Predictors of hospital discharge and mortality in patients with diabetes and COVID-19: updated results from the nationwide CORONADO study

AIMS/HYPOTHESIS: This is an update of the results from the previous report of the CORONADO (Coronavirus SARS-CoV-2 and Diabetes Outcomes) study, which aims to describe the outcomes and prognostic factors in patients with diabetes hospitalised for coronavirus disease-2019 (COVID-19). METHODS: The CORONADO initiative is a French nationwide multicentre study of patients with diabetes hospitalised for COVID-19 with a 28-day follow-up. The patients were screened after hospital admission from 10 March to 10 April 2020. We mainly focused on hospital discharge and death within 28 days. RESULTS: We included 2796 participants: 63.7% men, mean age 69.7 ± 13.2 years, median BMI (25th-75th percentile) 28.4 (25.0-32.4) kg/m(2). Microvascular and macrovascular diabetic complications were found in 44.2% and 38.6% of participants, respectively. Within 28 days, 1404 (50.2%; 95% CI 48.3%, 52.1%) were discharged from hospital with a median duration of hospital stay of 9 (5-14) days, while 577 participants died (20.6%; 95% CI 19.2%, 22.2%). In multivariable models, younger age, routine metformin therapy and longer symptom duration on admission were positively associated with discharge. History of microvascular complications, anticoagulant routine therapy, dyspnoea on admission, and higher aspartate aminotransferase, white cell count and C-reactive protein levels were associated with a reduced chance of discharge. Factors associated with death within 28 days mirrored those associated with discharge, and also included routine treatment by insulin and statin as deleterious factors. CONCLUSIONS/INTERPRETATION: In patients with diabetes hospitalised for COVID-19, we established prognostic factors for hospital discharge and death that could help clinicians in this pandemic period. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT04324736

Une méthode de suivi de la vulnérabilité systémique à l’érosion et la submersion marines

International audienc

Region-specific remodeling of the enteric nervous system and enteroendocrine cells in the colon of spinal cord injury patients

International audiencePatients with spinal cord injury (SCI) suffer from major bowel dysfunction, whose exact pathophysiology, particularly the involvement of the enteric nervous system or epithelial dysfunction is poorly understood. Herein, we aimed to characterize the mucosal biopsies of the right and left colon in SCI patients vs controls (CT): (1) remodeling of key enteric neurotransmitters, (2) remodeling of enteroendocrine cells, and (3) mucosal inflammation compared to those in controls. In SCI, mucosal ACh concentration was lower in the right colon as compared to CT, but no change was observed in the left colon, and AChE expression was lower in both the right and left colons than in CT. While the VIP concentration was similar in the right and left colons, VIP mRNA expression was increased in the right colon and decreased in the left colon, in SCI patients as compared to CT. Interestingly, 5-HT concentration was reduced in the left colon but not in the right colon in SCI patients. Moreover, in SCI patients, as compared to CT, SERT mRNA expression was selectively increased in the left colon while TPH1 mRNA expression was increased in the right and left colons. Although mucosal TNFα and IL-1β mRNA expression did not significantly differ between SCI and CT groups, we identified a significant positive correlation between TNFα and IL-1β mRNA expression and left colon transit time in the SCI group. In conclusion, region-specific changes occur in the enteric neurotransmitter, serotonergic, and inflammatory pathways in the colon of SCI patients. The significant correlations between these pathways and clinical parameters in the left colon further set a scientific basis for designing therapeutic targets to improve colonic motor dysfunction in patients.Biobank information: Spinal cord injury patients: PHRC ConstiCAPE-clinical trial NCT02566746. Controls: Anosain-clinical trial NCT03054415 and biobank of the "Institut des Maladies de l’Appareil Digestif (IMAD)" registered under number DC-2008-402

A method for monitoring systemic vulnerability to marine erosion and sea-flooding

Coastal development, combined with the intrinsic mobility of coasts and the context of climate change, tends to increase the vulnerability of coastal territories. This article proposes, on one hand, a renewed interdisciplinary approach to the concept of vulnerability allowing to overcome the nature/society dichotomy. On the other hand, the paper presents an inter-sectoral researchers-managers approach to build a series of indicators to monitor the four components of systemic vulnerability (hazards, stakes, management and representations). These indicators lay the ground for an integrated observatory, source of data for research as well as to inform decisions regarding the adaptation of coastal territories.Le phénomène de littoralisation du peuplement et des activités, associé à la mobilité intrinsèque des côtes et au contexte de changement climatique, tend à accroître la vulnérabilité des territoires côtiers. Cet article propose, d’une part, une approche interdisciplinaire renouvelée du concept de vulnérabilité permettant de dépasser la dichotomie nature/société. D’autre part, il présente une méthode intersectorielle chercheurs-gestionnaires de construction d’une série d’indicateurs de suivi des quatre composantes de la vulnérabilité systémique (aléa, enjeux, gestion et représentations). Ces indicateurs préfigurent un observatoire intégré, à la fois source de données pour la recherche, et au service des politiques publiques pour les territoires côtiers

Factors influencing the development of primary care data collection projects from electronic health records: a systematic review of the literature

Abstract Background Primary care data gathered from Electronic Health Records are of the utmost interest considering the essential role of general practitioners (GPs) as coordinators of patient care. These data represent the synthesis of the patient history and also give a comprehensive picture of the population health status. Nevertheless, discrepancies between countries exist concerning routine data collection projects. Therefore, we wanted to identify elements that influence the development and durability of such projects. Methods A systematic review was conducted using the PubMed database to identify worldwide current primary care data collection projects. The gray literature was also searched via official project websites and their contact person was emailed to obtain information on the project managers. Data were retrieved from the included studies using a standardized form, screening four aspects: projects features, technological infrastructure, GPs’ roles, data collection network organization. Results The literature search allowed identifying 36 routine data collection networks, mostly in English-speaking countries: CPRD and THIN in the United Kingdom, the Veterans Health Administration project in the United States, EMRALD and CPCSSN in Canada. These projects had in common the use of technical facilities that range from extraction tools to comprehensive computing platforms. Moreover, GPs initiated the extraction process and benefited from incentives for their participation. Finally, analysis of the literature data highlighted that governmental services, academic institutions, including departments of general practice, and software companies, are pivotal for the promotion and durability of primary care data collection projects. Conclusion Solid technical facilities and strong academic and governmental support are required for promoting and supporting long-term and wide-range primary care data collection projects

Antibiotic Prescriptions in Critically Ill Patients with Bloodstream Infection Due to ESBL-Producing Enterobacteriaceae: Compliance with the French Guidelines for the Treatment of Infections with Third-Generation Cephalosporin-Resistant Enterobacteriaceae—A Multicentric Retrospective Cohort Study

National and international guidelines were recently published regarding the treatment of Enterobacteriaceae resistant to third-generation cephalosporins infections. We aimed to assess the implementation of the French guidelines in critically ill patients suffering from extended-spectrum β-lactamase-producing Enterobacteriaceae bloodstream infection (ESBL-E BSI). We conducted a retrospective observational cohort study in the ICU of three French hospitals. Patients treated between 2018 and 2022 for ESBL-E BSI were included. The primary assessment criterion was the proportion of adequate empirical carbapenem prescriptions, defined as prescriptions consistent with the French guidelines. Among the 185 included patients, 175 received an empirical anti-biotherapy within 24 h of ESBL-E BSI onset, with a carbapenem for 100 of them. The proportion of carbapenem prescriptions consistent with the guidelines was 81%. Inconsistent prescriptions were due to a lack of prescriptions of a carbapenem, while it was recommended in 25% of cases. The only factor independently associated with adequate empirical carbapenem prescription was ESBL-E colonization (OR: 107.921 [9.303–1251.910], p = 0.0002). The initial empirical anti-biotherapy was found to be appropriate in 83/98 patients (85%) receiving anti-biotherapy in line with the guidelines and in 56/77 (73%) patients receiving inadequate anti-biotherapy (p = 0.06). Our results illustrate the willingness of intensivists to spare carbapenems. Promoting implementation of the guidelines could improve the proportion of initial appropriate anti-biotherapy in critically ill patients with ESBL-E BSI

Systemic vulnerability of coastal territories to erosion and marine flooding: A conceptual and methodological approach applied to Brittany (France)

International audienceThe attractiveness of the coasts tends to increase their exposure to erosion and marine flooding risks. This exposure is exacerbated by the effects of climate change, in particular sea level rise. To contribute to strategic thinking on the vulnerability of coastal areas, it is essential to develop, share and collectively maintain relevant knowledge on risks. This article will present the thinking behind the setting up of a coastal risks observatory in Brittany, a region located in north-western France. It relies on a conceptual approach to systemic vulnerability based on four components: hazards, assets, management, and social representations. Hazards and assets underpin the notion of risk and tend to increase the vulnerability, management tends to mitigate it, and representations can play a part in increasing or decreasing it depending on the context. To understand and analyze this system of vulnerability, our approach is based on the generation of a set of 62 indicators combined into different types of indices. A web-GIS interface was developed to navigate through and map this system of vulnerability. The difficulties associated with this type of synthetic approach will be discussed, whether they are related to data availability, to the links between scientific research and operational territorial management requirements, or to an understanding of the dynamics of all of the vulnerability components and their interactions. Ultimately, the approach developed has been successful in mobilising scientific and operational stakeholders around the co-construction of a diagnosis of territories with regard to their vulnerability to coastal risks

Aglycosylated extracellular loop of inwardly rectifying potassium channel 4.1 (KCNJ10) provides a target for autoimmune neuroinflammation

Abstract Multiple sclerosis is an autoimmune disease of the central nervous system. Yet, the autoimmune targets are still undefined. The extracellular e1 sequence of KCNJ10, the inwardly rectifying potassium channel 4.1, has been subject to fierce debate for its role as a candidate autoantigen in multiple sclerosis. Inwardly rectifying potassium channel 4.1 is expressed in the central nervous system but also in peripheral tissues, raising concerns about the central nervous system-specificity of such autoreactivity. Immunization of C57Bl6/J female mice with the e1 peptide (amino acids 83–120 of Kir4.1) induced anti-e1 immunoglobulin G- and T-cell responses and promoted demyelinating encephalomyelitis with B cell central nervous system enrichment in leptomeninges and T cells/macrophages in central nervous system parenchyma from forebrain to spinal cord, mostly in the white matter. Within our cohort of multiple sclerosis patients (n = 252), 6% exhibited high anti-e1 immunoglobulin G levels in serum as compared to 0.7% in the control cohort (n = 127; P = 0.015). Immunolabelling of inwardly rectifying potassium channel 4.1-expressing white matter glia with the anti-e1 serum from immunized mice increased during murine autoimmune neuroinflammation and in multiple sclerosis white matter as compared with controls. Strikingly, the mouse and human anti-e1 sera labelled astrocytoma cells when N-glycosylation was blocked with tunicamycin. Western blot confirmed that neuroinflammation induces Kir4.1 expression, including its shorter aglycosylated form in murine experimental autoencephalomyelitis and multiple sclerosis. In addition, recognition of inwardly rectifying potassium channel 4.1 using mouse anti-e1 serum in Western blot experiments under unreduced conditions or in cells transfected with the N-glycosylation defective N104Q mutant as compared to the wild type further suggests that autoantibodies target an e1 conformational epitope in its aglycosylated form. These data highlight the e1 sequence of inwardly rectifying potassium channel 4.1 as a valid central nervous system autoantigen with a disease/tissue-specific post-translational antigen modification as potential contributor to autoimmunity in some multiple sclerosis patients