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

An actor-centered, scalable land system typology for addressing biodiversity loss in the world’s tropical dry woodlands

Land use is a key driver of the ongoing biodiversity crisis and therefore also a major opportunity for its mitigation. However, appropriately considering the diversity of land-use actors and activities in conservation assessments and planning is challenging. As a result, top-down conservation policy and planning are often criticized for a lack of contextual nuance widely acknowledged to be required for effective and just conservation action. To address these challenges, we have developed a conceptually consistent, scalable land system typology and demonstrated its usefulness for the world's tropical dry woodlands. Our typology identifies key land-use actors and activities that represent typical threats to biodiversity and opportunities for conservation action. We identified land systems in a hierarchical way, with a global level allowing for broad-scale planning and comparative work. Nested within it, a regionalized level provides social-ecological specificity and context. We showcase this regionalization for five hotspots of land-use change and biodiversity loss in dry woodlands in Argentina, Bolivia, Mozambique, India, and Cambodia. Unlike other approaches to present land use, our typology accounts for the complexity of overlapping land uses. This allows, for example, assessment of how conservation measures conflict with other land uses, understanding of the social-ecological co-benefits and trade-offs of area-based conservation, mapping of threats, or targeting area-based and actor-based conservation measures. Moreover, our framework enables cross-regional learning by revealing both commonalities and social-ecological differences, as we demonstrate here for the world's tropical dry woodlands. By bridging the gap between global, top-down, and regional, bottom-up initiatives, our framework enables more contextually appropriate sustainability planning across scales and more targeted and social-ecologically nuanced interventions

An actor-centered, scalable land system typology for addressing biodiversity loss in the world’s tropical dry woodlands

Land use is a key driver of the ongoing biodiversity crisis and therefore also a major opportunity for its mitigation. However, appropriately considering the diversity of land-use actors and activities in conservation assessments and planning is challenging. As a result, top-down conservation policy and planning are often criticized for a lack of contextual nuance widely acknowledged to be required for effective and just conservation action. To address these challenges, we have developed a conceptually consistent, scalable land system typology and demonstrated its usefulness for the world's tropical dry woodlands. Our typology identifies key land-use actors and activities that represent typical threats to biodiversity and opportunities for conservation action. We identified land systems in a hierarchical way, with a global level allowing for broad-scale planning and comparative work. Nested within it, a regionalized level provides social-ecological specificity and context. We showcase this regionalization for five hotspots of land-use change and biodiversity loss in dry woodlands in Argentina, Bolivia, Mozambique, India, and Cambodia. Unlike other approaches to present land use, our typology accounts for the complexity of overlapping land uses. This allows, for example, assessment of how conservation measures conflict with other land uses, understanding of the social-ecological co-benefits and trade-offs of area-based conservation, mapping of threats, or targeting area-based and actor-based conservation measures. Moreover, our framework enables cross-regional learning by revealing both commonalities and social-ecological differences, as we demonstrate here for the world's tropical dry woodlands. By bridging the gap between global, top-down, and regional, bottom-up initiatives, our framework enables more contextually appropriate sustainability planning across scales and more targeted and social-ecologically nuanced interventions

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

International audienc