VA Cooperative Study Research Articles

Hypertension: is it more than just a numbers game?

Hypertension: is it more than just a numbers game?

Correction

We would like to report an erratum to the paper titled ‘Integrative analysis of multiple cancer genomic datasets under the heterogeneity model’ by Liu, Huang and Ma, Statistics in Medicine. The Acknowledgements should be ‘We thank the associate editor and two reviewers for careful review and insightful comments, which have led to a significant improvement of this article. This study has been partly supported by awards CA142774, CA165923 and CA152301 from NCI, NIH, DMS 1208225 from NSF, the VA Cooperative Studies Program of the Department of Veterans Affairs, Office of Research and Development, and 2012LD001 from National Bureau of Statistics of China.’

Recent Trends in the Incidence, Treatment, and Prognosis of Patients With Heart Failure and Atrial Fibrillation (the Worcester Heart Failure Study)

Atrial fibrillation (AF) and heart failure (HF) are common cardiovascular diseases and the co-occurrence of AF and HF has been associated with reduced survival. Data are needed on the potentially changing trends in the characteristics, treatment, and prognosis of patients with acute decompensated HF (ADHF) and AF. The study population consisted of 9,748 patients hospitalized with ADHF at 11 hospitals in the Worcester, Massachusetts, metropolitan area during 4 study years (1995, 2000, 2002, and 2004). Of the 9,748 patients admitted with ADHF, 3,868 (39.7%) had a history of AF and 449 (4.6%) developed new-onset AF during hospitalization. The rates of new-onset AF remained stable (4.9% in 1995; 5.0% in 2004), but the proportion of patients with pre-existing AF (34.5% in 1995; 41.6% in 2004) increased over time. New-onset and pre-existing AF were associated with older age, but pre-existing AF was more closely linked to a greater co-morbid disease burden. The use of HF therapies did not differ greatly by AF status. Despite this, new-onset AF was associated with a longer length of stay (7.5 vs 6.1 days) and greater in-hospital death rates (11.4% vs 6.6%). In contrast, pre-existing AF was associated with lower rates of postdischarge survival compared to patients with no AF (p <0.05 for all). The mortality rates improved significantly over time in patients with AF. In conclusion, AF was common among patients with ADHF, and the proportion of ADHF patients with co-occurring AF increased during the study period. Despite improving trends in survival, patients with ADHF and AF are at increased risk of in-hospital and postdischarge mortality.

Erectile Dysfunction

Erectile Dysfunction

Design of “Neuropsychological and Mental Health Outcomes of Operation Iraqi Freedom

ObjectiveThis study aimed to describe methodological challenges encountered in designing a follow-up assessment of US Army Soldiers who served in Operation Iraqi Freedom.Study Design and SettingThe Neurocognition Deployment Health Study...

Samuel C Kaim

Samuel C Kaim had a long life. He was born in New York City on 24 November 1911 and died on 24 March 2012 in Washington, DC. During this period, he saw and contributed to the birth and enormous growth of our field. His undergraduate training was in Cleveland at Western Reserve (Case Western) and his medical training in Switzerland at the University of Zurich, with a residency there at the Burgholzli Clinic. For his first, direct exposure to psychopharmacology, he was charged with administering insulin and metrazole seizure therapies. With little doubt, the residency had many influences on his later career. He conducted a private practice for several years in Illinois, interrupted by 4 years as a medical officer during WWII. In 1950, he took what was to be the first of many positions in the VA. First, he headed psychiatry and neurology at the VA Hospital in Coral Gables, Florida. The VA was becoming a major source of clinical trials at the time and Sam participated in these, using EEG techniques, and was among the first to show the profound effects of chlordiazepoxide in reducing or preventing both seizures and delirium tremens in alcohol withdrawal. In 1960, he went to the central office of the VA to become the head of research nationwide for psychiatry and neurology. He became a strong advocate of VA Cooperative Studies and decided to use this mechanism to pursue the benefits of chlordiazepoxide in the alcohol withdrawal syndrome, and it became widely recognized as the drug of choice for this use. The VA had been slow to recognize alcoholism as worthy of its own service. After considerable advocacy, Sam became the first director of an Alcoholism Service in the VA. He helped to compel armed forces personnel to recognize the significance of opioid dependence in Vietnam, leading a charge for expansion of his office in 1970 to become the Alcohol and Drug Dependence Services. Through his VA appointment, Sam had the opportunity to work with Jerome Jaffe when Jerry headed the Special Action Office for Drug Abuse Prevention. Together with their colleagues, they focused on development of the long-acting methadone, ℒ-α-acetyl-methadol (LAAM) for heroin treatment, and on development of naltrexone, the long-acting narcotic antagonist, as a useful agent in heroin addiction. Though it took until 1993 for LAAM to be approved by the FDA, their perseverance had an important role in the survival of these interesting interventions. Certainly, we have yet to discover the final place of naltrexone in medicine. Sam left the VA in 1975 and became director of staff of the National Academy of Sciences that coordinated one of the pilot studies of naltrexone in the treatment of heroin abuse. He was also a consultant to NIDA in a variety of roles through to the approval of naltrexone for marketing by the FDA. He vigorously continued a variety of activities with professional organizations until he retired in 1993. Those of you who enjoy good collegial conversation will be delighted by the interview conducted by Leo Hollister of the then 85-year-old Sam for our History of the ACNP. It illustrates many, many of the interesting characteristics of Sam. Sam Kaim is survived by his son, Edward, of Weston, Connecticut, and two stepchildren, Judith Plavnick Kiley of Arlington, Virginia, and Jonathan Plavnick of Perry Hall, Maryland.

Robot Therapy Tipping Point

From the Departments of Neurology and Epidemiology, Brown University, Providence, RI; VARRD Center of Excellence for Neurorestoration and Neurotechnology, Providence VA Medical Center, Providence, RI; Neuroscience Research, Mandell Multiple Sclerosis Center, Saint Francis Hospital, Hartford CT (ACL); and VA Cooperative Studies Program, VA Connecticut Healthcare System, West Haven, Yale University (PDG). All correspondence and requests for reprints should be addressed to: Albert C. Lo, MD, PhD, Providence VA Medical Center, Building 32, 830 Chalkstone Ave, Providence, RI 02908-4799. Dr Albert Lo has received travel expense reimbursement from Hocoma. He has no other relevant disclosures. For all other disclosures, Dr Lo has received grants and travel reimbursement from the Department of Veterans Affairs and the National Multiple Sclerosis Society. He has received travel reimbursement from Novartis, the Department of Defense, and the University of Pennsylvania. He has received funding from Acorda Therapeutics for an investigator-initiated project. He has received honorarium from Scripps, Braintree, and Los Rancho Amigos. Albert Lo and Peter Guarino are federal government employees. Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article.

Longitudinal analysis of the relationship between PTSD symptom clusters, cigarette use, and physical health-related quality of life

Posttraumatic stress disorder (PTSD) symptoms, particularly numbing and hyperarousal symptoms, are related to poor physical health-related quality of life (HRQoL). Tobacco dependence is also associated with poor HRQoL, and individuals with PTSD may smoke at higher rates than the general population. Our study aimed to examine the impact of quitting smoking and changes in PTSD symptoms over time on changes in physical HRQoL. The study used archival data from enrollees (N = 943) in a smoking cessation clinical trial for veterans with PTSD (VA Cooperative study #519). Two of the physical HRQoL domains were sensitive to changes in PTSD symptoms over time: General Health and Vitality. Our findings suggest that particular physical HRQoL domains may be subject to improvement if PTSD symptoms decrease over time.

Concordance between physiological arousal and subjective distress among vietnam combat veterans undergoing challenge testing for PTSD

This study examined concordance between physiological arousal and subjective distress during a laboratory challenge task. Data were collected during the multisite VA Cooperative Study 334 in the early 1990s examining psychophysiological arousal among combat-exposed Vietnam veterans with (n = 775) and without (n = 369) posttraumatic stress disorder (PTSD). Study participants were presented with 6 standardized neutral scenes and 6 standardized combat scenes. Participants provided a subjective rating of distress after each slide. During the presentation, levels of heart rate (HR) and skin conductance (SC) were recorded. Using linear mixed effects modeling, both HR level and SC level exhibited significant positive associations with subjective distress ratings (pr = .33, p < .001 and pr = .19, p < .001, respectively). Individuals with PTSD demonstrated greater concordance between their distress ratings and SC level during exposure to combat slides than participants without PTSD (pr = .28, p < .001 vs. pr = .18, p < .001). Although a significant association was found between subjective distress and HR reactivity and SC reactivity, these findings were not moderated by PTSD status. The results of these analyses suggest that patients' reports of distress during exposure-based treatments might serve as approximate measures of actual physiological arousal.

PTSD and depression as predictors of physical health-related quality of life in tobacco-dependent veterans

ObjectiveSmoking, depression and PTSD are related to poor physical health outcomes and health-related quality of life (HRQoL). Previous studies examining the effects of quitting smoking on HRQoL have been mixed. This study aimed to examine the effects of PTSD, depressive symptoms and smoking cessation on HRQoL in a sample receiving treatment for PTSD. MethodThis study utilized archival interview and self-report data from a clinical trial (VA Cooperative Study 519) that recruited tobacco dependent veterans with chronic PTSD (N=943). ResultsAnalyses were conducted using hierarchical linear modeling and indicated that PTSD and depressive symptoms differentially affected the various physical health status domains. Additionally, quitting smoking was associated with better self-perceived health status and social functioning. ConclusionOur findings further explain the interrelationships of PTSD, depression, and smoking in the prediction of physical HRQoL and advocate the importance of integrated care.

Editorial introductions

Current Opinion in Gastroenterology was launched in 1985. It is one of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of gastroenterology is divided into 12 sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Section Editors for this issue. SECTION EDITORS Claudio FiocchiClaudio FiocchiDr Fiocchi is originally from Rome, Italy. He graduated from the Santa Casa de Misericordia School of Medicine in São Paulo, Brazil, and moved to the Cleveland Clinic Foundation, in Cleveland, Ohio, USA, where he received additional training in internal medicine, gastroenterology and basic immunology. Dr Fiocchi is currently Professor of Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Cleveland, Ohio and Professor of Pathology and Pediatrics at Case Western Reserve University School of Medicine, Cleveland, Ohio. In addition, he is a Staff Member in the Departments of Pathobiology, Lerner Research Institute, and Gastroenterology & Hepatology, Digestive Disease Institute, Cleveland Clinic Foundation. Dr Fiocchi has published numerous papers and has served or serves on the editorial boards of several journals, including Gastroenterology, American Journal of Physiology, Inflammatory Bowel Diseases, Journal of Crohn's & Colitis, Current Opinion in Gastroenterology, and Digestive and Liver Disease. He has been or is a member of numerous study sections of the National Institutes of Health and the Crohn's & Colitis Foundation of America. He received the prestigious MERIT Award from the National Institutes of Health, and the Clifford and Jane Anthony Chair in Digestive Disease Research and Education. In addition, he is the recipient of the Premier Physician Award and the Henry Janowitz Lifetime Achievement Award in Inflammatory Bowel Disease from the Crohn's & Colitis Foundation of America. He is also Honorary Foreign Member of the Brazilian Academy of Medicine. Dr Fiocchi's research is focused on the pathogenesis of inflammatory bowel disease. Studies include the identification of mechanisms of mucosal T-cell death and survival in gut inflammation, investigation of tolerance of mucosal T-cells for the autologous enteric flora and its possible loss in IBD, characterization of the interactions between mucosal T-cells and endothelial and stromal cells, and the study of immune-driven angiogenesis and fibrogenesis in intestinal inflammation. Stuart J. SpechlerStuart J. SpechlerStuart Jon Spechler, M.D. is Chief of the Division of Gastroenterology at the Dallas VA Medical Center, USA, Professor of Medicine, and holder of the Berta M. and Cecil O. Patterson Chair in Gastroenterology at The University of Texas Southwestern Medical Center at Dallas, USA. He is a graduate of Boston University School of Medicine, USA, and he spent many years working in Boston, both at Boston University and at the Beth Israel Deaconess Medical Center and Harvard Medical School, USA, where he was the Director of the Center for Swallowing Disorders from 1990 to 1997. He has been in Dallas on the faculty of UT Southwestern Medical Center since 1997. Dr Spechler's research has focused primarily on disorders of the esophagus, especially gastroesophageal reflux disease and its complications. He chaired the VA Cooperative Study on gastroesophageal reflux disease that was conducted in the 1980s, and he now chairs a new VA Cooperative Study on the treatment of GERD that is refractory to treatment with proton pump inhibitors. Dr. Spechler has published more than 300 scientific reports, editorials, review articles, and book chapters on esophageal disorders. He is perhaps best known for his work in the areas of GERD, Barrett's esophagus and, most recently on eosinophilic esophagitis. Dr Spechler has served on the editorial boards of numerous journals including Gastroenterology, Gut, Alimentary Pharmacology and Therapeutics, and Diseases of the Esophagus, and he has served as Chair of the Gastroenterology Teaching Project and the Esophago-gastro-duodenal Section of the American Gastroenterological Association.

Cost and Cost-Effectiveness in a Randomized Trial of Long-Acting Risperidone for Schizophrenia

The effect of long-acting injectable (LAI) risperidone on health care costs was determined in a multisite clinical trial. Veterans Health Administration patients with unstable schizophrenia or schizoaffective disorder established by the Structured Clinical Interview for DSM-IV (N = 369) were randomized between 2006 and 2009 to long-acting risperidone or physician's choice of oral antipsychotic. Health care utilization and cost were tracked in administrative data. Medication administered by the trial was recorded on case report forms. Medication cost was based on unit costs to the US Medicaid program. Economic outcomes were assessed with the Quality of Well-Being instrument. Participants randomized to LAI risperidone (n = 187) incurred $14,916 per quarter in total health care costs, which was not significantly different from the $13,980 cost incurred by the control group (P = .732) (n = 182). The LAI group incurred $3,028 per quarter in medication cost, significantly more than the $1,913 incurred by the control group (P = .003). Hospitalization costs were $7,088 in the experimental group and $6,891 in the control group (P = .943); outpatient costs were $11,888 in the experimental group and $12,067 in the control group (P = .639). LAI risperidone did not result in better outcomes as evaluated by a measure of schizophrenia symptoms or an assessment of health related quality of life and incurred more adverse events. Patients with unstable schizophrenia were randomized in a practical trial of LAI risperidone. This antipsychotic significantly increased medication costs but did not reduce hospital or total health care cost or improve outcomes and was thus not cost-effective. ClinicalTrials.gov identifier: NCT00132314.

Smoking intensity and severity of specific symptom clusters in posttraumatic stress disorder

Smoking prevalence among patients with posttraumatic stress disorder (PTSD) is over 40%. Baseline data from the VA Cooperative Studies Program trial of integrated versus usual care for smoking cessation in veterans with PTSD (N = 863) were used in multivariate analyses of PTSD and depression severity, and 4 measures of smoking intensity: cigarettes per day (CPD), Fagerström Test for Nicotine Dependence (FTND), time to first cigarette, and expired carbon monoxide. Multivariate regression analysis showed the following significant associations: CPD with race (B = -7.16), age (B = 0.11), and emotional numbing (B =0 .16); FTND with race (B = -0.94), education (B = -0.34), emotional numbing (B = 0.04), significant distress (B = -0.12), and PHQ-9 (B = 0.04); time to first cigarette with education (B = 0.41), emotional numbing (B = -0.03), significant distress (B = 0.09), and PHQ-9 (B = -0.03); and expired carbon monoxide with race (B = -9.40). Findings suggest that among veterans with PTSD, White race and emotional numbing were most consistently related to increased smoking intensity and had more explanatory power than total PTSD symptom score. Results suggest specific PTSD symptom clusters are important to understanding smoking behavior in patients with PTSD.

NYHA class I heart failure is not ‘mild’

The cardinal features of chronic heart failure (CHF) are symptoms of exercise intolerance due breathlessness or fatigue in the presence of left ventricular dysfunction. A variety of scales can be used document the severity of symptoms, with the New York Heart Association (NYHA) score being the most common. Patients are grouped into one of four levels [ [1] The Criteria Committee of the New York Heart AssociationDiseases of the heart and blood vessels. in: Nomenclature and Criteria for Diagnosis. 7th ed. Little, Brown and Co, Boston1973: 286 Google Scholar ]. Although subjective, the NYHA classification predicts morbidity and mortality, particularly in large populations of patients with heart failure [ 2 Scrutinio D. Lagioia R. Ricci A. Clemente M. Boni L. Rizzon P. Prediction of mortality in mild to moderately symptomatic patients with left ventricular dysfunction. The role of the New York Heart Association classification, cardiopulmonary exercise testing, two-dimensional echocardiography and Holter monitoring. Eur Heart J. 1994; 15: 1089-1095 PubMed Google Scholar , 3 Smith R.F. Johnson G. Ziesche S. Bhat G. Blankenship K. Cohn J.N. Functional capacity in heart failure. Comparison of methods for assessment and their relation to other indexes of heart failure. The V-HeFT VA Cooperative Studies Group. Circulation. 1993; 87: VI88-VI93 PubMed Google Scholar ]. Importantly, it is the severity of the symptoms and not their nature that is related to outcome [ [4] Witte K.K. Clark A.L. Dyspnoea versus fatigue: additional prognostic information from symptoms in chronic heart failure?. Eur J Heart Fail. 2008; 10: 1224-1228 Crossref PubMed Scopus (13) Google Scholar ]. Patients with few symptoms might be labeled as having ‘mild’ heart failure and might receive less attention and less aggressive management than those with more severe symptoms. In order to quantify the adverse prognosis conferred by asymptomatic left ventricular dysfunction, we compared the clinical features and survival of CHF patients rendered asymptomatic by treatment, ‘mild’ chronic heart failure, with those of similarly aged control subjects.

An evaluation of patient self-testing competency of prothrombin time for managing anticoagulation: pre-randomization results of VA Cooperative Study #481–The Home INR Study (THINRS)

Prior studies suggest patient self-testing (PST) of prothrombin time (PT) can improve the quality of anticoagulation (AC) and reduce complications (e.g., bleeding and thromboembolic events). "The Home INR Study" (THINRS) compared AC management with frequent PST using a home monitoring device to high-quality AC management (HQACM) with clinic-based monitoring on major health outcomes. A key clinical and policy question is whether and which patients can successfully use such devices. We report the results of Part 1 of THINRS in which patients and caregivers were evaluated for their ability to perform PST. Study-eligible patients (n = 3643) were trained to use the home monitoring device and evaluated after 2-4 weeks for PST competency. Information about demographics, medical history, warfarin use, medications, plus measures of numeracy, literacy, cognition, dexterity, and satisfaction with AC were collected. Approximately 80% (2931 of 3643) of patients trained on PST demonstrated competency; of these, 8% (238) required caregiver assistance. Testers who were not competent to perform PST had higher numbers of practice attempts, higher cuvette wastage, and were less able to perform a fingerstick or obtain blood for the cuvette in a timely fashion. Factors associated with failure to pass PST training included increased age, previous stroke history, poor cognition, and poor manual dexterity. A majority of patients were able to perform PST. Successful home monitoring of PT with a PST device required adequate levels of cognition and manual dexterity. Training a caregiver modestly increased the proportion of patients who can perform PST.

Colonoscopy Withdrawal Time and Risk of Neoplasia at 5 Years: Results From VA Cooperative Studies Program 380

Withdrawal time (WT) has been proposed as a quality indicator for colonoscopy based on evidence that it is directly related to the rate of adenoma detection. Our objective was to test the hypothesis that baseline WT is inversely associated with the risk of finding neoplasia at interval colonoscopy. In all, 3,121 subjects, aged 50-75 years, had screening colonoscopy between 1994 and 1997 at 13 Veteran Affairs Medical Centers. In all, 1,193 subjects returned by protocol for surveillance within 5.5 years. In the 304 patients without polyps at baseline, we evaluated the contribution of baseline WT to their risk of interval neoplasia using bivariate and logistic regression analysis. We also examined the correlation between mean WT, baseline adenoma detection rate, and interval neoplasia rate at the medical-center level. The average WT at the baseline exam in subjects with neoplasia on follow-up was 15.3 min as compared with 13.2 min in subjects without neoplasia (P=0.18). In a logistic regression model, WT was not associated with the risk of interval neoplasia (P=0.07). At the medical-center level, mean WT was not correlated with the probability of finding interval neoplasia (P=0.61) but was positively correlated with adenoma detection rate at baseline (P=0.03). In this study with a mean baseline WT &12 min, there was no detectable association between WT and risk of future neoplasia. The medical center-level WT was positively correlated with adenoma detection. Therefore, above a certain threshold, WT may no longer be an adequate quality measure for screening colonoscopy.

Progress and Challenges in Colorectal Cancer Screening and Surveillance

Colorectal cancer is a leading cause of cancer death throughout the world. There is evidence that screening of average-risk individuals can result in mortality reduction with early cancer detection and cancer prevention by detection and removal of cancer precursor lesions. The optimal form of screening is not clear. Fecal screening tests can be performed at home at low initial cost, but current versions lack high sensitivity for cancer precursor lesions, and tests need to be repeated at regular intervals. Adherence to repeat testing for negative tests and referral for colonoscopy for positive tests are important elements of program effectiveness. Structural examinations of the colon are more invasive and may result in detection of both early cancer and cancer precursor lesions. Every screening program has advantages and limitations, but each program ultimately depends on quality and patient adherence.

Risk Factors for Transition From Normal Platelet Count to Severe Thrombocytopenia Among Patients with Chronic Liver Disease.

Abstract 3518Poster Board III-455 IntroductionThrombocytopenia [TCP] is a complication of advanced chronic liver disease [CLD]. We examined clinical factors related to the development of severe TCP among patients with initially normal platelet counts using laboratory, clinical, and administrative data from the Veterans Administration Healthcare System, New England region. MethodsAll patients with a diagnosis of CLD or hepatitis C who were seen in a VA hospital or in a VA outpatient clinic between 10/2002 and 9/2008 were included in this analysis. CLD diagnosis definitions included: 1) ICD9-CM code of 51.0 – 571.9, excluding 571.1at a clinic visit or hospital discharge 2) positive hepatitis C [Hep-C] antibody, and 3) elevated ALT (> 84 IU/dL) on two occasions at least 60 days. Subjects were required to have normal platelet counts (platelet count >150,000/μL) at baseline. Subjects were excluded if they had the following: 1) hepatorenal syndrome, coagulation disorders, immune TCP purpura, lupus erythematosis, rheumatoid arthritis, pernicious anemia, aplastic anemia or septicemia. Severe TCP was defined as a platelet count < 50,000/μL. Risk factors evaluated for the development of TCP included age, comorbidities (diabetes, alcoholic and/or drug dependence, chronic kidney disease, Hepatitis-C [Hep-C] status, hepatorenal syndrome, congestive heart failure [CHF], coronary artery disease, hypertension), resource utilization (infectious disease, gastrointestinal [GI] nephrology and/or hematology clinic visit), and current laboratory values (hemoglobin, ALT and MELD Score). All potential predictors were treated as time-varying exposures over the follow-up and updated at each interval. Relative risk was estimated using logistic regression with pooled repeated observations, using 3-month periods where risk factors at the beginning of a 3-month interval were used to predict severe TCP in that interval. Results6,102 subjects with Hep-C contributed a median follow-up of 1,414 days and had 82 events (1.34%) during the study. 5,358 Non Hep-C subjects contributed a median follow-up of 1,238 days and had 97 events (1.81%) during the study. The median platelet count among CLD patients at baseline was 238,000/μL (IQR 203,000/μL- 282,000/μL) and among Hep-C patients at baseline was 240,000 (IQR 205,000/μL- 285,000/μL). After multivariate adjustment, alcohol dependence [Odds ratio = 2.24, 95% confidence interval: (1.14, 4.39)], CHF [2.6 (1.05,6.43)], 5 unit change in MELD [1.13 (1.05,1.21)], GI clinic visits [1.89 (0.93,3.87)] and anti retroviral therapy [3.84 (1.60, 7.61)] increased the odds of severe TCP; while drug dependence [0.62 (0.34, 1.13)] and increasing hemoglobin [0.74 (0.65,0.84)] reduced the odds of severe TCP. In non Hep-C subjects, alcohol dependence [2.88 (1.58,5.25)], CHF [1.81 (0.9, 3.65)], 5 unit change in MELD [1.12 (1.03, 1.23)], hematology clinic [3.64 (1.91, 6.93)] current anti-retroviral therapy [6.65 (1.96, 22.6)] and ALT 42-84g/dL vs. ALT < 42g/dL [1.55 (0.78, 3.06)] increased the odds of severe TCP; while drug dependence [0.46 (0.17, 1.22)], increasing hemoglobin [0.68 (0.60, 0.78)] and ALT > 84g/dL vs. ALT < 42 reduced the odds of severe TCP. ConclusionsIn a population of veterans with chronic liver disease or hepatitis C infection with normal platelet counts > 150,000/μL at baseline, we estimate the incidence of development of severe thrombocytopenia to be between 1 and 2% over an average of 3 years of follow-up. Key clinical predictors of development of severe TCP included prevalent CHF diagnosis and changing MELD score. Specialist care referrals to hematologists and gastroenterologists, also identified patients likely to become severe TCP cases. As expected, antiretroviral therapies were associated with an increased risk of severe TCP over the follow-up. AcknowledgmentsGlaxoSmithKline provided research support for this project, with no restrictions on publication. The study was conducted using resources of the VA Cooperative Studies Program and VA Boston Healthcare System. Disclosures:Lawler:GlaxoSmithKline: Research Funding. Horblyuk:GlaxoSmithKline: Employment. Grotzinger:GlaxoSmithKline: Employment, Research Funding.

Decreased Cancer Risk After Iron Reduction in Patients With Peripheral Arterial Disease: Results From a Randomized Trial

Excess iron has been implicated in cancer risk through increased iron-catalyzed free radical-mediated oxidative stress. A multicenter randomized, controlled, single-blinded clinical trial (VA Cooperative Study #410) tested the hypothesis that reducing iron stores by phlebotomy would influence vascular outcomes in patients with peripheral arterial disease. Patients without a visceral malignancy in the last 5 years (n = 1277) were randomly assigned to control (n = 641) or iron reduction (n = 636). Occurrence of new visceral malignancy and cause-specific mortality data were collected prospectively. Cancer and mortality outcomes in the two arms were compared using intent-to-treat analysis with a Cox proportional hazards regression model. Statistical tests were two-sided. Patients were followed up for an average of 4.5 years. Ferritin levels were similar in both groups at baseline but were lower in iron reduction patients than control patients across all 6-month visits (mean = 79.7 ng/mL, 95% confidence interval [CI] = 73.8 to 85.5 ng/mL vs 122.5 ng/mL, 95% CI = 115.5 to 129.5 ng/mL; P < .001). Risk of new visceral malignancy was lower in the iron reduction group than in the control group (38 vs 60, hazard ratio [HR] = 0.65, 95% CI = 0.43 to 0.97; P = .036), and, among patients with new cancers, those in the iron reduction group had lower cancer-specific and all-cause mortality (HR = 0.39, 95% CI = 0.21 to 0.72; P = .003; and HR = 0.49, 95% CI = 0.29 to 0.83; P = .009, respectively) than those in the control group. Mean ferritin levels across all 6-monthly visits were similar in patients in the iron reduction and control groups who developed cancer but were lower among all patients who did not develop cancer than among those who did (76.4 ng/mL, 95% CI = 71.4 to 81.4 ng/mL, vs 127.1 ng/mL, 95% CI = 71.2 to 183.0 ng/mL; P = .017). Iron reduction was associated with lower cancer risk and mortality. Further studies are needed to define the role of body iron in cancer risk.

Is the collaborative chronic care model effective for patients with bipolar disorder and co-occurring conditions?

The effectiveness of bipolar collaborative chronic care models (B-CCMs) among those with co-occurring substance use, psychiatric, and/or medical conditions has not specifically been assessed. We assessed whether B-CCM effects are equivalent comparing those with and without co-occurring conditions. We reanalyzed data from the VA Cooperative Study #430 (n=290), an 11-site randomized controlled trial of the B-CCM compared to usual care. Moderators included common co-occurring conditions observed in patients with bipolar disorder, including substance use disorders (SUD), anxiety, psychosis; medical comorbidities (total number), and cardiovascular disease-related conditions (CVD). Mixed-effects regression models were used to determine interactive effects between moderators and 3-year primary outcomes. Treatment effects were comparable for those with and without co-occurring substance use and psychiatric conditions, although possibly less effective in improving physical quality of life in those with CVD-related conditions (Beta=-6.11;p=0.04). Limitations included multiple comparisons and underpowered analyses of moderator effects. B-CCM effects were comparable in patients with co-occurring conditions, indicating that the intervention may be generally applied. Specific attention to physical quality of life in those with CVD maybe warranted.