Randomized trials fit for the 21st century. A joint opinion from the European Society of Cardiology, American Heart Association, American College of Cardiology, and the World Heart Federation

© The Author(s) 2022. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. The articles are identical except for minor stylistic and spelling differences in keeping with each journal's style. When citing this article, a citation from any of the journals listed is appropriate. For commercial re-use, please contact [email protected] controlled trials are the cornerstone for reliably evaluating therapeutic strategies. However, during the past 25 years, the rules and regulations governing randomized trials and their interpretation have become increasingly burdensome, and the cost and complexity of trials has become prohibitive. The present model is unsustainable, and the development of potentially effective treatments is often stopped prematurely on financial grounds, while existing drug treatments or non-drug interventions (such as screening strategies or management tools) may not be assessed reliably. The current ‘best regulatory practice’ environment, and a lack of consensus on what that requires, too often makes it unduly difficult to undertake efficient randomized trials able to provide reliable evidence about the safety and efficacy of potentially valuable interventions. Inclusion of underrepresented population groups and lack of diversity also remain among the challenges.info:eu-repo/semantics/publishedVersio

‘Oh you pretty thing!’: How David Bowie ‘unlocked everybody’s inner queen’ in spite of the music press

The 1967 Sexual Offence Act decriminalised homosexual acts between men allowing gay men to discuss their sexuality in public. Few prominent popular musicians came-out until 1972 when David Bowie claimed that he was bisexual in an interview with Melody Maker. Music papers and Bowie had substantial cultural power: Bowie was a rising star and music papers recruited journalists who discussed and perpetuated social change. The subsequent conversation, however, reinforced negative stereotypes in constructing the queer subject and tried to safeguard commercial concerns due to the assumption that the market for popular music avoided queer music. This undermined arguments that associate permissive legislation with a permissive media and society, but, to some, representation alone empowered people and destabilised preconceptions about queer identity.Published versio

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

Impacts of Structural Change: Implications for policies supporting transition to a Green Economy

Lemma, and also clarified the definition of scientific concepts in the evaluation parameter binomial R Clopper-Pearson methodПриводятся лемма, её доказательство и уточненные определения научных понятий, которые касаются оценки биномиального параметра R по методу Клопера-ПирсонаПриводяться лема, її доказ та уточнені визначення наукових понять, які стосуються оцінки біноміального параметра R по методу Клопера-Пірсон