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

BackgroundMannitol is considered the gold standard hyperosmolar agent to decrease intracranial pressure (ICP) after traumatic brain injury. However, solutions of mannitol may crystallise when exposed to low temperatures, for example at high altitude or during helicopter rescues. If crystals are observed, the container should be warmed, shaken and then cooled to body temperature before administration which is inappropriate in daily emergency practice. Several studies show that hypertonic saline solution (HTSS) is comparable or potentially superior to mannitol: furthermore HTSS might have less adverse effect than mannitol and does not crystallise with low temperature. HTSS only exists in 500 mL glass vials, unfit for emergency practices which need compact unbreakable packaging.PurposeTo provide for emergency practices a ready-to-use HTSS of 7.5% sodium chloride infusion bag.Material and methodsInfusion bags were produced by aseptic process using the BAXA® EM2400 compounder. Ingredients used were sterile sodium chloride 20% (AGEPS®) and water for injectable preparation (Bbraun®) filled in an ethyl vinyl acetate infusion bag of 100 ml. Bags were stored at room temperature without light protection. Microbiological stability was assessed by performing sterility and endotoxin tests. The physicochemical study was performed by determining visual aspect, osmolality, sodium and chloride concentration at 0, 30 and 90 days.ResultsNeither precipitate nor any change in colour was observed after 90 days. Ion concentrations remained unchanged with 1320 mM (+3%); 1290 mM (+1%); 1240 mM (−3%) and osmolality of the HTSS were found to be 2560 mosm/L (0%); 2420 (-6%); and 2350 mosm/L (9%) respectively at 0, 30 and 90 days. At each time point, all microbiological results were negative.ConclusionThe automated compounding ensures quality and safety of production for a ready-to-use HTSS of 7.5% sodium chloride with a best-before-date of 90 days. The stability study is still on-going.Reference and/or Acknowledgements1. Helmy A, Vizcaychipi M, Gupta AK: Traumatic brain injury: intensive care management. Br J Anaesth, 2007; 99: 32–42.No conflict of interest

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BackgroundBiotherapies are mostly used in the treatment of chronic inflammatory rheumatism, such as rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis. Because they expose patients to a higher risk of infection, a urinary dipstick test (UDT) is performed in all patients who receive biotherapies.PurposeThe aim of this study was to evaluate the relevance of systematically performing a UDT in patients in the rheumatology day hospitalisation unit.Material and methodsA UDT was done for each patient during hospitalisation. When they were positive (positive nitrites and/or leukocytes strong), a cytobacteriological examination of urine (CBEU) was performed as well as a summary of clinical information.Results553 UDT were performed in 354 patients over 2 months. Median age of the patients was 56 years and 66% were female.From the 553 UDT performed, only 15 (3%) were positive: 10 UDT had only strong leukocytes and 5 had only positive nitrites. 3 positive UDT did not lead to a CBEU: 2 of them did not show any clinical signs and biotherapies were injected. The third patient was already septic on arrival and was receiving antibiotics. Of the 12 CBEU performed, 6 showed significant bacteriuria: 5 positive for Escherichia coli and 1 for Enterococcus faecalis.Among these 6 patients: 3 had asymptomatic bacteriuria and received their biotherapy and 3 were symptomatic. 2 patients were diagnosed with cystitis and pyelonephritis was discovered in a third patient. All were treated with an appropriate dose of ofloxacin. Only the patient with pyelonephritis did not receive biotherapy; for the other 2, the injection was delayed.ConclusionGiven the low frequency of abnormalities in the UDT, the therapeutic approach was modified in 3 cases and each time patients showed clinical signs. According to the literature, the risk of infection is higher during the first 6 months of treatment with biotherapies: 2 of the 3 patients had started their biotherapy less than a year before the onset of the urinary tract infection. Examination and clinical review should remain the primary elements in the diagnosis of a possible UTI and the therapeutic decision making.No conflict of interest.