Fonds de recherche du Québec

RATIONALE: Dexmedetomidine is associated with less delirium than benzodiazepines and better sleep architecture than either benzodiazepines or propofol; its effect on delirium and sleep when administered at night to patients requiring sedation remains unclear. OBJECTIVES: To determine if nocturnal dexmedetomidine prevents delirium and improves sleep in critically ill adults. METHODS: This two-center, double-blind, placebo-controlled trial randomized 100 delirium-free critically ill adults receiving sedatives to receive nocturnal (9:30 p.m. to 6:15 a.m.) intravenous dexmedetomidine (0.2 μg/kg/h, titrated by 0.1 μg /kg/h every 15 min until a goal Richmond Agitation and Sedation Scale score of -1 or maximum rate of 0.7 μg/kg/h was reached) or placebo until ICU discharge. During study infusions, all sedatives were halved; opioids were unchanged. Delirium was assessed using the Intensive Care Delirium Screening Checklist every 12 hours throughout the ICU admission. Sleep was evaluated each morning by the Leeds Sleep Evaluation Questionnaire. MEASUREMENTS AND MAIN RESULTS: Nocturnal dexmedetomidine (vs. placebo) was associated with a greater proportion of patients who remained delirium-free during the ICU stay (dexmedetomidine [40 (80%) of 50 patients] vs. placebo [27 (54%) of 50 patients]; relative risk, 0.44; 95% confidence interval, 0.23-0.82; P = 0.006). The average Leeds Sleep Evaluation Questionnaire score was similar (mean difference, 0.02; 95% confidence interval, 0.42-1.92) between the 34 dexmedetomidine (average seven assessments per patient) and 30 placebo (six per patient) group patients able to provide one or more assessments. Incidence of hypotension, bradycardia, or both did not differ significantly between groups. CONCLUSIONS: Nocturnal administration of low-dose dexmedetomidine in critically ill adults reduces the incidence of delirium during the ICU stay; patient-reported sleep quality appears unchanged. Clinical trial registered with www.clinicaltrials.gov (NCT01791296).

Glaucoma, a major cause of blindness worldwide, is a neurodegenerative optic neuropathy in which vision loss is caused by loss of retinal ganglion cells (RGCs). To better define the pathways mediating RGC death and identify targets for the development of neuroprotective drugs, we developed a high-throughput RNA interference screen with primary RGCs and used it to screen the full mouse kinome. The screen identified dual leucine zipper kinase (DLK) as a key neuroprotective target in RGCs. In cultured RGCs, DLK signaling is both necessary and sufficient for cell death. DLK undergoes robust posttranscriptional up-regulation in response to axonal injury in vitro and in vivo. Using a conditional knockout approach, we confirmed that DLK is required for RGC JNK activation and cell death in a rodent model of optic neuropathy. In addition, tozasertib, a small molecule protein kinase inhibitor with activity against DLK, protects RGCs from cell death in rodent glaucoma and traumatic optic neuropathy models. Together, our results establish a previously undescribed drug/drug target combination in glaucoma, identify an early marker of RGC injury, and provide a starting point for the development of more specific neuroprotective DLK inhibitors for the treatment of glaucoma, nonglaucomatous forms of optic neuropathy, and perhaps other CNS neurodegenerations.

The Public Population Project in Genomics and Society (P³G) is a not-for profit international consortium with members from more than 40 countries. Its objective is to lead, catalyze, and co-ordinate international efforts and expertise in order to optimize the use of population studies, biobanks, research databases, and other similar health and social science research infrastructures. The year 2011-2012 witnessed a plethora of special issues of journals on the return of results but few discussed the particular situation of population studies that serve as resources for future unspecified research. P³G considers it important to propose a policy that distinguishes between the contexts of population research and disease (clinical) research involving patients and then delineates actual and future obligations. The objectives of this Policy Statement are to: (1) delineate the particular characteristics of population studies, (2) distinguish the circumstances surrounding access by researchers to such studies, and (3) develop a framework for the return of research results and incidental findings.

In Brief Purpose: To compare 3 different assessment approaches at term to infants born preterm to predict motor and functional outcomes at 12 months adjusted age. Methods: Infants (n = 100) born at less than 32 weeks postconceptional age were assessed at term using the General Movements Assessment, Einstein Neonatal Neurobehavioral Assessment Scales, Test of Infant Motor Performance, and at 12 months adjusted age using the Alberta Infant Motor Scales, Peabody Developmental Motor Scales-2, Vineland Adaptive Behavior Scales-Daily Living Skills, and Battelle Developmental Inventory. Results: The General Movements Assessment (r2 = 0.04; p = 0.05) and the Test of Infant Motor Performance (r2 = 0.05; p = 0.04) predicted outcomes on the Peabody Developmental Motor Scales-2. The Test of Infant Motor Performance predicted outcomes on the Alberta Infant Motor Scales (r2 = 0.05; p = 0.04) and Vineland Adaptive Behavior Scales-Daily Living Skills (odds ratio: 0.93). Delays in functional performance were found. Conclusions: Neonatal tests at term explained a small but significant proportion of the variance in gross motor and daily living skills at 12 months adjusted age. Neonatal tests at term of infants born preterm explained a small but significant proportion of the variance in gross motor and daily living skills at 12 months adjusted age. Clinical Bottom Line: Barbara Sargent and Linda Fetters

Background: Tyrosinemia type I is a rare but severe genetic metabolic disorder. Nitisinone combined with a diet low in tyrosine and phenylalanine became first-line therapy in 1994.Objectives: To estimate the direct medical costs of health care services related to the treatment of tyrosinemia type I, taking into consideration the real-life efficacy of nitisinone.Methods: A cost–consequence analysis was performed for all children with a confirmed diagnosis of tyrosinemia type I who were treated in Quebec between January 1, 1984, and January 1, 2009. The costs of care were compared for 3 consecutive historical groups: no nitisinone (1984 to 1994), late intervention with nitisinone (first dose received between 1994 and 1997), and early intervention with nitisinone (first dose received between 1997 and 2008). Data were derived from patient charts, hospital databases, and the Régie de l’assurance maladie du Québec and MED-ÉCHO administrative databases. Costs were reported in 2008 Canadian dollars.Results: Nitisinone treatment was associated with significant reductions in the number and duration of hospital admissions, the number of admissions to a pediatric intensive care unit, and the number of liver transplants. The cost of hospitalization per person-year was significantly lower in the 2 groups treated with nitisinone: $673 and $5 590 for the early-intervention and late-intervention groups, respectively, as compared to $12 980 for the no-nitisinone group (p < 0.001). Hospital costs per person-year for liver transplant were $3 198 for the late-intervention group and $5 044 for the no-nitisinone group: there were no transplants in the early-intervention group. The cost of nitisinone per person-year was $51 493 for the early-intervention group and $64 895 for the lateintervention group.Conclusions: Nitisinone treatment significantly improved the outcomes of patients with tyrosinemia type I, while decreasing utilization of health care resources, liver transplants, and associated costs.RÉSUMÉContexte : La tyrosinémie de type I est un trouble génétique du métabolisme rare, mais grave. La prise de nitisinone en association à un régime pauvre en tyrosine et en phénylalanine est devenue le traitement de première intention en 1994.Objectifs : Offrir une estimation des coûts médicaux directs des services de santé liés au traitement de la tyrosinémie de type I, tout en tenant compte de l’efficacité réelle de la nitisinone.Méthodes : Une analyse coûts-conséquences a été réalisée pour chaque enfant ayant reçu un diagnostic de tyrosinémie de type I et ayant été traité au Québec entre le 1er janvier 1984 et le 1er janvier 2009. Les coûts des soins ont été comparés entre trois groupes historiques se suivant dans le temps : sans nitisinone (de 1984 à 1994), traitement tardif à la nitisinone (première dose reçue entre 1994 et 1997) et traitement précoce à la nitisinone (première dose reçue entre 1997 et 2008). Les données ont été obtenues à partir de dossiers médicaux de patients, de bases de données d’hôpitaux, de la base de données administrative de la Régie de l’assurance maladie du Québec et de la banque de données ministérielles MED-ÉCHO. Les coûts sont indiqués en dollars canadiens de 2008.Résultats : L’on a associé le traitement par nitisinone à d’importantes réductions : du nombre d’hospitalisations et de la durée des séjours à l’hôpital, du nombre d’admissions à l’unité de soins intensifs pédiatrique et du nombre de greffes hépatiques. Les coûts d’hospitalisation (par personne-année) étaient beaucoup plus faibles dans les deux groupes traités par nitisinone : 673 $ et 5 590 $ respectivement pour le groupe de traitement précoce et le groupe de traitement tardif, contre 12 980 $ pour le groupe sans traitement par nitisinone (p < 0,001). Les coûts d’hospitalisation (par personne-année) pour les greffes hépatiques étaient de 3 198 $ pour le groupe de traitement tardif et de 5 044 $ pour le groupe sans traitement par nitisinone; le groupe de traitement précoce n’a fait l’objet d’aucune greffe hépatique. Les coûts du traitement par nitisinone (par personne-année) étaient de 51 493 $ pour le groupe de traitement précoce et de 64 895 $ pour le groupe de traitement tardif.Conclusions : Le traitement par nitisinone améliore grandement les résultats thérapeutiques des patients souffrant de tyrosinémie de type I et réduit également le recours aux ressources en santé et à la greffe hépatique, diminuant ainsi les coûts associés.

Introduction: Persistent symptoms after COVID-19 infection ("long COVID") negatively affects almost half of COVID-19 survivors. Despite its prevalence, its pathophysiology is poorly understood, with multiple host systems likely affected. Here, we followed patients from hospital to discharge and used a systems-biology approach to identify mechanisms of long COVID. Methods: RNA-seq was performed on whole blood collected early in hospital and 4-12 weeks after discharge from 24 adult COVID-19 patients (10 reported post-COVID symptoms after discharge). Differential gene expression analysis, pathway enrichment, and machine learning methods were used to identify underlying mechanisms for post-COVID symptom development. Results: Compared to patients with post-COVID symptoms, patients without post-COVID symptoms had larger temporal gene expression changes associated with downregulation of inflammatory and coagulation genes over time. Patients could also be separated into three patient endotypes with differing mechanistic trajectories, which was validated in another published patient cohort. The "Resolved" endotype (lowest rate of post-COVID symptoms) had robust inflammatory and hemostatic responses in hospital that resolved after discharge. Conversely, the inflammatory/hemostatic responses of "Suppressive" and "Unresolved" endotypes (higher rates of patients with post-COVID symptoms) were persistently dampened and activated, respectively. These endotypes were accurately defined by specific blood gene expression signatures (6-7 genes) for potential clinical stratification. Discussion: This study allowed analysis of long COVID whole blood transcriptomics trajectories while accounting for the issue of patient heterogeneity. Two of the three identified and externally validated endotypes ("Unresolved" and "Suppressive") were associated with higher rates of post-COVID symptoms and either persistently activated or suppressed inflammation and coagulation processes. Gene biomarkers in blood could potentially be used clinically to stratify patients into different endotypes, paving the way for personalized long COVID treatment.

BACKGROUND: As part of reforms in 2015, the Ministry of Health and Social Services in Quebec, Canada mandated the national implementation of control rooms, making health system actors accountable for implementing value-based performance management. OBJECTIVE: To explore how do organizational actors appropriate control rooms as managerial tools to influence value-based performance in health systems. DESIGN: Multi-site organizational ethnographic case studies (N = 2) and narrative process analysis of triangulated qualitative data collected through non-participatory observations (179.5 h), individual semi-structured interviews (N = 34), and document review (N = 143). RESULTS: The process of appropriating control rooms plays a crucial role in achieving value-based performance management. Appropriating unfolds along three paths (cognitive, structural, technical) over three phases (implementing, testing, adapting). Implementing control rooms both produces and emerges from improvement capacities within healthcare organizations. Testing tools reveals that incompatibilities between tools, structures and values give rise to value-driven distributed clinical leadership. Adapting tools relies on the adaptability of organizations towards the value system driving the tools, rather than on the adaptability of tools to organizational design. CONCLUSION: There is no "one-size-fits-all" framework to design and support the successful appropriation of control rooms towards achieving value-based performance. However, we believe that consideration for the three distinct phases of appropriation and leveraging the right mechanism to support each phase is a first important step in reviving value in healthcare governance.

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Cats represent a potential source of Coxiella burnetii, the aetiological agent of Q fever in humans. The prevalence and risk factors of C. burnetii infection in farm, pet and feral cats were studied in Quebec, Canada, using a cross-sectional study. Serum samples were tested using a specific enzyme-linked immunosorbent assay (ELISA) for the presence of antibodies against C. burnetii, whereas rectal swabs were assayed using real-time quantitative polymerase chain reaction (qPCR) for the molecular detection of the bacteria. Potential risk factors for farm cats were investigated using clinical examinations, questionnaires and results from a concurrent study on C. burnetii farm status. A total of 184 cats were tested: 59 from ruminant farms, 73 pets and 52 feral cats. Among farm cats, 2/59 (3.4%) were ELISA-positive, 3/59 (5.1%) were ELISA-doubtful and 1/59 (1.7%) was qPCR-positive. All pets and feral cats were negative to C. burnetii ELISA and qPCR. Farm cat positivity was associated with a positive C. burnetii status on the ruminant farm (prevalence ratio = 7.6, P = 0.03). Our results suggest that although pet and feral cats do not seem to pose a great C. burnetii risk to public health, more active care should be taken when in contact with cats from ruminant farms.

Abstract As the evolution of our world has triggered complexity and technological sophistication, it is now essential to consider sound scientific evidence as an integral element of decision-making. Science advisers or chief scientists have to take into account many factors in giving advice. Depending on the nature and level of advice, factors such as the ideology of the governing body, the state of the social, economic and scientific development in the country or region, potential impacts on the health, environment and security of the community, the balance of risk and reward in various options, must all be considered. Canada has lived through a few of these issues in its recent experience with science advice and advisory systems. This article will elaborate on the impact and influence of changes in science advisory bodies at the federal and Quebec government levels and will provide a perspective on their impact. It examines the historical evolution of the advisory apparatus for science throughout Canada’s history and underscores some of their successes and failures under different regimes. The conclusion drawn in this article is that science and science advisory systems in Canada have lacked continuity and a solid foundation thus weakening efforts to enable sound science-based policy into decision-making. The article argues for a more institutionalized and pluralistic approach to ensuring that evidence and science advice can endure—both at the federal and provincial levels. In many ways, the experience with these advisory mechanisms suggests a growing need to ensure sound advice within increasingly complex decision-making as well as a demand by citizens to have scientific evidence considered more carefully in public policy and for the public interest. This article is published as part of a collection on scientific advice to governments.

La lutte contre l’intimidation au Québec survient comme une nouvelle priorité gouvernementale quatre ans après l’adoption du premier Plan d’action gouvernemental pour contrer la maltraitance envers les personnes aînées . Cet article fait suite à notre mémoire sur l’intimidation envers les personnes aînées publié dans le cadre d’une consultation publique sur le sujet. Il vise à approfondir la réflexion théorique et conceptuelle, alors amorcée, sur la différence entre la maltraitance et l’intimidation envers les personnes aînées afin de les distinguer clairement. Ce processus réflexif permet de proposer une définition de ce qu’est l’intimidation envers les personnes aînées, ainsi qu’un schéma conceptuel de la dynamique de ces situations.

Issu d’un travail collaboratif regroupant des spécialistes de l’éthique, de la philosophie, de l’informatique et de l’économie, le rapport « L’éthique au cœur de l’IA » vise à préciser et clarifier le rôle que doit occuper l’éthique à l’ère de l’intelligence artificielle (IA), et à mettre en lumière comment cette notion peut être appliquée et mise en œuvre de manière efficace et fructueuse. S’adressant à l’ensemble des individus engagés, de près ou de loin, dans le développement de l’IA, ce document met de l’avant une éthique centrée sur la réflexivité et le dialogue. Dans une volonté de traduire plus concrètement cette vision, il met en lumière l’approche méthodologique utilisée pour construire la Déclaration de Montréal et propose également quelques pistes de recommandation. En somme, le présent texte plaide pour l’inclusion d’une réelle réflexion éthique dans l’ensemble des étapes du processus de développement de l’IA. Il se veut ainsi une main tendue, un appel à la collaboration entre éthiciennes et éthiciens, développeuses et développeurs et membres de l’industrie afin de véritablement intégrer l’éthique au cœur de l’IA.

Les résultats d’analyse d’entretiens menés avec des enseignant.e.s en arts visuels, en danse, en musique et en art dramatique ont permis de mieux comprendre leurs perceptions concernant la culture des jeunes et les stratégies pour l’intégrer à leur enseignement. Parmi ces stratégies figurent la pédagogie négociée, le recours à des repères culturels ancrés dans la culture non formelle des élèves et l’aménagement d’espaces de rencontre entre cette culture et la culture transmise à l’école. Cette recherche permet d’enrichir la pratique enseignante de spécialistes en arts du secondaire souhaitant s’actualiser et rejoindre leurs élèves dans la complexité de leurs univers culturels.

Coconstruire la bioéthique de demain entre Sciences, Droit et Communauté / Co-Constructing Tomorrow’s Bioethics Between Science, Law and the Community. Un article de la revue Canadian Journal of Bioethics / Revue canadienne de bioéthique (Dialogue with Future Bioethicists) diffusée par la plateforme Érudit.

Dans le contexte de la crise sanitaire de COVID-19, la politisation de la science a été une réponse nécessaire aux défis posés. Si cette médiation (influencée par le politique) demeure une réponse stratégique, nous argumenterons qu’elle fût incomplète sur le plan éthique. L’analyse rétrospective de la situation met en évidence la nécessité d’étendre et de renforcer le rôle-conseil d’instances éthiques, telles qu’elles ont été intégrées au réseau de la santé pendant la pandémie. La complexité découlant d’une interaction soutenue entre les connaissances scientifiques, les politiques publiques et les instances éthiques nécessite d’approfondir et de poursuivre cette réflexion sur leur intégration en société, tout en posant un regard critique sur les dynamiques de pouvoir inhérentes à la santé publique.

International audience

As INGSA is set to celebrate its 10th anniversary conference in Rwanda, Rémi Quirion and David Budtz Pedersen reflect on the role of research, knowledge, and expertise in advancing evidence-based solutions. From climate change to pandemics and artificial intelligence, experts and researchers are needed as advisors to governments.

RemerciementsJe tiens à remercier Fabrice Fernandez qui a supervisé le mémoire de maîtrise à l'origine de cet ouvrage et qui a généreusement accepté d'en signer la préface.Son imagination sociologique et sa capacité à faire dialoguer la théorie et l'empirie ont durablement influencé ma conception de la recherche sociologique ; que les pages qui suivent en soient le témoignage.Je remercie chaudement ma

syndrome patients with statin use had better outcome in time to CRPC than patients without statin use.

Ce guide vise à fournir un cadre aux acteurs du monde du travail qui conçoivent, mettent en œuvre et/ou font le suivi des systèmes de gestion algorithmique. Ce guide a été pensé comme une boite à outils pour faciliter le dialogue et les processus de consultation et de négociation de la gestion algorithmique.