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

Healthcare provider perspective on barriers and facilitators in the care of pediatric injury patients at a tertiary hospital in Northern Tanzania: A qualitative study.

Pediatric injuries are a leading cause of morbidity and mortality in low- and middle-income countries (LMICs). The recovery of injured children in LMICs is often impeded by barriers in accessing and receiving timely and quality care at healthcare facilities. The purpose of this study was to identify the barriers and the facilitators in pediatric injury care at Kilimanjaro Christian Medical Center (KCMC), a tertiary zonal referral hospital in Northern Tanzania. In this study, focus group discussions (FGDs) were conducted by trained interviewers who were fluent in English and Swahili in order to examine the barriers and facilitators in pediatric injury care. Five FGDs were completed from February 2021 to July 2021. Participants (n = 30) were healthcare providers from the emergency department, burn ward, surgical ward, and pediatric ward. De-identified transcripts were analyzed with team-based, applied thematic analysis using qualitative memo writing and consensus discussions. Our study found barriers that impeded pediatric injury care were: lack of pediatric-specific injury training and care guidelines, lack of appropriate pediatric-specific equipment, staffing shortages, lack of specialist care, and complexity of cases due to pre-hospital delays in patients presenting for care due to cultural and financial barriers. Facilitators that improved pediatric injury care were: team cooperation and commitment, strong priority and triage processes, benefits of a tertiary care facility, and flexibility of healthcare providers to provide specialized care if needed. The data highlights barriers and facilitators that could inform interventions to improve the care of pediatric injury patients in Northern Tanzania such as: increasing specialized provider training in pediatric injury management, the development of pediatric injury care guidelines, and improving access to pediatric-specific technologies and equipment