Indicateurs de performance utiles pour soutenir la prise de décision par la médecine de famille dans la lutte contre le cancer

Les plateformes informatiques et les indicateurs de performance axés sur les données sont devenus plus pertinents que jamais pour fournir une aide à la décision à toutes les parties prenantes dans les soins de santé aux patients. La gestion des soins de santé est complexe et doit relever de nombreux défis pour améliorer son efficacité et sa performance. La pandémie de COVID-19 a ébranlé les systèmes de santé du monde entier. Malgré cela, le cancer demeure la première cause de décès et un problème de santé majeur dans les pays développés. Depuis la première vague de la pandémie en mars 2020, plusieurs médecins à travers le monde ont tiré la sonnette d'alarme sur les retards dans la prestation de certains soins, notamment dans le diagnostic du cancer. L’accès aux données et aux informations peuvent aider à suivre les trajectoires des patients en oncologie. Toutefois, une analyse poussée et le fait de disposer d'indicateurs de performance pour guider le processus décisionnel permettrait d'améliorer la prestation de soins. Or, l’utilisation d’indicateurs de performance n’est pas bien implantée, ni standardisée dans la pratique individuelle quotidienne des médecins de famille au Québec. Ce travail vise à combler cette lacune afin d’offrir une vue d’ensemble quant aux indicateurs pertinents, pouvant guider les médecins de famille dans leur pratique, plus particulièrement dans la lutte contre le cancer. Cette recherche brosse un portrait des métriques et des indicateurs de performance rapportés dans la littérature ainsi que la perception des médecins de famille sur les indicateurs de performance pour guider la trajectoire de soins des patients en oncologie. Il contribue aux connaissances dans le domaine de la gestion des soins de santé et sur les besoins des utilisateurs dans l’élaboration d’outils d’aide à la décision, notamment dans le dossier médical électronique.Abstract : IT platforms and data-driven performance indicators have become more relevant than ever to provide decision support to all stakeholders in patient care. Healthcare management is complex and faces many challenges to improve its efficiency and performance. The COVID-19 pandemic has shaken health systems around the world. Despite this, cancer remains the leading cause of death and a major health problem in developed countries. Since the first wave of the pandemic in March 2020, many doctors around the world have raised the alarm about delays in the provision of certain care, particularly in cancer diagnosis. Access to data and information can help track the trajectory of oncology patients, however, analyzing it and having performance indicators to guide decision making would improve care delivery. However, the use of performance indicators in the practice of family physicians in Quebec is not well established, nor is it standardized in the daily individual practice of family physicians in Quebec. This work aims to fill this gap in order to provide an overview of relevant indicators that can guide family physicians in their practice, particularly in the fight against cancer. This research provides a portrait of the metrics and performance indicators reported in the literature as well as family physicians' perceptions of performance indicators to guide the care pathway of oncology patients. It contributes to the knowledge in the field of health care management and on the needs of users in the development of decision support tools, particularly in the electronic medical record

Étude de l'efficacité pharmacologique de formulations d'oligonucléotides antisens pour cibler la P70S6 kinase suite à l'administration d'endothéline in vivo

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal

The Mixed Methods Appraisal Tool (MMAT) version 2018 for information professionals and researchers

INTRODUCTION: Appraising the quality of studies included in systematic reviews combining qualitative and quantitative evidence is challenging. To address this challenge, a critical appraisal tool was developed: the Mixed Methods Appraisal Tool (MMAT). The aim of this paper is to present the enhancements made to the MMAT. DEVELOPMENT: The MMAT was initially developed in 2006 based on a literature review on systematic reviews combining qualitative and quantitative evidence. It was subject to pilot and interrater reliability testing. A revised version of the MMAT was developed in 2018 based on the results from usefulness testing, a literature review on critical appraisal tools and a modified e-Delphi study with methodological experts to identify core criteria. TOOL DESCRIPTION: The MMAT assesses the quality of qualitative, quantitative, and mixed methods studies. It focuses on methodological criteria and includes five core quality criteria for each of the following five categories of study designs: (a) qualitative, (b) randomized controlled, (c) nonrandomized, (d) quantitative descriptive, and (e) mixed methods. CONCLUSION: The MMAT is a unique tool that can be used to appraise the quality of different study designs. Also, by limiting to core criteria, the MMAT can provide a more efficient appraisal

Study of overland flow with uncertain infiltration using stochastic tools

The saturated hydraulic conductivity is one of the key parameters in the modelling of overland flow water fluxes. In this study, this parameter is defined as a stochastic parameter, idealized as a piecewise constant random field with uniform distribution. This paper aims at investigating the effects of the spatial and temporal scales in uncertainty propagation within overland flow models, and at identifying the localization of the most influential saturated hydraulic conductivity using sensitivity analysis. The results show that the influence of saturated hydraulic conductivity depends on the soil saturation and its spatial localization. For instance, in case of low saturated soils, the most influent parameter is the one located downslope, whereas in case of high saturated soils, the most influent one is either the most infiltrating or the intermediate one. The results indicate where efforts should be concentrate when collecting input parameters to reduce modelling uncertainties

Molecular and functional characterization of a new X-linked chronic granulomatous disease variant (X91+) case with a double missense mutation in the cytosolic gp91phox C-terminal tail

AbstractWe report here two atypical cases of X-linked CGD patients (first cousins) in which cytochrome b558 is present at a normal level but is not functional (X91+). The mutations were localized by single-strand conformational polymorphism of reverse transcriptase–polymerase chain reaction amplified fragments and then identified by sequence analysis. They consisted in two base substitutions (C919 to A and C923 to G), changing His303 to Asn and Pro304 to Arg in the cytosolic gp91phox C-terminal tail. Mismatched polymerase chain reaction and genomic DNA sequencing showed that mothers had both wild-type and mutated alleles, confirming that this case was transmitted in an X-linked fashion. A normal amount of FAD was found in neutrophil membranes, both in the X91+ patients and their parents. Epstein–Barr virus-transformed B lymphocytes from the X91+ patients acidified normally upon stimulation with arachidonic acid, indicating that the mutated gp91phox still functioned as a proton channel. A cell-free translocation assay demonstrated that the association of the cytosolic factors p47phox and p67phox with the membrane fraction was strongly disrupted. We concluded that residues 303 and 304 are crucial for the stable assembly of the NADPH oxidase complex and for electron transfer, but not for its proton channel activity

Nacre, a natural, multi-use, and timely biomaterial for bone graft substitution

International audienceDuring the past two decades, with a huge and rapidly increasing clinical need for bone regeneration and repair, bone substitutes are more and more seen as a potential solution. Major innovation efforts are being made to develop such substitutes , some having advanced even to clinical practice. It is now time to turn to natural biomaterials. Nacre, or mother-of-pearl, is an organic matrix-calcium carbonate coupled shell structure produced by molluscs. In vivo and in vitro studies have revealed that nacre is osteoinductive, osteoconductive, biocompatible, and biodegradable. With many other outstanding qualities, nacre represents a natural and multi-use biomaterial as a bone graft substitute. This review aims at summarising the current needs in orthopaedic clinics and the challenges for the development of bone substitutes; most of all, we systematically review the physiological characteristics and biological evidence of nacre's effects centred on osteogen-esis, and finally we put forward the potential use of nacre as a bone graft substitute

The 20S proteasome core, active within apoptotic exosome-like vesicles, induces autoantibody production and accelerates rejection

Autoantibodies to components of apoptotic cells, such as anti-perlecan antibodies, contribute to rejection in organ transplant recipients. However, mechanisms of immunization to apoptotic components remain largely uncharacterized. We used large-scale proteomics, with validation by electron microscopy and biochemical methods, to compare the protein profiles of apoptotic bodies and apoptotic exosome-like vesicles, smaller extracellular vesicles released by endothelial cells downstream of caspase-3 activation. We identified apoptotic exosome-like vesicles as a central trigger for production of anti-perlecan antibodies and acceleration of rejection. Unlike apoptotic bodies, apoptotic exosome-like vesicles triggered the production of anti-perlecan antibodies in naïve mice and enhanced anti-perlecan antibody production and allograft inflammation in mice transplanted with an MHC (major histocompatibility complex)–incompatible aortic graft. The 20S proteasome core was active within apoptotic exosome-like vesicles and controlled their immunogenic activity. Finally, we showed that proteasome activity in circulating exosome-like vesicles increased after vascular injury in mice. These findings open new avenues for predicting and controlling maladaptive humoral responses to apoptotic cell components that enhance the risk of rejection after transplantation

Downregulation of Glutamine Synthetase, not glutaminolysis, is responsible for glutamine addiction in Notch1-driven acute lymphoblastic leukemia

The cellular receptor Notch1 is a central regulator of T-cell development, and as a consequence, Notch1 pathway appears upregulated in > 65% of the cases of T-cell acute lymphoblastic leukemia (T-ALL). However, strategies targeting Notch1 signaling render only modest results in the clinic due to treatment resistance and severe side effects. While many investigations reported the different aspects of tumor cell growth and leukemia progression controlled by Notch1, less is known regarding the modifications of cellular metabolism induced by Notch1 upregulation in T-ALL. Previously, glutaminolysis inhibition has been proposed to synergize with anti-Notch therapies in T-ALL models. In this work, we report that Notch1 upregulation in T-ALL induced a change in the metabolism of the important amino acid glutamine, preventing glutamine synthesis through the downregulation of glutamine synthetase (GS). Downregulation of GS was responsible for glutamine addiction in Notch1-driven T-ALL both in vitro and in vivo. Our results also confirmed an increase in glutaminolysis mediated by Notch1. Increased glutaminolysis resulted in the activation of the mammalian target of rapamycin complex 1 (mTORC1) pathway, a central controller of cell growth. However, glutaminolysis did not play any role in Notch1-induced glutamine addiction. Finally, the combined treatment targeting mTORC1 and limiting glutamine availability had a synergistic effect to induce apoptosis and to prevent Notch1-driven leukemia progression. Our results placed glutamine limitation and mTORC1 inhibition as a potential therapy against Notch1-driven leukemia.This work was supported by funds from the followinginstitutions: Agencia Estatal de Investigacion/Euro-pean Regional Development Fund, European Union(PGC2018-096244-B-I00, SAF2016-75442-R), Ministryof Science, Innovation and Universities of Spain,Spanish National Research Council—CSIC, InstitutNational de la Sante et de la Recherche Medicale—INSERM, Ligue Contre le Cancer—Gironde, Univer-site de Bordeaux, Fondation pour la Recherche Medi-cale, the Conseil Regional d’Aquitaine, SIRIC-BRIO,Fondation ARC and Institut Europeen de Chimie etBiologie. MJN was supported by a bourse d’excellencede la Federation Wallonie-Bruxelles (WBI) and a post-doctoral fellowship from Fondation ARC. We thankVincent Pitard (Flow Cytometry Platform, Universitede Bordeaux, France) for technical assistance in flowcytometry experiments. We thank Diana Cabrera(Metabolomics Platform, CIC bioGUNE, Spain) fortechnical assistance in metabolomics analysi

Corticosteroid therapy is associated with a decrease in mortality in a multicenter cohort of mechanically ventilated COVID-19 patients

peer reviewedRetrospectively analyzing the data of a multicenter cohort, we observed that mortality of patients with SARS-CoV-2 pneumoniatreated with mechanical ventilation was as high as 45% and median survival time was 82 days. In this series, the risk factors for mortality included age, renal and circulatory dysfunction, lymphopenia and the absence of corticosteroid use during the first week of mechanical ventilation. Corticosteroid therapy during the first week of mechanical ventilation was associated with a lower mortality (34% vs 48%) (p = 0,01)