ARIA digital anamorphosis : Digital transformation of health and care in airway diseases from research to practice

Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.Peer reviewe

Durvalumab Plus Carboplatin/Paclitaxel Followed by Maintenance Durvalumab With or Without Olaparib as First-Line Treatment for Advanced Endometrial Cancer: The Phase III DUO-E Trial

PURPOSE Immunotherapy and chemotherapy combinations have shown activity in endometrial cancer, with greater benefit in mismatch repair (MMR)-deficient (dMMR) than MMR-proficient (pMMR) disease. Adding a poly(ADP-ribose) polymerase inhibitor may improve outcomes, especially in pMMR disease. METHODS This phase III, global, double-blind, placebo-controlled trial randomly assigned eligible patients with newly diagnosed advanced or recurrent endometrial cancer 1:1:1 to: carboplatin/paclitaxel plus durvalumab placebo followed by placebo maintenance (control arm); carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib placebo (durvalumab arm); or carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib (durvalumab + olaparib arm). The primary end points were progression-free survival (PFS) in the durvalumab arm versus control and the durvalumab + olaparib arm versus control. RESULTS Seven hundred eighteen patients were randomly assigned. In the intention-to-treat population, statistically significant PFS benefit was observed in the durvalumab (hazard ratio [HR], 0.71 [95% CI, 0.57 to 0.89]; P = .003) and durvalumab + olaparib arms (HR, 0.55 [95% CI, 0.43 to 0.69]; P < .0001) versus control. Prespecified, exploratory subgroup analyses showed PFS benefit in dMMR (HR [durvalumab v control], 0.42 [95% CI, 0.22 to 0.80]; HR [durvalumab + olaparib v control], 0.41 [95% CI, 0.21 to 0.75]) and pMMR subgroups (HR [durvalumab v control], 0.77 [95% CI, 0.60 to 0.97]; HR [durvalumab + olaparib v control] 0.57; [95% CI, 0.44 to 0.73]); and in PD-L1-positive subgroups (HR [durvalumab v control], 0.63 [95% CI, 0.48 to 0.83]; HR [durvalumab + olaparib v control], 0.42 [95% CI, 0.31 to 0.57]). Interim overall survival results (maturity approximately 28%) were supportive of the primary outcomes (durvalumab v control: HR, 0.77 [95% CI, 0.56 to 1.07]; P = .120; durvalumab + olaparib v control: HR, 0.59 [95% CI, 0.42 to 0.83]; P = .003). The safety profiles of the experimental arms were generally consistent with individual agents. CONCLUSION Carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab with or without olaparib demonstrated a statistically significant and clinically meaningful PFS benefit in patients with advanced or recurrent endometrial cancer

Adherence to treatment in allergic rhinitis using mobile technology. The MASK Study

Background: Mobile technology may help to better understand the adherence to treatment. MASK-rhinitis (Mobile Airways Sentinel NetworK for allergic rhinitis) is a patient-centred ICT system. A mobile phone app (the Allergy Diary) central to MASK is available in 22 countries. Objectives: To assess the adherence to treatment in allergic rhinitis patients using the Allergy Diary App. Methods: An observational cross-sectional study was carried out on all users who filled in the Allergy Diary from 1 January 2016 to 1 August 2017. Secondary adherence was assessed by using the modified Medication Possession Ratio (MPR) and the Proportion of days covered (PDC) approach. Results: A total of 12143 users were registered. A total of 6949 users reported at least one VAS data recording. Among them, 1887 users reported >= 7 VAS data. About 1195 subjects were included in the analysis of adherence. One hundred and thirty-six (11.28%) users were adherent (MPR >= 70% and PDC = 70% and PDC = 1.50) and 176 (14.60%) were switchers. On the other hand, 832 (69.05%) users were non-adherent to medications (MPR Conclusion and clinical relevance: Adherence to treatment is low. The relative efficacy of continuous vs on-demand treatment for allergic rhinitis symptoms is still a matter of debate. This study shows an approach for measuring retrospective adherence based on a mobile app. This also represents a novel approach for analysing medication-taking behaviour in a real-world setting.Peer reviewe

Allergic Rhinitis and its Impact on Asthma (ARIA) Phase 4 (2018) : Change management in allergic rhinitis and asthma multimorbidity using mobile technology

Allergic Rhinitis and its Impact on Asthma (ARIA) has evolved from a guideline by using the best approach to integrated care pathways using mobile technology in patients with allergic rhinitis (AR) and asthma multimorbidity. The proposed next phase of ARIA is change management, with the aim of providing an active and healthy life to patients with rhinitis and to those with asthma multimorbidity across the lifecycle irrespective of their sex or socioeconomic status to reduce health and social inequities incurred by the disease. ARIA has followed the 8-step model of Kotter to assess and implement the effect of rhinitis on asthma multimorbidity and to propose multimorbid guidelines. A second change management strategy is proposed by ARIA Phase 4 to increase self-medication and shared decision making in rhinitis and asthma multimorbidity. An innovation of ARIA has been the development and validation of information technology evidence-based tools (Mobile Airways Sentinel Network [MASK]) that can inform patient decisions on the basis of a self-care plan proposed by the health care professional.Peer reviewe

Increased serum miR-193a-5p during non-alcoholic fatty liver disease progression: diagnostic and mechanistic relevance

Background & Aims: Serum microRNAs (miRNAs) levels are known to change in non-alcoholic fatty liver disease (NAFLD) and may serve as useful biomarkers. This study aimed to profile miRNAs comprehensively at all NAFLD stages.Methods: We profiled 2,083 serum miRNAs in a discovery cohort (183 NAFLD cases representing the complete NAFLD spectrum and 10 population controls). MiRNA libraries generated by HTG EdgeSeq were sequenced by Illumina NextSeq. Selected serum miRNAs were profiled in 372 additional NAFLD cases and 15 population controls by quantitative reverse transcriptase-polymerase chain reaction.Results: Levels of 275 miRNAs differed between cases and population controls. Fewer differences were seen within individual NAFLD stages but miR-193a-5p consistently the showed increased levels in all comparisons. Relative to NAFL/NASH with mild fibrosis (stage 0/1), three miRNAs (miR-193a-5p, miR-378d and miR378d) were increased in cases with NASH and clinically significant fibrosis (stage 2-4), seven (miR193a-5p, miR-378d, miR-378e, miR-320b, c, d & e) increased in cases with NAFLD Activity Score (NAS) 5-8 compared with lower NAS, and three (miR-193a-5p, miR-378d, miR-378e) increased but one (miR-19b-3p) decreased in steatosis, activity, and fibrosis "activity" (SAF-A) score 2-4 compared with lower SAF-A. The significant findings for miR-193a-5p were replicated in the additional NAFLD cohort. Studies in Hep G2 cells showed that following palmitic acid treatment, miR-193a-5p expression decreased significantly. Gene targets for miR-193a-5p were investigated in liver RNAseq data for a case subgroup (n=80); liver GPX8 levels correlated positively with serum miR-193a-5p. Conclusions: Serum miR-193a-5p levels correlate strongly with NAFLD activity grade and fibrosis stage. MiR-193a-5p may have a role in the hepatic response to oxidative stress and is a potential clinically tractable circulating biomarker for progressive NAFLD

Mortalités massives de moules bleues dans les secteurs mytilicoles : description et facteurs liés

Depuis 2014, des épisodes de mortalité massive notamment en Charente-Maritime et en Vendée, ont été rapportés sur la « moule bleue » élevée principalement sur bouchots (pieux en chêne plantés verticalement) ou sur filières (cordes verticales sous flotteurs). Ces épisodes affectent significativement l’économie des entreprises mytilicoles. Plusieurs hypothèses ont été émises pour expliquer ce phénomène : agents pathogènes, contamination environnementale notamment par des pesticides, «asphyxie» des moules par excès de matière en suspension, réchauffement climatique, acidificationdes eaux, baisse des ressources alimentaires, ou stress physiologique. etc...

Rapport de synthèse sur la communication et la valorisation des données liées à l’étude MORBLEU et aux mortalités de moules bleues en France

Ce rapport s’inscrit dans le cadre du projet MORBLEU mené par l’Ifremer entre 2015 et 2019 en réponse à une demande de la DPMA. Ce document présente une synthèse des éléments de communication et de valorisation des données et des connaissances, liées à l’étude MORBLEU et aux mortalités de moules bleues en France sur cette période

Marine cytophaga-like bacteria (CLB) isolated from diseased reared sea bass (Dicentrarchus labrax L.) from French mediterranean coast

During spring of 1993, an epizootic outbreak occurred in a sea bass farm, located on the French Mediterranean coast. The cumulative mortality reached 25%. First examination of cutaneous lesions revealed filamentous bundles of flexuous bacteria which exhibited gliding motility. Bacterial growth was obtained only from skin lesions. The biochemical characteristics of isolates are described. Pathogenicity tests of representative slrains were carried out. Until fuller data is available, the pathogen here reported was provisionally identified as a Cytophaga·like bacterium (CLB)

Projet de recherche "MORBLEU". Environnement des écosystèmes mytilicoles et crises de mortalité récentes, quelles interactions? Etude des facteurs pouvant favoriser les surmortalités de moules bleues (Mytilus edulis) dans les pertuis charentais et en Vendée (2014-2016)

Durant l’hiver 2014 jusqu’à mai 2014, des mortalités exceptionnelles (50-100%) ont affectées la moule bleue, Mytilus edulis dans les Pertuis Charentais (principalement secteur du Pertuis Breton) et en Vendée. A la demande du Ministère (DPMA) une expertise environnementale a été demandée à l’Ifremer. L’expertise a permis de montrer que les conditions hydrologiques de l’hiver 2014 ne permettent pas de mettre en évidence une cause environnementale à ces mortalités exceptionnelles. Les analyses en pathologie réalisées ont révélées dans les moules la présence de bactéries appartenant au groupe bactérien Vibrio splendidus, dont la virulence a été confirmée expérimentalement. Dans ce contexte, la DPMA a sollicité l’Ifremer pour conduire en 20105 une étude prospective et descriptive qui préciserait les conditions qui favorisent les surmortalités de moules en lien avec des Vibrio. L’étude, MORtalité moules BLEUes-MORBLEU-, proposée en réponse à la demande publique est constituée d’actions de recherche multidisciplinaires, multi-échelles, qui s’appuie sur cinq laboratoires de l’Ifremer et sur le réseau d'observation MYTILOBS. Cette étude a été reconduite pour l’année 2016. Les objectifs généraux du projet MORBLEU sont d’identifier des facteurs associés ou potentiellement corrélés avec les mortalités de moules observées dans les Pertuis Charentais : facteurs environnementaux (biotiques, abiotiques et hydrodynamiques) et facteurs intrinsèques aux animaux (traits d'histoire de vie, qualité cytogénétique et physiologie). Nous présentons rapidement la démarche, les objectifs de chaque action (hydrodynamique, contexte environnemental physico-chimique et biotique, génétique), et une vue partielle des résultats analysés pour l’année 2015 (dynamique des mortalités de moules dans les Pertuis, conditions hydrodynamiques et la connectivité des masses d’eau, paramètres physico-chimiques, contaminants, diversité planctonique, statut génétique et qualité cytogénétique,…)

Mortalités massives de l’Huître creuse. Synthèse - Rapport final des études menées sur les mortalités de naissains d’huîtres creuses C. gigas sur le littoral charentais pour la période de 2007 à 2012

Since 2008, the French oyster-farming sector has been confronted with exceptionally high rates of mortality affecting spats (less than one year old) of the Pacific oyster, C. gigas, of between 60 and 90% at all rearing sites and in Pertuis Charentais sea. The objective of this document is to provide an overview of the research and studies carried out by Ifremer in Poitou-Charentes since the emergence of this phenomenon. The actions presented were funded by IFREMER, and CPER Poitou-Charentes 2007-2013.Depuis 2008, l’ostréiculture française est confrontée à une surmortalité exceptionnelle des naissains (environ un an) d’huîtres creuses (C. gigas). Les taux de mortalité atteignent 60 à 90% sur tous les sites des Pertuis Charentais. L’objectif de ce rapport est de présenter les études et recherches conduites sur ce thème par l’Ifremer, depuis l’émergence du phénomène. Les actions ont été financées par IFREMER et le CPER Poitou-Charentes 2007-2013