Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Development of the Self-Efficacy as Faculty Change Agent for Diversity (SE-FCA-D) Scale

This publication provides an overview of the development of the Self-Efficacy as Faculty Change Agent for Diversity (SE-FCA-D) scale. The 5-item scale recently appeared as an additional module on the Higher Education and Research Institute (HERI) Faculty Survey 2019-2020 for the 10 BUILD programs within the Diversity Program Consortium that are participating in the Enhance Diversity Study, supported by the National Institutes of Health (NIH U54GM119024). The piloted scale is meant to measure DPC Hallmark of Success FAC-16: “Strong self-efficacy to act as a change agent to enhance diversity in biomedical research and research training environments” (DPC, 2019). Once data are available, scale validation will move forward and findings will be shared

Evaluating efforts to diversify the biomedical workforce: the role and function of the Coordination and Evaluation Center of the Diversity Program Consortium

Abstract Background The National Institutes of Health (NIH)-funded Diversity Program Consortium (DPC) includes a Coordination and Evaluation Center (CEC) to conduct a longitudinal evaluation of the two signature, national NIH initiatives - the Building Infrastructure Leading to Diversity (BUILD) and the National Research Mentoring Network (NRMN) programs - designed to promote diversity in the NIH-funded biomedical, behavioral, clinical, and social sciences research workforce. Evaluation is central to understanding the impact of the consortium activities. This article reviews the role and function of the CEC and the collaborative processes and achievements critical to establishing empirical evidence regarding the efficacy of federally-funded, quasi-experimental interventions across multiple sites. The integrated DPC evaluation is particularly significant because it is a collaboratively developed Consortium Wide Evaluation Plan and the first hypothesis-driven, large-scale systemic national longitudinal evaluation of training programs in the history of NIH/National Institute of General Medical Sciences. Key highlights To guide the longitudinal evaluation, the CEC-led literature review defined key indicators at critical training and career transition points – or Hallmarks of Success. The multidimensional, comprehensive evaluation of the impact of the DPC framed by these Hallmarks is described. This evaluation uses both established and newly developed common measures across sites, and rigorous quasi-experimental designs within novel multi-methods (qualitative and quantitative). The CEC also promotes shared learning among Consortium partners through working groups and provides technical assistance to support high-quality process and outcome evaluation internally of each program. Finally, the CEC is responsible for developing high-impact dissemination channels for best practices to inform peer institutions, NIH, and other key national and international stakeholders. Implications A strong longitudinal evaluation across programs allows the summative assessment of outcomes, an understanding of factors common to interventions that do and do not lead to success, and elucidates the processes developed for data collection and management. This will provide a framework for the assessment of other training programs and have national implications in transforming biomedical research training

Baseline Characteristics of the 2015-2019 First Year Student Cohorts of the NIH Building Infrastructure Leading to Diversity (BUILD) Program.

ObjectiveThe biomedical/behavioral sciences lag in the recruitment and advancement of students from historically underrepresented backgrounds. In 2014 the NIH created the Diversity Program Consortium (DPC), a prospective, multi-site study comprising 10 Building Infrastructure Leading to Diversity (BUILD) institutional grantees, the National Research Mentoring Network (NRMN) and a Coordination and Evaluation Center (CEC). This article describes baseline characteristics of four incoming, first-year student cohorts at the primary BUILD institutions who completed the Higher Education Research Institute, The Freshmen Survey between 2015-2019. These freshmen are the primary student cohorts for longitudinal analyses comparing outcomes of BUILD program participants and non-participants.DesignBaseline description of first-year students entering college at BUILD institutions during 2015-2019.SettingTen colleges/universities that each received <$7.5mil/yr in NIH Research Project Grants and have high proportions of low-income students.ParticipantsFirst-year undergraduate students who participated in BUILD-sponsored activities and a sample of non-BUILD students at the same BUILD institutions. A total of 32,963 first-year students were enrolled in the project; 64$30,000/yr and 25% were their family's first generation in college.Planned outcomesPrimary student outcomes to be evaluated over time include undergraduate biomedical degree completion, entry into/completion of a graduate biomedical degree program, and evidence of excelling in biomedical research and scholarship.ConclusionsThe DPC national evaluation has identified a large, longitudinal cohort of students with many from groups historically underrepresented in the biomedical sciences that will inform institutional/national policy level initiatives to help diversify the biomedical workforce

Cardiovascular Efficacy and Safety of Bococizumab in High-Risk Patients

BACKGROUN