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Recherche Clinique en Oncologie dans les territoires ultramarins: freins, atouts et les moyens à disposition
No full textInternational audienceIntroductionRéduire les inégalités territoriales d’accès aux soins et aux innovations en oncologie est un objectif de la stratégie décennale de lutte contre le cancer. Les populations des territoires d’Outre-mer (OM) sont confrontées à des limites en matière d'accès à la recherche clinique en oncologie.Methodes : L’article vise à partager un état des lieux exhaustif des défis observés au développement de la recherche clinique en oncologie dans les territoires OM mais aussi des moyens identifiés pour y répondre ; et illustrer avec des succès récents en terme de mise en place de programme de recherche clinique en oncologie.Résultats : La recherche clinique en oncologie dans les territoires d'outre-mer français présente des défis uniques, auxquels la couverture des surcoûts dômiens par les tutelles, les réponses législatives pour lever les contraintes réglementaires, le déploiement des solutions innovantes, la télémedecine, la formation continue en distanciel, le partenariat patient, l’apport des chercheurs en SHS et les collaborations académiques sont autant de dispositifs éprouvés pour surmonter ces obstacles. Plusieurs centres ont démontré récemment la faisabilité d’une recherche clinique en oncologie en OM de qualité. Ces initiatives sont à soutenir et à étendre en s’adaptant aux besoins et à la réalité de chaque territoire. En investissant sur les territoires ultramarins, les tutelles locales et nationales peuvent renforcer les capacités des acteurs locaux pour développer une recherche clinique en oncologie répondant aux besoins de la population et à la réalité de ces territoires.Conclusion : Des centres ultramarins ont su relever les défis et ont démontré la faisabilité de mener des projets de recherche cliniques en oncologie pour permettre l'accès des patients ultramarins aux traitements oncologiques innovants et contribuer à l'avancement des connaissances scientifiques en oncologie
Bioavailable human metabolites from TOTUM-448 (plant-based formulation) maintain liver cell functionality in a hyperlipidic context that drives MASLD onset
No full textInternational audienceLipotoxic and inflammatory environment drives metabolic dysfunction-associated steatotic liver disease (MASLD) onset. As most conventional treatments present adverse side effects, alternative options such as preventive nutritional interventions have been developed, though further clinical validation is needed. In this study, we conducted an innovative ex vivo clinical investigation to examine how circulating metabolites generated after oral intake of TOTUM-448 (a plant-based, polyphenol-rich formulation) may influence hepatocyte function. UHPLC-MS/MS analysis confirmed and characterized the bioavailable polyphenol metabolites present in human serum. This metabolite-enriched serum was further used to treat HepG2 hepatocytes, with or without palmitate pretreatment (250 µM). The effects of TOTUM-448–derived metabolites on hepatocytes were evaluated by monitoring cell viability, lipid metabolism, inflammation, oxidative stress, and endoplasmic reticulum (ER) stress, all of which are central features of MASLD. Treated hepatocytes exhibited resistance to palmitate-induced lipotoxic stress, showing reduced intracellular lipid accumulation. TOTUM-448–derived metabolites also prevented the palmitate-induced upregulation of inflammatory gene expression. Additionally, while palmitate strongly upregulated CHOP and XBP1 mRNA expression as well as ATF6 and Caspase-3 activities, the presence of TOTUM-448–derived metabolites restored these ER stress markers to normal levels
Effect of a 1-month methotrexate delay on pneumococcal vaccine immunogenicity and disease control in patients with early rheumatoid arthritis (VACIMRA): an open-label randomised trial
No full textInternational audienceBackground: Pneumococcal vaccination is recommended for patients with rheumatoid arthritis. Because immunosuppressant therapies for rheumatoid arthritis hinder vaccine efficacy, vaccination should be administered before initiating immunosuppressive drugs. We aimed to compare humoral responses in patients with rheumatoid arthritis receiving the pneumococcal 13-valent conjugate vaccine (PCV13) before methotrexate initiation or simultaneously.Methods: In this randomised, multicentre, open-label trial, patients were recruited from 26 rheumatology departments in 22 university hospitals and four general hospitals in France. Adult patients (aged 18-80 years) with active rheumatoid arthritis (Disease Activity Score in 28 joints >3·2), who were naive to targeted disease-modifying anti rheumatic drugs (DMARDs), had not had methotrexate or leflunomide in the past 3 months, and had no previous pneumococcal vaccinations were included. Patients were excluded in case of treatment with methotrexate or with leflunomide within the previous 3 months and absolute or relative contraindications to methotrexate. Patients were vaccinated with PCV13 at randomisation, before being randomly assigned (1:1) to either the immediate group (methotrexate treatment [maximum dose 15 mg per week] initiated at the same time as PCV13 vaccine) or the delay group (methotrexate initiated 1 month after PCV13 vaccine). Randomisation was stratified by sex (self-reported) and DMARD naive status. 2 months later, patients in both groups were vaccinated with the 23-valent pneumococcal polysaccharide vaccine. Humoral responses, disease activity, infections, and adverse events were assessed at baseline and at 1, 3, 6, and 12 months after PCV13. The primary outcome was the responder rate at 1 month, defined by positive responses against at least three of five target serotypes (ie, 1, 3, 5, 7F, and 19A). Responders were defined according to a 2 or more-fold increase in IgG concentrations with ELISA or opsonophagocytic assay compared with baseline. The main analysis was performed in the modified intention-to-treat population, including all randomly assigned patients with a valid measure of the primary endpoint, analysed in their assigned group. There was no involvement of people with lived experience in the study design or implementation. The trial was registered at ClinicalTrials.gov (NCT01942174) and is completed.Findings: Between Sept 27, 2013, and Oct 10, 2019, 276 patients with rheumatoid arthritis were randomly assigned. 27 patients were excluded, of whom four patients dropped out, and 249 patients were included in the modified intention-to-treat population (126 [51%] in the delay group and 123 [49%] in the immediate group). 174 (70%) patients were female and 75 (30%) were male, the mean age at enrolment was 55·6 years (SD 14·8). Responder rates were higher in the delay group compared with the immediate group for IgG concentrations (relative risk 1·46 [95% CI 1·10-1·92]; p=0·02) and for opsonophagocytic assay activity (1·65 [1·25-2·19]; p=0·01), adjusted for sex and true DMARD naive status. At 12 months, antibody functional activity was significantly higher for eight of 13 serotypes in the delay group. Cumulative doses of corticosteroids and the number of patients who had targeted DMARDs were similar between groups throughout. 72 (11%) of 649 adverse events were serious (including one vaccine-related serious adverse event) in both groups and were equally frequent between groups, and the rheumatoid arthritis disease activity score remained comparable during follow-up.Interpretation: In patients with early rheumatoid arthritis, the PCV13 vaccine administered 1 month before methotrexate allowed for improved immunological responses without significant effect on disease control during one year of follow-up. Future steps are to confirm these results with PCV20 or PCV21 and assess the best time frame for the booster vaccine
Le désir de maternité des femmes du Puy-de-dôme en 2024 : étude qualitative phénoménologique auprès des femmes nullipares de 18 à 45 ans
No full textIntroduction: a fundamental subject rooted in the history of humanity, the desire for motherhood has regained attention, particularly in the context of the call for "réarmement démographique" launched by Emmanuel Macron. This study aimed to provide an overview of how women living in Puy-de-Dôme perceive motherhood in 2024, to identify the factors influencing this reflection, and to shed light on reproductive health-related choices.Method: a qualitative phenomenological study was conducted through a descriptive and hermeneutic analysis of semi-structured interviews with twelve nulliparous women aged 23 to 41, all residing in the Puy-de-Dôme department.Results: three main profiles emerged: an instinctive desire for motherhood, a clearly stated non-desire, and an uncertain or evolving desire. One in three women expressed no wish to have children. Despite the uniqueness of each story, common themes appeared regarding personal questioning, individual experiences, reproductive choices, and the need for support.Discussion: the desire for motherhood lies at the intersection of personal, social, and contemporary dynamics, aligning with trends observed in existing studies. This subject highlights the growing role of midwives in the overall health of women, particularly among younger populations.Conclusion: these accounts call for a rethinking of current narratives. It seems essential to amplify women's voices through a national study.Introduction : sujet fondamental ancré dans l’histoire de l’humanité, le désir de maternité suscite un regain d’intérêt, notamment dans le contexte de l’appel au « réarmement démographique » lancé par Emmanuel Macron. Cette étude visait à dresser un état des lieux du rapport des femmes du Puy-de-Dôme à la maternité en 2024, à identifier les facteurs influençant cette réflexion et à éclairer les choix en matière de santé génésique.Méthode : une étude qualitative phénoménologique a été menée à partir d’une analyse descriptive et herméneutique d’entretiens semi-directifs réalisés auprès de douze femmes nullipares de 23 à 41 ans résidant dans le Puy-de-Dôme.Résultats : trois profils se sont dégagés : un désir instinctif de maternité, un non-désir affirmé, et un désir incertain ou évolutif. Une femme sur trois a exprimé ne pas souhaiter d’enfant. Malgré leurs singularités, les récits ont révélé des constantes autour des questionnements, de la dimension personnelle, des choix en santé génésique et des besoins d’accompagnement.Discussion : le désir de maternité s’inscrit à la croisée de logiques personnelles, sociales et contemporaines, en cohérence avec les dynamiques mises en évidence dans les études existantes. Ce sujet met en lumière la place croissante des sages-femmes dans la santé globale des femmes notamment chez les plus jeunes.Conclusion : ces témoignages appellent à repenser les discours actuels. Il semble essentiel d’amplifier la parole des femmes via une étude nationale
The role of the sympathetic component of the autonomic nervous system on pain before and after third molar extraction– an observational cohort study
No full textInternational audienceBackground: Assessing heart rate variability (HRV) before a standardized surgery would help to explore further the relationship between the autonomic nervous system and pain.Methods: A single-center prospective cohort of 117 patients (55% female) scheduled for third molar extraction underwent a preoperative resting measurement of arterial pressure followed by an HRV recording, then potentiated by a Valsalva maneuver and a deep breathing challenge. Finally, pain sensitivity was assessed by hand immersion in hot water. All surgeries were conducted under local anesthesia, with or without sedation. The primary outcome was a composite pain/analgesia score (CPAS) incorporating both pain intensity and analgesic drug intake; it was adjusted to the type of anesthesia by within-subgroup ranking.Results: The increase in heart rate in the Valsalva maneuver, and the low- to high-frequency ratio (LF/HF) in the deep breathing, were inversely correlated to preoperative heat pain, which was correlated itself to the CPAS (ρ = 0.195; p = 0.035). The only other parameter influencing CPAS was the increase in heart rate in the Valsalva maneuver, with an inverse correlation (ρ = - 0.191; p = 0.046). While age tended to impair HRV, particularly in its parasympathetic component, and while men displayed a stronger parasympathetic response than women, neither age nor sex interacted with these effects. Neither preoperative arterial pressure nor the occurrence of parental hypertension influenced the pain outcomes.Discussion: Although the identified relationships were not particularly strong, they are consistent with an influence of the sympathetic component of the autonomic nervous system. However, they do not support the interest of HRV assessment to predict postoperative pain in current practice
Sensation of time passing during meals and risks of eating disorders: A pilot study in a non-clinical sample
No full textInternational audienceThis study investigated the relationship between perceived passage of time during meals and eating disorder risk in young women. Researchers hypothesized that individuals at higher risk would experience a slower passage of time and explored the connection between time perception and eating behaviors like meal duration and time to satiety. Forty female participants shared a standardized meal while being observed. Participants self-reported pre-meal hunger, meal start/end times, and time to satiety, and completed questionnaires assessing eating disorder risk (SCOFF), general tendencies toward food cravings, and meal liking. Results showed a correlation between higher SCOFF scores and slower perceived passage of time, even after controlling for meal duration. Increased social interaction and higher BMI were associated with faster time perception. No significant relationship was found between time perception and time to satiety. These findings suggest that distorted time perception may be a factor contributing to maladaptive eating patterns. The slower passage of time experienced by individuals with higher eating disorder risk could be due to heightened negative emotions and anxiety regarding food. Further research is needed to explore the underlying mechanisms and potential implications for interventions targeting time awareness and well-being in the prevention and treatment of eating disorders
Relation entre composition corporelle, sexe et respiration mitochondriale du tissu adipeux de patients atteints de cancers digestifs
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Disease Progression in Multiple System Atrophy: The ASPIRE Multi‐Modal Biomarker Study
No full textInternational audienceObjective The objective of this study was to characterize changes in candidate biomarkers in early multiple system atrophy (MSA) and identify baseline predictors of faster progression. Methods This 1‐year, multicenter, prospective study assessed clinical, neuroimaging (3T‐magnetic resonance imaging [MRI], dopamine transporter single‐photon emission computed tomography [DaT‐SPECT]), and neurofilament light chain (NfL) changes in patients with early MSA (< 5 years from symptom onset) and healthy controls (HCs). Clinical and biomarker changes from baseline to 6 months (M6) and 12 months (M12) were analyzed. Survival status was collected at 24 months. Mixed linear regression analyzed repeated measures, whereas univariate regression identified biomarkers linked to progression. Sample size simulations were conducted for future trials. Results Forty‐one patients with MSA and 20 HCs were included in this study. The Unified Multiple System Atrophy Rating Scale (UMSARS)‐I + II scores worsened (mean percent change from baseline was 19.8% at M6; 95% confidence interval [CI] = 13.3 to 26.4% and 31.1% 95% CI = 24.9 to 37.2% at M12). Patients with MSA showed increased cerebellar white matter and pons atrophy (M6 = −5.9 to −2.8% and M12 = −9 to −4.9%) and decreased striatal specific binding ratio (SBR; M6 = −15.8 to −7.9% and M12 = −24 to −10.4%). Patients with multiple system atrophy parkinsonian (MSA‐P) exhibited greater striatal SBR reduction, whereas patients with multiple system atrophy cerebellar (MSA‐C) had greater cerebellar and pons atrophy, evident at M6. Baseline brainstem and pons volume predicted clinical worsening at M6, whereas SBR predicted worsening at M12. Higher plasma NfL levels correlated with early dropout (14% at M12), worse UMSARS scores, lower SBR, and increased mortality risk within 24 months. Interpretation Neuroimaging changes occur within 6 months in early MSA. High plasma NfL levels are linked to increased mortality and dropout risk. Longitudinal biomarker assessments provide valuable insights into disease progression. ANN NEUROL 202
Effect on Dyskinesia of the Early Combination of Amantadine to Levodopa‐Therapy in Parkinson's Disease: A Randomized, Placebo‐Controlled Study ( PREMANDYSK )
No full textInternational audienceAbstract Objective Investigate the efficacy of immediate‐release (IR) amantadine in reducing the risk of peak‐dose dyskinesia in early Parkinson's disease (PD) as add‐on to levodopa. Background While the use of amantadine to manage dyskinesia in PD is well supported by controlled clinical trials, data on its efficacy in patients without motor complications remain limited. Methods This 22‐month, multicenter, randomized, placebo‐controlled trial (NCT01538329) enrolled early PD patients on stable levodopa (≥150 mg/day for ≤1 year) without motor complications. The study included three double‐blind phases: an 18‐month treatment phase with adjunct amantadine‐IR (200 mg/day) or placebo (Period 1), a 3‐month delayed‐start phase where all participants received amantadine‐IR (Period 2), and a 1‐month washout with placebo (Period 3). The primary outcome was dyskinesia incidence at month 18; secondary outcomes included dyskinesia rates at the end of Periods 2 and 3 to assess potential long‐lasting mechanisms of the drug. Exploratory outcomes investigated the potential effects of amantadine‐IR on motor and non‐motor symptoms and quality of life. Results A total of 207 patients were randomized to amantadine‐IR (N = 99) or placebo (N = 108). Significantly fewer patients in the amantadine‐IR group developed dyskinesia versus placebo during Period 1 (11% vs. 22%, P = 0.025), while the mean daily dose of levodopa (95% CI) increased by 70 (21–119) mg less ( P = 0.005). The proportion of patients with dyskinesia was less in the amantadine‐IR group versus placebo at the end of Periods 2 and 3, but the difference was not statistically significant (12% vs. 20%, P = 0.13 and 16% vs. 22%, P = 0.23, respectively). Mild but significant positive effects on freezing of gait, fatigue, and quality of life were observed during Period 1. The safety profile of amantadine‐IR was in line with previous reports. Conclusions Adjunctive amantadine‐IR in early PD halved dyskinesia incidence over 18 months. Long‐lasting mechanisms could not be demonstrated and merit further investigation. Exploratory positive findings on the potential benefit of amantadine‐IR on symptoms like freezing of gait and fatigue also call for further investigation. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
Noninvasive ventilation in postoperative critically ill patients with morbid obesity: secondary analysis of the EXTUBOBESE multicentre randomised clinical trial
No full textInternational audienceBackground - The optimal method to prevent treatment failure after tracheal extubation in postoperative critically ill patients with obesity and morbid obesity remains unknown. Methods - We conducted a secondary analysis of the EXTUBOBESE multicentre RCT comparing prophylactic noninvasive ventilation (NIV) and oxygen therapy (high-flow nasal oxygen [HFNO] and standard oxygen) in 585 postoperative critically ill patients with obesity (BMI ≥30 kg m) and morbid obesity (BMI ≥40 kg m). The primary outcome was treatment failure within 3 days after extubation, a composite of reintubation within 3 days (also analysed separately as secondary outcome), switch to the other study treatment, or premature study treatment discontinuation. The primary outcome analysis used a χ test. A Cox model was used for time without reintubation. Results - Treatment failure occurred in 39/292 patients (13.4%) in the NIV group and in 70/293 patients (23.9%) in the oxygen therapy group (absolute risk difference: -10.5; 95% confidence interval: -16.8 to -4.3). Similar results were found when analysing separately HFNO from standard oxygen in the oxygen therapy group. Reintubation rate was 8.6% (25 patients) in the NIV group and 9.9% (29 patients) in the oxygen therapy group (P=0.58). Interaction test was significant for level of obesity (P=0.045). Time without reintubation according to level of obesity significantly differed between NIV group and oxygen therapy group (P=0.02) in patients with BMI ≥40 kg m, but not in patients with 30≤BMI<40 kg m (P=0.70). Conclusions - Among postoperative critically ill adults with obesity undergoing tracheal extubation, our results suggest that use of noninvasive ventilation is effective to reduce treatment failure in comparison with oxygen therapy alone. These effects were more pronounced in patients with morbid obesity. Clinical trial registration - NCT04014920