28 research outputs found

    Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

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    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

    Dry-season leaf flushing of Enterolobium cyclocarpum (ear-pod tree): above- and belowground phenology and water relations

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    Above- and belowground phenology and water relations of Enterolobium cyclocarpum Jacq. trees in the dry forest of Santa Rosa National Park, Costa Rica were studied during two consecutive phenological cycles, from November 1998 to June 2000. Aboveground phenological activity, including leaf shedding, growth and maturation of dormant fruits, new leaf flushing and flowering, occurred during the dry season. Measurements of leaf water potential, stomatal conductance and sap flow indicated that stomata of newly flushed leaves remained essentially closed until the onset of the first rains, suggesting that the main factor accounting for the favorable water balance of dry-season flushed leaves was their capacity to restrict water loss. Evidence of a contribution from stem and root water stores to shoot expansion was mixed because only the first dry-season flushing episode monitored was accompanied by a marked decrease in stem and root water potentials. Fine root production did not precede leaf flushing, occurred only after the onset of the rainy season and stopped under drought conditions, suggesting that soil water content was the most important variable controlling fine root dynamics in this species.The Andrew W. Mellon Foundation/[]//Estados UnidosUCR::VicerrectorĂ­a de InvestigaciĂłn::Unidades de InvestigaciĂłn::Ciencias Agroalimentarias::EstaciĂłn Experimental AgrĂ­cola Fabio Baudrit Moreno (EEAFBM)UCR::VicerrectorĂ­a de Docencia::Ciencias BĂĄsicas::Facultad de Ciencias::Escuela de BiologĂ­
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