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

Complex Interventions Deserve Complex Evaluations: A Transdisciplinary Approach to Evaluation of a Preventive Personalized Medicine Intervention

Non-communicable diseases (NCDs) are the largest cause of disability and death globally. The human and financial costs of NCDs have raised questions of sustainability for many health systems. Personalized, preventive health interventions are an innovative way to address NCDs, but it is difficult to measure their effectiveness using standard evaluation methods. This article describes a novel approach to evaluation by coupling transdisciplinary methods with realist theory to design and pilot a health outcomes evaluation for a personalized medicine approach to NCD prevention in Istanbul, Turkey. Research and practice stakeholders contributed to study design, research questions, validation of results, and recommendations through interactive workshops, consistent dialogue, and reflection. They co-created a customized outcome measurement framework and recommendations that promote sustainability and continuous improvement of future evaluations. The participatory methods helped resolve the dichotomy between patient, practitioner, and researcher focus in the evaluation and improved stakeholders' data literacy. This research contributes to the body of evidence advocating for the use of non-standard methods such as transdisciplinary research to evaluate the effectiveness of complex interventions. The results of the pilot evaluation are also presented as a case study

An analysis of survivorship care strategies in national cancer control plans in Africa

PURPOSE: In 2017, the World Health Organization urged member states to develop and implement national cancer control plans (NCCPs) and to anticipate and promote cancer survivor follow-up care, which is a critical yet often overlooked component of NCCPs. This study aims to examine the inclusion of cancer survivorship-related strategies and objectives in NCCPs of African countries. METHODS: Independent reviewers extracted strategies, objectives, and associated indicators related to survivorship care from 21 current or recently expired NCCPs in African countries. Building on a similar analysis of the US state cancer control plans, reviewers categorized these strategies according to an adapted version of the ten recommendations for comprehensive survivorship care detailed in the 2006 National Academy of Medicine report. RESULTS: A total of 202 survivorship-related strategies were identified, with all NCCPs including between 1 and 23 references to survivorship. Eighty-three (41%) strategies were linked to measurable indicators, and 128 (63%) of the survivorship-related strategies were explicitly focused on palliative care. The most frequent domains referenced were models of coordinated care (65 strategies), healthcare professional capacity (45), and developing and utilizing evidence-based guidelines (23). The least-referenced domains were survivorship care plans (4) and adequate and affordable health insurance (0). CONCLUSIONS: The results of this study indicate that survivorship objectives and strategies should extend beyond palliative care to encompass all aspects of survivorship and should include indicators to measure progress. IMPLICATIONS FOR CANCER SURVIVORS: Stakeholders can use this baseline analysis to identify and address gaps in survivorship care at the national policy level