La clinique externe : comment peut-elle prétendre aux rôles de porte d’entrée et de plaque tournante?

Cet article présente un survol du plan de transformation des services adopté en 1998 à l'Hôpital Louis-H. Lafontaine. Les auteurs présentent l'historique, les principes et les modèles, le rôle joué par les cliniques externes ainsi que les défis à relever par tous, collègues et partenaires, pour mener à bien cet immense projet.This article presents an overview of the plan of transformation of services adopted in 1998 at Louis-H. Lafontaine Hospital. The authors present the history, principles and models, the role played by outpatients clinics as well as the challenges related to the implementation of this new plan.Este articulo presenta un sobrevuelo del plan de transformación de servicios adoptado en 1998 por el hospital Louis-H Lafontaine. Los autores presentan el histórico, los principios y los modelos. El papel desempeñado por las clínicas externas, como también los desafíos que se presentan a todos, colegas y aliados, para llevar a cabo y bien, este gran proyecto

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old