Design of VA CoronavirUs Research and Efficacy Studies-1 (VA CURES-1): A double-blind, randomized placebo-controlled trial of COVID-19 convalescent plasma in hospitalized patients with early respiratory compromise.

Background: Effective therapeutics for severe acute respiratory syndrome CoronaVirus-2 (SARS-CoV-2) infection are evolving. Under Emergency Use Authorization, COVID-19 convalescent plasma (CCP) was widely used in individuals hospitalized for COVID-19, but few randomized controlled trials supported its efficacy to limit respiratory failure or death.

Methods: VA CoronavirUs Research and Efficacy Studies-1 (VA CURES-1) was a double-blind, multi-site, placebo-controlled, randomized clinical trial evaluating the efficacy and safety of CCP with conventional therapy in hospitalized Veterans with SARS-CoV-2 infection and early respiratory compromise (requirement for oxygen).

Penetrance and Pleiotropy of Polygenic Risk Scores for Schizophrenia, Bipolar Disorder, and Depression Among Adults in the US Veterans Affairs Health Care System.

Importance: Serious mental illnesses, including schizophrenia, bipolar disorder, and depression, are heritable, highly multifactorial disorders and major causes of disability worldwide.

Objective: To benchmark the penetrance of current neuropsychiatric polygenic risk scores (PRSs) in the Veterans Health Administration health care system and to explore associations between PRS and broad categories of human disease via phenome-wide association studies.

Design, Setting, And Participants: Extensive Veterans Health Administration's electronic health records were assessed from October 1999 to January 2021, and an embedded cohort of 9378 individuals with confirmed diagnoses of schizophrenia or bipolar 1 disorder were found.

Designing and implementing methodology for double-blind, placebo-controlled clinical trials using blood products within the Department of Veterans Affairs.

Background: Success in conducting clinical trials during the coronavirus disease of 2019 pandemic requires the ability to innovate and adapt. There are well-established procedures for the blinding of investigational agents, especially medications, in placebo-controlled randomized clinical trials within the Veterans Health Administration. However, these procedures, managed by research pharmacists, may not apply to investigational agents that are not exclusively managed by pharmacy, such as blood products, including coronavirus disease of 2019 convalescent plasma (plasma).

Genome-Wide Association Studies of Schizophrenia and Bipolar Disorder in a Diverse Cohort of US Veterans.

Background: Schizophrenia (SCZ) and bipolar disorder (BIP) are debilitating neuropsychiatric disorders, collectively affecting 2% of the world's population. Recognizing the major impact of these psychiatric disorders on the psychosocial function of more than 200 000 US Veterans, the Department of Veterans Affairs (VA) recently completed genotyping of more than 8000 veterans with SCZ and BIP in the Cooperative Studies Program (CSP) #572.

Methods: We performed genome-wide association studies (GWAS) in CSP #572 and benchmarked the predictive value of polygenic risk scores (PRS) constructed from published findings.

Plaque Regression and Endothelial Progenitor Cell Mobilization With Intensive Lipid Elimination Regimen (PREMIER).

Background: Low-density lipoproteins (LDLs) are removed by extracorporeal filtration during LDL apheresis. It is mainly used in familial hyperlipidemia. The PREMIER trial (Plaque Regression and Progenitor Cell Mobilization With Intensive Lipid Elimination Regimen) evaluated LDL apheresis in nonfamilial hyperlipidemia acute coronary syndrome patients treated with percutaneous coronary intervention.

Genome-wide association study of cognitive performance in U.S. veterans with schizophrenia or bipolar disorder.

Cognitive impairment is a frequent and serious problem in patients with various forms of severe mental illnesses (SMI), including schizophrenia (SZ) and bipolar disorder (BP). Recent research suggests genetic links to several cognitive phenotypes in both SMI and in the general population. Our goal in this study was to identify potential genomic signatures of cognitive functioning in veterans with severe mental illness and compare them to previous findings for cognition across different populations.

Noncommercial US Funders' Policies on Trial Registration, Access to Summary Results, and Individual Patient Data Availability.

Importance: Incomplete information about existing research is an underlying cause of research waste. National and international initiatives and requirements have been launched to address this issue.

Objectives: To characterize current clinical trial transparency policies among the largest noncommercial US funders and examine whether the policies are concordant with international funders.

Trial of Prazosin for Post-Traumatic Stress Disorder in Military Veterans.

Background: In randomized trials, prazosin, an α-adrenoreceptor antagonist, has been effective in alleviating nightmares associated with post-traumatic stress disorder (PTSD) in military veterans.

Methods: We recruited veterans from 13 Department of Veterans Affairs medical centers who had chronic PTSD and reported frequent nightmares. Participants were randomly assigned to receive prazosin or placebo for 26 weeks; the drug or placebo was administered in escalating divided doses over the course of 5 weeks to a daily maximum of 20 mg in men and 12 mg in women.

Physical Health Conditions Among a Population-Based Cohort of Vietnam-Era Women Veterans: Agreement Between Self-Report and Medical Records.

Background: Little is known about medical morbidity among women Vietnam-era veterans, or the long-term physical health problems associated with their service. This study assessed agreement comparing data on physical health conditions from self-report and medical records from a population-based cohort of women Vietnam-era Veterans from the Health of Vietnam Era Women's Study (HealthViEWS).

Materials And Methods: Women Vietnam-era veterans (n = 4219) self-completed a survey and interview on common medical conditions.

Effect of Antidepressant Switching vs Augmentation on Remission Among Patients With Major Depressive Disorder Unresponsive to Antidepressant Treatment: The VAST-D Randomized Clinical Trial.

Importance: Less than one-third of patients with major depressive disorder (MDD) achieve remission with their first antidepressant.

Objective: To determine the relative effectiveness and safety of 3 common alternate treatments for MDD.

Design, Setting, And Participants: From December 2012 to May 2015, 1522 patients at 35 US Veterans Health Administration medical centers who were diagnosed with nonpsychotic MDD, unresponsive to at least 1 antidepressant course meeting minimal standards for treatment dose and duration, participated in the study.

Longitudinal Examination of Posttraumatic Stress Disorder as a Long-Term Outcome of Iraq War Deployment.

The mental health toll of the Iraq and Afghanistan Wars on military veterans has been considerable, yet little is known about the persistence of these adverse outcomes, especially relative to predeployment status. We prospectively examined posttraumatic stress disorder (PTSD) as a long-term consequence of warzone deployment, integrating data collected from 2003-2014. In the Neurocognition Deployment Health Study, we measured PTSD symptoms in US Army soldiers before and shortly after Iraq War deployment.

Long-Term Trajectories of PTSD in Vietnam-Era Veterans: The Course and Consequences of PTSD in Twins.

We estimated the temporal course of posttraumatic stress disorder (PTSD) in Vietnam-era veterans using a national sample of male twins with a 20-year follow-up. The complete sample included those twins with a PTSD diagnostic assessment in 1992 and who completed a DSM-IV PTSD diagnostic assessment and a self-report PTSD checklist in 2012 (n = 4,138). Using PTSD diagnostic data, we classified veterans into 5 mutually exclusive groups, including those who never had PTSD, and 4 PTSD trajectory groups: (a) early recovery, (b) late recovery, (c) late onset, and (d) chronic.

Prevalence of Post-Traumatic Stress Disorder in Aging Vietnam-Era Veterans: Veterans Administration Cooperative Study 569: Course and Consequences of Post-Traumatic Stress Disorder in Vietnam-Era Veteran Twins.

Objective: The prevalence of post-traumatic stress disorder (PTSD) among aging Vietnam-era veterans is not well characterized.

Methods: In a cross-sectional study, 5,598 male Vietnam-era veterans and members of the Vietnam Era Twin Registry were assessed for PTSD using the Composite International Diagnostic Interview. Current symptoms were measured with the PTSD Checklist (PCL).

Prevalence of Posttraumatic Stress Disorder in Vietnam-Era Women Veterans: The Health of Vietnam-Era Women's Study (HealthVIEWS).

Importance: Many Vietnam-era women veterans served in or near war zones and may have experienced stressful or traumatic events during their service. Although posttraumatic stress disorder (PTSD) is well studied among men who served in Vietnam, no major epidemiologic investigation of PTSD among women has been performed.

Objectives: To assess (1) the onset and prevalence of lifetime and current PTSD for women who served during the Vietnam era, stratified by wartime location (Vietnam, near Vietnam, or the United States), and (2) the extent to which wartime location was associated with PTSD, with adjustment for demographics, service characteristics, and wartime exposures.

The VA augmentation and switching treatments for improving depression outcomes (VAST-D) study: Rationale and design considerations.

Because two-thirds of patients with Major Depressive Disorder do not achieve remission with their first antidepressant, we designed a trial of three "next-step" strategies: switching to another antidepressant (bupropion-SR) or augmenting the current antidepressant with either another antidepressant (bupropion-SR) or with an atypical antipsychotic (aripiprazole). The study will compare 12-week remission rates and, among those who have at least a partial response, relapse rates for up to 6 months of additional treatment. We review seven key efficacy/effectiveness design decisions in this mixed "efficacy-effectiveness" trial.

Posttraumatic stress disorder and incidence of type-2 diabetes: a prospective twin study.

Growing evidence has linked posttraumatic stress disorder (PTSD) to insulin resistance and type-2 diabetes, but most previous studies were cross-sectional. We examined the association between PTSD and incidence of diabetes in a prospective study of middle-aged male twins from the Vietnam Era Twin Registry. Lifetime PTSD was diagnosed at baseline with the Diagnostic Interview Schedule (DIS) according to DSM-III-R criteria.

The genetics of functional disability in schizophrenia and bipolar illness: Methods and initial results for VA cooperative study #572.

Given the prominence of cognitive impairments and disability associated with schizophrenia and bipolar disorder, substantial interest has arisen in identifying determinants of the diseases and their features. Genetic variation has been linked to skills that underlie disability ("functional capacity" or FC), highlighting need for understanding of these relationships. We describe the design and methods of a large, multisite, observational study focusing on the genetics of functional disability in schizophrenia and bipolar disorder, presenting initial data on recruitment, and characterization of the sample.

Veterans Healthcare Administration providers' attitudes and perceptions regarding pragmatic trials embedded at the point of care.

Background The Veterans Healthcare Administration (VA) is implementing an adaptation of a pragmatic trial program, Point of Care Research (POC-R). The goal of POC-R is to embed research into clinical practice, contributing to a Learning Healthcare System. Provider acceptance and participation in POC-R is essential to its successful implementation.

The association of PTSD with physical and mental health functioning and disability (VA Cooperative Study #569: the course and consequences of posttraumatic stress disorder in Vietnam-era veteran twins).

Purpose: To assess the relationship of posttraumatic stress disorder (PTSD) with health functioning and disability in Vietnam-era Veterans.

Methods: A cross-sectional study of functioning and disability in male Vietnam-era Veteran twins. PTSD was measured by the Composite International Diagnostic Interview; health functioning and disability were assessed using the Veterans RAND 36-Item Health Survey (VR-36) and the World Health Organization Disability Assessment Schedule 2.