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

Socio-economic inequalities in all-cause mortality in Europe: an exploration of the role of heightened social mobility

The larger than expected socio-economic inequalities in health in more egalitarian countries might be explained by a heightened social mobility in these countries. Therefore, the aim of this explorative study was to examine the associations between country-level social mobility, income inequality and socio-economic differences in all-cause mortality, using country-level secondary data from 12 European countries. Both income equality and social mobility were found to be associated with larger socio-economic differences in mortality, particularly in women. These findings suggest that social mobility and income equality, beside their shiny side of improving population health, might have a shady side of increasing socio-economic health inequalities

The silent burden of stigmatisation: a qualitative study among Dutch people with a low socioeconomic position

Abstract Background In-depth qualitative research into perceived socioeconomic position-related stigmatisation among people living at the lower end of our socioeconomic hierarchy is necessary for getting more insight in the possible downside of living in an increasingly meritocratic and individualistic society. Methods Seventeen interviews were conducted among a group of Dutch people with a low socioeconomic position to examine their experiences with stigmatisation, how they coped with it and what they perceived as consequences. Results Social reactions perceived by participants related to being inferior, being physically recognisable as a poor person, and being responsible for their own financial problems. Participants with less experience of living in poverty, a heterogeneous social network and greater sense of financial responsibility seemed to be more aware of stigmas than people with long-term experience of poverty, a homogeneous social network and less sense of financial responsibility. Perceived stigmatisation mainly had emotional consequences. To maintain a certain level of self-respect, participants tried to escape from reality, showed their strengths or confronted other people who expressed negative attitudes towards them. Conclusion Despite the good intentions of policies to enhance self-reliance, responsibility and active citizenship, these policies and related societal beliefs might affect people at the lower end of our socioeconomic hierarchies by making them feel inferior, ashamed and blamed, especially when they cannot meet societal expectations or when they feel treated disrespectfully, unjustly or unequally by social workers or volunteers of charity organisations