Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke — the second leading cause of death worldwide — were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries

Patients de médecine hébergés en chirurgie à l'hopital de Langon (pertinence des hospitalisations et qualité de prise en charge)

BORDEAUX2-BU Santé (330632101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Elaboration et validation d'un outil identifiant les facteurs associés à l'application des recommandations professionnelles par les médecins dans les services de médecine polyvalente en Aquitaine

BORDEAUX2-BU Santé (330632101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Evaluation des effets d'une intervention complexe

L'évaluation des effets d'une intervention complexe est une des étapes d'un processus plus large de recherche, partant de la construction ou la modélisation de l'intervention jusqu'à son déploiement. Elle consiste à mesurer l'efficacité ou l'impact de cette intervention, c'est à dire à analyser sa capacité à produire du changement. Il s'agit d'obtenir une mesure non biaisée des effets moyens de l'intervention, à partir d'un panel de paramètres prédéterminés, en s'appuyant sur l'hypothèse d'un lien causal entre l'intervention et le résultat mesuré. Cet article est consacré à l'évaluation des effets d'une intervention complexe et se concentre sur les spécificités méthodologiques des trois étapes clés de cette évaluation : 1) la modélisation de l'intervention et l'analyse de faisabilité, préalables incontournables à l'évaluation des effets ; 2) le choix du schéma d'étude et des effets à mesurer, socles méthodologiques de l'évaluation des effets ; et 3) l'analyse de processus, menée en parallèle de l'évaluation des effets, pour une appréciation indispensable de l'application de l'intervention et du contexte dans lequel elle s'intègre. Les propos sont illustrés par cinq projets d'évaluation d'effets d'intervention.La problématique spécifique de l'évaluation des effets d'une intervention complexe est bien de sortir de la simple recherche de causalité entre l'intervention et ses effets pour aller vers la compréhension des mécanismes d'efficacité, par une prise en compte du contexte et des conditions réelles d'implantation de l'intervention. L'enjeu est par là même d'embrasser et non réduire la complexité de la situation interventionnelle, condition de son déploiement et généralisation.Appraising the effects of a complex intervention is one step in a more broadly based research process, from the construction or modelling of the intervention to its actual deployment. It consists in measuring the effectiveness or impact of the intervention, i.e. analyzing its capacity to produce change. The aim of this article is to obtain unbiased measurement of the average effects of an intervention, based on a panel of predetermined parameters and on the assumption of a causal link between the intervention and the measured result. This article is consequently devoted to evaluation of the effects of a complex intervention and focuses on the methodological challenges of its three key stages : 1) modelling of the intervention and feasibility analysis, essential prerequisites ; 2) the choice of study design and of the effects to be measured, that is to say the methodological premises ; and 3) process analysis, carried out in parallel with the evaluation of effects, leading to an indispensable appraisal of the intervention implementation and of the context into which it is integrated. The article is illustrated by five intervention impact assessment projects. A specific objective when evaluating the effects of a complex intervention consists in (a) moving away from a simple search for causality involving the intervention and its effects and (b) toward understanding of the effectiveness mechanisms, once again taking into account the context and the actual conditions of implementation. The challenge is to embrace rather than limit the complexity of the intervention, this being an essential prerequisite for its successful deployment and eventual generalization

Rev Epidemiol Sante Publique

Nous proposons un cadre méthodologique destiné aux experts impliqués dans l'appui à la décision concernant les interventions de santé publique. Le cadre méthodologique comprend quatre éléments : 1) une série de neuf questions, formulées en termes non techniques, pertinentes pour juger de l'utilité d'une intervention, considérée à un moment donné dans un contexte donné ; 2) une traduction de ces questions en concepts liés à l'évaluation des interventions (définition de l'intervention, de sa cible et de son objectif, efficacités potentielle et réelle, sécurité, efficience et équité) ; 3) une organisation logique des informations nécessaires pour répondre aux questions ; 4) un algorithme permettant de traduire les informations disponibles en recommandations sur l'utilité réelle de l'intervention dans le contexte où les questions ont été posées. Chaque étape est illustrée par des questions posées sur des interventions de sécurité routière, le dépistage, la transfusion sanguine et des mesures proposées pendant la pandémie de COVID-19. La décision peut être facilitée si les experts fournissent aux décideurs un résumé formel des forces et faiblesses des connaissances, fondé sur une analyse de toutes les facettes de l'utilité potentielle d'une intervention.We have designed a methodological framework for experts involved in the support of decision-making in public health interventions. The methodological framework consists of four elements: 1) A series of nine questions, formulated in non-technical terms, relevant to assessment of the usefulness of an intervention, at a given time in a given context; 2) Translation of these questions into concepts related to the evaluation of interventions (definition of the intervention, its target and objective, potential and actual effectiveness, safety, efficiency, and equity); 3) Logical organization of the information needed to address and answer the questions; and 4) An algorithm to translate the available information into recommendations on the real usefulness of the intervention in the context in which the questions were raised. Each step is illustrated by questions raised about road safety interventions, screening, blood transfusion and measures proposed during the COVID-19 pandemic. Decision-making can be facilitated if experts provide decision-makers with a formal summary of the strengths and weaknesses of existing knowledge, based on an analysis of all facets of an intervention's potential usefulness

Development of an evidence-based reference framework for care coordination with a focus on the micro level of integrated care: A mixed method design study combining scoping review of reviews and nominal group technique

BACKGROUND: Because of the limits in conceptualisation of care coordination linked to a large array of care coordination models and definitions available, a care coordination framework is needed with a particular focus on the micro level. OBJECTIVE: To develop an evidence-based reference framework for person-centred care coordination interventions based on international validated definitions. METHODS: This two-step mixed-methods study included first, a scoping review of reviews focus on the impact of care coordination interventions and then, a nominal group technique. The scoping review aimed at identifying the components of the four dimensions of the framework (contexts, activities, actors and tools, and effects). The nominal group technique was to select the relevant components of the dimension 'activities' of the reference framework. RESULTS: The scoping review selected 52 articles from the 1407 retrieved at first. The nominal group selected the 66 most relevant activities from the 159 retrieved in the literature (28 activities of care organisation, 24 activities of care, and 14 activities of facilitation). CONCLUSION: This operational framework focused on care coordination at the micro level, is a useful and innovative tool, applicable in any clinical condition, and in any health care system for describing, implementing and evaluating care coordination programmes

BMC Health Serv Res

BACKGROUND: Facing the increasing cancer incidence and cancer survivorship, many national strategic cancer plans have identified cancer care coordination as a priority for health service improvement. However, the high variability of practices, the diversity of definitions and underlying concepts increases the existing difficulty to standardise, replicate, transpose and assess care coordination within the French health system context. The EPOCK national study aims at evaluating practices and the working context of hospital-based cancer care coordination nurses, based on a previously designed reference framework for care coordination within the French health system context. METHODS: EPOCK is based on a comprehensive evaluation of nursing professions in cancer care coordination, considered as a complex intervention. Phase 1 (theoretical phase) will define and design a theoretical reference framework for care coordination in France through an international literature review, aiming to identify relevant models and all components of the expected framework and a structured consensus method, the Nominal group technique, aiming to select and prioritise the most relevant components already found in the literature review with regard to the French healthcare system; phase 2 (Operational phase) will consist in an in-depth analysis of practices, contexts, perceptions and attitudes related to care coordination occupations by nurses in oncology and all stakeholders (related professionals, patients and their caregivers) through a multicentric cross-sectional mixed-method evaluative study. The observed practices and contexts will be finally compared with the theoretical reference framework using both inductive and deductive approaches. DISCUSSION: This study will result in an evaluation framework identifying key models and key elements relative to cancer care coordination interventions that can be used to guide management of cancer care coordination nursing occupations within the French healthcare system. EPOCK would also assist in public decision-making to identify optimal targets, skills profiles and scope of actions for cancer coordination professions. Finally, EPOCK will describe typology of nurse practices in cancer care coordination and thus obtain precise preliminary information essential for drafting a medico-economic evaluation study of these new nursing professions' impact. TRIAL REGISTRATION: Clinicaltrial.gov registration: NCT03350776 , 11/22/2017

Sequelae and Quality of Life in Patients Living at Home 1 Year After a Stroke Managed in Stroke Units

International audienceIntroduction: Knowledge about residual deficiencies and their consequences on daily life activities among stroke patients living at home 1-year after the initial event managed in stroke units is poor. This multi-dimensional study assessed the types of deficiencies, their frequency and the consequences that the specific stroke had upon the daily life of patients.Methods: A cross-sectional survey, assessing, using standardized scales, 1 year post-stroke disabilities, limitations of activities, participation and quality of life, was carried out by telephone interview and by mail in a sample of stroke patients who returned home after having been initially managed in a stroke unit.Results: A total of 161 patients were included (142 able to answer the interview on their own; 19 needing a care-giver). Amongst a sub-group of the patients interviewed, 55.4% (95% Confidence Interval [47.1-63.7]) complained about pain and 60.0% (95% CI [51.4-68.6]) complained of fatigue; about 25% presented neuropsychological or neuropsychiatric disability. Whilst 87.3% (95% CI [81.7-92.9]) were independent for daily life activities, participation in every domains and quality of life scores, mainly in daily activity, pain, and anxiety subscales, were low.Conclusion: Despite a good 1-year post-stroke functional outcome, non-motor disabling symptoms are frequent amongst patients returned home and able to be interviewed, contributing to a low level of participation and a poor quality of life. Rehabilitation strategies focused on participation should be developed to break the vicious circle of social isolation and improve quality of life

Arch Cardiovasc Dis

BACKGROUND: Indicators of the appropriateness of oral anticoagulant prescriptions are lacking, despite the major contribution they could make to improve quality of care. AIM: To identify and select such indicators according to their utility and operational implementation. METHODS: A literature review was conducted to identify indicators of the appropriateness of oral anticoagulant prescriptions according to the guidelines of health authorities and European learned societies. A first list of indicators was identified from guidelines related to general or targeted clinical situations. A two-round Delphi consensus process, completed by a synthesis meeting, was then set up to ask European experts to rate the utility and operational implementation of the indicators on a qualitative binary scale. An indicator was selected if >/=80% of the experts judged it both useful and implementable (strong consensus). RESULTS: We selected 32 references, from which 84 indicators were identified. Nineteen indicators were short-listed for submission to expert judgment. Twenty-two experts participated in the Delphi process. Sixteen indicators obtained strong consensus for selection; three indicators did not achieve consensus. Two-thirds of the selected indicators focused on the appropriateness of oral anticoagulant prescriptions in general or in patients with atrial fibrillation; the other third focused on the appropriateness of prescriptions in patients with a prosthetic heart valve, venous thromboembolism or trauma. CONCLUSION: This work addresses the current lack of indicators of the appropriateness of oral anticoagulant prescriptions. The selected indicators will be implemented from the hospital information system to assess their metrological properties to detect inappropriate prescriptions