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

Implementing One-at-a-Time Therapy in community addiction and mental health centres: a retrospective exploration of the implementation process and initial outcomes

Abstract Background The Department of Health of the Government of New Brunswick and Regional Health Authorities elected to implement Stepped Care 2.0 (SC2.0) in 2021, and began with One-at-a-Time (OAAT) therapy in Community Addiction and Mental Health Centres (CAMHCs) to facilitate rapid access to addiction and mental healthcare. This study: 1) explicated the process of implementing OAAT therapy as it aligned to evidence-based implementation frameworks and strategies; 2) assessed readiness for change among providers during the implementation; and 3) evaluated initial client and system outcomes. Methods The process of implementing OAAT therapy within CAMHCs was documented and retrospectively aligned with the Active Implementation Frameworks-Stages of Implementation, Consolidated Framework for Implementation Research, and incorporated strategies endorsed by the Expert Recommendations for Implementing Change. Providers working in CAMHCs completed online asynchronous courses in OAAT therapy and SC2.0, and were recruited to participate in research on perceptions of organizational readiness. Initial outcomes of the implementation were evaluated through client satisfaction surveys administered in CAMHCs and system performance indicators. Results Aligning with implementation stages, key strategies included: 1) continuously monitoring readiness and soliciting stakeholder feedback for iterative improvement; 2) building a representative implementation team with engaged leaders; 3) creating a comprehensive implementation plan on staff training, communication, and system changes; and 4) supporting sustainability. Providers who participated in research (N = 170, ~ 50% response rate) agreed that their organization was ready for implementation, and that OAAT therapy delivered within a SC2.0 framework was acceptable, appropriate, and feasible. More than 3,600 OAAT therapy sessions were delivered during the initial implementation stage, and waitlists were reduced by 64.1%. The majority of clients who completed surveys (N = 1240, ~ 35% response rate) reported that their OAAT therapy session was helpful, with a minority reporting that additional intervention was needed. Conclusions Thoughtful planning and execution, aligned with evidence-based implementation frameworks and strategies, played an important role in this provincial change initiative. Implementation steps outlined can help inform others looking to enact large-scale change

Effect of Antiplatelet Therapy on Survival and Organ Support–Free Days in Critically Ill Patients With COVID-19

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