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

UN Decade on Ecosystem Restoration: key considerations for Africa

To support and scale up global restoration efforts, the United Nations (UN) has proclaimed 2021–2030 the “UN Decade on Ecosystem Restoration.” The Decade offers significant opportunities for and challenges to restoration, in particular for Africa, a continent that has a large need and potential for restoration. We thus argue that the Decade must be a success in and for Africa, and for this to happen, opportunities and challenges to achieving its goals must be promptly identified, and considered in the planning and implementation of restoration. Here, we outline six key areas that should be considered at a strategic level by African countries during the Decade. These are: (1) ensuring effective oversight and governance relevant to Africa; (2) translating the goals to meet the African context; (3) making the case for restoration amid multiple development demands; (4) growing an African restoration community of practice based on regional need; (5) collaborating to improve restoration outcomes; and (6) establishing an Africa-relevant evidence base for restoration. We believe that these six key areas—even though they are not all novel—are currently not addressed at a level that matches the scale of the problem on the continent. Although the specific actions to be taken under each key area are dependent on the restoration context, integrating these key areas in the planning and implementation of restoration efforts will likely lead to improved restoration outcomes during the Decade

UN Decade on Ecosystem Restoration : key considerations for Africa

To support and scale up global restoration efforts, the United Nations (UN) has proclaimed 2021-2030 the "UN Decade on Ecosystem Restoration." The Decade offers significant opportunities for and challenges to restoration, in particular for Africa, a continent that has a large need and potential for restoration. We thus argue that the Decade must be a success in and for Africa, and for this to happen, opportunities and challenges to achieving its goals must be promptly identified, and considered in the planning and implementation of restoration. Here, we outline six key areas that should be considered at a strategic level by African countries during the Decade. These are: (1) ensuring effective oversight and governance relevant to Africa; (2) translating the goals to meet the African context; (3) making the case for restoration amid multiple development demands; (4) growing an African restoration community of practice based on regional need; (5) collaborating to improve restoration outcomes; and (6) establishing an Africa-relevant evidence base for restoration. We believe that these six key areas-even though they are not all novel-are currently not addressed at a level that matches the scale of the problem on the continent. Although the specific actions to be taken under each key area are dependent on the restoration context, integrating these key areas in the planning and implementation of restoration efforts will likely lead to improved restoration outcomes during the Decade.Peer reviewe