Affronter des enjeux clés liés à l’évaluation du rôle de promoteur de la santé

Introduction: Although the CanMEDS framework sets the standard for Canadian training, health advocacy competence does not appear to factor heavily into high stakes assessment decisions. Without forces motivating uptake, there is little movement by educational programs to integrate robust advocacy teaching and assessment practices. However, by adopting CanMEDS, the Canadian medical education community endorses that advocacy is required for competent medical practice. It’s time to back up that endorsement with meaningful action. Our purpose was to aid this work by answering the key questions that continue to challenge training for this intrinsic physician role. Methods: We used a critical review methodology to both examine literature relevant to the complexities impeding robust advocacy assessment, and develop recommendations. Our review moved iteratively through five phases: focusing the question, searching the literature, appraising and selecting sources, and analyzing results. Results: Improving advocacy training relies, in part, on the medical education community developing a shared vision of the Health Advocate (HA) role, designing, implementing, and integrating developmentally appropriate curricula, and considering ethical implications of assessing a role that may be risky to enact. Conclusion: Changes to assessment could be a key driver of curricular change for the HA role, provided implementation timelines and resources are sufficient to make necessary changes meaningful. To truly be meaningful, however, advocacy first needs to be perceived as valuable. Our recommendations are intended as a roadmap for transforming advocacy from a theoretical and aspirational value into one viewed as having both practical relevance and consequential implications. Introduction : Bien que le référentiel CanMEDS établisse les normes en matière de formation et de pratique médicale au Canada, la compétence de promotion de la santé (PS) ne semble pas peser lourd aux étapes décisives du continuum de la formation médicale. En l’absence de facteurs incitatifs, les programmes de formation sont peu enclins à intégrer des pratiques solides d’enseignement et d’évaluation en matière de PS. Un système de soins de santé marqué par l’iniquité appelle pourtant des efforts de sensibilisation. En adoptant le référentiel CanMEDS, le milieu canadien de l’éducation médicale a reconnu que la PS est nécessaire à la pratique compétente de la médecine. Il est temps que cet engagement soit traduit en actions concrètes. Méthodes : Employant une méthode d’analyse critique, nous avons examiné les écrits qui peuvent éclairer les obstacles à l’évaluation sérieuse de la PS et avons formulé des recommandations. L’examen a été effectué de manière itérative en cinq étapes : définition de la question de recherche, recherche documentaire, évaluation et sélection des sources, et analyse des résultats. Résultats : L’amélioration de la formation en matière de PS suppose, entre autres, que le milieu de l’éducation médicale s’attèle aux enjeux clés suivants : 1) l’élaborer une vision commune de la PS, 2) concevoir, mettre en œuvre et intégrer des programmes d’études évolutifs et 3) considérer les répercussions éthiques de l’évaluation d’un rôle qui comporte une part de risque. Conclusion : Le manque de visibilité et d’attention accordées à la PS dans la formation amène de nombreux apprenants à se demander si leur compétence en la matière compte vraiment. Nous estimons que la promotion de la santé est au cœur des soins centrés sur le patient. Nous lançons donc un appel à redoubler nos efforts collectifs pour faire passer la PS du statut de simple aspiration et de valeur théorique à celui d’une valeur ayant une pertinence et des incidences concrètes

Prediction Aided Tapering In rheumatoid arthritis patients treated with biOlogicals (PATIO): protocol for a randomized controlled trial

Background: Biological disease-modifying anti-rheumatic drugs (bDMARDs) are effective in the treatment of rheumatoid arthritis (RA) but are expensive and increase the risk of infection. Therefore, in patients with a stable low level of disease activity or remission, tapering bDMARDs should be considered. Although tapering does not seem to affect long-term disease control, (short-lived) flares are frequent during the tapering process. We have previously developed and externally validated a dynamic flare prediction model for use as a decision aid during stepwise tapering of bDMARDs to reduce the risk of a flare during this process. Methods: In this investigator-initiated, multicenter, open-label, randomized (1:1) controlled trial, we will assess the effect of incorporating flare risk predictions into a bDMARD tapering strategy. One hundred sixty RA patients treated with a bDMARD with stable low disease activity will be recruited. In the control group, the bDMARD will be tapered according to “disease activity guided dose optimization” (DGDO). In the intervention group, the bDMARD will be tapered according to a strategy that combines DGDO with the dynamic flare prediction model, where the next bDMARD tapering step is not taken in case of a high risk of flare. Patients will be randomized 1:1 to the control or intervention group. The primary outcome is the number of flares per patient (DAS28-CRP increase > 1.2, or DAS28-CRP increase > 0.6 with a current DAS28-CRP ≥ 2.9) during the 18-month follow-up period. Secondary outcomes include the number of patients with a major flare (flare duration ≥ 12 weeks), bDMARD dose reduction, adverse events, disease activity (DAS28-CRP) and patient-reported outcomes such as quality of life and functional disability. Health Care Utilization and Work Productivity will also be assessed. Discussion: This will be the first clinical trial to evaluate the benefit of applying a dynamic flare prediction model as a decision aid during bDMARD tapering. Reducing the risk of flaring during tapering may enhance the safety and (cost)effectiveness of bDMARD treatment. Furthermore, this study pioneers the field of implementing predictive algorithms in clinical practice. Trial registration: Dutch Trial Register number NL9798, registered 18 October 2021, https://www.trialregister.nl/trial/9798. The study has received ethical review board approval (number NL74537.041.20)

Heat Shock Proteins Can Be Surrogate Autoantigens for Induction of Antigen Specific Therapeutic Tolerance in Rheumatoid Arthritis

Technologies that enable induction of therapeutic tolerance may revolutionize the treatment of autoimmune diseases by their supposed potential to induce drug-free and lasting disease remission. In combination with diagnostic tests that screen for individuals at risk, these approaches may offer chances to halt disease before serious damage in the tissues can occur. In fact, for healthy individuals at risk, this could lead to a preventive form of vaccination. For therapeutic tolerance to re-instate natural self-tolerance it seems essential to induce tolerance for the critical autoantigens involved in disease. However, for most autoimmune diseases such antigens are poorly defined. This is the case for both disease inciting autoantigens and antigens that become involved through epitope spreading. A possible source of surrogate auto-antigens expressed in tissues during inflammation are heat shock proteins (HSP) or stress proteins. In this mini-review we discuss unique characteristics of HSP which provide them with the capacity to inhibit inflammatory processes. Various studies have shown that epitopes of HSP60 and HSP70 molecules can function as vaccines to downregulate a variety of autoimmune inflammatory diseases. Currently, several research groups are developing cell therapies with the intention to reach therapeutic tolerance. In this review, in which we are proposing to ex vivo load tolerant dendritic cells with a Treg inducing HSP70 derived peptide called B29, we are discussing the chances to develop this as an autologous tolDC therapeutic tolerance therapy for rheumatoid arthritis

Management of adult-onset Still's disease:evidence- and consensus-based recommendations by experts

Objectives: Adult-onset Still's disease (AOSD) is a rare condition characterized by fevers, rash, and arthralgia/arthritis; most doctors treating AOSD in the Netherlands treat &lt;5 patients per year. Currently, there is no internationally accepted treatment guideline for AOSD. The objectives of this study were to conduct a Delphi panel aimed at reaching consensus about diagnostic and treatment strategies for patients with AOSD and to use the outcomes as a basis for a treatment algorithm. Methods: The Delphi panel brought together 18 AOSD experts: rheumatologists, internists and paediatricians. The Delphi process consisted of three rounds. In the first two rounds, online lists of questions and statements were completed. In the third round, final statements were discussed during a virtual meeting and a final vote took place. Consensus threshold was set at 80%. Two targeted literature searches were performed identifying the level of evidence of the consensus-based statements. Results: Consensus was reached on 29 statements, including statements related to diagnosis and diagnostic tests, definition of response and remission, the therapy, the use of methotrexate and tapering of treatment. The panel consented on reduction of the use of glucocorticoids to avoid side effects, and preferred the use of biologics over conventional treatment. The role of IL-1 and IL-6 blocking agents was considered important in the treatment of AOSD. Conclusion: In this Delphi panel, a high level of consensus was achieved on recommendations for diagnosis and therapy of AOSD that can serve as a basis for a treatment guideline.</p

Management of adult-onset Still's disease:evidence- and consensus-based recommendations by experts

Objectives: Adult-onset Still's disease (AOSD) is a rare condition characterized by fevers, rash, and arthralgia/arthritis; most doctors treating AOSD in the Netherlands treat &lt;5 patients per year. Currently, there is no internationally accepted treatment guideline for AOSD. The objectives of this study were to conduct a Delphi panel aimed at reaching consensus about diagnostic and treatment strategies for patients with AOSD and to use the outcomes as a basis for a treatment algorithm. Methods: The Delphi panel brought together 18 AOSD experts: rheumatologists, internists and paediatricians. The Delphi process consisted of three rounds. In the first two rounds, online lists of questions and statements were completed. In the third round, final statements were discussed during a virtual meeting and a final vote took place. Consensus threshold was set at 80%. Two targeted literature searches were performed identifying the level of evidence of the consensus-based statements. Results: Consensus was reached on 29 statements, including statements related to diagnosis and diagnostic tests, definition of response and remission, the therapy, the use of methotrexate and tapering of treatment. The panel consented on reduction of the use of glucocorticoids to avoid side effects, and preferred the use of biologics over conventional treatment. The role of IL-1 and IL-6 blocking agents was considered important in the treatment of AOSD. Conclusion: In this Delphi panel, a high level of consensus was achieved on recommendations for diagnosis and therapy of AOSD that can serve as a basis for a treatment guideline.</p

Combined field inoculations of pseudomonas bacteria, arbuscular mycorrhizal fungi, and entomopathogenic nematodes and their effects on wheat performance

In agricultural ecosystems, pest insects, pathogens, and reduced soil fertility pose major challenges to crop productivity and are responsible for significant yield losses worldwide. Management of belowground pests and diseases remains particularly challenging due to the complex nature of the soil and the limited reach of conventional agrochemicals. Boosting the presence of beneficial rhizosphere organisms is a potentially sustainable alternative and may help to optimize crop health and productivity. Field application of single beneficial soil organisms has shown satisfactory results under optimal conditions. This might be further enhanced by combining multiple beneficial soil organisms, but this remains poorly investigated. Here, we inoculated wheat plots with combinations of three beneficial soil organisms that have different rhizosphere functions and studied their effects on crop performance. Plant beneficial Pseudomonas bacteria, arbuscular mycorrhizal fungi (AMF), and entomopathogenic nematodes (EPN), were inoculated individually or in combinations at seeding, and their effects on plant performance were evaluated throughout the season. We used traditional and molecular identification tools to monitor their persistence over the cropping season in augmented and control treatments, and to estimate the possible displacement of native populations. In three separate trials, beneficial soil organisms were successfully introduced into the native populations and readily survived the field conditions. Various Pseudornonas, mycorrhiza, and nematode treatments improved plant health and productivity, while their combinations provided no significant additive or synergistic benefits compared to when applied alone. EPN application temporarily displaced some of the native EPN, but had no significant long-term effect on the associated food web. The strongest positive effect on wheat survival was observed for Pseudomonas and AMF during a season with heavy natural infestation by the frit fly, Oscinella frit, a major pest of cereals. Hence, beneficial impacts differed between the beneficial soil organisms and were most evident for plants under biotic stress. Overall, our findings indicate that in wheat production under the test conditions the three beneficial soil organisms can establish nicely and are compatible, but their combined application provides no additional benefits. Further studies are required, also in other cropping systems, to fine-tune the functional interactions among beneficial soil organisms, crops, and the environment

Tracking CNS and systemic sources of oxidative stress during the course of chronic neuroinflammation

The functional dynamics and cellular sources of oxidative stress are central to understanding MS pathogenesis but remain elusive, due to the lack of appropriate detection methods. Here we employ NAD(P)H fluorescence lifetime imaging to detect functional NADPH oxidases (NOX enzymes) in vivo to identify inflammatory monocytes, activated microglia, and astrocytes expressing NOX1 as major cellular sources of oxidative stress in the central nervous system of mice affected by experimental autoimmune encephalomyelitis (EAE). This directly affects neuronal function in vivo, indicated by sustained elevated neuronal calcium. The systemic involvement of oxidative stress is mirrored by overactivation of NOX enzymes in peripheral CD11b(+) cells in later phases of both MS and EAE. This effect is antagonized by systemic intake of the NOX inhibitor and anti-oxidant epigallocatechin-3-gallate. Together, this persistent hyper-activation of oxidative enzymes suggests an "oxidative stress memory" both in the periphery and CNS compartments, in chronic neuroinflammation