Optimizing Antidepressant Use in Geriatric Depression: Expert Consensus from French societies of geriatrics, old age psychiatry and clinical pharmacy (SFGG, SF3PA and SFPC)

International audienceBackgroundLate-life depression refers to a depression occurring in older adults, typically defined as individuals aged 65 years and older. It is common and often mismanaged due to complex clinical profiles, polypharmacy and limited evidence-based guidance. Existing tools poorly address psychiatric nuances in older adults. This work aims to develop French recommendations based on experts consensus on the use of antidepressant in unipolar late-life depression, to guide safer prescribing practicesespecially in primary care-and address a major public health issue.MethodsThis tool was developed using a Delphi survey, based on a review of literature published between 2014 and 2024 and focused on "antidepressants" and "late-life depression" available on PubMed. Experts from various fields: geriatric psychiatry, clinical pharmacy and general practice, rated items using a 9point Likert scale. Items with a median score ≥ 7 and at least 80% agreement were validated and included in the final version of the tool.ResultsTwenty to twenty-three experienced experts per round, different from the authors of the proposed items, participated in a four-round Delphi process. The resulting tool, based on evidence and clinical expertise, includes 57 validated items across 10 sections and a stepped-care algorithm for treating major depression in older adults. It addresses drug choice, dosing, monitoring, comorbidities, and treatment resistance, prioritizing safe first-line options like sertraline, citalopram, and escitalopram.ConclusionA Delphi survey involving multidisciplinary experts led to a French consensus tool for prescribing antidepressants in unipolar late-life depression. It integrates clinical evidence and expert judgment to address treatment complexity, drug safety and resistance. The tool offers practical, stepwise recommendations tailored to primary care, aiming to optimize antidepressant use, reduce iatrogenesis, and improve patient outcomes

High-risk genomic consensus validation for patients with newly diagnosed multiple myeloma using next-generation sequencing

International audienceThe prognostic heterogeneity of multiple myeloma is mainly driven by the genomic features of myeloma cells. The International Myeloma Society (IMS)/International Myeloma Working Group (IMWG) recently proposed a high-risk (HR) genomic model to have a consensus definition of genomic risk. We performed next-generation sequencing in the form of a panel on samples from 6528 patients with newly diagnosed multiple myeloma (NDMM) and 1583 patients at first relapse between 2019 and 2024. We observed that 22.4% of patients at diagnosis and 36.7% of patients at first relapse were classified as high risk according to the Consensus Genomic Staging. Clinical data were available for 2695 patients at diagnosis. After a median follow-up of 35 months, the median progression-free survival (PFS) was 30 months for patients with HR NDMM and 51 months for standard-risk (SR) patients (P< .0001). The HR cytogenetic criteria from the Revised- International Staging System score were not able to differentiate between HR and SR patients based on the IMS/IMWG genomic subgroups. Looking at each criterion independently, we found that the presence of del(17p), TP53 mutation, biallelic del(1p32), or the combination of intermediate-risk cytogenetics (gain 1q, del(1p32), t(4;14), t(14;16), t(14;20)) significantly reduced the PFS when compared with SR patients. Moreover, patients with several cumulating criteria had an even worse prognosis. Among SR patients, classified according to the genomic definition with normal creatinine, the median PFS for those with high β2-microglobulin was not significantly different from that of patients with normal β2-microglobulin level. This study validated the IMS/IMWG genomic definition of HR myeloma in a large cohort of patients diagnosed from 2019 onwards

Subcutaneous infliximab in inflammatory bowel disease: bridging the gap between theory and practice.

International audienceBackground: At the end of the past century, infliximab (IFX), the first-in-class biological therapy approved in inflammatory bowel disease (IBD), dramatically modified the therapeutic armamentarium. The recent development of subcutaneous (SC) formulations of IFX offers a promising alternative, with the potential to improve patient convenience, adherence, and overall outcomes. This review explores the clinical evidence supporting the initiation of SC IFX and the transition from intravenous (IV) to SC IFX.Methods: Comprehensive review using MEDLINE (source PUBMED).Results: Comparative studies have shown that SC IFX is associated with higher IFX serum concentration levels than IV, fewer neutralizing antibodies and similar levels of remission. Real-world studies have confirmed that switching from IV to SC IFX 120 mg is well accepted with a low risk of relapse. The ease of at-home administration has been associated with improved patient satisfaction and reduced healthcare burdens. The adoption of SC IFX could profoundly change the therapeutic landscape, offering a more patient-centered approach to long-term disease control but some questions remain, particularly about the place of IFX in certain populations.Conclusion: In this article, we reviewed the known and unknown data on SC IFX to provide a comprehensive summary and assist IBD physicians in integrating this knowledge into everyday clinical practice

Évaluation de l’impact de la thérapie manuelle dans la prise en charge des lombalgies non spécifiques : revue de la portée des critères utilisés dans les essais cliniques

International audienceBackground: Low Back Pain (LBP) is the leading cause of disability worldwide, 90% of which is nonspecific. Manual therapy is one of the recommended treatment modalities. However, reported outcomes may be variable. This review aims to identify their scope in the context of the development of a Core Outcome Set (COS), which is defined as « an agreed standardised set of outcomes that should be measured and reported, as a minimum, in all clinical trials in specific areas of health or health care ».Methods: A scoping review with risk of bias assessment of randomised controlled trials (RCTs) of manual therapy for nonspecific LBP was conducted using MEDLINE, CENTRAL, PEDro, WebOfScience and ClinicalTrials.gov, from 2010 up to August 2024. Manual therapy was considered the use, alone or in combination, of manipulations (high velocity, low amplitude), mobilisations (low-grade velocity, small-to-large amplitude) or soft tissue relaxation (especially massage, trigger points, muscle contractions).Results: Out of 3929 articles, 147 RCTs and 74 protocols were included. Two main outcomes emerged: pain intensity (assessed by numerical rating scale or visual analogue scale) and disability (mostly assessed by Rolland-Morris Disability Questionnaire or Oswestry Disability Index). Range of motion is the most frequent clinical outcome assessed. Psychological factors such as fear-avoidance beliefs, kinesiophobia and catastrophising, and healthcare consumption, particularly medication, are also frequent. Most of the outcomes were patient-reported outcomes.Conclusion: Consistent with a previous COS on nonspecific low back pain, manual therapy appears to address the same outcomes. Clinical trials in manual therapy should focus on using the existing COS by measuring pain intensity using a numerical rating scale, disability using the ODI 2.1a or the 24-item RMDQ, health-related quality of life using the SF-12 or the 10-item PROMIS. Additionally, due to the gap between clinical research and pain experience, trials should consider conducting subgroup analyses to identify effects on outcomes related to gender or age, paying particular attention to health inequalities by carrying out analyses based on socioeconomic status, as these factors are well known to significantly impact pain experience and access to care.Review protocol: PROSPERO registration CRD42024576475, COMET Database registration 3229.Introduction : La lombalgie est la principale cause d’incapacité dans le monde, jusqu’à 95% étant non spécifiques. La thérapie manuelle est l’une des modalités de traitement recommandées. Cependant, les critères de jugement utilisés peuvent être variables. Cette revue vise à développer un Core Outcome Set (COS), défini comme “un ensemble standardisé de critères devant être mesurés et rapportés, au minimum, dans tous les essais cliniques dans des domaines spécifiques de la santé ou des soins de santé”, pour la prise en charge des lombalgies non spécifiques en thérapie manuelle.Méthodes : Une revue de la portée avec analyse du risque de biais d’essais contrôlés randomisés (ECR) sur la prise en charge en thérapie manuelle des lombalgies non spécifiques a été menée sur MEDLINE, CENTRAL, PEDro, WebOfScience et ClinicalTrials.gov, de 2010 à août 2024. La thérapie manuelle incluait manipulations (haute vélocité, faible amplitude), mobilisations (faible vélocité, faible à grande amplitude) et relaxation des tissus mous (massages, points gâchettes, contractions musculaires).Résultats : Sur 3 929 articles, 147 ECR et 74 protocoles ont été inclus. Deux critères principaux ont émergé : l’intensité de la douleur (échelle numérique ou visuelle analogique) et l’incapacité (Rolland Morris Disability Questionnaire (RMDQ) ou Oswestry Disability Index (ODI). L’amplitude des mouvements était le résultat clinique le plus fréquent. Les facteurs psychologiques (croyances de peur-évitement, kinésiophobie, catastrophisme) et la consommation de soins de santé (médicaments) étaient aussi régulièrement rapportés. La plupart des résultats étaient des résultats rapportés par les patients.Conclusion : Les critères identifiés concordent avec le COS préexistant pour les lombalgies non spécifiques. Les essais cliniques doivent mesurer la douleur via une échelle numérique, l’incapacité par l’ODI 2.1a ou le RMDQ-24, et la qualité de vie par le SF-12 ou le PROMIS-10. La réalisation d’analyses de sous-groupes basées sur le genre, l’âge et le statut socio-économique est préconisée pour intégrer les inégalités de santé et la variabilité de l’expérience de la douleur.Enregistrement du protocole : PROSPERO CRD42024576475, Base de données COMET 3229

Efficacy of targeted therapies for metastatic small bowel adenocarcinoma treatment: a retrospective study by AGEO

International audienceBackground:Small bowel adenocarcinoma (SBA) is a rare malignancy with poor prognosis. In metastatic disease, evidence regarding the efficacy of chemotherapy (CT) combined with bevacizumab or anti-EGFR agents is limited to small studies. This study aimed to assess, in real-world practice, the effectiveness of first-line CT combined with targeted therapies (TT)—either antiangiogenic (AA) or anti-EGFR—compared with CT alone in patients with metastatic SBA (mSBA) and proficient mismatch repair/microsatellite stable (pMMR/MSS) status.Patients and Methods:This retrospective multicentre study included all patients receiving at least one cycle of CT with or without TT for mSBA. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), objective response rate (ORR), and safety. Analyses used inverse probability of treatment weighting (IPTW) in univariable Cox models to account for potential confounding factors that were unbalanced between groups.Results:A total of 255 patients were included: 153 received CT alone, 45 CT+AA, and 16 CT+anti-EGFR as first-line therapy. Median PFS was 8.0 months with CT alone versus 11.9 months with CT+AA (IPTW HR=0.38; 95% CI: 0.29–0.49; p<0.0001). Median OS was 15.9 versus 23.1 months (IPTW HR=0.38; 95% CI: 0.28–0.51; p<0.0001). ORR did not differ significantly (33.8% vs 43.2%; p=0.26). Among 78 patients with RAS wild-type tumours, outcomes did not significantly differ between CT alone and CT+anti-EGFR groups.Conclusion:Adding antiangiogenic therapy to CT significantly improved PFS and OS in first-line treatment of mSBA, warranting confirmation through prospective randomized trials

Systematic analysis of snRNA genes reveals frequent RNU2-2 variants in dominant and recessive developmental and epileptic encephalopathies

International audienceVariants in spliceosomal small nuclear RNA (snRNA) genes RNU4-2 (ReNU syndrome), RNU5B-1 , and RNU2-2 have recently been linked to dominant neurodevelopmental disorders (NDDs), revealing a major, previously overlooked role for noncoding snRNAs in human disease. Here, we systematically analysed 200 potentially functional snRNA genes in a French cohort comprising 26,911 individuals with rare disorders and through international collaborations. We identify de novo and biallelic variants in RNU2-2 associated with both dominant and recessive NDDs in 126 individuals from 108 unrelated families. Recessive RNU2-2 NDD is at least twice as frequent as the dominant NDD caused by n.4G>A and n.35A>G, and often arises from a de novo variant in trans with an inherited allele, reflecting the high mutability of snRNA genes. Dominant and recessive RNU2-2 -NDDs share overlapping clinical features with frequent epilepsy. Blood transcriptomics and DNA methylation analyses revealed subtle, variant-specific effects on splicing and episignatures. Our findings support a gradient-of-impact model and a continuum between dominant and recessive inheritance, establishing RNU2-2 variants as a frequent cause of NDDs, nearly as prevalent as ReNU syndrome

Female pulmonologists experienced poorer health and reduced quality of life related to their professional activities

International audienceBackground: Despite increasing gender parity in medical school enrolment, disparities in career progression and physician well-being persist. This study evaluated professional experiences, health status and perceived gender-related barriers among pulmonologists in France.Methods: A nationwide, anonymous cross-sectional survey (546-item) was distributed to all French pulmonologists between July 2023 and February 2024. Data included work-related health disorders, career paths and gender perceptions. Gender differences in dissatisfaction and health issues were assessed (chi 2 and Fisher's exact tests). Multivariate logistic regression models were used to evaluate the impact of gender on career outcomes.Results: A total of 586 pulmonologists responded (21% response rate), 57% of whom were women; median age of 38 (interquartile range 32–49) years. Job satisfaction was moderate (mean± sd score of 3.5±1.0, out of 5)). Mental health issues were common. 51.5% reported anxiety, 22.0% burnout, 16.9% depression and over 60% had sleep disturbances. Women reported significantly higher rates of anxiety (58.8% versus 44.2%), burnout (27.9% versus 15.4%) and anxiolytic use (23.0% versus 14.5%) than men. Gender was a limiting factor in career choices (OR 1.99, 95% CI 1.41–2.80) and opportunities (OR 2.22, 95% CI 1.57–3.15), particularly among female physicians with children. Women were more likely than men to adjust their career plans for family reasons (18% versus 12%) or job offers (67.0% versus 33.1%). In multivariate analyses, gender remained a limiting factor in career choices (OR 2.00, 95% CI 1.39–2.90) and opportunities (OR 2.39, 95%CI 1.65–3.48), after adjustment for age, number of children and practice settings.Conclusion: This national survey highlights notable gender-based disparities in mental health and career advancement among French pulmonologists

A Swiss army knife for the treatment of bone cancers: a new multifunctional platform based upon SPIONs@copper-doped bioactive glass core-shell nanoparticles

International audienceCore-shell nanometric heterostructures combining a magnetic core and a mesoporous bioactive glass shell doped with copper ions (γ-Fe2O3@SiO2-CaO-CuO) were synthesised by iron salts co-precipitation, and by a modified Stöber sol-gel method using a cationic surfactant (CTAB) as templating agent. Heterostructures with different dopant concentrations were obtained, and their structure, morphology and composition were characterized using a large set of techniques (XRD, FTIR, TEM, nitrogen gas sorption, ICP-OES and MAS-NMR). Their magnetic properties were assessed by AC magnetometry and their specific absorption rate determined under multiple sets of magnetic field amplitudes (4-24 kA/m) and frequencies (146 and 280 kHz), proving their capacity to produce heat under an alternative magnetic field. NMR relaxometry experiments were performed and confirm the possibility of using those materials as negative (T2-weighted) contrast agents in magnetic resonance imaging. Their in vitro bioactivity was evaluated after immersion in Simulated Body Fluid (SBF) at 37°C. All samples showed a fast hydroxyapatite crystal formation, only slightly delayed (from 3 to 24h) when Cudoped. Cytotoxic evaluations indicated a dose-dependent effect, but at a concentration of 0.25 mg/mL, none of the samples presented signs of cytotoxicity after 7 days. The antibacterial property of the mostly doped sample was assessed on Staphylococcus aureus. This study represents the first step in the development of a multifunctional synthetic biocompatible nanomaterial combining bone regeneration and antibacterial effect, under possible monitoring by MRI and a potential cancer treatment by magnetic hyperthermia

Evaluating the applicability of ESGO quality indicators in the surgical management of endometrial cancer: Insights from a Francogyn cohort

International audienceBackground: Endometrial cancer (EC) is a significant health concern in France, necessitating high-quality surgical care to improve patient outcomes. The European Society of Gynaecological Oncology (ESGO) established quality indicators (QIs) to standardize and improve management.Objective: This study evaluates the applicability of ESGO QIs in a real-world setting across 13 centers in France.Methods: This retrospective multicenter cohort study included 2789 patients surgically treated for EC from 2001 to 2020. Demographic data, surgical techniques, adherence to ESGO QIs and trends over time were analyzed. Key indicators analyzed included multidisciplinary team discussions, pre-operative imaging adequacy, surgical techniques employed, and molecular classifications.Results: All patients were discussed in multidisciplinary meetings. Adequate preoperative imaging was achieved in 80.63 % of cases. Minimally invasive surgery was performed in 66.12 % of early-stage patients, showing a significant year-on-year increase from 12 % in 2001 to 85 % in 2020. Among obese patients, 60.78 % underwent laparoscopic procedures, with a conversion rate to open surgery of 3.57 %. Molecular classification results highlighted 35 % of patients as low risk and 32 % as high risk.Conclusion: Our findings indicate that adherence to actual ESGO QIs has substantially improved the quality of surgical management for endometrial cancer in France, despite some areas requiring further enhancement. A coordinated political approach is essential to address existing barriers and ensure consistent implementation of these quality standards across all centers, ultimately aiming to elevate patient care and outcomes in the French healthcare system

Guidelines on Antibiotic Prophylaxis in Surgery 2024

International audienceObjectiveTo provide guidelines for antibiotic prophylaxis in surgery and interventional medicine.DesignA consensus committee of 167 experts from the French Society of Anaesthesia and Intensive Care Medicine (Société française d'anesthésie et de réanimation, SFAR) and 28 surgery and interventional medicine learned societies was convened. A formal conflict-of-interest (COI) policy was developed at the beginning of the process and enforced throughout. The entire guideline construction process was conducted independently of any industrial funding (i.e., pharmaceutical, medical devices). The authors were required to follow the rules of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence. The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasised.MethodsThe latest SFAR guidelines on antibiotic prophylaxis in surgery and interventional medicine were published in 2018. The literature is now sufficient for an update. The aim of this expert panel guidelines is to evaluate antibiotic prophylaxis in surgery and interventional medicine. The experts studied questions within 2 fields and 9 domains. Each question was formulated according to the PICO (Patients Intervention Comparison Outcome) model and the evidence profiles were produced. An extensive literature review and recommendations were carried out and analysed according to the GRADE® methodology.ResultsThe experts' synthesis work and the application of the GRADE® method resulted in 9 tables of recommendations dealing, by specialty, on antibiotic prophylaxis in surgery and interventional medicine. Among the formalised recommendations, several have high levels of evidence (GRADE 1+) and low levels of evidence (GRADE 2+). For many recommendations, the GRADE method could not be applied, resulting in expert opinions. After 2 rounds of scoring and amendment, strong agreement was reached for all the recommendations.ConclusionsThere was strong agreement among experts for all the recommendations to improve practices for antibiotic prophylaxis in surgery and interventional medicine