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

Just Satisfaction? What Drives Public and Participant Satisfaction with Courts and Tribunals - A Review of Recent Evidence

This document reports a review of recent evidence (published from 2000 onwards) on what factors may be related to public and participant (non-professional users, witnesses and jurors) satisfaction with courts and tribunals. It only includes evidence based on studies which meet particular standards of method and reporting. Most of the studies reviewed relate to England and Wales, but relevant evidence from other jurisdictions is also included. The review reveals: 1. The evidence base is dominated by studies either wholly in the criminal sphere or which fail to disaggregate civil and criminal contexts. 2. There is a distinct scarcity of robust, well-analysed data on what the general public thinks about civil and family courts and tribunals and what underlies those perceptions. 3. Similarly, there is little data on what businesses think of courts and tribunals. 4. Data on participants, outside of the criminal context in particular, also lacks depth. Consideration should be given to how the resource expended on user surveys in the courts and tribunals services is most effectively used to provide a more robust evidence base. 5. As a result of weaknesses in the evidence base, we cannot say with authority whether the public, or indeed those who have participated in civil or family cases, are generally satisfied with those courts and tribunals, and why they are satisfied (or not). Lack of such data about a key public institution is concerning. 6. The evidence that exists suggests that outcomes, and the perceived fairness of those outcomes; attitudes and contextual issues (such as attitudes to crime and the quality of the court environment and support); and participant judgments about the fairness of court or tribunal process all have an independent relationship with (and so may ‘drive’) public and participant satisfaction with courts and tribunals. The evidence on whether demographic characteristics have an independent influence is more mixed. 7. On the whole, and whilst acknowledging the weaknesses in the evidence base highlighted above, the weight of the evidence suggests that it is i participant judgments about the fairness of the process not the outcomes that participants receive which are most important in influencing the levels of their satisfaction. 8. There is a lack of evidence comparing consumer perspectives with professional evaluations of underlying systems and behaviours. An adversarial justice system may inevitably lead to some dissatisfaction, amongst some participants, as it seeks to balance competing interests. Meaningful research on ‘just’ satisfaction needs to scrutinise that balance

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

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