OBJECTIVE:The efficacy of adjuvant chemotherapy (AC) in improving survival for patients with sarcoma is debated. We performed a cost-effectiveness analysis (CEA) comparing AC vs. no AC for non-metastatic sarcoma based on the nationwide retrospective study DEEPSARC. METHODS:The CEA was carried out over a 1-, 3-, and five-year horizon, using data from the French NETSARC+ database linked to the French national health data system (SNDS).There was no age limit and no specific histological type selection in the reference case analysis. Costs (expressed in 2021 EUR) were provided by the SNDS from the French national health insurance perspective. Incremental cost effectiveness ratios (ICER) were expressed in cost per life-year gained (LYG). Propensity score analysis with 1:1 matching was undertaken. Sensitivity and subgroup analyses were performed. RESULTS:Of the 33,548 patients from the French NETSARC+ database, 24,539 were linked to the SNDS. A total of 14,808 patients diagnosed between 2012 and 2017 were included in the reference case analysis with 2,784 patients after propensity score matching. Mean costs (SD) [95% CI] differences per patient between AC and no AC were €12,826 (36,758) [10,883-14,719], €15,706 (49,849) [13,330-18,383], and €16,841 (56,060) [13,590-19,657] at 1, 3, and 5 years, respectively. Mean overall survival differences per patient (in years) were 0.0066 (0.1685) [-0.0021 to 0.0157], -0.0728 (0.9336) [-0.1237 to -0.0229], and -0.1204 (1.3595) [-0.1926 to -0.0475] at 1, 3, and 5 years, respectively. ICER was €1,934,511 [-11,767,351-15,829,959] per LYG at 1 year. AC lagged behind at 3 and 5 years. CONCLUSIONS:In the reference case analysis, AC outperformed its use in terms of outcomes at 1 year, but a high level of willingness to pay would be required for AC to be cost-effective. At 3 and 5 years, AC was deemed to be not cost-effective for patients with non-metastatic sarcoma.

Introduction La prise en charge de la dermatite atopique (DA) a connu une révolution thérapeutique depuis l’autorisation du dupilumab, avec l’émergence de nouvelles biothérapies et des inhibiteurs de Janus kinase (JAKi). Les recommandations européennes ne privilégient pas un traitement systémique particulier, tandis que l’Agence européenne des médicaments a émis un avertissement sur la sécurité d’emploi des JAKi, restreignant leurs prescriptions. Dans ce contexte, nous avons réalisé une étude sur les schémas de prescription des biothérapies et des JAKi en vie réelle. Méthodes À partir du Système national des données de santé, nous avons constitué une cohorte d’adultes atteints de DA sévère ayant initié un nouveau traitement systémique immunomodulateur (dupilumab, tralokinumab, abrocitinib, baricitinib, upadacitinib) entre 2018 et 2024. Nous avons décrit l’évolution temporelle des prescriptions, les parcours thérapeutiques des patients et le nombre de lignes de traitement. Afin de caractériser mensuellement ces parcours, une analyse de séquences d’états a été réalisée, suivie d’un clustering permettant de regrouper les patients présentant des trajectoires thérapeutiques similaires. Résultats Au total, 25490 adultes ont été inclus : 92% ont initié une biothérapie et 8% un JAKi. Le dupilumab est resté le traitement systémique le plus prescrit sur l’ensemble de la période, les autres systémiques se sont ajoutés à l’arsenal thérapeutique sans réduire son utilisation. Parmi les patients suivis au moins un an, 92% ont initié un traitement par dupilumab, et plus des deux tiers l’ont poursuivi sur une année complète. Nous avons observé qu'une partie des patients ont arrêté le traitement sans en changer, 21% d’entre eux ne recevant plus aucun traitement systémique un an après l’initiation. L’analyse par clustering a montré que l’utilisation du dupilumab était associée à un âge plus élevé, à la présence d’asthme et à un nombre plus important de comorbidités comparativement aux JAKi. Discussion/Conclusion Malgré l’élargissement de l’arsenal thérapeutique, et l’efficacité reconnu des JAKi, le dupilumab est le traitement systémique le plus utilisé pour la DA sévère, avec une persistance à un an élevée.

BACKGROUND:DEEPSARC, one of the first projects running on the Health Data Hub, aimed to identify real-life treatment regimens that could improve overall survival. The project is based on matching the national database of the sarcoma reference network with the SNDS. OBJECTIVES:We aimed to report a transparent description of the linking process and its results. METHODS:The sarcoma database encompasses 33 548 patients matching the selection criteria divided into three subsets: 13507 patients with a complete dataset gathering clinical and pathological data; 5844 patients with clinical data alone; and 14 197 patients with pathological data alone. As no ICD-10 code reliably identifies patients with sarcoma, the subpopulation extracted from the SNDS was extended to 3 million patients who underwent surgery for their cancer. An indirect record linkage process used a combination (called a signature) of so-called chaining variables to uniquely identify a pair of patients from each of the bases. Two metrics (signature robustness and overall quality) were calculated for ease of interpretation. RESULTS:The overall matching rate of 73.1% (24 539 pairs out of 33 548 observations), reaching 90.5% in the intersection of the sarcomas databases (with extended data, 12 225 pairs out of 13 507 observations). CONCLUSION:An optimized and transparent process led to a moderate matching rate but enhanced the confidence in true matching. Representativeness is an issue related to the missing data pattern across the three NETSARC databases. For instance, an individual present only in the RREPS database has a greater probability of not being linked.

Introduction Les données épidémiologiques françaises de référence englobent tous les cancers primitifs du foie ne distinguant pas le principal type qui est le carcinome hépatocellulaire (CHC) et reposent sur des données ne couvrant pas l’ensemble du territoire (zone registres). Objectif : décrire l’épidémiologie du CHC selon le sexe, dans une cohorte française représentative. Méthodes Les cas de CHC (tous âges) ont été identifiés par le code CIM-10 C22.0 dans l’échantillon représentatif à 2% du Système National des Données de Santé (ESND) entre 2015 et 2021. Les taux d’incidence, prévalence et de mortalité ont été calculés selon le sexe (référence : population totale ESND) et extrapolés à l’échelle nationale (données INSEE). Les méthodes de survie utilisées étaient : Kaplan–Meier et modèle de Cox. Résultats Au total, 246 femmes et 961 hommes ont été inclus. En 2021, l’incidence du CHC était de 20,4/100000PA chez les hommes et 4,5/100000PA chez les femmes (soit 6654 nouveaux cas chez les hommes, 1575 chez les femmes en France). La prévalence était de 67,7/100000PA chez les hommes et 14,6/100000PA chez les femmes (soit 22083 cas chez les hommes, 5079 chez les femmes en France) (augmentation significative par rapport à 2015). La mortalité était de 8,1/100000PA chez les hommes et 2/100000PA chez les femmes (soit 2662 décès chez les hommes, 696 chez les femmes). Les rapports de risque femmes/hommes étaient RRF/H=0.22 (p<0.001), RRF/H=0.21 (p<0.001) et RRF/H=0.25 (p<0.00) respectivement pour l’incidence, la prévalence et la mortalité. Ces écarts tendaient à croître depuis 2015 (incidence : RRF/H=0.31, p<0.001, prévalence : RRF/H=0.25, p<0.001).La survie à 2 ans était de 31% chez les femmes et 37% chez les hommes (p log-rank=0.01). Cette différence était observée uniquement après 65 ans, et s’expliquait par l’âge, l’alcool et le tabac. Discussion/Conclusion Cette étude représentative, précise les disparités épidémiologiques selon le sexe concernant le CHC en France, invitant à mieux comprendre les mécanismes biologiques /comportementaux sous-jacents afin de promouvoir un dépistage plus précoce et une prise en charge équitable

Introduction L’émulation d’essai cible permet de reproduire la structure d’un essai clinique à partir de données observationnelles afin d’estimer un effet causal tout en limitant les biais. Elle offre un cadre pertinent pour explorer le repositionnement thérapeutique, notamment celui de la colchicine, dont les propriétés anti-inflammatoires pourraient être bénéfiques en prévention secondaire de l’AVC ischémique. Cette efficacité n’a pas été démontré dans les essais cliniques possiblement par manque de puissance. L’objectif était d’évaluer en vie réelle cette efficacité à partir du Système National des Données de Santé. Méthodes Etaient inclus les adultes hospitalisés pour un premier AVC ischémique non cardio-embolique entre 2012 et 2021, traités par antigoutteux de fond dans les deux années précédentes et sans contre-indication à la colchicine. L’intervention correspondait à l’initiation d’un traitement par colchicine dans les six mois suivant la sortie d’hospitalisation, comparée à l’absence d’initiation. La méthode de cloning-censoring and weighting a été utilisée. Le critère principal était la récidive d’AVC ischémique; le critère secondaire, la survenue d’un évènement vasculaire (syndrome coronarien aigu, AVC ischémique ou décès d’origine vasculaire). Le suivi s’étendait de la sortie d’hospitalisation jusqu’à la survenue de l’événement, la perte de vue, la déviation du protocole ou deux ans après l’éligibilité. Résultats Parmi 18 833 sujets éligibles, (68% d’hommes; âge médian 79 ans (IQR = [69; 83])), 512 ont reçu de la colchicine dans les 6 mois post-AVC. A deux ans, le rapport de risque (RR) pour la récidive d’AVC était de 0,72 (IC95% = [0,63-0,83]), et de 0,80 (IC95% = [0,70–0,89]) pour tout évènement vasculaire. Les analyses de sensibilité (période d’intervention à 3 mois ou suivi jusqu’à 5 ans) donnaient des résultats similaires. Discussion/Conclusion Cette étude retrouve un effet de la colchicine en prévention secondaire de l’AVC ischémique similaire aux résultats des essais cliniques avec une meilleure précision. Ces résultats soulignent la pertinence des approches d’émulation d’essai cible pour le repositionnement thérapeutique et la nécessité d’études complémentaires.

Abstract Introduction Mitral transcatheter edge-to-edge repair (M-TEER) is increasingly used. Reverse remodeling is expected to impact prognosis, yet pre-operative prediction of the beneficial impact of MR treatment remains limited. Objective We aimed to describe the impact of M-TEER on heart remodeling according to etiology and to define pre-intervention parameters that might predict this beneficial heart remodeling after M-TEER. Methods Consecutive isolated M-TEER patients recruited between 2019 and 2022 were considered. Patients who died or required re-operation within 30 days were excluded (n=9). Preoperative and follow-up echocardiograms were all recorded in the same tertiary center. A core lab analysis was conducted. Patients without follow up at the TEER-center were not included in the final analysis. Transthoracic echocardiography (TTE), including speckle tracking imaging for LV, RV and LA, was analyzed alongside clinical characteristics. Cardiovascular events and other occurrences were recorded up to a 24-month follow-up. The relative variation in left ventricular end-diastolic indexed volume compared to baseline and according to the etiology group was the primary outcome. Results Eighty-six (out of 146) patients were included in the final analysis (55% men, 55% functional MR, median LVEF 56%, IQR [45-64]), no major difference in the final analysis population compared to the whole cohort. The decrease in left ventricular end-diastolic volume indexed (LVEDVi) was greater in primary MR (-16.4% vs -7.06%, p-value=0.04). No reverse remodeling was found for LA. Baseline global longitudinal strain (GLS) (p=0.03) but also RV free wall strain (RV FWS) (p=0.02) were independent parameters to predict change in LVEDVi (Fig.1). In secondary MR, NYHA functional class improvement after TEER was also associated with relative change in GLS between baseline and follow-up. Conclusion Mitral TEER has a greater impact on LVEDVi in primary MR. LV and RV Speckle tracking parameters are the most reliable parameters to predict the amount of reverse remodeling expected after M-TEER. RV function should be assessed precisely before M-TEER. LA remodeling was non-significant after M-TEER in an elderly population with high prevalence of AF. Baseline GLS and LV reverse remodeling

Chronic liver diseases (CLD) are frequent in Europe, including in France and mainly driven by alcohol, metabolic dysfunction (diabetes and obesity) and viral hepatitis. Despite risk factors are well established and easy to identify, CLD are frequently diagnosed at an advanced stage, translating into poor prognosis. Descriptive data on the burden of CLD in France remain scarce and health trajectories of these patients are uncharted. However, such data are crucial to guide clinical practice, to determine target population for personalized public health policies and to develop innovative strategies to reduce inequities in access to healthcare and ultimately improve survival. The aim of the French RESONANCE cohort is to provide a detailed description of CLD burden in France and study health trajectories. RESONANCE cohort was obtained leveraging data from the French National Health Database (Système National des Données de Santé (SNDS)). Patients with at least one CLD specific International Classification of Diseases, 10th Revision (ICD-10) code (including primary liver cancer (PLC) and rare diseases), procedure, biology, or drug and/or a cause of death related to one of these ICD-10 codes identified between 2013–2021, were targeted from the 2% representative SNDS sample (ESND). Demographic characteristics, etiologies, risk factors, comorbidities, data on social environment and healthcare accessibility, as well as severity of the liver disease at diagnosis and medical management were assessed. This protocol article describes the procedures used to build the cohort and main variables and defines the research objectives. Data extraction and cohort construction have been completed and 26,663 incident and prevalent cases of CLD had been identified between 2015 and 2021. Incident cases account for almost 75% of the patients included. The collection of follow-up data, including vital status and mortality information, is complete. This protocol will enable a detailed, real-world analysis of epidemiology, care trajectories and outcomes of chronic liver diseases across France. With a particular focus on gender and socio-economic disparities, it offers an unique opportunity to identify vulnerable populations and informing proportionate universalism strategies in prevention and care. All necessary accreditations for secure data access have been obtained and a RESONANCE is registered in the health data hub under No F20230224144925, projet number 26266080. According to French regulation (Articles L1461-1 and R1461-13 of the French Public Health Code), studies conducted using anonymized SNDS data do not require approval from an Institutional Review Board (IRB) or ethics committee, or patient individual consent, since no directly identifiable data are used and no contact with patients occurs.

INTRODUCTION:People with epilepsy present an excess risk of mortality, but questions remain regarding the underlying causes and risk distribution. Here, we estimated the excess mortality by age and sex among adults and adolescents with epilepsy in France and identified their main causes. METHODS:A national cohort study was conducted between 2009 and 2019, with adults and adolescents aged between 12 and 60 years and having at least one hospitalization, assurance record, or delivery of anti-seizure medication linked to epilepsy on the French National Health Data System (SNDS). Mortality rates and standardized mortality ratios (SMR) were estimated according to age and sex. Specific causes of death from death certificates were also explored. RESULTS:Between 2009 and 2019, 619,753 patients were included, of whom 60,033 (9.7%) died during follow-up, corresponding to a mortality rate of 9.55 [9.30; 9.79] per 1,000 person-years. Compared with the general population, people with epilepsy had a 3.33-fold higher risk of death [3.24; 3.41], with a higher risk in women than in men, with SMRs of 4.11 [3.94; 4.29] and 2.99 [2.90; 3.09], respectively. Excess mortality was found for all causes of death, particularly neurological causes. Women with epilepsy presented a higher excess risk of death than men, especially between 20 and 40 years old. CONCLUSION:Our findings provide further evidence of increased mortality in patients with epilepsy. Remarkably, we found major differences according to sex, which have been largely overlooked so far. The fact that young women with epilepsy are at risk poses additional clinical and societal challenges.

Introduction: Oral isotretinoin is the only effective treatment for severe acne without an alternative. Isotretinoin has been linked to the occurrence of acute psychiatric disorders outside suicidal behaviors. There are few large-scale epidemiological studies in this area, and the putative associations are unclear. Our objective was to determine whether adolescents and young adults have an elevated risk of acute-onset psychiatric disorder requiring hospital treatment within 2 months of starting isotretinoin treatment. Methods: Our data source was the French national health insurance database (Syst & egrave;me National des Donn & eacute;es de Sant & eacute;, SNDS), 2010-2015. We performed a case-time-control study nested in an exhaustive, nationwide cohort of all French adolescents and young adults aged 10-25 years treated with isotretinoin. The outcome was an acute-onset psychiatric disorder requiring hospitalization (including anxiety, depressive, mood, adjustment, and psychotic disorders). A conditional logistic model was used to estimate odds ratios (ORs) with their 95% confidence interval (CI) for acute psychiatric events. Results: 2,284 acute-onset psychiatric disorder requiring hospitalization were recorded for the study population of 262,786 patients. Among the patients with at least one psychiatric event, 88 had started taking isotretinoin in the risk period (0-2 months before the date of the event), versus 81 in the reference period (2-4 months before the event). A comparison with the 383 and 355 time-trend matched controls who started taking isotretinoin in the risk and reference periods, respectively, yielded a case-time-control OR (95% CI) of 1.01 (0.72-1.41). Conclusion: Psychiatric events managed outside the hospital system were not recorded. Our findings are reassuring for clinicians concerning the risk of severe acute-onset psychiatric events after isotretinoin initiation.

AIMS:In the Tri.FR trial, tricuspid transcatheter edge-to-edge repair (T-TEER) reduced severity of tricuspid regurgitation (TR) and improved the composite clinical score, driven by patient-reported outcomes. The purpose of this study was to describe the longitudinal impact of T-TEER on different dimensions and items of quality of life compared with guideline-directed medical treatment (OMT) alone. METHODS AND RESULTS:Patients were randomized to T-TEER +OMT (n = 152) or OMT alone (n = 148). Health status was assessed at baseline, 6 weeks, 6 months, and 1 year using the Kansas City Cardiomyopathy Questionnaire (KCCQ) and the Minnesota Living with Heart Failure (MLHF) Questionnaire. Mixed effects linear regression analysed changes over time. Patients receiving T-TEER + OMT experienced a significant increase in KCCQ overall summary score (KCCQ-OS) at all time points: +17.0 points (95% confidence interval [CI] 13.1-21.5) at 6 weeks, +15.9 points (95% CI 11.2-20.6) at 6 months, and +18.7 points (95% CI 13.8-23.6) at 1 year. The mean between-group difference in KCCQ-OS was +10.3 points (95% CI 5.6-15.0) in favour of T-TEER + OMT, evident at 6 weeks and sustained for 1 year. Similarly, MLHF total scores improved significantly in the T-TEER group (mean between-group difference -8.61 points, 95% CI -12.6 to -4.6), including physical (-3.9, 95% CI -5.9 to -1.9) and emotional (-2.2, 95% CI -3.4 to -1.0) subscales. CONCLUSIONS:Compared with OMT alone, T-TEER resulted in substantial, multidimensional, and sustained improvements in patient-reported quality of life. These findings reinforce the value of T-TEER in managing severe symptomatic TR.

INTRODUCTION:(Pre-)clinical studies have not ruled out a potential risk of second primary cancer (SCP) under the effect of some new androgen receptor pathway inhibitors (ARPIs), especially enzalutamide (ENZ). METHODS:Using the French health reimbursement claims database (Système National des Données de Santé), we designed a case-control study nested in a 2013-2020 cohort of new users of androgen-deprivation therapy. The cases were patients with a first diagnosis of SPC, identified beyond 12 months following cohort entry and up to December 31st, 2021; up to 10 controls were matched per case, based on age and cohort entry date. The main analysis focused on patients who had not switched to a different ARPI. Applying a one-year lag time, we determined the most frequent and longest cumulative exposure patterns to abiraterone (ABI) or ENZ and estimated the odds ratios. RESULTS:The cohort comprised 147 092 patients, including 7928 cases and 78 554 controls eligible for analysis. The SPCs mainly involve the digestive organs, the urinary tract, or the lungs. Recent and short exposure to ENZ was associated with SPC: OR 1.7, 95% CI [1.2-2.4]. Recent one full year of exposure to ABI, as well as full-year plus part of the second year, was associated with SPC: OR 1.8 [1.2-2.7] and 2.3 [1.3-4.0], respectively. DISCUSSION/CONCLUSION:SPC cases were mainly observed among recently exposed patients, which could be linked to a detection bias. The insufficient number of patients exposed over many years means that no definitive conclusions can be drawn.