IMPORTANCEThe benefit of high-dose dexamethasone and oxygenation strategies vs standard of care for patients with severe acute hypoxemic respiratory failure (AHRF) caused by COVID-19 pneumonia is debated.OBJECTIVES To assess the benefit of high-dose dexamethasone compared with standard of care dexamethasone, and to assess the benefit of high-flow nasal oxygen (HFNO 2 ) or continuous positive airway pressure (CPAP) compared with oxygen support standard of care (O 2 SC). DESIGN, SETTING, AND PARTICIPANTSThis multicenter, placebo-controlled randomized clinical trial was conducted in 19 intensive care units (ICUs) in France from April 2020 to January 2021. Eligible patients were consecutive ICU-admitted adults with COVID-19 AHRF. Randomization used a 2 × 3 factorial design for dexamethasone and oxygenation strategies; patients not eligible for at least 1 oxygenation strategy and/or already receiving invasive mechanical ventilation (IMV) were only randomized for dexamethasone. All patients were followed-up for 60 days. Data were analyzed from May 26 to July 31, 2021.INTERVENTIONS Patients received standard dexamethasone (dexamethasone-phosphate 6 mg/d for 10 days [or placebo prior to RECOVERY trial results communication]) or high-dose dexamethasone (dexamethasone-phosphate 20 mg/d on days 1-5 then 10 mg/d on days 6-10). Those not requiring IMV were additionally randomized to O 2 SC, CPAP, or HFNO 2 . MAIN OUTCOMES AND MEASURESThe main outcomes were time to all-cause mortality, assessed at day 60, for the dexamethasone interventions, and time to IMV requirement, assessed at day 28, for the oxygenation interventions. Differences between intervention groups were calculated using proportional Cox models and expressed as hazard ratios (HRs). RESULTS Among 841 screened patients, 546 patients (median [IQR] age, years; 414 [75.8%] men) were randomized between standard dexamethasone (276 patients, including 37 patients who received placebo) or high-dose dexamethasone (270 patients). Of these, 333 patients were randomized among O 2 SC (109 patients, including 56 receiving standard dexamethasone), CPAP (109 patients, including 57 receiving standard dexamethasone), and HFNO 2 (115 patients, including 56 receiving standard dexamethasone). There was no difference in 60-day mortality between standard and high-dose dexamethasone groups (HR, 0.96 [95% CI, 0.69-1.33]; P = .79). There was no significant difference for the cumulative incidence of IMV criteria at day 28 among O 2 support groups (O 2 SC vs CPAP: HR, 1.08 [95% CI, 0.71-1.63]; O 2 SC vs HFNO 2 : HR, 1.04 [95% CI, 0.69-1.55]) or 60-day mortality (O 2 SC vs CPAP: HR, 0.97 [95% CI, 0.58-1.61; O 2 SC vs HFNO 2 : HR, 0.89 [95% CI,). Interactions between interventions were not significant. CONCLUSIONS AND RELEVANCEIn this randomized clinical trial among ICU patients with COVID-19-related AHRF, high-dose dexamethasone did not significantly improve 60-day survival. The oxygenation strategies in patients who were not initially receiving IMV did not significantly modify 28-day risk of...

IMPORTANCEOveractivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19.ObjectiveTo determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19.DESIGN, SETTING, AND PARTICIPANTSIn 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).INTERVENTIONSPatients 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 MEASURESThe 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.RESULTSOn 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 RELEVANCEIn 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 REGISTRATIONClinicalTrials.gov Identifier: NCT02735707

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BackgroundPrimary care patients are often cited as a cause of Emergency Department overcrowding (ED). The aim of this study was to evaluate a physician led redirection procedure of selected patients towards an out of hours general practice (OHGP) in an Emergency Department with 55,000 admissions per year.MethodsObservational monocentric study over a period of 2 months. Every patient redirected to the OHGP was included and subsequently contacted by telephone to answer a standardized questionnaire, in order to measure:Redirection rate over the entire period and during weekdays or weekends/holidayRate of redirected patients who went to the OHGPRate of redirected patients who consulted in an ED in the next 72 h for the same reasonRedirected patients’ satisfaction rateResultsDuring the study period 9551 patients presented to the ED, of which 288 were redirected towards the OHGP (3%). The redirection rate was 1.9% during weekdays and 5.7% during weekends/holiday (p < 0.001). Of the redirected patients, 77% answered the telephone interview.Ninety percent of these patients consulted the OHGP. The main reasons for not consulting were: unduly long wait, opening hours not suitable, too costly. The rate of redirected patients who consulted in an ED in the following 72 h for the same reason was 4.1%. The satisfaction rate was 79.6% among interviewed patients.ConclusionsA physician led procedure to redirect selected patients from the ED towards an OHGP results in a low redirection rate, unlikely to have a significant effect on ED patient flow. However, the procedure is safe and well accepted by a majority of patients.

BackgroundThe aim of this study was to determine whether: (1) the quick Sequential (Sepsis-related) Organ Failure Assessment (qSOFA) and National Early Warning Score (NEWS) clinical prediction tools alone, (2) modified versions of these prediction tools that integrate lactate into their scores, or (3) use of the two tools in tandem with lactate better predicts in-hospital 28-day mortality among adult EDpatients with suspected infection.MethodsFrom 1 January through 31 December 2018, this retrospective cohort study enrolled consecutive adult patients with suspected infection evaluated at two EDs in France. Patients were included if blood cultures were obtained and non-prophylactic antibiotics were administered in the ED. qSOFA, NEWS criteria and lactate measurements were recorded when patients were clinically suspected of having an infection. Two composite scores (lactate qSOFA (LqSOFA) and lactate NEWS (LNEWS)) integrating lactate were created. Diagnostic test performances for predicting in-hospital mortality within 28days were assessed for qSOFA≥2, LqSOFA≥2, qSOFA≥2 or lactate≥2 mmol/L, and for NEWS≥7, LNEWS≥7, and NEWS≥7 or lactate≥2 mmol/L.Results1003 patients were included, 130 (13%) of whom had died by day 28. Sensitivities for 28-day mortality were 50% (95%CI41% to 59%) for qSOFA≥2,69% (95% CI60% to 77%) for LqSOFA≥2,77% (95% CI69% to 84%) for qSOFA or lactate≥2 mmol/L; and 69% (95% CI60% to 77%) for NEWS≥7, 80% (95% CI72% to 86%) for LNEWS≥7, 87% (95% CI80% to 92%) for NEWS≥7 or lactate≥2 mmol/L.ConclusionLactate used in tandem with qSOFA or NEWS yielded higher sensitivities in predicting in-hospital 28-day mortality, as compared with integration of lactate into these prediction tools or usage of the tools independently.