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

Une méta-analyse de l’efficacité des thérapies cognitivo-comportementales dans le traitement de la dépression chez les personnes âgées

A comprehensive meta-analysis was conducted using studies of cognitive-behavioural-therapy based interventions (CBT-BIs) for late-life depression. Patient characteristics, CBT modality, and other study variables were analyzed using subgroup and metaregression analysis methods. Results showed the collective treatment effect of CBT-BIs for reducing late-life depression to be moderate (g = -0.63) with significant heterogeneity (I2 = 66.12%). CBT-BIs were found to be no more effective immediately posttreatment than other psychological treatments, pharmacotherapy, or combination interventions. The data support the notion that CBT is more effective in the long term.On a mené une méta-analyse approfondie d’après des interventions basées sur la thérapie cognitivo-comportementale (IB-TCC) conçues pour le traitement de la dépression à un âge avancé. On analysa les caractéristiques du patient, les modalités de la TCC et d’autres variables de l’étude, en ayant recours à des méthodes d’analyse de sous-groupe et d’analyse de métarégression. Les résultats ont révélé que l’effet du traitement collectif des IB-TCC en vue d’atténuer la dépression en âge avancé était moyen (g = -0,63) et considérablement hétérogène (I2 = 66,12 %). On a conclu que les IB-TCC ne se révélaient pas plus efficaces immédiatement après le traitement que les autres types de traitements psychologiques, pharmacothérapeutiques ou que les interventions combinées. Les données semblent indiquer que la TCC est plus efficace à long terme

Defining risk acceptance criteria in occupational settings: A case study in the furniture industrial sector

The use of appropriate acceptance criteria in the risk assessment process for occupational accidents is an important issue but often overlooked in the literature, particularly when new risk assessment methods are proposed and discussed. In most cases, there is no information on how or by whom they were defined, or even how companies can adapt them to their own circumstances. Bearing this in mind, this study analysed the problem of the definition of risk acceptance criteria for occupational settings, defining the quantitative acceptance criteria for the specific case study of the Portuguese furniture industrial sector. The key steps to be considered in formulating acceptance criteria were analysed in the literature review. By applying the identified steps, the acceptance criteria for the furniture industrial sector were then defined. The Cumulative Distribution Function (CDF) for the injury statistics of the industrial sector was identified as the maximum tolerable risk level. The acceptable threshold was defined by adjusting the CDF to the Occupational, Safety & Health (OSH) practitioners’ risk acceptance judgement. Adjustments of acceptance criteria to the companies’ safety cultures were exemplified by adjusting the Burr distribution parameters. An example of a risk matrix was also used to demonstrate the integration of the defined acceptance criteria into a risk metric. This work has provided substantial contributions to the issue of acceptance criteria for occupational accidents, which may be useful in overcoming the practical difficulties faced by authorities, companies and experts

Effect of Antiplatelet Therapy on Survival and Organ Support–Free Days in Critically Ill Patients With COVID-19

International audienc