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

Poverty Status, Health Behaviours, and Health: Implications for Social Assistance and Health Care Policy

This study investigated the relationships among poverty status, health behaviours, and the health of 130 Albertans living in poor families. For the purposes of this study, poverty status indicated whether poor families were receiving social assistance along with comprehensive health care benefits or whether they were working poor without comprehensive health care benefits. Findings from seven separate path analyses indicate that poverty status was differentially related to the health of participants. Specifically, working poor respondents were found to be generally healthier than their social assistance counterparts except in those instances in which the working poor were prevented from filling needed prescriptions because they lacked the economic resources to do so. The paper concludes with a discussion of the implications of these findings for social assistance and health care policies.

Welfare or Work: Which is Better for Canadian Children?

This study examined whether the employment status of parents in poor families is a predictor of child development by comparing the verbal development of preschool children in working poor and welfare-dependent families. Findings show that verbal development scores of both groups of children were below the norm, regardless of parents' source of income. Findings also indicated that children from working poor families had slightly higher levels of verbal development than children from welfare-dependent families and that these developmental differences were only partially attributable to differences in home and family characteristics of the two groups. The study has a number of important implications for welfare reform policy and research in Canada.

The protocol for the Families First Edmonton trial (FFE): a randomized community-based trial to compare four service integration approaches for families with low-income

BACKGROUND: Families with low incomes experience an array of health and social challenges that compromise their resilience and lead to negative family outcomes. Along with financial constraints, there are barriers associated with mental and physical health, poorer education and language. In addition, vulnerable populations experience many services as markedly unhelpful. This combination of family and service barriers results in reduced opportunities for effective, primary-level services and an increased use of more expensive secondary-level services (e.g., emergency room visits, child apprehensions, police involvement). A systematic review of effective interventions demonstrated that promotion of physical and mental health using existing service was critically important. METHODS/DESIGN: The Families First Edmonton Trial (FFE) tests four service integration approaches to increase use of available health and social services for families with low-income. It is a randomized, two-factor, single-blind, longitudinal effectiveness trial where low-income families (1168) were randomly assigned to receive either (1) Family Healthy Lifestyle plus Family Recreation service integration (Comprehensive), (2) Family Healthy Lifestyle service integration, (3) Family Recreation service integration, or (4) existing services. To be eligible families needed to be receiving one of five government income assistance programs. The trial was conducted in the City of Edmonton between January 2006 and August 2011. The families were followed for a total of three years of which interventional services were received for between 18 and 24 months. The primary outcome is the number of family linkages to health and social services as measured by a customized survey tool “Family Services Inventory”. Secondary outcomes include type and satisfaction with services, cost of services, family member health, and family functioning. Where possible, the measures for secondary outcomes were selected because of their standardization, the presence of published norming data, and their utility as comparators to other studies of low-income families. As an effectiveness trial, community and government partners participated in all committees through a mutually agreed upon governance model and helped manage and problem solve with researchers. DISCUSSION: Modifications were made to the FFE trial based on the pragmatics of community-based trials. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT0070532