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

The Three NITRCs: A Guide to Neuroimaging Neuroinformatics Resources

Information management is critical as the landscape of neuroscience related shared resources (data, software, computation, etc.) expands. Since 2006, the Neuroimaging Informatics Tools and Resources Clearinghouse (NITRC: RRID:nif-0000-00202) has provided a comprehensive support infrastructure for resources in the neuroimaging domain. Funded by the NIH Blueprint for Neuroscience Research as well as four NIH institutes , NITRC’s mission is to facilitate finding and comparing neuroimaging resources for neuroimaging analyses. Over the years the scope of these resources has expanded to support scientific domains from MR to PET, SPECT, CT, MEG/EEG, optical imaging, genetic imaging, clinical neuroinformatics and computational neuroscience. A broad set of initiatives have been developed to support these research areas

The NITRC image repository

The Neuroimaging Informatics Tools and Resources Clearinghouse (NITRC - www.nitrc.org) suite of services include a resources registry, image repository and a cloud computational environment to meet the needs of the neuroimaging researcher. NITRC provides image-sharing functionality through both the NITRC Resource Registry (NITRC-R), where bulk data files can be released through the file release system (FRS), and the NITRC Image Repository (NITRC-IR), a XNAT-based image data management system. Currently hosting 14 projects, 6845 subjects, and 8285 MRI imaging sessions, NITRC-IR provides a large array of structural, diffusion and resting state MRI data. Designed to be flexible about management of data access policy, NITRC provides a simple, free, NIH-funded service to support resource sharing in general, and image sharing in particular