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

Etude d'un procédé de dépôt de films de diamant nanocristallin par CVD assistée par plasma micro-onde en régimes continu et pulsé (application à la réalisation de filtres à ondes acoustiques de surface)

L étude d un procédé de dépôt de films de diamant nanocristallin (DNC) assisté par plasma micro-onde pulsé en mélange Ar/H2/CH4, est réalisée. Un modèle numérique 1D, développé précédemment au LIMHP, est validé expérimentalement par des mesures de spectroscopie d absorption effectuées sur le système de Swan du radical C2. L analyse du plasma reposant sur les bilans réactionnels, les profils spatiaux et temporels des grandeurs de la décharge montre que la chimie est principalement gouvernée par la thermique. Le plasma est caractérisé par une température de gaz très élevée et une forte teneur en hydrogène atomique. A l interface plasma/surface sont générées les espèces potentiellement précurseurs du dépôt de DNC : les radicaux C2, CH3, CH2, CH et l atome de carbone. Bien que les espèces clefs de croissance ne soient pas formellement identifiées, une analyse critique des résultats de la littérature concernant les phénomènes de germination secondaire se déroulant lors du dépôt de DNC est obtenue. Elle conduit à remettre en question les conclusions de May et al. excluant le radical C2 comme espèce de croissance. L optimisation des propriétés morphologique, topographique et électrique des films de DNC, en vue de la conception de filtres à ondes acoustiques de surface (SAW) fonctionnant à fréquence élevée, est obtenue par la modulation de la puissance injectée et l ajustement des paramètres de dépôt. Associés à la lithographie électronique, la faible rugosité de surface, la faible taille de grains et le caractère résistif des films de DNC, élaborés à basse fréquence, permettent la réalisation de dispositifs SAW en structure multicouches IDTs/AlN/DNC fonctionnant jusqu à 4 GHz.The study of a nanocrystalline diamond (NCD) film deposition process enhanced by microwave and pulsed Ar/H2/CH4 plasma is reported. The validation of a 1D model, previously developed at the LIMHP, is experimentally carried out by absorption spectroscopy measurements performed on C2 Swan system. Analysis of the discharge is based on reactional kinetics balances, as well as the spatial and temporal distributions of different species. It shows that the plasma chemistry is controlled by gas temperature (Tg). The plasma is characterized by high Tg and hydrogen atoms density. Potential NCD growth precursor species such as C2, CH3, CH2, CH radicals and C atoms are produced near the substrate. Although no key species is clearly identified, an exhaustive review of other groups results about the secondary nucleation growth involved during NCD deposition is made. It leads to reconsider May et al. s conclusions which exclude C2 radical for growth processes. In order to achieve surface acoustic waves (SAW) devices working at high frequency, optimisation of structural and electrical properties of NCD films is obtained by modulating microwave power and adjusting process parameters. SAW devices based on IDTs/AlN/NCD layer structure, operating at 4 Ghz, are obtained using combination of electron-beam lithography and NCD films elaborated at low frequency and characterized by small grain size, low surface roughness and high electrical resistivity.PARIS13-BU Sciences (930792102) / SudocSudocFranceF

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

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