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

Analyse à haute résolution spatiale et temporelle de la connectivité entre la rivière Matane et son aquifère alluvial lors d'évènement de crue

Les interactions entre les eaux de surface et souterraines d'une plaine alluviale graveleuse se produisent à condition que les formations géologiques leur soient favorables. La présente recherche vise à documenter les interactions entre la rivière Matane et de son aquifère alluvial graveleux pendant des événements de crue. L' objectif est de mieux comprendre les mécanismes responsables des inondations par exfiltration de la nappe en surface alors qu'il y a absence de débordement de la rivière. Cette étude est réalisée à Saint-René-de-Matane sur un site caractérisé par la présence d' un ancien méandre abandonné ainsi que par la présence de quelques anciens chenaux de débordement. L'approche méthodologique adoptée se base sur la mise en place d'un réseau de 16 piézomètres et deux stations limnimétriques mesurant, à un intervalle de 15 minutes, la charge hydraulique de l'aquifère alluvial et les niveaux de la rivière, ainsi que leurs températures sur une période s'étalant de juin 2011 à décembre 2011. L'analyse statistique des séries temporelles des niveaux de la rivière et de la charge hydraulique a ensuite été réalisée afin de comprendre les liens entre les deux environnements. Les résultats de la recherche montrent que l'ensemble de l'aquifère alluvial de la vallée de Matane répond à la pression exercée par la hausse du niveau de la rivière lors du passage de la crue. L'amplitude des fluctuations de la charge dépend de la distance au chenal, de la magnitude de l'événement, mais aussi du temps de montée de la crue. Les analyses par corrélations-croisées montrent la propagation d'une onde de pression souterraine à travers l'entièreté de la plaine à chacune des crues. Son amplitude et sa vitesse de propagation sont fortement dépendantes des conditions hydroclimatiques. L'exfiltration de la nappe se produit à des débits variant de 238 à 492 m3 S-I , selon la position dans la plaine. Le passage d'une crue peut engendrer le changement de direction de l'écoulement local de la plaine. Cette recherche montre qu'une rivière a une plus grande extension spatiale et temporelle que ce que l'on observe dans son chenal et révèle la présence d'une connectivité dynamique entre une rivière et sa plaine graveleuse

Optimized assay and storage conditions for enzyme activity profiling of ectomycorrhizae

The aim of a joint effort by different research teams was to provide an improved procedure for enzyme activity profiling of field-sampled ectomycorrhizae, including recommendations on the best conditions and maximum duration for storage of ectomycorrhizal samples. A more simplified and efficient protocol compared to formerly published procedures was achieved by using manufactured 96-filter plates in combination with a vacuum manifold and by optimizing incubation times. Major improvements were achieved by performing the series of eight enzyme assays with a single series of root samples instead of two series, reducing the time needed for sample preparation, minimizing error-prone steps such as pipetting and morphotyping, and facilitating subsequent DNA analyses due to the reduced sequencing effort. The best preservation of samples proved to be storage in soil at 4\textendash6°C in the form of undisturbed soil cores containing roots. Enzyme activities were maintained for up to 4 weeks under these conditions. Short-term storage of washed roots and ectomycorrhizal tips overnight in water did not cause substantial changes in enzyme activity profiles. No optimal means for longer-term storage by freezing at -20°C or storage in 100% ethanol were recommended

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

International audienc