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

Global Surgery 2030: evidence and solutions for achieving health, welfare, and economic development.

Remarkable gains have been made in global health in the past 25 years, but progress has not been uniform. Mortality and morbidity from common conditions needing surgery have grown in the world’s poorest regions, both in real terms and relative to other health gains. At the same time, development of safe, essential, life-saving surgical and anaesthesia care in low-income and middle-income countries (LMICs) has stagnated or regressed. In the absence of surgical care, case-fatality rates are high for common, easily treatable conditions including appendicitis, hernia, fractures, obstructed labour, congenital anomalies, and breast and cervical cancer. In 2015, many LMICs are facing a multifaceted burden of infectious disease, maternal disease, neonatal disease, non-communicable diseases, and injuries. Surgical and anaesthesia care are essential for the treatment of many of these conditions and represent an integral component of a functional, responsive, and resilient health system. In view of the large projected increase in the incidence of cancer, road traffic injuries, and cardiovascular and metabolic diseases in LMICs, the need for surgical services in these regions will continue to rise substantially from now until 2030. Reduction of death and disability hinges on access to surgical and anaesthesia care, which should be available, affordable, timely, and safe to ensure good coverage, uptake, and outcomes. Despite growing need, the development and delivery of surgical and anaesthesia care in LMICs has been nearly absent from the global health discourse. Little has been written about the human and economic effect of surgical conditions, the state of surgical care, or the potential strategies for scale-up of surgical services in LMICs. To begin to address these crucial gaps in knowledge, policy, and action, the Lancet Commission on Global Surgery was launched in January, 2014. The Commission brought together an international, multi- disciplinary team of 25 commissioners, supported by advisors and collaborators in more than 110 countries and six continents. We formed four working groups that focused on thedomains of health-care delivery and management; work-force, training, and education; economics and finance; and information management. Our Commission has five key messages, a set of indicators and recommendations to improve access to safe, affordable surgical and anaesthesia care in LMICs, and a template for a national surgical plan

Advancing the global public health agenda for NAFLD: a consensus statement

Non-alcoholic fatty liver disease (NAFLD) is a potentially serious liver disease that affects approximately one-quarter of the global adult population, causing a substantial burden of ill health with wide-ranging social and economic implications. It is a multisystem disease and is considered the hepatic component of metabolic syndrome. Unlike other highly prevalent conditions, NAFLD has received little attention from the global public health community. Health system and public health responses to NAFLD have been weak and fragmented, and, despite its pervasiveness, NAFLD is largely unknown outside hepatology and gastroenterology. There is only a nascent global public health movement addressing NAFLD, and the disease is absent from nearly all national and international strategies and policies for non-communicable diseases, including obesity. In this global Delphi study, a multidisciplinary group of experts developed consensus statements and recommendations, which a larger group of collaborators reviewed over three rounds until consensus was achieved. The resulting consensus statements and recommendations address a broad range of topics — from epidemiology, awareness, care and treatment to public health policies and leadership — that have general relevance for policy-makers, health-care practitioners, civil society groups, research institutions and affected populations. These recommendations should provide a strong foundation for a comprehensive public health response to NAFLD

Advancing the global public health agenda for NAFLD: a consensus statement

© Springer Nature Limited 2021, corrected publication 2021Non-alcoholic fatty liver disease (NAFLD) is a potentially serious liver disease that affects approximately one-quarter of the global adult population, causing a substantial burden of ill health with wide-ranging social and economic implications. It is a multisystem disease and is considered the hepatic component of metabolic syndrome. Unlike other highly prevalent conditions, NAFLD has received little attention from the global public health community. Health system and public health responses to NAFLD have been weak and fragmented, and, despite its pervasiveness, NAFLD is largely unknown outside hepatology and gastroenterology. There is only a nascent global public health movement addressing NAFLD, and the disease is absent from nearly all national and international strategies and policies for non-communicable diseases, including obesity. In this global Delphi study, a multidisciplinary group of experts developed consensus statements and recommendations, which a larger group of collaborators reviewed over three rounds until consensus was achieved. The resulting consensus statements and recommendations address a broad range of topics - from epidemiology, awareness, care and treatment to public health policies and leadership - that have general relevance for policy-makers, health-care practitioners, civil society groups, research institutions and affected populations. These recommendations should provide a strong foundation for a comprehensive public health response to NAFLD.info:eu-repo/semantics/publishedVersio

Global Surgery 2030: evidence and solutions for achieving health, welfare, and economic development

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