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

Barriers to adaptation in Newcastle upon Tyne, UK: Preliminary findings

Greenhouse gases in the atmosphere and the inertia of the climate system means that adaptation to new ‘normal’weather patterns is needed. Uncertainties in climate science means adaptation will be challenging, requiring an iterative approach. Considerable progress in adaptation has been made in the United Kingdom (UK), but some vulnerable groups are marginalised from this process. The nature of destitution in the UK means that official statistics – and therefore adaptation plans – exclude significant numbers of vulnerable people. Social vulnerability is increasing in the UK due to the global recession, the reform of the public sector and welfare changes. Extreme weather exacerbates pressures on Local Government who are financially stressed to the point that delivery of statutory functions are threatened, thereby making adaptation planning extremely challenging. Effective options to tackle this challenge are governed by two key factors. First, acknowledging evidence based policy insufficiently accounts for constraints on adaptive capacity. Second, effective adaptation requires broader involvement in decision making. Developing adaptive capacity will require considerable effort, particularly for vulnerable groups. Adaptation cannot occur in isolation from socio-economic and political drivers, yet the resource implications of dealing with increasing social vulnerability and climate extremes are poorly understood and not currently factored into decision making

Collaborative platform to facilitate engineering decision-making

Measures taken to address climate change and sustainability, more generally, imply a major reconfiguration of infrastructure systems and the built environment. Action across so many functions necessarily involves a range of organisations that may have differing priorities and motivations. This paper presents the concept of a decision theatre and describes how this approach was tested by co-designing, with a range of stakeholders, two events to identify the current vulnerabilities of the city of Newcastle upon Tyne to a storm event and to investigate the effectiveness of adaptation options to surface water flooding. The collaborative environment improved understanding of the physical and social vulnerabilities in the city, defined research questions relevant to society, improved the consideration of policy suggestions grounded in reality and improved the joint ownership of the issues and the facility itself. The lessons learned helped develop a long-term vision for a more widely applicable research and engagement facility for exploring and understanding decision-making with a range of stakeholders, including the general public

Climate change, marginalised communities and considered debate within Scotland’s climate emergency

The announcement by the Scottish Government of a global ‘climate emergency’ in May 2019, and the selection of Glasgow as the host city for the main COP26 talks to be held in late 2021 has helped focus attention to the impact of climate change in Scotland. The COVID-19 pandemic has also brought into sharp focus the disproportionate effect that shocks and stresses have on already vulnerable people and places. This short communication aims to contribute to these debates by clarifying existing strengths and open issues for an evidence-driven response to climate change in Scotland’s marginalised communities. Growing support for rapid and radical climate action, both in Scotland and overseas, brings into question the role of learned societies and reasoned debate within a climate emergency. To this end, we synthesise recent Scotland-based research into issues relating to climate justice and, drawing on the outcomes of a workshop held in summer 2019, identify aspects where good progress has been made and areas where further work is required for an evidence-driven and just response to climate change in Scotland and beyond