VL 289 IS 25 BP 17610 EP 17619 DI 10.1074/jbc.M114.551747 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AJ9HE UT WOS:000338018100026 PM 24742671 ER PT J AU Pietrzak, RH el-Gabalawy, R Tsai, J Sareen, J Neumeister, A Southwick, SM AF Pietrzak, Robert H. el-Gabalawy, Renee Tsai, Jack Sareen, Jitender Neumeister, Alexander Southwick, Steven M. TI Typologies of posttraumatic stress disorder in the US adult population SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Posttraumatic stress disorder; Depression; Trauma ID ALCOHOL-USE-DISORDER; PSYCHIATRIC DIAGNOSTIC MODULES; LATENT CLASS ANALYSIS; IV AUDADIS-IV; INTERNALIZING SUBTYPES; PERSONALITY-DISORDERS; UNITED-STATES; RELIABILITY; MODEL; RISK AB Back,ground: Posttraumatic stress disorder (PTSD) is characterized by heterogeneous clusters of re-experiencing, avoidance, numbing, and hyperarousal symptoms. However, data are lacking regarding the predominant, population-based typologies of this disorder, and how they are linked to trauma-related characteristics, psychiatric comorbidities, and health-related quality of life. Methods: We used latent class analyses (LCAs) to evaluate predominant typologies of PTSD in a nationally representative sample of 2463 U.S. adults with PTSD. Multinomial logistic regression analyses were then conducted to evaluate trauma-related characteristics, psychiatric comorbidities, and health-related quality of life variables associated with these typologies. Results: LCAs revealed three predominant typologies of PTSD Anxious-Re-experiencing (weighted prevalence=32.2%), Dysphoric (32.8%), and High Symptom (35.0%). Compared to the Dysphoric class, the Anxious-Re-experiencing and High Symptom classes were more likely to report sexual assault, physical assault, and military combat as their worst traumatic events; had an earlier age of onset and longer duration of PTSD; and were more likely to be diagnosed with nicotine dependence and borderline personality disorder, to have attempted suicide, and had poorer physical health-related quality of life (HRQoL). The High Symptom class had increased odds of all disorders, suicide attempts, and the poorest HRQoL. Limitations: Diagnoses were based on DSM-IV criteria and cross-sectional analyses preclude examination of how PTSD typologies are temporally related to other variables. Conclusion: PTSD in the general U.S. adult population is characterized by three predominant typologies, which are differentially linked to trauma and clinical characteristics. These findings underscore the importance of personalized approaches to the assessment, monitoring, and treatment of PTSD that take into consideration the heterogeneous manifestations of this disorder. Published by Elsevier B.V. C1 [Pietrzak, Robert H.; Southwick, Steven M.] US Dept Vet Affairs, Natl Ctr Posttraumat Stress Disorder, VA Connecticut Healthcare Syst, West Haven, CT USA. [Pietrzak, Robert H.; Tsai, Jack; Southwick, Steven M.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [el-Gabalawy, Renee; Sareen, Jitender] Univ Manitoba, Dept Psychol, Winnipeg, MB R3T 2N2, Canada. [Tsai, Jack] US Dept Vet Affairs, New England Mental Illness Res Educ & Clin Ctr, West Haven, CT USA. [Sareen, Jitender] Univ Manitoba, Dept Psychiat, Winnipeg, MB R3T 2N2, Canada. [Sareen, Jitender] Univ Manitoba, Dept Community Hlth Sci, Winnipeg, MB R3T 2N2, Canada. [Neumeister, Alexander] NYU, Sch Med, Dept Psychiat, New York, NY USA. [Neumeister, Alexander] NYU, Sch Med, Dept Radiol, New York, NY USA. RP Pietrzak, RH (reprint author), Yale Univ, Sch Med, Natl Ctr PTSD,Dept Psychiat, Clin Neurosci Div,VA Connecticut Hlth Care Syst, 950 Campbell Ave 151E, West Haven, CT 06516 USA. EM robert.pietrzak@yale.edu FU National Institute on Alcohol Abuse and Alcoholism (NIAAA); National Institute on Drug Abuse (NIDA); United States Department of Veterans Affairs National Center for Posttraumatic Stress Disorder FX The National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) is funded by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) with supplemental support front the National Institute on Drug Abuse (NIDA). Preparation of this report was supported in part by the United States Department of Veterans Affairs National Center for Posttraumatic Stress Disorder and a private donation. NR 21 TC 9 Z9 9 U1 0 U2 20 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 EI 1573-2517 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD JUN 20 PY 2014 VL 162 BP 102 EP 106 DI 10.1016/j.jad.2014.03.024 PG 5 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AG4JO UT WOS:000335386000018 PM 24767013 ER PT J AU Fling, BW Cohen, RG Mancini, M Carpenter, SD Fair, DA Nutt, JG Horak, FB AF Fling, Brett W. Cohen, Rajal G. Mancini, Martina Carpenter, Samuel D. Fair, Damien A. Nutt, John G. Horak, Fay B. TI Functional Reorganization of the Locomotor Network in Parkinson Patients with Freezing of Gait SO PLOS ONE LA English DT Article ID SUPPLEMENTARY MOTOR AREA; HUMAN BASAL GANGLIA; COGNITIVE CONTROL; DISEASE; BRAIN; CONNECTIVITY; MOVEMENT; CORTEX; PEDUNCULOPONTINE; NEUROPHYSIOLOGY AB Freezing of gait (FoG) is a transient inability to initiate or maintain stepping that often accompanies advanced Parkinson's disease (PD) and significantly impairs mobility. The current study uses a multimodal neuroimaging approach to assess differences in the functional and structural locomotor neural network in PD patients with and without FoG and relates these findings to measures of FoG severity. Twenty-six PD patients and fifteen age-matched controls underwent resting-state functional magnetic resonance imaging and diffusion tensor imaging along with self-reported and clinical assessments of FoG. After stringent movement correction, fifteen PD patients and fourteen control participants were available for analysis. We assessed functional connectivity strength between the supplementary motor area (SMA) and the following locomotor hubs: 1) subthalamic nucleus (STN), 2) mesencephalic and 3) cerebellar locomotor region (MLR and CLR, respectively) within each hemisphere. Additionally, we quantified structural connectivity strength between locomotor hubs and assessed relationships with metrics of FoG. FoG+ patients showed greater functional connectivity between the SMA and bilateral MLR and between the SMA and left CLR compared to both FoG- and controls. Importantly, greater functional connectivity between the SMA and MLR was positively correlated with i) clinical, ii) self-reported and iii) objective ratings of freezing severity in FoG+, potentially reflecting a maladaptive neural compensation. The current findings demonstrate a reorganization of functional communication within the locomotor network in FoG+ patients whereby the higher-order motor cortex (SMA) responsible for gait initiation communicates with the MLR and CLR to a greater extent than in FoG- patients and controls. The observed pattern of altered connectivity in FoG+ may indicate a failed attempt by the CNS to compensate for the loss of connectivity between the STN and SMA and may reflect a loss of lower-order, automatic control of gait by the basal ganglia. C1 [Fling, Brett W.; Mancini, Martina; Nutt, John G.; Horak, Fay B.] Oregon Hlth & Sci Univ, Dept Neurol, Sch Med, Portland, OR 97201 USA. [Carpenter, Samuel D.; Fair, Damien A.] Oregon Hlth & Sci Univ, Sch Med, Dept Behav Neurosci, Portland, OR 97201 USA. [Fair, Damien A.] Oregon Hlth & Sci Univ, Sch Med, Dept Psychiat, Portland, OR 97201 USA. [Cohen, Rajal G.] Univ Idaho, Dept Psychol & Commun Studies, Moscow, ID 83843 USA. [Horak, Fay B.] Portland VA Med Ctr, Portland, OR USA. RP Fling, BW (reprint author), Oregon Hlth & Sci Univ, Dept Neurol, Sch Med, Portland, OR 97201 USA. EM fling@ohsu.edu FU Pacific Northwest Udall Center (PANUC); National Institute on Aging [R37 AG006457]; National Multiple Sclerosis Society [MB0011]; Oregon Clinical and Translational Research Institute (OCTRI) from the National Center for Research Resources (NCRR) a component of the National Institutes of Health (NIH) [UL1 RR024140]; NIH Roadmap for Medical Research FX This work was supported by pilot awards from the Pacific Northwest Udall Center (PANUC; RC), a MERIT award from the National Institute on Aging (FH: R37 AG006457), and a postdoctoral Mentored Research Award from the National Multiple Sclerosis Society (Horak #MB0011). Additional support was provided from the Oregon Clinical and Translational Research Institute (OCTRI), grant number UL1 RR024140 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 58 TC 44 Z9 44 U1 1 U2 16 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 17 PY 2014 VL 9 IS 6 AR e100291 DI 10.1371/journal.pone.0100291 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AK5YM UT WOS:000338503400101 PM 24937008 ER PT J AU Lin, FJ Pickard, AS Krishnan, JA Joo, MJ Au, DH Carson, SS Gillespie, S Henderson, AG Lindenauer, PK McBurnie, MA Mularski, RA Naureckas, ET Vollmer, WM Lee, TA AF Lin, Fang-Ju Pickard, A. Simon Krishnan, Jerry A. Joo, Min J. Au, David H. Carson, Shannon S. Gillespie, Suzanne Henderson, Ashley G. Lindenauer, Peter K. McBurnie, Mary Ann Mularski, Richard A. Naureckas, Edward T. Vollmer, William M. Lee, Todd A. CA CONCERT Consortium TI Measuring health-related quality of life in chronic obstructive pulmonary disease: properties of the EQ-5D-5L and PROMIS-43 short form SO BMC MEDICAL RESEARCH METHODOLOGY LA English DT Article DE COPD; EQ-5D-5L; PROMIS; Psychometric properties ID FUNCTIONAL LIMITATIONS; CHRONIC ILLNESS; COPD SEVERITY; ITEM BANKS; DYSPNEA; ASTHMA; DISABILITY; VALIDITY AB Background: The Patient Reported Outcomes Measurement Information System 43-item short form (PROMIS-43) and the five-level EQ-5D (EQ-5D-5L) are recently developed measures of health-related quality of life (HRQL) that have potentially broad application in evaluating treatments and capturing burden of respiratory-related diseases. The aims of this study were: (1) to examine their psychometric properties in patients with chronic obstructive pulmonary disease (COPD), and (2) to identify dimensions of HRQL that differ and do not differ by lung function. Methods: We conducted a multi-center, cross-sectional study ("COPD Outcomes-based Network for Clinical Effectiveness & Research Translation" [CONCERT]). We analyzed patients who met spirometric criteria for COPD, and completed EQ-5D-5L and PROMIS questionnaires. Disease severity was graded based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification. Pulmonary function test, PROMIS-43, EQ-5D (index score and EQ-Visual Analog Scale [EQ-VAS]), six minute walk test (6MWT), and three dyspnea scales (mMRC, Borg, FACIT-Dyspnea) were administered. Validity and reliability of EQ-5D-5L and PROMIS-43 were examined, and differences in HRQL by GOLD grade were assessed. Results: Data from 670 patients with COPD were analyzed (mean age 68.5 years; 58% male). More severe COPD was associated with more problems with mobility, self-care and usual activities (all p-values <0.01) according to EQ-5D-5L. Related domains on EQ-5D-5L, PROMIS and clinical measures were moderately (r = 0.30-0.49) to strongly (r = 0.50) correlated. A statistically significant trend of decreasing HRQL with more severe lung functions was observed for EQ-5D-5L index scores, EQ-VAS scores, and PROMIS physical function and social roles. Conclusions: Results supported the validity of EQ-5D-5L and PROMIS-43 in COPD patients, and indicate that physical function and social activities decrease with level of lung function by GOLD grade, but not pain, mental health, sleep or fatigue as reported by patients. C1 [Lin, Fang-Ju; Pickard, A. Simon; Krishnan, Jerry A.; Lee, Todd A.] Univ Illinois, Chicago, IL 60607 USA. [Krishnan, Jerry A.; Joo, Min J.] Univ Illinois Hosp & Hlth Sci Syst, Chicago, IL USA. [Au, David H.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Au, David H.] Univ Washington, Seattle, WA 98195 USA. [Carson, Shannon S.; Henderson, Ashley G.] Univ N Carolina, Chapel Hill, NC USA. [Gillespie, Suzanne; McBurnie, Mary Ann; Mularski, Richard A.; Vollmer, William M.] Kaiser Permanente Northwest Ctr Hlth Res, Portland, OR USA. [Lindenauer, Peter K.] Baystate Med Ctr, Springfield, MA USA. [Lindenauer, Peter K.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Naureckas, Edward T.] Univ Chicago, Chicago, IL 60637 USA. [Pickard, A. Simon] Univ Illinois, Coll Pharm, Dept Pharm Syst Outcomes & Policy, Chicago, IL 60612 USA. RP Pickard, AS (reprint author), Univ Illinois, Chicago, IL 60607 USA. EM pickard1@uic.edu OI LIN, FANG-JU/0000-0002-8249-7481 FU National Heart, Lung, and Blood Institute [NHLBI RC2 HL101618]; Graduate College of the University of Illinois at Chicago; Veteran Affairs Health Services Research & Development (VA HSRD) FX The COPD Outcomes-based Network for Clinical Effectiveness and Research Translation (CONCERT) was funded by the National Heart, Lung, and Blood Institute (NHLBI RC2 HL101618). Fang-Ju Lin was supported by the Graduate College of the University of Illinois at Chicago (2012/2013 Dean's Scholar Award). The sponsors had no role in the design of the study, collection and analysis of the data, interpretation of results or the writing of this manuscript. Dr. David Au received funding from the Veteran Affairs Health Services Research & Development (VA HSR&D). The opinions expressed represent those of the authors and do not necessarily reflect those of the Department of Veterans Affairs. NR 42 TC 9 Z9 9 U1 3 U2 14 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2288 J9 BMC MED RES METHODOL JI BMC Med. Res. Methodol. PD JUN 16 PY 2014 VL 14 AR 78 DI 10.1186/1471-2288-14-78 PG 12 WC Health Care Sciences & Services SC Health Care Sciences & Services GA AK3DX UT WOS:000338304400001 PM 24934150 ER PT J AU Overduin, J Tylee, TS Frayo, RS Cummings, DE AF Overduin, Joost Tylee, Tracy S. Frayo, R. Scott Cummings, David E. TI Hyperosmolarity in the small intestine contributes to postprandial ghrelin suppression SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE ghrelin; intestinal osmolarity; 3-O-methylglucose; lactulose; satiation ID GASTRIC BYPASS-SURGERY; NUTRIENT-DRIVEN SATIETY; GLUCAGON-LIKE PEPTIDE-1; PLASMA GHRELIN; FOOD-INTAKE; SHORT-TERM; INGESTIVE BEHAVIOR; BARIATRIC SURGERY; ANOREXIA-NERVOSA; LIDOCAINE SPRAY AB Plasma levels of the orexigenic hormone ghrelin are suppressed by meals with an efficacy dependent on their macronutrient composition. We hypothesized that heterogeneity in osmolarity among macronutrient classes contributes to these differences. In three studies, the impact of small intestinal hyperosmolarity was examined in Sprague-Dawley rats. In study 1, isotonic, 2.5X, and 5X hypertonic solutions of several agents with diverse absorption and metabolism properties were infused duodenally at a physiological rate (3 ml/10 min). Jugular vein blood was sampled before and at 30, 60, 90, 120, 180, 240, and 300 min after infusion. Plasma ghrelin was suppressed dose dependently and most strongly by glucose. Hyperosmolar infusions of lactulose, which transits the small intestine unabsorbed, and 3-O-methylglucose (3-O-MG), which is absorbed like glucose but remains unmetabolized, also suppressed ghrelin. Glucose, but not lactulose or 3-O-MG, infusions increased plasma insulin. In study 2, intestinal infusions of hyperosmolar NaCl suppressed ghrelin, a response that was not attenuated by coinfusion with the neural blocker lidocaine. In study 3, we reconfirmed that the low-osmolar lipid emulsion Intralipid suppresses ghrelin more weakly than isocaloric (but hypertonic) glucose. Importantly, raising Intralipid's osmolarity to that of the glucose solution by nonabsorbable lactulose supplementation enhanced ghrelin suppression to that seen after glucose. Hyperosmolar ghrelin occurred particularly during the initial 3 postinfusion hours. We conclude that small intestinal hyperosmolarity 1) is sufficient to suppress ghrelin, 2) may combine with other postprandial mechanisms to suppress ghrelin, 3) might contribute to altered ghrelin regulation after gastric bypass surgery, and 4) may inform dietary modifications for metabolic health. C1 Univ Washington, Sch Med, Seattle, WA 98195 USA. [Cummings, David E.] VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. RP Cummings, DE (reprint author), VA Puget Sound Hlth Care Syst, Box 358280 Mail Stop 111, Seattle, WA 98195 USA. EM davidec@u.washington.edu FU National Institute of Health [NIDDK RO1 DK61516] FX The studies in this paper were supported by National Institute of Health grant NIDDK RO1 DK61516 awarded to D. E. Cummings. NR 96 TC 1 Z9 1 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 EI 1522-1547 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD JUN 15 PY 2014 VL 306 IS 12 BP C1108 EP C1116 DI 10.1152/ajpgi.00072.2014 PG 9 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA AK4UZ UT WOS:000338420900008 PM 24789208 ER PT J AU Deyo, RA Dworkin, SF Amtmann, D Andersson, G Borenstein, D Carragee, E Carrino, J Chou, R Cook, K DeLitto, A Goertz, C Khalsa, P Loeser, J Mackey, S Panagis, J Rainville, J Tosteson, T Turk, D Von Korff, M Weiner, DK AF Deyo, Richard A. Dworkin, Samuel F. Amtmann, Dagmar Andersson, Gunnar Borenstein, David Carragee, Eugene Carrino, John Chou, Roger Cook, Karon DeLitto, Anthony Goertz, Christine Khalsa, Partap Loeser, John Mackey, Sean Panagis, James Rainville, James Tosteson, Tor Turk, Dennis Von Korff, Michael Weiner, Debra K. TI Report of the NIH Task Force on Research Standards for Chronic Low Back Pain SO SPINE LA English DT Article DE low back pain; chronic low back pain; research standards; minimum data set; NIH Task Force ID CLINICAL-PRACTICE GUIDELINE; DEFINING CHRONIC PAIN; INFORMATION-SYSTEM PROMIS; FUNCTION ITEM BANK; QUALITY-OF-LIFE; PRIMARY-CARE; PROGNOSTIC APPROACH; SCREENING TOOL; START BACK; OUTCOME MEASURES AB Despite rapidly increasing intervention, functional disability due to chronic low back pain (cLBP) has increased in recent decades. We often cannot identify mechanisms to explain the major negative impact cLBP has on patients' lives. Such cLBP is often termed nonspecific and may be due to multiple biologic and behavioral etiologies. Researchers use varied inclusion criteria, definitions, baseline assessments, and outcome measures, which impede comparisons and consensus. Therefore, NIH Pain Consortium charged a research task force to draft standards for research on cLBP. The resulting multidisciplinary panel recommended using 2 questions to define cLBP; classifying cLBP by its impact (defined by pain intensity, pain interference, and physical function); use of a minimum data set to describe research participants (drawing heavily on the Patient Reported Outcomes Measurement Information System methodology); reporting "responder analyses" in addition to mean outcome scores; and suggestions for future research and dissemination. The Pain Consortium has approved the recommendations, which investigators should incorporate into NIH grant proposals. The research task force believes that these recommendations will advance the field, help resolve controversies, and facilitate future research addressing the genomic, neurological, and other mechanistic substrates of cLBP. We expect that the research task force recommendations will become a dynamic document and undergo continual improvement. Perspective: A task force was convened by the NIH Pain Consortium with the goal of developing research standards for cLBP. The results included recommendations for definitions, a minimum data set, reporting outcomes, and future research. Greater consistency in reporting should facilitate comparisons among studies and the development of phenotypes. C1 [Deyo, Richard A.; Chou, Roger] Oregon Hlth & Sci Univ, Portland, OR 97239 USA. [Dworkin, Samuel F.; Amtmann, Dagmar; Loeser, John; Turk, Dennis] Univ Washington, Seattle, WA 98195 USA. [Andersson, Gunnar] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Borenstein, David] George Washington Univ, Washington, DC USA. [Carragee, Eugene; Mackey, Sean] Stanford Univ, Stanford, CA 94305 USA. [Carrino, John] Johns Hopkins Univ, Baltimore, MD USA. [Cook, Karon] Northwestern Univ, Evanston, IL USA. [DeLitto, Anthony; Weiner, Debra K.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [DeLitto, Anthony; Weiner, Debra K.] Univ Pittsburgh, Pittsburgh, PA USA. [Goertz, Christine] Palmer Coll Chiropract, Davenport, IA USA. [Khalsa, Partap] Natl Ctr Complementary & Alternat Med, Bethesda, MD USA. [Panagis, James] NIAMSD, Bethesda, MD 20892 USA. [Rainville, James] New England Baptist Hosp, Roxbury Crossing, MA USA. [Tosteson, Tor] Dartmouth Coll, Hanover, NH USA. [Von Korff, Michael] Grp Hlth Res Inst, Seattle, WA USA. RP Deyo, RA (reprint author), Oregon Hlth & Sci Univ, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM deyor@ohsu.edu FU National Center for Complementary and Alternative Medicine; National Institute for Arthritis and Musculoskeletal and Skin Diseases FX Supported by the National Center for Complementary and Alternative Medicine and the National Institute for Arthritis and Musculoskeletal and Skin Diseases. NR 127 TC 13 Z9 13 U1 9 U2 19 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 EI 1528-1159 J9 SPINE JI SPINE PD JUN 15 PY 2014 VL 39 IS 14 BP 1128 EP 1143 DI 10.1097/BRS.0000000000000434 PG 16 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA AL5HL UT WOS:000339164300014 PM 24887571 ER PT J AU Zhang, Z Duckart, J Slatore, CG Fu, Y Petrik, AF Thorp, ML Cohen, DM AF Zhang, Zheng Duckart, Jonathan Slatore, Christopher G. Fu, Yi Petrik, Amanda F. Thorp, Micah L. Cohen, David M. TI Individuality of the plasma sodium concentration SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE human; hyponatremia; osmoregulation; population ID NEPHROGENIC DIABETES-INSIPIDUS; DAY-TO-DAY; SERUM CONSTITUENTS; INAPPROPRIATE ANTIDIURESIS; INTRAINDIVIDUAL VARIATION; INDUCED HYPONATREMIA; ANALYTIC COMPONENTS; WATER-DEPRIVATION; RECEPTOR GENE; LONG-TERM AB Older literature has suggested that the plasma sodium concentration is not individual, that it is neither intrinsic to an individual nor reproducible, longitudinally. We recently observed that the plasma sodium concentration is heritable. Because demonstrable heritability requires individuality of the relevant phenotype, we hypothesized that the plasma sodium concentration was substantially individual. In two large health plan-based cohorts, we demonstrated individuality of the plasma sodium concentration over a 10-yr interval; the intraclass correlation coefficient (ICC) averaged 0.4-0.5. The individuality of plasma sodium increased significantly with age. Plasma sodium individuality was equal to or only slightly less than that for plasma glucose but was less than the individuality for creatinine. The individuality of plasma sodium was further confirmed by comparing the Pearson correlation coefficient for within-individual versus between-individual pairs of sodium determinations and via application of the agreement index. Furthermore, the distribution of all sodium determinations for all participants within a population was similar to the distribution for the mean sodium concentration for individuals within that population. Therefore, the near-normal distribution of plasma sodium measurements within a population is likely not attributable to assay-specific factors but rather to genuine and durable biological variability in the osmotic set point. In aggregate, these data strongly support the individuality of the plasma sodium concentration. They further indicate that serial plasma sodium values for any given individual tend to cluster around a patient-specific set point and that these set points vary among individuals. C1 [Fu, Yi; Cohen, David M.] Oregon Hlth & Sci Univ, Dept Med, Div Nephrol & Hypertens, Portland, OR 97239 USA. [Petrik, Amanda F.; Thorp, Micah L.] Kaiser Permanente Northwest, Ctr Hlth Res, Portland, OR USA. [Zhang, Zheng] Brown Univ, Sch Med, Dept Biostat, Providence, RI 02912 USA. [Slatore, Christopher G.] Oregon Hlth & Sci Univ, Dept Med, Div Pulm & Crit Care Med, Portland, OR 97239 USA. [Fu, Yi; Cohen, David M.] Portland VA Med Ctr, Sect Nephrol, Portland, OR USA. [Slatore, Christopher G.] Portland VA Med Ctr, Sect Pulm & Crit Care Med, Portland, OR USA. [Duckart, Jonathan] Portland VA Med Ctr, Portland, OR USA. RP Cohen, DM (reprint author), Oregon Hlth & Sci Univ, Mailcode CH12R,3303 SW Bond Ave, Portland, OR 97239 USA. EM cohend@ohsu.edu RI Zhang, Zheng/J-2388-2014 OI Zhang, Zheng/0000-0003-2497-0362; Slatore, Christopher/0000-0003-0958-8122 FU National Institutes of Health; Department of Veterans Affairs; American Heart Association; Kaiser Permanente Northwest Center for Health Research; Veterans Administration Health Services Research and Development Career Development Award; Portland Veterans Affairs Medical Center (Portland, OR) FX This work was supported by grants from the National Institutes of Health, Department of Veterans Affairs, and American Heart Association (to D. M. Cohen) and by the Kaiser Permanente Northwest Center for Health Research (to A. F. Petrik and M. L. Thorp). C. G. Slatore is supported by a Veterans Administration Health Services Research and Development Career Development Award and resources from the Portland Veterans Affairs Medical Center (Portland, OR). NR 52 TC 9 Z9 9 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X EI 1522-1466 J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD JUN 15 PY 2014 VL 306 IS 12 BP F1534 EP F1543 DI 10.1152/ajprenal.00585.2013 PG 10 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA AK3VW UT WOS:000338354200014 PM 24717732 ER PT J AU Abrahamson, EE Foley, LM Hitchens, TK Dixon, CE Ikonomovic, MD AF Abrahamson, E. E. Foley, L. M. Hitchens, T. K. Dixon, C. E. Ikonomovic, M. D. TI MEMANTINE HYDROCHLORIDE AS A THERAPY FOR TRAUMATIC BRAIN INJURY: A PRECLINICAL STUDY USING THE CCI INJURY MODEL IN RATS SO JOURNAL OF NEUROTRAUMA LA English DT Meeting Abstract CT 32nd Annual National Neurotrauma Symposium CY JUN 29-JUL 02, 2014 CL San Francisco, CA DE cerebral blood flow; controlled cortical impact; excitotoxicity; glutamate C1 [Abrahamson, E. E.; Ikonomovic, M. D.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Abrahamson, E. E.; Ikonomovic, M. D.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. [Ikonomovic, M. D.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Dixon, C. E.] Univ Pittsburgh, Dept Neurosurg, Pittsburgh, PA USA. [Foley, L. M.; Hitchens, T. K.] Carnegie Mellon Univ, Pittsburgh NMR Ctr, Pittsburgh, PA 15213 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 EI 1557-9042 J9 J NEUROTRAUM JI J. Neurotrauma PD JUN 15 PY 2014 VL 31 IS 12 MA C2-31 BP A87 EP A87 PG 1 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA AK5DC UT WOS:000338443600236 ER PT J AU Dixon, CE Yan, HQ Ma, X Empey, P Poloyac, S Feldman, K Kochanek, PM AF Dixon, C. E. Yan, H. Q. Ma, X. Empey, P. Poloyac, S. Feldman, K. Kochanek, P. M. TI DOSE-RESPONSE EVALUATION OF SIMVASTATIN IN THE CONTROLLED CORTICAL IMPACT MODEL: OPERATION BRAIN TRAUMA THERAPY CONSORTIUM SO JOURNAL OF NEUROTRAUMA LA English DT Meeting Abstract CT 32nd Annual National Neurotrauma Symposium CY JUN 29-JUL 02, 2014 CL San Francisco, CA DE consortium; controlled cortical impact; rats; simvastatin C1 [Dixon, C. E.; Yan, H. Q.; Ma, X.; Empey, P.; Poloyac, S.] Univ Pittsburgh, Pittsburgh, PA USA. [Dixon, C. E.; Feldman, K.; Kochanek, P. M.] Univ Pittsburgh, CCM, Safar Ctr Resuscitat, Pittsburgh, PA USA. [Dixon, C. E.; Yan, H. Q.; Ma, X.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RI Kochanek, Patrick/D-2371-2015 OI Kochanek, Patrick/0000-0002-2627-913X NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 EI 1557-9042 J9 J NEUROTRAUM JI J. Neurotrauma PD JUN 15 PY 2014 VL 31 IS 12 MA D1-19 BP A107 EP A107 PG 1 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA AK5DC UT WOS:000338443600291 ER PT J AU Folmer, RL Hutter, M Belding, H Papesh, M Grush, L Leek, M Gallun, F AF Folmer, R. L. Hutter, M. Belding, H. Papesh, M. Grush, L. Leek, M. Gallun, F. TI ELECTROPHYSIOLOGICAL EVIDENCE OF AUDITORY AND COGNITIVE DYSFUNCTION IN VETERANS EXPOSED TO HIGH-INTENSITY BLASTS SO JOURNAL OF NEUROTRAUMA LA English DT Meeting Abstract CT 32nd Annual National Neurotrauma Symposium CY JUN 29-JUL 02, 2014 CL San Francisco, CA DE auditory brainstem response; auditory processing; event-related potentials; N200; P300 C1 [Folmer, R. L.; Hutter, M.; Belding, H.; Papesh, M.; Gallun, F.] NCRAR, Portland VA Med Ctr, Portland, OR USA. [Folmer, R. L.; Gallun, F.] Oregon Hlth & Sci Univ, Dept Otolaryngol, Portland, OR 97201 USA. [Grush, L.] Univ Colorado, Boulder, CO 80309 USA. [Leek, M.] VA Loma Linda, Loma Linda, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 EI 1557-9042 J9 J NEUROTRAUM JI J. Neurotrauma PD JUN 15 PY 2014 VL 31 IS 12 MA B3-05 BP A57 EP A57 PG 1 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA AK5DC UT WOS:000338443600152 ER PT J AU Hsieh, CL Niemi, EC Wang, SH Lee, C Bingham, D Zhang, J Charo, I Huang, EJ Liu, J Nakamura, MC AF Hsieh, C. L. Niemi, E. C. Wang, S. H. Lee, C. Bingham, D. Zhang, J. Charo, I Huang, E. J. Liu, J. Nakamura, M. C. TI CCR2 DEFICIENCY IMPAIRS MACROPHAGE INFILTRATION AND IMPROVES COGNITIVE FUNCTION AFTER TRAUMATIC BRAIN INJURY SO JOURNAL OF NEUROTRAUMA LA English DT Meeting Abstract CT 32nd Annual National Neurotrauma Symposium CY JUN 29-JUL 02, 2014 CL San Francisco, CA DE behavior studies; CCR2; flow cytometry; inflammation; macrophage; traumatic brain injury C1 [Hsieh, C. L.; Niemi, E. C.; Wang, S. H.; Lee, C.; Bingham, D.; Zhang, J.; Charo, I; Huang, E. J.; Liu, J.; Nakamura, M. C.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Hsieh, C. L.; Niemi, E. C.; Lee, C.; Bingham, D.; Zhang, J.; Huang, E. J.; Liu, J.; Nakamura, M. C.] San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 EI 1557-9042 J9 J NEUROTRAUM JI J. Neurotrauma PD JUN 15 PY 2014 VL 31 IS 12 MA D1-31 BP A111 EP A111 PG 1 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA AK5DC UT WOS:000338443600303 ER PT J AU Papesh, MA Gallun, F Leek, M Billings, CJ Folmer, R Storzbach, D AF Papesh, M. A. Gallun, F. Leek, M. Billings, C. J. Folmer, R. Storzbach, D. TI BLAST EXPOSURE IMPAIRS THE BRAIN'S ABILITY TO MODULATE SENSITIVITY TO SENSORY INFORMATION: EVIDENCE FROM THE VETERAN POPULATION SO JOURNAL OF NEUROTRAUMA LA English DT Meeting Abstract CT 32nd Annual National Neurotrauma Symposium CY JUN 29-JUL 02, 2014 CL San Francisco, CA DE auditory; blast exposure; sensory processing; traumatic brain injury; veterans C1 [Papesh, M. A.; Gallun, F.; Leek, M.; Billings, C. J.; Folmer, R.; Storzbach, D.] OHSU, Portland, OR USA. [Gallun, F.; Leek, M.; Billings, C. J.; Folmer, R.; Storzbach, D.] Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 EI 1557-9042 J9 J NEUROTRAUM JI J. Neurotrauma PD JUN 15 PY 2014 VL 31 IS 12 MA A5-02 BP A43 EP A43 PG 1 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA AK5DC UT WOS:000338443600113 ER PT J AU Yan, HQ Carlson, S Li, Y Henchir, J Ma, X Dixon, CE AF Yan, H. Q. Carlson, S. Li, Y. Henchir, J. Ma, X. Dixon, C. E. TI EFFECT OF TRAUMATIC BRAIN INJURY ON WILD-TYPE ALPHA-SYNUCLEIN EXPRESSION IN RAT HIPPOCAMPUS SO JOURNAL OF NEUROTRAUMA LA English DT Meeting Abstract CT 32nd Annual National Neurotrauma Symposium CY JUN 29-JUL 02, 2014 CL San Francisco, CA DE alpha-synuclein; immunofluorescence; traumatic brain injury; Western blot C1 [Yan, H. Q.; Carlson, S.; Li, Y.; Henchir, J.; Ma, X.; Dixon, C. E.] Univ Pittsburgh, Pittsburgh, PA USA. [Yan, H. Q.; Carlson, S.; Li, Y.; Henchir, J.; Ma, X.; Dixon, C. E.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 EI 1557-9042 J9 J NEUROTRAUM JI J. Neurotrauma PD JUN 15 PY 2014 VL 31 IS 12 MA C3-23 BP A97 EP A97 PG 1 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA AK5DC UT WOS:000338443600263 ER PT J AU Schneider, PM Pellegrini, CN Wang, YF Fein, AS Reynolds, MR Curtis, JP Masoudi, FA Varosy, PD AF Schneider, Preston M. Pellegrini, Cara N. Wang, Yongfei Fein, Adam S. Reynolds, Matthew R. Curtis, Jeptha P. Masoudi, Frederick A. Varosy, Paul D. TI Prevalence of Guideline-Directed Medical Therapy Among Patients Receiving Cardiac Resynchronization Therapy Defibrillator Implantation in the National Cardiovascular Data Registry During the Years 2006 to 2008 SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CHRONIC HEART-FAILURE; RANDOMIZED-TRIAL; ASSOCIATION; MORTALITY; SURVIVAL; HOSPITALIZATIONS; ENALAPRIL; PERFORMANCE; CARVEDILOL; MORBIDITY AB Cardiac resynchronization therapy (CRT) reduces morbidity and mortality among selected patients with left ventricular systolic dysfunction and severe heart failure symptoms despite guideline-directed medical therapy (GDMT). Contemporaneous guidelines provided clear recommendations regarding selection of patients for CRT, including that all patients should first receive GDMT with beta blockers and renin-angiotensin axis antagonists. Prevalence of GDMT among real-world patients receiving CRT defibrillators (CRT-D) has not been well studied. We identified 45,392 patients in the National Cardiovascular Data Registry Implantable Cardioverter-Defibrillator Registry who underwent first CRT-D implantation for primary prevention of sudden death from January 2006 to June 2008. We calculated the proportion of patients with contemporaneous class I guideline indications for CRT-D, the proportion receiving GDMT for heart failure, and the proportion receiving GDMT who had class I guideline indications for CRT-D. Among patients without contraindications, 87% were prescribed beta blockers, 78% an angiotensin-converting enzyme inhibitor or an angiotensin II receptor inhibitor, and 70% both a beta blocker and an angiotensin-converting enzyme or angiotensin II receptor inhibitor at discharge. Finally, 50% of patients met class I guideline indications and were prescribed GDMT at discharge; 9% neither met class I indications nor were prescribed GDMT at discharge. The major limitation of this study is the lack of dosage information in the Implantable Cardioverter-Defibrillator Registry and lack of prescribing information at times other than discharge. In conclusion, many patients receiving CRT-D are not receiving GDMT at discharge. Ensuring that all patients receiving CRT-D are also receiving GDMT appears to be a quality improvement target. (C) 2014 Elsevier Inc. All rights reserved. C1 [Schneider, Preston M.; Masoudi, Frederick A.; Varosy, Paul D.] Univ Colorado, Div Cardiol, Aurora, CO 80045 USA. [Pellegrini, Cara N.] Univ Calif San Francisco, Dept Med, Cardiac Electrophysiol Sect, Sect Cardiol,San Francisco Vet Adm Med Ctr, San Francisco, CA 94143 USA. [Pellegrini, Cara N.] Univ Calif San Francisco, Dept Med, Div Cardiol, Sect Cardiol,San Francisco Vet Adm Med Ctr, San Francisco, CA 94143 USA. [Wang, Yongfei; Curtis, Jeptha P.] Yale Univ, Sch Med, New Haven, CT USA. [Fein, Adam S.; Reynolds, Matthew R.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Masoudi, Frederick A.; Varosy, Paul D.] Colorado Cardiovasc Outcomes Res CCOR Grp, Denver, CO USA. [Masoudi, Frederick A.] Kaiser Permanente Colorado Inst Hlth Res, Denver, CO USA. [Masoudi, Frederick A.] Denver Hlth Med Ctr, Denver, CO USA. [Varosy, Paul D.] Vet Adm Eastern Colorado Healthcare Syst, Div Cardiol, Denver, CO USA. RP Schneider, PM (reprint author), Univ Colorado, Div Cardiol, Anschutz Med Campus, Aurora, CO 80045 USA. EM Preston.Schneider@ucdenver.edu FU NCATS NIH HHS [UL1 TR001082]; NHLBI NIH HHS [T32 HL007822] NR 27 TC 4 Z9 4 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD JUN 15 PY 2014 VL 113 IS 12 BP 2052 EP 2056 DI 10.1016/j.amjcard.2014.03.049 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AJ4KE UT WOS:000337644300019 PM 24793671 ER PT J AU Muir, AM Ren, YS Butz, DH Davis, NA Blank, RD Birk, DE Lee, SJ Rowe, D Feng, JQ Greenspan, DS AF Muir, Alison M. Ren, Yinshi Butz, Delana Hopkins Davis, Nicholas A. Blank, Robert D. Birk, David E. Lee, Se-Jin Rowe, David Feng, Jian Q. Greenspan, Daniel S. TI Induced ablation of Bmp1 and Tll1 produces osteogenesis imperfecta in mice SO HUMAN MOLECULAR GENETICS LA English DT Article ID BONE MORPHOGENETIC PROTEIN-1; PROCOLLAGEN-C-PROTEINASE; MAMMALIAN TOLLOID-LIKE; DENTIN MATRIX PROTEIN-1; LATENT MYOSTATIN; TGF-BETA; IN-VIVO; METALLOPROTEINASES; WNT; ACTIVATION AB Osteogenesis imperfecta (OI), or brittle bone disease, is most often caused by dominant mutations in the collagen I genes COL1A1/COL1A2, whereas rarer recessive OI is often caused by mutations in genes encoding collagen I-interacting proteins. Recently, mutations in the gene for the proteinase bone morphogenetic 1 (BMP1) were reported in two recessive OI families. BMP1 and the closely related proteinase mammalian tolloid-like 1 (mTLL1) are co-expressed in various tissues, including bone, and have overlapping activities that include biosynthetic processing of procollagen precursors into mature collagen monomers. However, early lethality of Bmp1- and Tll1-null mice has precluded use of such models for careful study of in vivo roles of their protein products. Here we employ novel mouse strains with floxed Bmp1 and Tll1 alleles to induce postnatal, simultaneous ablation of the two genes, thus avoiding barriers of Bmp1(-/-) and Tll1(-/-) lethality and issues of functional redundancy. Bones of the conditionally null mice are dramatically weakened and brittle, with spontaneous fractures-defining features of OI. Additional skeletal features include osteomalacia, thinned/porous cortical bone, reduced processing of procollagen and dentin matrix protein 1, remarkably high bone turnover and defective osteocyte maturation that is accompanied by decreased expression of the osteocyte marker and Wnt-signaling inhibitor sclerostin, and by marked induction of canonical Wnt signaling. The novel animal model presented here provides new opportunities for in-depth analyses of in vivo roles of BMP1-like proteinases in bone and other tissues, and for their roles, and for possible therapeutic interventions, in OI. C1 [Muir, Alison M.; Butz, Delana Hopkins; Davis, Nicholas A.; Greenspan, Daniel S.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Cell & Regenerat Biol, Madison, WI 53792 USA. [Muir, Alison M.] Univ Wisconsin, Genet Lab, Madison, WI 53792 USA. [Ren, Yinshi; Feng, Jian Q.] Baylor Coll Dent, Texas A&M Hlth Sci Ctr, Dept Biomed Sci, Dallas, TX 75246 USA. [Blank, Robert D.] William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Madison, WI USA. [Blank, Robert D.] Univ Wisconsin, Sch Med & Publ Hlth, Div Endocrinol Diabet & Metab, Dept Med, Madison, WI 53792 USA. [Birk, David E.] Univ S Florida, Morsani Coll Med, Dept Pharmacol & Physiol, Tampa, FL USA. [Lee, Se-Jin] Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA. [Rowe, David] Univ Connecticut, Sch Dent Med, Dept Reconstruct Sci Biomat & Skeletal Dev, Farmington, CT 06032 USA. RP Greenspan, DS (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Dept Cell & Regenerat Biol, Room K4-430,Box 4672,600 Highland Ave, Madison, WI 53792 USA. EM dsgreens@wisc.edu RI Birk, David/I-4072-2012 OI Birk, David/0000-0002-4865-9088; Blank, Robert Daniel/0000-0003-2950-1944; Greenspan, Daniel/0000-0001-8096-7446 FU National Institutes of Health [AR60636, AR59685, AR54753, AR44745, DE018486, AR53815, AR47746] FX This work was supported by grants AR60636 and AR59685 (to S.-J.L.), AR54753 (to R. D. B.), AR44745 (to D. E. B.), DE018486 (to J.F.), and AR53815 and AR47746 (to D. S. G.) from the National Institutes of Health. NR 67 TC 14 Z9 15 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JUN 15 PY 2014 VL 23 IS 12 BP 3085 EP 3101 DI 10.1093/hmg/ddu013 PG 17 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA AI7CJ UT WOS:000337038600002 PM 24419319 ER PT J AU Agostoni, P Swenson, ER Fumagalli, R Salvioni, E Cattadori, G Farina, S Bussotti, M Tamplenizza, M Lombardi, C Bonacina, D Brioschi, M Caravita, S Modesti, P Revera, M Giuliano, A Meriggi, P Faini, A Bilo, G Banfi, C Parati, G AF Agostoni, Piergiuseppe Swenson, Erik R. Fumagalli, Roberto Salvioni, Elisabetta Cattadori, Gaia Farina, Stefania Bussotti, Maurizio Tamplenizza, Margherita Lombardi, Carolina Bonacina, Daniele Brioschi, Maura Caravita, Sergio Modesti, Pietro Revera, Miriam Giuliano, Andrea Meriggi, Paolo Faini, Andrea Bilo, Grzegorz Banfi, Cristina Parati, Gianfranco TI Acute high-altitude exposure reduces lung diffusion: Data from the HIGHCARE Alps Project (vol 188, pg 223, 2013) SO RESPIRATORY PHYSIOLOGY & NEUROBIOLOGY LA English DT Correction C1 [Agostoni, Piergiuseppe; Salvioni, Elisabetta; Cattadori, Gaia; Farina, Stefania; Brioschi, Maura; Banfi, Cristina] IRCCS, Ctr Cardiol Monzino, I-20138 Milan, Italy. [Swenson, Erik R.] Univ Washington, VA Med Ctr, Dept Med, Div Pulm Crit Care & Med, Seattle, WA 98108 USA. [Agostoni, Piergiuseppe] Dept Clin Sci & Community Hlth, I-20138 Milan, Italy. [Swenson, Erik R.] Univ Washington, VA Med Ctr, VA Puget Sound Hlth Care Syst, Div Pulm & Crit Care & Med,Dept Med, Seattle, WA 98108 USA. [Fumagalli, Roberto; Bonacina, Daniele] Univ Milano Bicocca, Dipartimento Med Sperimentale, Osped S Gerardo Monza, Unita Operat Anestesia & Rianimaz 1, Milan, Italy. [Bussotti, Maurizio] IRCCS, Fdn S Maugeri, I-20138 Milan, Italy. [Tamplenizza, Margherita] Univ Milan, CIMAINA, Milan, Italy. [Lombardi, Carolina; Caravita, Sergio; Revera, Miriam; Giuliano, Andrea; Faini, Andrea; Bilo, Grzegorz; Parati, Gianfranco] S Luca Hosp, Ist Auxol Italian, Dept Cardiol, I-20149 Milan, Italy. [Revera, Miriam; Parati, Gianfranco] Univ Milano Bicocca, Dept Clin Med & Prevent, I-20149 Milan, Italy. [Modesti, Pietro] Univ Florence, Dipartimento Area Crit Med Chirurg, I-50134 Florence, Italy. [Modesti, Pietro] IRCCS Ctr Santa Maria Ulivi Pozzolat, Fdn Don C Gnocchi, Florence, Italy. [Meriggi, Paolo] Fdn Don Carlo Gnocchi, Polo Tecnol Biomed Technol Dept, I-20148 Milan, Italy. RP Agostoni, P (reprint author), Ctr Cardiol Monzino, Via Parea 4, I-20138 Milan, Italy. EM piergiuseppe.agostoni@unimi.it RI Modesti, Pietro Amedeo/B-2638-2012; Bilo, Grzegorz/J-8694-2016; Parati, Gianfranco/K-7151-2016 OI Modesti, Pietro Amedeo/0000-0002-9511-2173; Bilo, Grzegorz/0000-0002-5104-9176; Parati, Gianfranco/0000-0001-9402-7439 NR 1 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1569-9048 EI 1878-1519 J9 RESP PHYSIOL NEUROBI JI Respir. Physiol. Neuro. PD JUN 15 PY 2014 VL 197 BP 53 EP 53 DI 10.1016/j.resp.2014.03.008 PG 1 WC Physiology; Respiratory System SC Physiology; Respiratory System GA AH8AW UT WOS:000336357500008 ER PT J AU Zhou, YX Yu, F Duong, T AF Zhou, Yongxia Yu, Fang Duong, Timothy TI Multiparametric MRI Characterization and Prediction in Autism Spectrum Disorder Using Graph Theory and Machine Learning SO PLOS ONE LA English DT Article ID INFERIOR FRONTAL GYRUS; FUNCTIONAL CONNECTIVITY; CORTICAL THICKNESS; FEATURE-SELECTION; BRAIN; CHILDREN; CORTEX; AGE; FLUCTUATIONS; PERFORMANCE AB This study employed graph theory and machine learning analysis of multiparametric MRI data to improve characterization and prediction in autism spectrum disorders (ASD). Data from 127 children with ASD (13.5 +/- 6.0 years) and 153 age- and gender-matched typically developing children (14.5 +/- 5.7 years) were selected from the multi-center Functional Connectome Project. Regional gray matter volume and cortical thickness increased, whereas white matter volume decreased in ASD compared to controls. Small-world network analysis of quantitative MRI data demonstrated decreased global efficiency based on gray matter cortical thickness but not with functional connectivity MRI (fcMRI) or volumetry. An integrative model of 22 quantitative imaging features was used for classification and prediction of phenotypic features that included the autism diagnostic observation schedule, the revised autism diagnostic interview, and intelligence quotient scores. Among the 22 imaging features, four (caudate volume, caudate-cortical functional connectivity and inferior frontal gyrus functional connectivity) were found to be highly informative, markedly improving classification and prediction accuracy when compared with the single imaging features. This approach could potentially serve as a biomarker in prognosis, diagnosis, and monitoring disease progression. C1 [Zhou, Yongxia] Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. [Yu, Fang; Duong, Timothy] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, South Texas Vet Hlth Care Syst, Dept Vet Affairs,Dept Ophthalmol, San Antonio, TX 78229 USA. RP Duong, T (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, South Texas Vet Hlth Care Syst, Dept Vet Affairs,Dept Ophthalmol, San Antonio, TX 78229 USA. EM duongt@uthscsa.edu OI Zhou, Yongxia (Sharon)/0000-0002-4931-2318 FU NINDS NIH HHS [R01 NS039135] NR 56 TC 13 Z9 13 U1 4 U2 12 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 12 PY 2014 VL 9 IS 6 AR e90405 DI 10.1371/journal.pone.0090405 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AK8TP UT WOS:000338701300001 PM 24922325 ER PT J AU Chirinos, JA Gurubhagavatula, I Teff, K Rader, DJ Wadden, TA Townsend, R Foster, GD Maislin, G Saif, H Broderick, P Chittams, J Hanlon, AL Pack, AI AF Chirinos, Julio A. Gurubhagavatula, Indira Teff, Karen Rader, Daniel J. Wadden, Thomas A. Townsend, Raymond Foster, Gary D. Maislin, Greg Saif, Hassam Broderick, Preston Chittams, Jesse Hanlon, Alexandra L. Pack, Allan I. TI CPAP, Weight Loss, or Both for Obstructive Sleep Apnea SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID POSITIVE AIRWAY PRESSURE; C-REACTIVE PROTEIN; CARDIOVASCULAR-DISEASE; HYPERTENSIVE PATIENTS; INSULIN SENSITIVITY; METABOLIC SYNDROME; LOW-CARBOHYDRATE; BLOOD-PRESSURE; SEVERE OBESITY; RISK-FACTORS AB BACKGROUND Obesity and obstructive sleep apnea tend to coexist and are associated with inflammation, insulin resistance, dyslipidemia, and high blood pressure, but their causal relation to these abnormalities is unclear. METHODS We randomly assigned 181 patients with obesity, moderate-to-severe obstructive sleep apnea, and serum levels of C-reactive protein (CRP) greater than 1.0 mg per liter to receive treatment with continuous positive airway pressure (CPAP), a weight-loss intervention, or CPAP plus a weight-loss intervention for 24 weeks. We assessed the incremental effect of the combined interventions over each one alone on the CRP level (the primary end point), insulin sensitivity, lipid levels, and blood pressure. RESULTS Among the 146 participants for whom there were follow-up data, those assigned to weight loss only and those assigned to the combined interventions had reductions in CRP levels, insulin resistance, and serum triglyceride levels. None of these changes were observed in the group receiving CPAP alone. Blood pressure was reduced in all three groups. No significant incremental effect on CRP levels was found for the combined interventions as compared with either weight loss or CPAP alone. Reductions in insulin resistance and serum triglyceride levels were greater in the combined-intervention group than in the group receiving CPAP only, but there were no significant differences in these values between the combined-intervention group and the weight-loss group. In per-protocol analyses, which included 90 participants who met prespecified criteria for adherence, the combined interventions resulted in a larger reduction in systolic blood pressure and mean arterial pressure than did either CPAP or weight loss alone. CONCLUSIONS In adults with obesity and obstructive sleep apnea, CPAP combined with a weight-loss intervention did not reduce CRP levels more than either intervention alone. In secondary analyses, weight loss provided an incremental reduction in insulin resistance and serum triglyceride levels when combined with CPAP. In addition, adherence to a regimen of weight loss and CPAP may result in incremental reductions in blood pressure as compared with either intervention alone. C1 [Chirinos, Julio A.; Gurubhagavatula, Indira] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Chirinos, Julio A.; Gurubhagavatula, Indira; Rader, Daniel J.; Wadden, Thomas A.; Townsend, Raymond; Maislin, Greg; Saif, Hassam; Broderick, Preston; Pack, Allan I.] Univ Penn, Perelman Sch Med, Hosp Univ Penn, Philadelphia, PA 19104 USA. [Teff, Karen] Monell Chem Senses Ctr, Philadelphia, PA USA. [Foster, Gary D.] Temple Univ, Sch Med, Philadelphia, PA 19122 USA. [Chittams, Jesse; Hanlon, Alexandra L.] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. RP Chirinos, JA (reprint author), Univ Penn, Div Cardiol, Rm 8B111,Univ & Woodland Aves, Philadelphia, PA 19104 USA. EM julio.chirinos@uphs.upenn.edu FU National Heart, Lung, and Blood Institute [HL-R01080076, P01 HL094307]; Novo Nordisk; Nutrisystem; Orexigen; Boehringer Ingelheim; Weight Watchers; ConAgra Foods; Tate and Lyle; UnitedHealth Group FX Supported by grants from the National Heart, Lung, and Blood Institute (HL-R01080076, to Dr. Chirinos; and P01 HL094307, to Dr. Pack).; Dr. Wadden reports receiving fees for serving on advisory boards for Novo Nordisk, Nutrisystem, and Orexigen, consulting fees from Boehringer Ingelheim, and grant support from Weight Watchers, Novo Nordisk, and Nutrisystem. Dr. Foster reports receiving fees for serving on advisory boards for ConAgra Foods, Tate and Lyle, and UnitedHealth Group and reports being an employee of Weight Watchers. No other potential conflict of interest relevant to this article was reported. NR 42 TC 94 Z9 94 U1 3 U2 24 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 12 PY 2014 VL 370 IS 24 BP 2265 EP 2275 DI 10.1056/NEJMoa1306187 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA AI7BB UT WOS:000337033700006 PM 24918371 ER PT J AU Drye, LT Spragg, D Devanand, DP Frangakis, C Marano, C Meinert, CL Mintzer, JE Munro, CA Pelton, G Pollock, BG Porsteinsson, AP Rabins, PV Rosenberg, PB Schneider, LS Shade, DM Weintraub, D Yesavage, J Lyketsos, CG AF Drye, Lea T. Spragg, David Devanand, D. P. Frangakis, Constantine Marano, Christopher Meinert, Curtis L. Mintzer, Jacobo E. Munro, Cynthia A. Pelton, Gregory Pollock, Bruce G. Porsteinsson, Anton P. Rabins, Peter V. Rosenberg, Paul B. Schneider, Lon S. Shade, David M. Weintraub, Daniel Yesavage, Jerome Lyketsos, Constantine G. CA CitAD Res Grp TI Changes in QTc Interval in the Citalopram for Agitation in Alzheimer's Disease (CitAD) Randomized Trial SO PLOS ONE LA English DT Article ID ANTIDEPRESSANT USE; HEALTHY-SUBJECTS; CLINICAL-TRIAL; MORTALITY; POPULATION; AGE; DISPERSION; PEOPLE; GENDER; IMPACT AB Background: A Food and Drug Administration (FDA) safety communication in August 2011 warned that citalopram was associated with a dose dependent risk of QT prolongation and recommended dose restriction in patients over the age of 60 but did not provide data for this age group. Methods: CitAD was a randomized, double-masked, placebo-controlled, multicenter clinical trial for agitation in Alzheimer's disease (AD). Participants were assigned to citalopram (target dose of 30 mg/day) or placebo in a 1:1 ratio. 186 people, 181 of whom were over the age of 60, having probable AD with clinically significant agitation were recruited from September 2009 to January 2013. After the FDA safety communication about citalopram, ECG was added to the required study procedures before enrollment and repeated at week 3 to monitor change in QTc interval. Forty-eight participants were enrolled after enhanced monitoring began. Results: Citalopram treatment was associated with a larger increase in QTc interval than placebo (difference in week 3 QTc adjusting for baseline QTc: 18.1 ms [95% CI: 6.1, 30.1]; p = 0.004). More participants in the citalopram group had an increase >= 30 ms from baseline to week 3 (7 in citalopram versus 1 in placebo; Fisher's exact p = 0.046), but only slightly more in the citalopram group met a gender-specific threshold for prolonged QTc (450 ms for males; 470 ms for females) at any point during follow-up (3 in citalopram versus 1 in placebo, Fisher's exact p = 0.611). One of the citalopram participants who developed prolonged QTc also displayed ventricular bigeminy. No participants in either group had a cardiovascular-related death. Conclusion: Citalopram at 30 mg/day was associated with improvement in agitation in patients with AD but was also associated with QT prolongation. C1 [Drye, Lea T.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. [Drye, Lea T.] Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Clin Trials, Baltimore, MD USA. [Spragg, David] Johns Hopkins Univ Hosp, Electrophysiol Lab, Baltimore, MD 21287 USA. [Spragg, David; Rosenberg, Paul B.] Johns Hopkins Bayview Med Ctr, Baltimore, MD USA. [Devanand, D. P.] Columbia Univ, Coll Phys & Surg, Div Geriatr Psychiat, New York, NY USA. [Frangakis, Constantine] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA. [Marano, Christopher] Johns Hopkins Univ, Sch Med, Div Geriatr Psychiat & Neuropsychiat, Johns Hopkins Bayview Med Ctr, Baltimore, MD USA. [Meinert, Curtis L.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Meinert, Curtis L.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA. [Mintzer, Jacobo E.] Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Clin Biotechnol Res Inst, Roper St Francis Healthcare,Dept Hlth Studies, Charleston, SC 29425 USA. [Munro, Cynthia A.] Johns Hopkins Bayview & Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD USA. [Munro, Cynthia A.] Johns Hopkins Bayview & Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD USA. [Pelton, Gregory] Columbia Univ, New York State Psychiat Inst, Coll Phys & Surg, Div Geriatr Psychiat, New York, NY USA. [Pollock, Bruce G.] Univ Toronto, Campbell Family Mental Hlth Res Inst, Div Geriatr Psychiat, Toronto, ON, Canada. [Pollock, Bruce G.] Univ Toronto, Ctr Addict & Mental Hlth, Toronto, ON, Canada. [Porsteinsson, Anton P.] Univ Rochester, Sch Med & Dent, Alzheimers Dis Care Res & Educ Program AD CARE, Rochester, NY USA. [Rabins, Peter V.; Rosenberg, Paul B.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [Rabins, Peter V.] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [Schneider, Lon S.] Univ So Calif, Keck Sch Med, Dept Psychiat, Los Angeles, CA 90033 USA. [Schneider, Lon S.] Univ So Calif, Keck Sch Med, Dept Neurol, Los Angeles, CA 90033 USA. [Schneider, Lon S.] Univ So Calif, Keck Sch Med, Dept Gerontol, Los Angeles, CA 90033 USA. [Shade, David M.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Pulm Med, Baltimore, MD USA. [Shade, David M.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Shade, David M.] Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Clin Trials, Baltimore, MD USA. [Weintraub, Daniel] Univ Penn, Parkinsons Dis Res Educ & Clin Ctr PADRECC, Mental Illness Res Educ & Clin Ctr,Dept Psychiat, Perelman Sch Med,Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Univ Penn, Parkinsons Dis Res Educ & Clin Ctr PADRECC, Mental Illness Res Educ & Clin Ctr,Dept Neurol, Perelman Sch Med,Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Yesavage, Jerome] Stanford Univ, Mental Illness Res Educ & Clin Ctr, Vet Affairs Palo Alto Hlth Care Syst, Aging Clin Res Ctr,Dept Psychiat,Sch Med, Palo Alto, CA 94304 USA. [Yesavage, Jerome] Stanford Univ, Sch Med, Dept Behav Sci, Palo Alto, CA 94304 USA. [Lyketsos, Constantine G.] Johns Hopkins Bayview & Johns Hopkins Sch Med, Dept Psychiat & Behav Sci, Memory & Alzheimers Treatment Ctr, Baltimore, MD USA. RP Drye, LT (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. EM ldrye@jhsph.edu FU National Institute on Aging; National Institute of Mental Health [R01AG031348] FX Grant funding: National Institute on Aging and National Institute of Mental Health, R01AG031348. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 30 TC 13 Z9 13 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 10 PY 2014 VL 9 IS 6 AR e98426 DI 10.1371/journal.pone.0098426 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AN9SD UT WOS:000340947700020 PM 24914549 ER PT J AU Kini, V Soufi, MK Deo, R Epstein, AE Bala, R Riley, M Groeneveld, PW Shalaby, A Dixit, S AF Kini, Vinay Soufi, Mohamad Khaled Deo, Rajat Epstein, Andrew E. Bala, Rupa Riley, Michael Groeneveld, Peter W. Shalaby, Alaa Dixit, Sanjay TI Appropriateness of Primary Prevention Implantable Cardioverter-Defibrillators at the Time of Generator Replacement Are Indications Still Met? SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE ICD generator replacement; implantable cardioverter-defibrillator; sudden cardiac death ID VENTRICULAR EJECTION FRACTION; CARDIAC RESYNCHRONIZATION THERAPY; HEART-FAILURE; MYOCARDIAL-INFARCTION; NONISCHEMIC CARDIOMYOPATHY; COST-EFFECTIVENESS; SURVIVAL; SHOCKS; DEATH; STRATIFICATION AB Objectives This study sought to determine how often patients with primary prevention implantable cardioverter-defibrillators (ICDs) meet guideline-derived indications at the time of generator replacement. Background Professional societies have developed guideline criteria for the appropriate implantation of an ICD for the primary prevention of sudden cardiac death. It is unknown whether patients continue to meet criteria when their devices need replacement for battery depletion. Methods We performed a retrospective chart review of patients undergoing replacement of primary prevention ICDs at 2 tertiary Veterans Affairs Medical Centers. Indications for continued ICD therapy at the time of generator replacement included a left ventricular ejection fraction (LVEF) <= 35% or receipt of appropriate device therapy. Results In our cohort of 231 patients, 59 (26%) no longer met guideline-driven indications for an ICD at the time of generator replacement. An additional 79 patients (34%) had not received any appropriate ICD therapies and had not undergone reassessment of their LVEF. Patients with an initial LVEF of 30% to 35% were less likely to meet indications for ICD therapy at the time of replacement ( odds ratio: 0.52; 95% confidence interval: 0.30 to 0.88; p = 0.01). Patients without ICD indications subsequently received appropriate ICD therapies at a significantly lower rate than patients with indications ( 2.8% vs. 10.7% annually, p < 0.001). If ICD generator explantations were performed instead of replacements in the patients without ICD indications, the cost savings would be $1.6 million. Conclusions Approximately 25% of patients who receive primary prevention ICDs may no longer meet guideline indications for ICD use at the time of generator replacement, and these patients receive subsequent ICD therapies at a significantly lower rate. (C) 2014 by the American College of Cardiology Foundation C1 [Kini, Vinay; Deo, Rajat; Epstein, Andrew E.; Bala, Rupa; Riley, Michael; Dixit, Sanjay] Hosp Univ Penn, Philadelphia, PA 19104 USA. [Soufi, Mohamad Khaled; Shalaby, Alaa] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Epstein, Andrew E.; Groeneveld, Peter W.; Dixit, Sanjay] Philadelphia VA Med Ctr, Pittsburgh, PA USA. RP Dixit, S (reprint author), Hosp Univ Penn, 9 Founders Pavill,3400 Spruce St, Philadelphia, PA 19104 USA. EM Sanjay.dixit@uphs.upenn.edu FU National Institutes of Health [K23DK089118]; Boston Scientific; Medtronic; St. Jude Medical; Biotronik FX Dr. Epstein has received honoraria from Boston Scientific, Medtronic, and St. Jude Medical; and research grants from Biotronik, Boston Scientific, Medtronic, and St. Jude Medical. Dr. Dixit has received a research grant from Medtronic. Dr. Deo has received support from grant number K23DK089118 from the National Institutes of Health. Drs. Epstein, Bala, Riley, Deo, and Dixit have received fellowship support from Boston Scientific, Medtronic, and St. Jude Medical. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 26 TC 34 Z9 34 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JUN 10 PY 2014 VL 63 IS 22 BP 2388 EP 2394 DI 10.1016/j.jacc.2014.03.025 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AJ0PG UT WOS:000337356800010 PM 24727249 ER PT J AU Huang, DL Abrass, IB Young, BA AF Huang, Deborah L. Abrass, Itamar B. Young, Bessie A. TI Medication safety and chronic kidney disease in older adults prescribed metformin: a cross-sectional analysis SO BMC NEPHROLOGY LA English DT Article DE Aged; Chronic kidney disease; Diabetes mellitus; Drug prescriptions; Medication safety; Metformin; Renal insufficiency ID GLOMERULAR-FILTRATION-RATE; EVALUATION PROGRAM KEEP; ELDERLY-PATIENTS; RENAL-FUNCTION; CREATININE CLEARANCE; SERUM CREATININE; LACTIC-ACIDOSIS; UNITED-STATES; PREVALENCE; EQUATIONS AB Background: Medication safety in patients with chronic kidney disease (CKD) is a growing concern. This is particularly relevant in older adults due to underlying CKD. Metformin use is contraindicated in patients with abnormal kidney function; however, many patients are potentially prescribed metformin inappropriately. We evaluated the prevalence of CKD among older adults prescribed metformin for type 2 diabetes mellitus using available equations to estimate kidney function and examined demographic characteristics of patients who were potentially inappropriately prescribed metformin. Methods: We conducted a cross-sectional analysis of older adults aged >= 65 years prescribed metformin from March 2008-March 2009 at an urban tertiary-care facility in Seattle, Washington, USA. CKD was defined using National Kidney Foundation-Kidney Disease Outcomes Quality Initiative criteria. Creatinine clearance was calculated using the Cockcroft-Gault equation; estimated glomerular filtration rate was calculated using the abbreviated Modification of Diet in Renal Disease (MDRD) and CKD-Epidemiology (EPI) Collaboration equations. Regression analyses were used to determine the associations between demographic characteristics and prevalent CKD. Results: Among 356 subjects (median age 69 years, 52.5% female, 39.4% non-Hispanic black), prevalence of stage 3 or greater CKD calculated by any of the equations was 31.4%. The Cockcroft-Gault equation identified more subjects as having CKD (23.7%) than the abbreviated MDRD (21.1%) or CKD-EPI (21.7%) equations (P < 0.001). Older age (OR = 1.13, 95% CI 1.08-1.19) and female sex (OR = 2.51, 95% CI 1.44-4.38) were associated with increased odds of potentially inappropriate metformin prescription due to CKD; non-Hispanic black race was associated with decreased odds of potentially inappropriate metformin prescription due to CKD (OR = 0.41, 95% CI 0.23-0.71). Conclusions: CKD is common in older adults prescribed metformin for type 2 diabetes, raising concern for potentially inappropriate medication use. No single equation to estimate kidney function may accurately identify CKD in this population. Medication safety deserves greater consideration among elderly patients due to the widespread prevalence of CKD. C1 [Huang, Deborah L.] Univ Washington, Div Gen Internal Med, Seattle, WA 98105 USA. [Abrass, Itamar B.] Univ Washington, Div Gerontol & Geriatr Med, Seattle, WA 98105 USA. [Young, Bessie A.] Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Ctr Innovat Vet Centered & Va, Epidemiol Res & Informat Ctr, Seattle, WA USA. [Young, Bessie A.] Univ Washington, Kidney Res Inst, Div Nephrol, Seattle, WA 98105 USA. RP Huang, DL (reprint author), Univ Washington, Div Gen Internal Med, Box 354765,4245 Roosevelt Way NE, Seattle, WA 98105 USA. EM huangdx@uw.edu FU John A. Hartford Foundation Center of Excellence in Geriatric Medicine and Training Grant; NIH [NIDDK R01DK079745-01]; Department of Veterans Affairs, VA Puget Sound Health Care System, Seattle, Washington, USA FX DLH: This work was supported by a John A. Hartford Foundation Center of Excellence in Geriatric Medicine and Training Grant. BAY is supported by the Department of Veterans Affairs, VA Puget Sound Health Care System, Seattle, Washington, USA, and NIH grant NIDDK R01DK079745-01. The funders had no role in the design and conduct of the study; collection, management, analysis and interpretation of the data; or preparation, review, or approval of the manuscript. NR 28 TC 3 Z9 3 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2369 J9 BMC NEPHROL JI BMC Nephrol. PD JUN 7 PY 2014 VL 15 AR 86 DI 10.1186/1471-2369-15-86 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA AJ0EQ UT WOS:000337322800001 PM 24906409 ER PT J AU Volkman, JE Luger, TM Harvey, KLL Hogan, TP Shimada, SL Amante, D McInnes, DK Feng, H Houston, TK AF Volkman, Julie E. Luger, Tana M. Harvey, Kimberly L. L. Hogan, Timothy P. Shimada, Stephanie L. Amante, Daniel McInnes, D. Keith Feng, Hua Houston, Thomas K. TI The National Cancer Institute's Health Information National Trends Survey [HINTS]: a national cross-sectional analysis of talking to your doctor and other healthcare providers for health information SO BMC FAMILY PRACTICE LA English DT Article DE Health information needs; Sources for health information; Doctor-patient communication; National cross-sectional survey ID DECISION-MAKING; INTERNET; SEEKING; COMMUNICATION; LITERACY; PROFILE; TRUST; WEB AB Background: The need to understand preferred sources of health information remains important to providing patient-centered care. The Internet remains a popular resource for health information, but more traditional sources may still be valid for patients during a recent health need. This study sought to understand the characteristics of patients that turn to their doctor or healthcare provider first for a recent health or medical information need. Methods: Using the national cross-sectional survey, Health Information National Trend Study [HINTS], characteristics of those who sought a doctor or healthcare provider for a recent health information need were compared to other sources. Weighted survey responses from Cycle 1 and Cycle 2 of the HINTS survey were used for multivariable logistic regression. Results: A total 5,307 patient responses were analyzed. Overall, those who seek a doctor or healthcare provider first for a health need are female, 46-64 years, White non-Hispanic, educated, in good health and users of the Internet. Yet, adjusted logistic regressions showed that those who sought a doctor or healthcare provider first during a recent health information need compared to other sources were most likely to be 65+ years, in poor health, less educated and have health insurance. Conclusions: Patients who seek their doctor or healthcare provider first for health information rather than other sources of information represent a unique population. Doctors or healthcare providers remain an important resource for these patients during recent needs, despite the wide use of the Internet as a source of health information. C1 [Volkman, Julie E.; Luger, Tana M.; Harvey, Kimberly L. L.; Hogan, Timothy P.; Shimada, Stephanie L.; McInnes, D. Keith; Feng, Hua; Houston, Thomas K.] US Dept Vet Affairs, eHlth Qual Enhancement Res Initiat, Bedford, MA 01730 USA. [Volkman, Julie E.; Harvey, Kimberly L. L.; Hogan, Timothy P.; Shimada, Stephanie L.; Amante, Daniel; Feng, Hua; Houston, Thomas K.] Univ Massachusetts, Sch Med, Worcester, MA 01605 USA. [Shimada, Stephanie L.; McInnes, D. Keith] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02118 USA. RP Volkman, JE (reprint author), US Dept Vet Affairs, eHlth Qual Enhancement Res Initiat, 200 Springs Rd, Bedford, MA 01730 USA. EM julie.volkman@va.gov FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development FX This material is the result of work supported with resources and the use of facilities at the U.S. Department of Veterans Affairs, eHealth Quality Enhancement Research Initiative (QUERI) EHQ 10-190 at the Bedford, MA Veterans Affairs Medical Center. Drs. Volkman, Luger, Hogan, Shimada, McInnes, Feng, Houston, and Ms. Harvey, and Mr. Amante's efforts were supported in part by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government. A subset of these analyses was presented at the Society of Behavioral Medicine Annual Meeting, March 2013. NR 32 TC 3 Z9 3 U1 2 U2 10 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2296 J9 BMC FAM PRACT JI BMC Fam. Pract. PD JUN 6 PY 2014 VL 15 AR 111 DI 10.1186/1471-2296-15-111 PG 8 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA AK3ID UT WOS:000338315900001 PM 24906558 ER PT J AU Cheah, CY Burbury, K Apperley, JF Huguet, F Pitini, V Gardembas, M Ross, DM Forrest, D Genet, P Rousselot, P Patton, N Smith, G Dunbar, CE Ito, S Aguiar, RCT Odenike, O Gimelfarb, A Cross, NCP Seymour, JF AF Cheah, Chan Y. Burbury, Kate Apperley, Jane F. Huguet, Francoise Pitini, Vincenzo Gardembas, Martine Ross, David M. Forrest, Donna Genet, Philippe Rousselot, Philippe Patton, Nigel Smith, Graeme Dunbar, Cynthia E. Ito, Sawa Aguiar, Ricardo C. T. Odenike, Olatoyosi Gimelfarb, Alla Cross, Nicholas C. P. Seymour, John F. TI Patients with myeloid malignancies bearing PDGFRB fusion genes achieve durable long-term remissions with imatinib SO BLOOD LA English DT Article ID FACTOR RECEPTOR-BETA; CHRONIC MYELOMONOCYTIC LEUKEMIA; MYELOPROLIFERATIVE DISORDERS; MESYLATE; DISEASE; REARRANGEMENT; EOSINOPHILIA; EFFICACY; THERAPY; TEL AB Myeloid neoplasms and eosinophilia with rearrangements of PDGFRB are uncommon Philadelphia-negative myeloproliferative neoplasms. Patients are typically male, with morphologic features of a Philadelphia-negative chronic myeloproliferative syndrome or chronic myelomonocytic leukemia with eosinophilia. Reciprocal translocations involving PDGFRB result in fusion genes with constitutively activated receptor tyrosine kinase sensitive to inhibition with imatinib. We present an updated and expanded analysis of a cohort of 26 such patients treated with imatinib. After a median follow-up of 10.2 years (range, 1.8-17 years), the 10-year overall survival rate was 90% (95% confidence interval, 64%-97%); after median imatinib duration of 6.6 years (range, 0.1-12 years), the 6-year progression-free survival rate was 88% (95% confidence interval, 65%-96%). Of the patients, 96% responded; no patients who achieved a complete cytogenetic (n 5 13) or molecular (n = 8) remission lost their response or progressed to blast crisis. Imatinib is well-tolerated and achieves excellent long-term responses in patients with PDGFRB rearrangements. C1 [Cheah, Chan Y.; Burbury, Kate; Seymour, John F.] Peter MacCallum Canc Ctr, Dept Haematol, East Melbourne, Vic 8006, Australia. [Cheah, Chan Y.; Burbury, Kate; Seymour, John F.] Univ Melbourne, Parkville, Vic 3052, Australia. [Apperley, Jane F.] Univ London Imperial Coll Sci Technol & Med, Fac Med, Dept Haematol, London, England. [Huguet, Francoise] Ctr Hosp Univ, Dept Haematol, Toulouse, France. [Pitini, Vincenzo] Oncol Med & Trapianto Midollo Osseo, Messina, Italy. [Gardembas, Martine] Ctr Hosp Univ, Dept Haematol, Angers, France. [Ross, David M.] South Australia Pathol, Haematol, Adelaide, SA, Australia. [Ross, David M.] Univ Adelaide, Sch Med, Adelaide, SA, Australia. [Ross, David M.] Flinders Univ S Australia, Sch Med, Adelaide, SA 5001, Australia. [Forrest, Donna] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. [Genet, Philippe] Hop Victor Dupouy, Dept Haematol, Argenteuil, France. [Rousselot, Philippe] Hop Versailles, Dept Haematol, Le Chesnay, France. [Rousselot, Philippe] Univ Versailles St Quentin, Le Chesnay, France. [Patton, Nigel] Auckland City Hosp, Dept Haematol, Auckland, New Zealand. [Smith, Graeme] St James Univ Hosp, Dept Haematol, Leeds, W Yorkshire, England. [Dunbar, Cynthia E.; Ito, Sawa] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Aguiar, Ricardo C. T.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Aguiar, Ricardo C. T.] Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78284 USA. [Odenike, Olatoyosi] Univ Chicago, Dept Med, Hematol Oncol Sect, Chicago, IL 60637 USA. [Gimelfarb, Alla] Northshore Univ Hlth Syst, Chicago, IL USA. [Cross, Nicholas C. P.] Univ Southampton, Fac Med, Southampton SO9 5NH, Hants, England. RP Seymour, JF (reprint author), Peter MacCallum Canc Ctr, Dept Haematol, East Melbourne, Vic 8006, Australia. EM john.seymour@petermac.org RI Cross, Nicholas/B-4817-2009 OI Cross, Nicholas/0000-0001-5481-2555; Ross, David/0000-0001-7171-2935; Cheah, Chan Yoon/0000-0001-7988-1565 FU Victorian Cancer Agency [CTCB11_18]; Haematology Society of Australia and New Zealand FX The authors thank Dr N. Carvalho and Dr E. Velloso (Sao Paulo, Brazil) for clinical updates and Professor Francois Xavier Mahon for providing molecular analysis for French patients. This work was funded in part by the Victorian Cancer Agency (grant CTCB11_18) and the Haematology Society of Australia and New Zealand (New Investigator Scholarship). NR 25 TC 26 Z9 26 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD JUN 5 PY 2014 VL 123 IS 23 BP 3574 EP 3577 DI 10.1182/blood-2014-02-555607 PG 4 WC Hematology SC Hematology GA AQ2LF UT WOS:000342616900016 PM 24687085 ER PT J AU Criner, GJ Connett, JE Aaron, SD Albert, RK Bailey, WC Casaburi, R Cooper, JAD Curtis, JL Dransfield, MT Han, MK Make, B Marchetti, N Martinez, FJ Niewoehner, DE Scanlon, PD Sciurba, FC Scharf, SM Sin, DD Voelker, H Washko, GR Woodruff, PG Lazarus, SC AF Criner, G. J. Connett, J. E. Aaron, S. D. Albert, R. K. Bailey, W. C. Casaburi, R. Cooper, J. A. D., Jr. Curtis, J. L. Dransfield, M. T. Han, M. K. Make, B. Marchetti, N. Martinez, F. J. Niewoehner, D. E. Scanlon, P. D. Sciurba, F. C. Scharf, S. M. Sin, D. D. Voelker, H. Washko, G. R. Woodruff, P. G. Lazarus, S. C. CA COPD Clinical Res Network Canadian Inst Hlth Res TI Simvastatin for the Prevention of Exacerbations in Moderate-to-Severe COPD SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID OBSTRUCTIVE PULMONARY-DISEASE; MRC/BHF HEART PROTECTION; PLACEBO-CONTROLLED TRIAL; QUALITY-OF-LIFE; STATIN USE; RANDOMIZED-TRIAL; LUNG-FUNCTION; MORTALITY; INHIBITORS; POPULATION AB BACKGROUND Retrospective studies have shown that statins decrease the rate and severity of exacerbations, the rate of hospitalization, and mortality in chronic obstructive pulmonary disease (COPD). We prospectively studied the efficacy of simvastatin in preventing exacerbations in a large, multicenter, randomized trial. METHODS We designed the Prospective Randomized Placebo-Controlled Trial of Simvastatin in the Prevention of COPD Exacerbations (STATCOPE) as a randomized, controlled trial of simvastatin (at a daily dose of 40 mg) versus placebo, with annual exacerbation rates as the primary outcome. Patients were eligible if they were 40 to 80 years of age, had COPD (defined by a forced expiratory volume in 1 second [FEV1] of less than 80% and a ratio of FEV1 to forced vital capacity of less than 70%), and had a smoking history of 10 or more pack-years, were receiving supplemental oxygen or treatment with glucocorticoids or antibiotic agents, or had had an emergency department visit or hospitalization for COPD within the past year. Patients with diabetes or cardiovascular disease and those who were taking statins or who required statins on the basis of Adult Treatment Panel III criteria were excluded. Participants were treated from 12 to 36 months at 45 centers. RESULTS A total of 885 participants with COPD were enrolled for approximately 641 days; 44% of the patients were women. The patients had a mean (+/-SD) age of 62.2+/-8.4 years, an FEV1 that was 41.6+/-17.7% of the predicted value, and a smoking history of 50.6+/-27.4 pack-years. At the time of study closeout, the low-density lipoprotein cholesterol levels were lower in the simvastatin-treated patients than in those who received placebo. The mean number of exacerbations per person-year was similar in the simvastatin and placebo groups: 1.36+/-1.61 exacerbations and 1.39+/-1.73 exacerbations, respectively (P = 0.54). The median number of days to the first exacerbation was also similar: 223 days (95% confidence interval [CI], 195 to 275) and 231 days (95% CI, 193 to 303), respectively (P = 0.34). The number of nonfatal serious adverse events per person-year was similar, as well: 0.63 events with simvastatin and 0.62 events with placebo. There were 30 deaths in the placebo group and 28 in the simvastatin group (P = 0.89). CONCLUSIONS Simvastatin at a daily dose of 40 mg did not affect exacerbation rates or the time to a first exacerbation in patients with COPD who were at high risk for exacerbations. (Funded by the National Heart, Lung, and Blood Institute and the Canadian Institutes of Health Research; STATCOPE ClinicalTrials.gov number, NCT01061671.) C1 [Criner, G. J.; Marchetti, N.] Temple Univ, Sch Med, Dept Pulm & Crit Care Med, Philadelphia, PA 19140 USA. [Connett, J. E.] Univ Minnesota, Sch Publ Hlth, Dept Biostat, Minneapolis, MN USA. [Connett, J. E.] Univ Minnesota, Data Coordinating Ctr, Minneapolis, MN USA. [Niewoehner, D. E.] Univ Minnesota, Dept Pulm Allergy Crit Care & Sleep Med, Minneapolis, MN USA. [Scanlon, P. D.] Mayo Clin, Dept Pulm & Crit Care Med, Rochester, MN USA. [Aaron, S. D.] Univ Ottawa, Ottawa Hosp Res Inst, Ottawa, ON, Canada. [Sin, D. D.] Univ British Columbia, Dept Med, Vancouver, BC, Canada. [Sin, D. D.] Univ British Columbia, Inst Heart & Lung Hlth, James Hogg Res Ctr, Vancouver, BC, Canada. [Albert, R. K.] Denver Hlth Med Ctr, Dept Med, Denver, CO USA. [Make, B.] Natl Jewish Hlth, Div Pulm Crit Care & Sleep Med, Denver, CO USA. [Bailey, W. C.; Dransfield, M. T.] Univ Alabama Birmingham, Dept Pulm Allergy & Crit Care Med, Birmingham, AL 35205 USA. [Cooper, J. A. D., Jr.] Univ Alabama Birmingham, Pulm Sect, Birmingham, AL USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Casaburi, R.] Harbor UCLA Res & Educ Inst, Los Angeles, CA USA. [Curtis, J. L.] Vet Affairs Med Ctr, Dept Pulm Med, Ann Arbor, MI USA. [Curtis, J. L.] Univ Michigan, Ann Arbor, MI 48109 USA. [Han, M. K.; Martinez, F. J.] Univ Michigan Hlth Syst, Dept Pulm & Crit Care Med, Ann Arbor, MI USA. [Sciurba, F. C.] Univ Pittsburgh, Med Ctr, Dept Pulm Allergy & Crit Care Med, Pittsburgh, PA USA. [Scharf, S. M.] Univ Maryland, Dept Pulm & Crit Care Med, Baltimore, MD 21201 USA. [Washko, G. R.] Brigham & Womens Hosp, Dept Pulm & Crit Care Med, Boston, MA 02115 USA. [Woodruff, P. G.; Lazarus, S. C.] Univ Calif San Francisco, Dept Pulm & Crit Care Med, San Francisco, CA 94143 USA. RP Criner, GJ (reprint author), Temple Univ, Sch Med, Temple Lung Ctr, 745 Parkinson Pavil,3401 N Broad St, Philadelphia, PA 19140 USA. EM gerard.criner@tuhs.temple.edu OI Aaron, Shawn/0000-0002-4762-3542; Curtis, Jeffrey/0000-0001-5191-4847 FU National Heart, Lung, and Blood Institute; Canadian Institutes of Health Research FX Funded by the National Heart, Lung, and Blood Institute and the Canadian Institutes of Health Research; STATCOPE ClinicalTrials.gov number, NCT01061671. NR 44 TC 94 Z9 99 U1 3 U2 24 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 5 PY 2014 VL 370 IS 23 BP 2201 EP 2210 DI 10.1056/NEJMoa1403086 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA AI3AF UT WOS:000336729900008 PM 24836125 ER PT J AU Mortensen, EM Halm, EA Pugh, MJ Copeland, LA Metersky, M Fine, MJ Johnson, CS Alvarez, CA Frei, CR Good, C Restrepo, MI Downs, JR Anzueto, A AF Mortensen, Eric M. Halm, Ethan A. Pugh, Mary Jo Copeland, Laurel A. Metersky, Mark Fine, Michael J. Johnson, Christopher S. Alvarez, Carlos A. Frei, Christopher R. Good, Chester Restrepo, Marcos I. Downs, John R. Anzueto, Antonio TI Association of Azithromycin With Mortality and Cardiovascular Events Among Older Patients Hospitalized With Pneumonia SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID COMMUNITY-ACQUIRED PNEUMONIA; BACTEREMIC PNEUMOCOCCAL PNEUMONIA; EMPIRIC ANTIBIOTIC-THERAPY; DIFFUSE PANBRONCHIOLITIS; ELDERLY-PATIENTS; MACROLIDE ANTIBIOTICS; ANTIMICROBIAL THERAPY; SECONDARY PREVENTION; VETERANS-AFFAIRS; BETA-LACTAM AB IMPORTANCE Although clinical practice guidelines recommend combination therapy with macrolides, including azithromycin, as first-line therapy for patients hospitalized with pneumonia, recent research suggests that azithromycin may be associated with increased cardiovascular events. OBJECTIVE To examine the association of azithromycin use with all-cause mortality and cardiovascular events for patients hospitalized with pneumonia. DESIGN Retrospective cohort study comparing older patients hospitalized with pneumonia from fiscal years 2002 through 2012 prescribed azithromycin therapy and patients receiving other guideline-concordant antibiotic therapy. SETTING This study was conducted using national Department of Veterans Affairs administrative data of patients hospitalized at any Veterans Administration acute care hospital. PARTICIPANTS Patients were included if they were aged 65 years or older, were hospitalized with pneumonia, and received antibiotic therapy concordant with national clinical practice guidelines. MAIN OUTCOMES AND MEASURES Outcomes included 30- and 90-day all-cause mortality and 90-day cardiac arrhythmias, heart failure, myocardial infarction, and any cardiac event. Propensity score matching was used to control for the possible effects of known confounders with conditional logistic regression. RESULTS Of 73 690 patients from 118 hospitals identified, propensity-matched groups were composed of 31 863 patients exposed to azithromycin and 31 863 matched patients who were not exposed. There were no significant differences in potential confounders between groups after matching. Ninety-day mortality was significantly lower in those who received azithromycin (exposed, 17.4%, vs unexposed, 22.3%; odds ratio [On 0.73; 95% CI, 0.70-0.76). However, we found significantly increased odds of myocardial infarction (5.1% vs 4.4%; OR, 1.17; 95% CI,1.08-1.25) but not any cardiac event (43.0% vs 42.7%; OR, 1.01; 95% CI, 0.98-1.05), cardiac arrhythmias (25.8% vs 26.0%; OR, 0.99; 95% CI, 0.95-1.02), or heart failure (26.3% vs 26.2%; OR, 1.01; 95% CI, 0.97-1.04). CONCLUSIONS AND RELEVANCE Among older patients hospitalized with pneumonia, treatment that included azithromycin compared with other antibiotics was associated with a lower risk of 90-day mortality and a smaller increased risk of myocardial infarction. These findings are consistent with a net benefit associated with azithromycin use. Copyright 2014 American Medical Association. All rights reserved. C1 [Mortensen, Eric M.; Johnson, Christopher S.; Alvarez, Carlos A.] VA North Texas Hlth Care Syst, Dallas, TX USA. [Mortensen, Eric M.; Halm, Ethan A.; Johnson, Christopher S.; Alvarez, Carlos A.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Alvarez, Carlos A.] Texas Tech Univ, Hlth Sci Ctr, Dallas, TX USA. [Pugh, Mary Jo; Restrepo, Marcos I.; Downs, John R.; Anzueto, Antonio] South Texas Vet Hlth Care Syst, VERDICT Res Program, San Antonio, TX USA. [Pugh, Mary Jo; Frei, Christopher R.; Restrepo, Marcos I.; Downs, John R.; Anzueto, Antonio] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Fine, Michael J.; Good, Chester] Univ Pittsburgh, VA Ctr Hlth Equ Res & Promot, VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Copeland, Laurel A.] Cent Texas Vet Hlth Care Syst Jointly Scott & Whi, Ctr Appl Hlth Res, Temple, TX USA. [Metersky, Mark] Univ Connecticut, Med Ctr, Farmington, CT USA. [Frei, Christopher R.] Univ Texas Austin, Austin, TX 78712 USA. RP Mortensen, EM (reprint author), Dallas VA Med Ctr, Gen Internal Med Sect, 4500 S Lancaster,Ste 111E, Dallas, TX 75216 USA. EM eric.mortensen@utsouthwestern.edu RI Restrepo, Marcos/H-4442-2014 OI Pugh, Mary Jo/0000-0003-4196-7763; Mortensen, Eric/0000-0002-3880-5563; Copeland, Laurel/0000-0002-9478-0209 FU National Institute of Nursing Research [R01NR010828]; National Heart, Lung, and Blood Institute [K23HL096054] FX This study was supported by a grant from the National Institute of Nursing Research (R01NR010828), and Dr Restrepo was supported by the National Heart, Lung, and Blood Institute (K23HL096054). This material is the result of work supported with resources and the use of facilities at the VA North Texas Health Care System. NR 45 TC 45 Z9 49 U1 2 U2 12 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 4 PY 2014 VL 311 IS 21 BP 2199 EP 2208 DI 10.1001/jama.2014.4304 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA AI2DU UT WOS:000336668400021 PM 24893087 ER PT J AU Pereira, JB Svenningsson, P Weintraub, D Bronnick, K Lebedev, A Westman, E Aarsland, D AF Pereira, Joana B. Svenningsson, Per Weintraub, Daniel Bronnick, Kolbjorn Lebedev, Alexander Westman, Eric Aarsland, Dag TI Initial cognitive decline is associated with cortical thinning in early Parkinson disease SO NEUROLOGY LA English DT Article ID SURFACE-BASED ANALYSIS; HUMAN CEREBRAL-CORTEX; SOCIETY TASK-FORCE; ALZHEIMERS-DISEASE; BRAIN ATROPHY; IMPAIRMENT; DEMENTIA; PROGRESSION; BIOMARKERS; INCIDENT AB Objectives: Our aim was to assess cortical thickness in a large multicenter cohort of drug-naive patients with early Parkinson disease (PD), with and without mild cognitive impairment (MCI), and explore the cognitive correlates of regional cortical thinning. Methods: One hundred twenty-three newly diagnosed patients with PD and 56 healthy controls with 3-tesla structural MRI scans and complete neuropsychological assessment from the Parkinson's Progression Markers Initiative were included. Modified Movement Disorders Society Task Force level II criteria were applied to diagnose MCI in PD. FreeSurfer image processing and analysis software was used to measure cortical thickness across groups and the association with cognitive domains and tests. Results: In patients with MCI, atrophy was found in temporal, parietal, frontal, and occipital areas compared with controls. Specific regional thinning in the right inferior temporal cortex was also found in cognitively normal patients. Memory, executive, and visuospatial performance was associated with temporoparietal and superior frontal thinning, suggesting a relationship between cognitive impairment and both anterior and posterior cortical atrophy in the whole patient sample. Conclusions: These findings confirm that MCI is associated with widespread cortical atrophy. In addition, they suggest that regional cortical thinning is already present at the time of diagnosis in patients with early, untreated PD who do not meet the criteria for MCI. Together, the results indicate that cortical thinning can serve as a marker for initial cognitive decline in early PD. C1 [Pereira, Joana B.; Westman, Eric] Karolinska Inst, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden. [Aarsland, Dag] Karolinska Inst, Dept Neurobiol Care Sci & Soc, Ctr Alzheimers Dis Res, Stockholm, Sweden. [Svenningsson, Per] Karolinska Inst, Ctr Mol Med, Dept Neurol & Clin Neurosci, Stockholm, Sweden. [Svenningsson, Per] Karolinska Univ Hosp, Stockholm, Sweden. [Weintraub, Daniel] Univ Penn, Philadelphia VA Med Ctr, Perelman Sch Med, Dept Psychiat & Neurol, Philadelphia, PA 19104 USA. [Bronnick, Kolbjorn] Stavanger Univ Hosp, Norwegian Ctr Movement Disorders, Stavanger, Norway. [Lebedev, Alexander; Aarsland, Dag] Stavanger Univ Hosp, Ctr Age Related Med, Dept Psychiat, Stavanger, Norway. RP Pereira, JB (reprint author), Karolinska Inst, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden. EM joana.pereira@ki.se RI Westman, Eric/H-5771-2011 OI Pereira, Joana/0000-0002-4604-2711; Lebedev, Alexander/0000-0002-0319-2357; Westman, Eric/0000-0002-3115-2977; Aarsland, Dag/0000-0001-6314-216X FU Michael J. Fox Foundation for Parkinson's Research; Abbott; Avid Radiopharmaceuticals; Biogen Idec; Bristol-Myers Squibb; Covance; Elan; GE Healthcare; Genentech; GSK-GlaxoSmithKline; Lilly; Merck; MSD-Meso Scale Discovery; Pfizer; Roche; UCB; Marie Curie fellowship for postdoctoral researchers [FP7-PEOPLE-2012-IEF-328758] FX Parkinson's Progression Markers Initiative, a public-private partnership, is funded by the Michael J. Fox Foundation for Parkinson's Research and funding partners, including Abbott, Avid Radiopharmaceuticals, Biogen Idec, Bristol-Myers Squibb, Covance, Elan, GE Healthcare, Genentech, GSK-GlaxoSmithKline, Lilly, Merck, MSD-Meso Scale Discovery, Pfizer, Roche, and UCB (www.ppmi-info.org/fundingpartners). J.B.P. was funded by a Marie Curie fellowship for postdoctoral researchers (grant no FP7-PEOPLE-2012-IEF-328758). NR 39 TC 30 Z9 32 U1 2 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD JUN 3 PY 2014 VL 82 IS 22 BP 2017 EP 2025 DI 10.1212/WNL.0000000000000483 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA AQ5BQ UT WOS:000342818100017 PM 24808018 ER PT J AU Naik, AD McCullough, LB AF Naik, Aanand D. McCullough, Laurence B. TI Health Intuitions Inform Patient-Centered Care SO AMERICAN JOURNAL OF BIOETHICS LA English DT Editorial Material ID MANAGEMENT C1 [Naik, Aanand D.] Michael E DeBakey VA Med Ctr, Houston Ctr Innovat Qual Effectiveness & Safety I, Houston, TX 77030 USA. [Naik, Aanand D.; McCullough, Laurence B.] Baylor Coll Med, Houston, TX 77030 USA. RP Naik, AD (reprint author), Michael E DeBakey VA Med Ctr 152, Houston Ctr Innovat Qual Effectiveness & Safety, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM anaik@bcm.edu FU Houston Center for Innovations in Quality, Effectiveness and Safety [CIN 13-413] FX This work was supported in part by the Houston Center for Innovations in Quality, Effectiveness and Safety (#CIN 13-413). NR 7 TC 5 Z9 5 U1 0 U2 4 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 EI 1536-0075 J9 AM J BIOETHICS JI Am. J. Bioeth. PD JUN 3 PY 2014 VL 14 IS 6 BP 1 EP 3 DI 10.1080/15265161.2014.915650 PG 3 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA AH1EK UT WOS:000335862400001 PM 24809597 ER PT J AU Ng, B AF Ng, B. TI FACTORS ASSOCIATED WITH METHOTREXATE TREATMENT DURATION, INCLUDING SUBCUTANEOUS USE, IN PATIENTS WITH RHEUMATOID ARTHRITIS: OBSERVATIONS FROM THE VETERANS AFFAIRS DATABASE SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract CT 15th Annual European Congress of Rheumatology (EULAR) CY JUN 11-14, 2014 CL Paris, FRANCE C1 [Ng, B.] VA Puget Sound Healthcare Syst, Div Rheumatol, Seattle, WA USA. [Ng, B.] Univ Washington, Seattle, WA 98195 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 EI 1468-2060 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUN PY 2014 VL 73 SU 2 MA THU0115 BP 217 EP 218 DI 10.1136/annrheumdis-2014-eular.3021 PG 2 WC Rheumatology SC Rheumatology GA AX4RT UT WOS:000346919801132 ER PT J AU Nagaraja, V Spiegel, BM Hays, RD Khanna, P Chang, L Melmed, GY Bolus, R Khanna, D AF Nagaraja, V. Spiegel, B. M. Hays, R. D. Khanna, P. Chang, L. Melmed, G. Y. Bolus, R. Khanna, D. TI DEVELOPMENT AND VALIDATION OF PATIENT-REPORTED OUTCOMES MEASUREMENT INFORMATION SYSTEM (PROMIS (R)) GASTROINTESTINAL (GI) SYMPTOM SCALES IN SYSTEMIC SCLEROSIS SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract CT 15th Annual European Congress of Rheumatology (EULAR) CY JUN 11-14, 2014 CL Paris, FRANCE C1 [Nagaraja, V.; Khanna, P.; Khanna, D.] Univ Michigan, Div Rheumatol, Ann Arbor, MI 48109 USA. [Spiegel, B. M.] Vet Affairs Greater Los Angeles Healthcare Syst, Div Gastroenterol, Los Angeles, CA USA. [Hays, R. D.] Univ Calif Los Angeles, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA USA. [Chang, L.; Bolus, R.] Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Los Angeles, CA 90095 USA. [Melmed, G. Y.] Cedars Sinai Med Ctr, Div Gastroenterol, Los Angeles, CA 90048 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 EI 1468-2060 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUN PY 2014 VL 73 SU 2 MA FRI0223 BP 463 EP 463 DI 10.1136/annrheumdis-2014-eular.2423 PG 1 WC Rheumatology SC Rheumatology GA AX4RT UT WOS:000346919802328 ER PT J AU Singh, JA AF Singh, J. A. TI THE IMPACT OF GOUT ON PATIENT'S LIVES AND DIFFERENCES BY RACE AND GENDER: A PATIENT PERSPECTIVE SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract CT 15th Annual European Congress of Rheumatology (EULAR) CY JUN 11-14, 2014 CL Paris, FRANCE C1 [Singh, J. A.] Univ Alabama Birmingham, Birmingham, AL USA. [Singh, J. A.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 EI 1468-2060 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUN PY 2014 VL 73 SU 2 MA SAT0520 BP 779 EP 780 DI 10.1136/annrheumdis-2014-eular.1147 PG 2 WC Rheumatology SC Rheumatology GA AX4RT UT WOS:000346919804247 ER PT J AU Singh, JA AF Singh, J. A. TI FACILITATORS AND BARRIERS TO ADHERENCE TO URATE-LOWERING THERAPY IN AFRICAN-AMERICANS WITH GOUT: A QUALITATIVE STUDY SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract CT 15th Annual European Congress of Rheumatology (EULAR) CY JUN 11-14, 2014 CL Paris, FRANCE C1 [Singh, J. A.] Univ Alabama Birmingham, Birmingham, AL USA. [Singh, J. A.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 EI 1468-2060 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUN PY 2014 VL 73 SU 2 MA SAT0519 BP 779 EP 779 DI 10.1136/annrheumdis-2014-eular.1148 PG 1 WC Rheumatology SC Rheumatology GA AX4RT UT WOS:000346919804246 ER PT J AU Singh, JA Bharat, A Edwards, L AF Singh, J. A. Bharat, A. Edwards, L. TI AN INTERNET SURVEY OF COMMON TREATMENTS USED BY PATIENTS WITH GOUT SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract CT 15th Annual European Congress of Rheumatology (EULAR) CY JUN 11-14, 2014 CL Paris, FRANCE C1 [Singh, J. A.] Birmingham VA Med Ctr, Birmingham, AL USA. [Singh, J. A.; Bharat, A.] Univ Alabama Birmingham, Birmingham, AL USA. [Edwards, L.] Univ Florida, Gainesville, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 EI 1468-2060 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUN PY 2014 VL 73 SU 2 MA AB0833 BP 1078 EP 1078 DI 10.1136/annrheumdis-2014-eular.4846 PG 1 WC Rheumatology SC Rheumatology GA AX4RT UT WOS:000346919806113 ER PT J AU Bessette, L Liote, F Moragues, C Moericke, R Zhang, Z Ferreira, A Lecomte, P Kessabi, S Tian, H Li, L Singh, J AF Bessette, L. Liote, F. Moragues, C. Moericke, R. Zhang, Z. Ferreira, A. Lecomte, P. Kessabi, S. Tian, H. Li, L. Singh, J. TI BURDEN OF REFRACTORY GOUTY ARTHRITIS AMONG DIFFICULT-TO-TREAT PATIENTS OVER ONE YEAR: POST- HOC ANALYSIS FROM MOTION OBSERVATIONAL STUDY SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract CT 15th Annual European Congress of Rheumatology (EULAR) CY JUN 11-14, 2014 CL Paris, FRANCE C1 [Bessette, L.] CHUL, Quebec City, PQ, Canada. [Liote, F.] Hosp Lariboisiere, Paris, France. [Moragues, C.] Hosp Platon, Barcelona, Spain. [Moericke, R.] Inst Pravent Med, Magdeburg, Germany. [Moericke, R.] Klin Forsch GbR, Magdeburg, Germany. [Zhang, Z.] Haerbin Med Univ, Affiliated Hosp 1, Haerbin City, Peoples R China. [Ferreira, A.; Lecomte, P.; Kessabi, S.] Novartis Pharmaceut AG, Basel, Switzerland. [Tian, H.] Novartis Pharmaceut, E Hanover, NJ USA. [Li, L.] Novartis Pharmaceut, Shanghai, Peoples R China. [Singh, J.] Univ Alabama Birmingham, Birmingham, AL USA. [Singh, J.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 EI 1468-2060 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUN PY 2014 VL 73 SU 2 MA AB1069 BP 1154 EP 1155 DI 10.1136/annrheumdis-2014-eular.4348 PG 2 WC Rheumatology SC Rheumatology GA AX4RT UT WOS:000346919806349 ER PT J AU Bessette, L Liote, F Moragues, C Moericke, R Zhang, Z Lecomte, P Ferreira, A Kessabi, S Tian, H Li, L Singh, J AF Bessette, L. Liote, F. Moragues, C. Moericke, R. Zhang, Z. Lecomte, P. Ferreira, A. Kessabi, S. Tian, H. Li, L. Singh, J. TI DISEASE BURDEN OF REFRACTORY GOUTY ARTHRITIS: A ONE YEAR MULTINATIONAL PROSPECTIVE OBSERVATIONAL STUDY SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract CT 15th Annual European Congress of Rheumatology (EULAR) CY JUN 11-14, 2014 CL Paris, FRANCE C1 [Bessette, L.] CHUL, Quebec City, PQ, Canada. [Liote, F.] Hop Lariboisiere, F-75475 Paris, France. [Moragues, C.] Hosp Platon, Barcelona, Spain. [Moericke, R.] Inst Pravent Med, Magdeburg, Germany. [Moericke, R.] Klin Forsch GbR, Magdeburg, Germany. [Zhang, Z.] Haerbin Med Univ, Affiliated Hosp 1, Haerbin City, Peoples R China. [Lecomte, P.; Ferreira, A.; Kessabi, S.] Novartis Pharmaceut AG, Basel, Switzerland. [Tian, H.] Novartis Pharmaceut, E Hanover, NJ USA. [Li, L.] Novartis Pharmaceut, Shanghai, Peoples R China. [Singh, J.] Univ Alabama Birmingham, Birmingham, AL USA. [Singh, J.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 EI 1468-2060 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUN PY 2014 VL 73 SU 2 MA AB1068 BP 1154 EP 1154 DI 10.1136/annrheumdis-2014-eular.4215 PG 1 WC Rheumatology SC Rheumatology GA AX4RT UT WOS:000346919806348 ER PT J AU Drapeau, E Dorr, NP Elder, GA Buxbaum, JD AF Drapeau, Elodie Dorr, Nate P. Elder, Gregory A. Buxbaum, Joseph D. TI Absence of strong strain effects in behavioral analyses of Shank3-deficient mice SO DISEASE MODELS & MECHANISMS LA English DT Article DE Shank3; Phelan-McDermid syndrome; Autism spectrum disorders; 22q13; Mouse strain; Genetic modifier; Behavior ID AUTISM SPECTRUM DISORDERS; 22Q13 DELETION SYNDROME; COPY NUMBER VARIATION; INBRED MOUSE STRAINS; POSTSYNAPTIC DENSITY PROTEINS; KNOCKOUT MICE; MUTANT MICE; SYNAPTIC FUNCTION; LABORATORY MICE; SHANK FAMILY AB Haploinsufficiency of SHANK3, caused by chromosomal abnormalities or mutations that disrupt one copy of the gene, leads to a neurodevelopmental syndrome called Phelan-McDermid syndrome, symptoms of which can include absent or delayed speech, intellectual disability, neurological changes and autism spectrum disorders. The SHANK3 protein forms a key structural part of the post-synaptic density. We previously generated and characterized mice with a targeted disruption of Shank3 in which exons coding for the ankyrin-repeat domain were deleted and expression of full-length Shank3 was disrupted. We documented specific deficits in synaptic function and plasticity, along with reduced reciprocal social interactions, in Shank3 heterozygous mice. Changes in phenotype owing to a mutation at a single locus are quite frequently modulated by other loci, most dramatically when the entire genetic background is changed. In mice, each strain of laboratory mouse represents a distinct genetic background and alterations in phenotype owing to gene knockout or transgenesis are frequently different across strains, which can lead to the identification of important modifier loci. We have investigated the effect of genetic background on phenotypes of Shank3 heterozygous, knockout and wild-type mice, using C57BL/6, 129SVE and FVB/Ntac strain backgrounds. We focused on observable behaviors with the goal of carrying out subsequent analyses to identify modifier loci. Surprisingly, there were very modest strain effects over a large battery of analyses. These results indicate that behavioral phenotypes associated with Shank3 haploinsufficiency are largely strain-independent. C1 [Drapeau, Elodie; Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Seaver Autism Ctr Res & Treatment, New York, NY 10029 USA. [Drapeau, Elodie; Dorr, Nate P.; Elder, Gregory A.; Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Elder, Gregory A.; Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA. [Elder, Gregory A.] Icahn Sch Med Mt Sinai, Dept Neurol, New York, NY 10029 USA. [Elder, Gregory A.] James J Peters VA Med Ctr, Neurol Serv, Bronx, NY 10468 USA. [Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Dept Pharmacol & Syst Therapeut, New York, NY 10029 USA. [Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Syst Biol Ctr New York, New York, NY 10029 USA. [Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA. [Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY 10029 USA. [Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA. RP Buxbaum, JD (reprint author), Icahn Sch Med Mt Sinai, Seaver Autism Ctr Res & Treatment, New York, NY 10029 USA. EM joseph.buxbaum@mssm.edu OI Buxbaum, Joseph/0000-0001-8898-8313 FU National Institutes of Health [R01MH093725]; Beatrice and Samuel A. Seaver Foundation; Simons Foundation Autism Research Initiative FX This work was supported by the National Institutes of Health [grant number: R01MH093725], the Beatrice and Samuel A. Seaver Foundation, and the Simons Foundation Autism Research Initiative. NR 75 TC 9 Z9 9 U1 1 U2 7 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 1754-8403 EI 1754-8411 J9 DIS MODEL MECH JI Dis. Model. Mech. PD JUN PY 2014 VL 7 IS 6 BP 667 EP 681 DI 10.1242/dmm.013821 PG 15 WC Cell Biology; Pathology SC Cell Biology; Pathology GA AT5SQ UT WOS:000345002600008 PM 24652766 ER PT J AU Hershenberg, R Gros, DF Brawman-Mintzer, O AF Hershenberg, Rachel Gros, Daniel F. Brawman-Mintzer, Olga TI Role of Atypical Antipsychotics in the Treatment of Generalized Anxiety Disorder SO CNS DRUGS LA English DT Review ID FUMARATE QUETIAPINE XR; SEROTONIN REUPTAKE INHIBITORS; OBSESSIVE-COMPULSIVE DISORDER; PLACEBO-CONTROLLED TRIAL; POSTTRAUMATIC-STRESS-DISORDER; MAJOR DEPRESSIVE DISORDER; OPEN-LABEL TRIAL; DOUBLE-BLIND; PANIC DISORDER; PRIMARY-CARE AB Evidence-based treatment approaches for generalized anxiety disorder (GAD) comprise psychotherapy, pharmacotherapy, or a combination of the two. First-line pharmacotherapy agents include selective serotonin reuptake inhibitors, selective serotonin-norepinephrine reuptake inhibitors, and, in certain European guidelines, pregabalin, which gained European Commission approval. Although short- and long-term efficacy have been established for these agents in controlled trials, response rates of 60-70 % are insufficient, remission rates are relatively modest, and relapse rates considerable. Moreover, questions increasingly arise regarding tolerability and side-effect profiles. As an alternative, antipsychotics have long been of interest for the treatment of anxiety disorders, but investigation had been tempered by their potential for irreversible side effects. With the improved side-effect profiles of atypical antipsychotics, these agents are increasingly being investigated across Axis I disorders. Atypical antipsychotics such as quetiapine, aripiprazole, olanzapine, and risperidone have been shown to be helpful in addressing a range of anxiety and depressive symptoms in individuals with schizophrenia and schizoaffective disorders, and have since been used in the treatment of a range of mood and anxiety disorders. In this article, we review the efficacy and tolerability of atypical antipsychotics as adjunctive therapy and/or monotherapy for individuals with GAD, a currently off-label indication. The most evidence has accumulated for quetiapine. Findings suggest that approximately 50 % of participants tolerate the side effects, most commonly sedation and fatigue. Among this subset, those who continue treatment demonstrate significant reductions in anxiety when used as adjunctive therapy or monotherapy. The appropriateness of the use of antipsychotics in the treatment of GAD is discussed. C1 [Hershenberg, Rachel] Philadelphia VA Med Ctr, Educ & Clin Ctr, VISN Mental Illness Res 4, Philadelphia, PA 19104 USA. [Hershenberg, Rachel] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Gros, Daniel F.; Brawman-Mintzer, Olga] Ralph H Johnson VA Med Ctr, Mental Hlth Serv, Charleston, SC USA. [Gros, Daniel F.; Brawman-Mintzer, Olga] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. RP Brawman-Mintzer, O (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, 171 Ashley Ave, Charleston, SC 29425 USA. EM rhersh@mail.med.upenn.edu; mintzero@musc.edu FU Forest Laboratories FX This material is the result of work supported with resources and the use of facilities of the VISN 4 Mental Illness Research, Education, and Clinical Center, Philadelphia Veterans Affairs Medical Center, Philadelphia, PA, USA, and the Ralph H. Johnson Veterans Affairs Medical Center. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the US government. There were no conflicts of interest in the preparation of this manuscript for Drs. Rachel Hershenberg or Daniel F. Gros. Dr. Olga Brawman-Mintzer received grant support from Forest Laboratories. NR 97 TC 8 Z9 9 U1 3 U2 16 PU ADIS INT LTD PI NORTHCOTE PA 5 THE WAREHOUSE WAY, NORTHCOTE 0627, AUCKLAND, NEW ZEALAND SN 1172-7047 EI 1179-1934 J9 CNS DRUGS JI CNS Drugs PD JUN PY 2014 VL 28 IS 6 BP 519 EP 533 DI 10.1007/s40263-014-0162-6 PG 15 WC Clinical Neurology; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AT0FT UT WOS:000344613300004 PM 24794100 ER PT J AU Basu, PP Shah, NJ Siriki, R Rahaman, M AF Basu, P. Patrick Shah, Niraj J. Siriki, Ravi Rahaman, Md TI Telaprevir with Adjusted Dose of Ribavirin in Naive CHC-G1: Efficacy and Treatment in CHC in Hemodialysis Population. TARGET C Trial- A Placebo Randomized Control Clinical Trial. SO LIVER TRANSPLANTATION LA English DT Meeting Abstract CT Joint International Congress of ILTS, ELITA and LICAGE CY JUN 04-07, 2014 CL London, ENGLAND SP ILTS, ELITA, LICAGE C1 [Basu, P. Patrick] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. [Siriki, Ravi; Rahaman, Md] NSLIJHS Hofstra North Shore LIJ Sch Med, New York, NY USA. [Shah, Niraj J.] Icahn Sch Med Mt Sinai, James J Peters VA Med Ctr, New York, NY 10029 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1527-6465 EI 1527-6473 J9 LIVER TRANSPLANT JI Liver Transplant. PD JUN PY 2014 VL 20 SU 1 MA P-298 BP S244 EP S244 PG 1 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA AM6FU UT WOS:000339959602150 ER PT J AU Basu, PP Shah, NJ Aloysius, M AF Basu, P. Patrick Shah, Niraj J. Aloysius, Mark TI Role of Intravenous N-Acetyl Cysteine (NAC) With Steroid in Acute Alcoholic Hepatitis (AAH) With High Morbidity Score: A Randomized Open Label Prospective Clinical Pilot Trial SO LIVER TRANSPLANTATION LA English DT Meeting Abstract CT Joint International Congress of ILTS, ELITA and LICAGE CY JUN 04-07, 2014 CL London, ENGLAND SP ILTS, ELITA, LICAGE C1 [Basu, P. Patrick] Columbia Sch Phys & Surg, New York, NY USA. [Basu, P. Patrick; Aloysius, Mark] Kings Cty Hosp Med Ctr, New York, NY USA. [Shah, Niraj J.] Mt Sinai Sch Med, James J Peters VA Med Ctr, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1527-6465 EI 1527-6473 J9 LIVER TRANSPLANT JI Liver Transplant. PD JUN PY 2014 VL 20 SU 1 MA P-54 BP S168 EP S168 PG 1 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA AM6FU UT WOS:000339959601203 ER PT J AU Basu, PP Shah, NJ Aloysius, M AF Basu, P. Patrick Shah, Niraj J. Aloysius, Mark TI Role of Mycophenolate Mofetil (MMF) in Steroid Non Responsive Severe Acute Alcoholic Hepatitis: A Randomized Open Label Placebo Control Prospective Clinical Pilot Trial SO LIVER TRANSPLANTATION LA English DT Meeting Abstract CT Joint International Congress of ILTS, ELITA and LICAGE CY JUN 04-07, 2014 CL London, ENGLAND SP ILTS, ELITA, LICAGE C1 [Basu, P. Patrick] Columbia Sch Phys & Surg, New York, NY USA. [Aloysius, Mark] Kings Cty Hosp, Med Ctr, New York, NY USA. [Shah, Niraj J.] Mt Sinai Sch Med, James J Peters VA Med Ctr, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1527-6465 EI 1527-6473 J9 LIVER TRANSPLANT JI Liver Transplant. PD JUN PY 2014 VL 20 SU 1 MA O-122 BP S142 EP S142 PG 1 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA AM6FU UT WOS:000339959601122 ER PT J AU Basu, PP Shah, NJ Aloysius, M Siriki, R Rahaman, M AF Basu, P. Patrick Shah, Niraj J. Aloysius, Mark Siriki, Ravi Rahaman, Md TI Romiplostim's Effect to Optimize SVR with Telaprevir, Ribavirin, And Peg Interferon-alfa 2a in Thrombocytopenic Cirrhotics with Chronic Hepatitis C. A Placebo Controlled Prospective Clinical Trial: RESTRAINT C Trial. SO LIVER TRANSPLANTATION LA English DT Meeting Abstract CT Joint International Congress of ILTS, ELITA and LICAGE CY JUN 04-07, 2014 CL London, ENGLAND SP ILTS, ELITA, LICAGE C1 [Basu, P. Patrick] Columbia Univ Coll Phys & Surg, New York, NY USA. [Basu, P. Patrick; Aloysius, Mark; Siriki, Ravi; Rahaman, Md] NSLIJHS, Hofstra North Shore LIJ Sch Med, New York, NY USA. [Shah, Niraj J.] Mt Sinai Sch Med Mt Sinai, James J Peters VA Med Ctr, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1527-6465 EI 1527-6473 J9 LIVER TRANSPLANT JI Liver Transplant. PD JUN PY 2014 VL 20 SU 1 MA O-69 BP S124 EP S124 PG 1 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA AM6FU UT WOS:000339959601069 ER PT J AU Liu, QL Rehman, H Krishnasamy, Y Schnellmann, R Lemasters, J Zhong, Z AF Liu, Qinlong Rehman, Hasibur Krishnasamy, Yasodha Schnellmann, Rick Lemasters, John Zhong, Zhi TI AMP-Activated Protein Kinase (AMPK) Deficiency Increases Mitochondrial Dysfunction after Liver Transplantation in Mice SO LIVER TRANSPLANTATION LA English DT Meeting Abstract CT Joint International Congress of ILTS, ELITA and LICAGE CY JUN 04-07, 2014 CL London, ENGLAND SP ILTS, ELITA, LICAGE C1 [Liu, Qinlong; Rehman, Hasibur; Krishnasamy, Yasodha; Schnellmann, Rick; Lemasters, John; Zhong, Zhi] Med Univ S Carolina, Charleston, SC USA. [Schnellmann, Rick] Ralph H Johnson VA Med Ctr, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1527-6465 EI 1527-6473 J9 LIVER TRANSPLANT JI Liver Transplant. PD JUN PY 2014 VL 20 SU 1 MA P-518 BP S312 EP S312 PG 1 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA AM6FU UT WOS:000339959602387 ER PT J AU Shores, MM Biggs, ML Arnold, AM Smith, NL Longstreth, WT Kizer, JR Hirsch, CH Cappola, AR Matsumoto, AM AF Shores, Molly M. Biggs, Mary L. Arnold, Alice M. Smith, Nicholas L. Longstreth, W. T., Jr. Kizer, Jorge R. Hirsch, Calvin H. Cappola, Anne R. Matsumoto, Alvin M. TI Testosterone, Dihydrotestosterone, and Incident Cardiovascular Disease and Mortality in the Cardiovascular Health Study SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID LOW SERUM TESTOSTERONE; CORONARY-ARTERY DISEASE; ENDOGENOUS SEX-HORMONES; POPULATION-BASED COHORT; OLDER MEN; PLASMA TESTOSTERONE; ELDERLY-MEN; ANDROGEN DEFICIENCY; PREDICT MORTALITY; MASS-SPECTROMETRY AB Context: Low testosterone (T) is associated with prevalent cardiovascular disease (CVD) and mortality. DHT, a more potent androgen, may also be associated with CVD and mortality, but few studies have examined this. Objective: The study objective was to examine whether T and DHT are risk factors for incident CVD and mortality. Design: In a longitudinal cohort study, we evaluated whether total T, calculated free T (cFT), DHT, and calculated free DHT were associated with incident CVD and mortality in men in the Cardiovascular Health Study (mean age 76, range 66-97 years) who were free of CVD at the time of blood collection. Main Outcome: The main outcomes were incident CVD and all-cause mortality. Results: Among 1032 men followed for a median of 9 years, 436 incident CVD events and 777 deaths occurred. In models adjusted for cardiovascular risk factors, total T and cFT were not associated with incident CVD or all-cause mortality, whereas DHT and calculated free DHT had curvilinear associations with incident CVD (P < .002 and P = .04, respectively) and all-cause mortality (P < .001 for both). Conclusions: In a cohort of elderly men, DHT and calculated free DHT were associated with incident CVD and all-cause mortality. Further studies are needed to confirm these results and to clarify the underlying physiologic mechanisms. C1 [Shores, Molly M.; Smith, Nicholas L.; Matsumoto, Alvin M.] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Smith, Nicholas L.] VA Epidemiol Res & Informat Ctr, Seattle, WA 98108 USA. [Shores, Molly M.] Univ Washington, Dept Psychiat & Behav Sci, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA. [Biggs, Mary L.; Arnold, Alice M.] Univ Washington, Dept Biostat, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA. [Smith, Nicholas L.; Longstreth, W. T., Jr.] Univ Washington, Dept Epidemiol, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA. [Longstreth, W. T., Jr.] Univ Washington, Dept Neurol, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA. [Matsumoto, Alvin M.] Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA. [Kizer, Jorge R.] Albert Einstein Coll Med, Dept Med, Bronx, NY 10461 USA. [Kizer, Jorge R.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA. [Hirsch, Calvin H.] Univ Calif Davis, Dept Internal Med, Davis, CA 95616 USA. [Cappola, Anne R.] Univ Penn, Dept Internal Med, Div Endocrinol, Philadelphia, PA 19104 USA. RP Shores, MM (reprint author), VA Puget Sound Hlth Care Syst, 1660 South Columbian Way,S-116A, Seattle, WA 98108 USA. EM molly.shores@va.gov FU VA Research Service; VA Epidemiology Research and Information Center; VA Geriatric Research, Education and Clinical Center; NIH [1R01HL091952]; National Heart, Lung, and Blood Institute [HHSN268201200036C, N01-HC-85239, N01 HC-55222, N01-HC-85079, N01-HC-85080, N01-HC-85081, N01-HC-85082, N01-HC-85083, N01-HC85086, HL080295]; National Institute on Aging [AG-023629] FX This work was supported by the VA Research Service, the VA Epidemiology Research and Information Center, and the VA Geriatric Research, Education and Clinical Center; by NIH 1R01HL091952 and contracts HHSN268201200036C, N01-HC-85239, N01 HC-55222, N01-HC-85079, N01-HC-85080, N01-HC-85081, N01-HC-85082, N01-HC-85083, N01-HC85086, and Grant HL080295 from the National Heart, Lung, and Blood Institute, with additional contribution from the National Institute of Neurological Disorders and Stroke. Additional support was provided by AG-023629 from the National Institute on Aging. A full list of principal CHS investigators and institutions can be found at http://www.chs-nhlbi.org. NR 43 TC 26 Z9 26 U1 0 U2 4 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 2014 VL 99 IS 6 BP 2061 EP 2068 DI 10.1210/jc.2013-3576 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AP8PI UT WOS:000342340500047 PM 24628549 ER PT J AU Donnelly, JP Baddley, JW Wang, HE AF Donnelly, John P. Baddley, John W. Wang, Henry E. TI Reply to "Acute Sinusitis and Pharyngitis as Inappropriate Indications for Antibiotic Use" SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Letter ID RESPIRATORY-TRACT INFECTIONS C1 [Donnelly, John P.; Wang, Henry E.] Univ Alabama Birmingham, Dept Emergency Med, Birmingham, AL USA. [Baddley, John W.] Univ Alabama Birmingham, Dept Med, Div Infect Dis, Birmingham, AL 35294 USA. [Baddley, John W.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Baddley, JW (reprint author), Univ Alabama Birmingham, Dept Med, Div Infect Dis, Birmingham, AL 35294 USA. EM jbaddley@uab.edu OI Donnelly, John/0000-0002-0646-9470 FU None [HS013852] NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 EI 1098-6596 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUN PY 2014 VL 58 IS 6 BP 3573 EP 3573 DI 10.1128/AAC.02779-14 PG 1 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA AK9VP UT WOS:000338776900082 PM 24829388 ER EF