Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

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

Addressing healthcare for migrants and ethnic minorities in Europe: A review of training programmes

Background: The global phenomenon of migration has dramatically changed the social context in which healthcare professionals operate. European states are facing a growing need to effectively train healthcare professionals to understand and respond appropriately to the diverse needs of migrants and ethnic minorities. While many European Union (EU) countries have adopted specific initiatives, there is considerable variation in these activities and few examples of evaluation of the quality of these training courses. Aims: This article describes findings from a review conducted as a part of the ‘Training packages for health professionals to improve access and quality of health services for migrants and ethnic minorities, including the Roma (MEM-TP)’ project, which sought to identify and assess training programmes for health professionals delivered in Europe between 2004 and 2013. Methods: The review and analysis of training materials comprised three components: (1) a review of the published and unpublished literature, (2) a survey addressing national contact persons, and representatives of international organisations and non-governmental organisations and (3) an assessment of the quality of the training programmes identified. Results: The review showed that training programmes tend to be characterised by low levels of participant involvement in training development, delivery and evaluation. Training programmes often lacked an explicit pedagogical approach, did not systematically focus on outcomes in training design, implementation and evaluation, and were poorly linked to key organisational and policy support. Finally, while cultural competence continues to be the broad conceptual approach used in training programmes, alternate approaches such as intersectionality, equity and person-centred care are emergent. Conclusion: Training programmes in Europe can be further improved in order to ensure an effective response to the diverse needs of patients, carers, health professionals and the community

Healthcare professionals' perspective on delivering personalised and holistic care:using the Theoretical Domains Framework

BACKGROUND: Interventions to improve personalised and holistic care delivery by healthcare professionals are more likely to be effective if they target the factors influencing specific behaviours. This study reports on the development and testing of a questionnaire to identify perspectives of healthcare professionals’ personalised and holistic care behaviours based on the Theoretical Domains Framework. METHODS: The study was conducted in public health services in Victoria, Australia. The questionnaire was developed and pilot-tested with behaviour change researchers and healthcare professionals. Doctors, nurses and midwives were recruited via notices and email invitations from Safer Care Victoria's website and mailing lists of healthcare professionals and invited to completed the questionnaire online (hosted on Qualtrics). Health services administrators and allied health professionals were excluded from the study. Confirmatory factor analysis was undertaken to generate the model of best fit and group differences were tested using univariate tests. RESULTS: One hundred and four healthcare professionals from public health services in Victoria, Australia, completed the 39-item questionnaire focusing on specific personalised and holistic care behaviours. The final model consisted of 13 factors and 39 items, and CFA produced an acceptable fit, as well as adequate levels of discriminant validity and internal consistency (α = 0.60 to 0.84). Seven domains, “social influence”, “motivation & goals”, “environmental context and resources’, “skills”, ‘beliefs about consequences”, “behaviour regulation” and “nature of behaviour” were identified. Significant differences in the factors influencing these behaviours were found in groups with different years of experience and role seniority. These findings suggest that future interventions need to be targeted to specific groups. CONCLUSION: This study identified the specific behaviours and the factors associated with performance of personalised and holistic care among healthcare professionals. The findings suggest several interventions and policy functions may be taken to improve personalised and holistic care. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12913-022-07630-1

Research priorities in health communication and participation:International survey of consumers and other stakeholders

Abstract: To identify research priorities of consumers and other stakeholders to inform Cochrane Reviews in ‘health communication and participation’ (including such concepts as patient experience, shared decision-making and health literacy)..