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Background: Heatwaves are becoming longer and more frequent. Despite the availability of open environmental data, little is operable and formatted for primary care use., Aim: Create a user-friendly online mapping tool to assess the vulnerability of communities to heatwaves for use by primary care practitioners. This study questioned what knowledge needed to be deployed, who needed to participate and how the knowledge should be shared., Design & Setting: A participatory action-research project based on knowledge mobilization in France as part of the Green Data for Health Challenge., Method: Knowledge was summarized on the factors most affecting heatwave vulnerability in a collaborative process, enabling a consensus on data variables and mobilised content for the online tool. Purposive sampling included primary care stakeholders with Regional Health Agencies (ARS), Public Health France, and data scientists., Results and Conclusion: Nineteen participants participated in ten co-construction workshops, a brainstorming carousel strategy and five weekly co-design meetings between December 2022 and June 2023. The heatwave vulnerability variable was constructed using surface temperature, social deprivation, vegetation coverage, and presence of air conditioning equipment. Identified experts mobilized data on the national composite indicator at the communal level for heatwave morbidity. There is no standard platform for sharing environmental data in France. This co-creation study offers a new approach to incorporating environmental data on heatwaves into primary care consultations. We demonstrate the importance of knowledge mobilisation in primary care to bridge the research-practice gap. Integrating primary care records with environmental data may promote broader applications for planetary health research., (Copyright © 2024, The Authors.)

Rational: Studies are needed to determine if multimorbidity screening and management reduce the rate of multimorbidity accumulation in patients with chronic inflammatory rheumatic diseases (IRD)., Objectives: This study evaluates the impact of systematic screening programme on patient care and hospitalisation rates., Methods: Patients with IRD who participated in the screening programme (exposed patients) were identified within the French national health database and matched with controls. Two sets of analysis were performed: one with multivariate analysis and a second using a propensity score matching to ensure comparability between exposed patients and controls. The primary endpoint (PE) was a composite score assessing the dispensation of multimorbidity-preventing drugs, including vaccines, lipid-lowering agents, antiosteoporotic medications and antiplatelet drugs, during the year following the index date., Results: The first analysis included 286 exposed patients and 858 controls, demonstrating a higher rate of meeting the PE in exposed patients (adjusted OR=1.6 (1.2-2.2), p<0.01). Propensity score matching resulted in 281 exposed patients and 281 controls. Exposed patients exhibited a significantly higher rate of meeting the PE compared with controls (54.8% vs 44.5%; OR=1.5; p=0.015), with increased utilisation of vaccines, cholesterol-lowering drugs and antiosteoporotic medications. Furthermore, emergency admission and hospitalisations for fracture, cardiovascular events or infection were significantly less frequent in the exposed group (7.1% vs 15.3%; OR=0.42, p<0.01), with a reduction in severe infections (0.7% vs 3.9%; p=0.03)., Conclusion: Systematic multimorbidity screening in patients with IRD boosted preventive medication use and reduced hospital admissions, justifying time and resource allocation for screening., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Generation of human induced pluripotent stem cells (iPSCs) through reprogramming was a transformational change in the field of regenerative medicine that led to new possibilities for drug discovery and cell replacement therapy. Several protocols have been established to differentiate hiPSCs into neuronal lineages. However, low differentiation efficiency is one of the major drawbacks of these approaches. Here, we compared the efficiency of two methods of neuronal differentiation from iPSCs cultured in two different culture media, StemFlex Medium (SFM) and Essential 8 Medium (E8M). The results indicated that iPSCs cultured in E8M efficiently generated different types of neurons in a shorter time and without the growth of undifferentiated nonneuronal cells in the culture as compared with those generated from iPSCs in SFM. Furthermore, these neurons were validated as functional units immunocytochemically by confirming the expression of mature neuronal markers (i.e., NeuN, β tubulin, and Synapsin I) and whole cell patch-clamp recordings. Long-read single-cell RNA sequencing confirms the presence of upper and deep layer cortical layer excitatory and inhibitory neuronal subtypes in addition to small populations of GABAergic neurons in day 30 neuronal cultures. Pathway analysis indicated that our protocol triggers the signaling transcriptional networks important for the process of neuronal differentiation in vivo . NEW & NOTEWORTHY Low differentiation efficiency is one of the major drawbacks of the existing protocols to differentiate iPSCs into neuronal lineages. Here, we present time-efficient and robust approach of neuronal differentiation leading to the generation of functional brain units, cortical layer neurons. We found iPSCs cultured in Essential 8 media (E8M) resulted in neuronal differentiation without the signs of growth of spontaneously differentiated cells in culture at any point in 35 days compared with Stemflex media (SFM).

Background: The PRADO-IC (Programme de Retour à Domicile après une Insuffisance Cardiaque) is a transition care program designed to improve the coordination of care between hospital and home that was generalized in France in 2014. The PRADO-IC consists of an administrative assistant who visits patients during hospitalization to schedule follow-up visits. The aim of the present study was to evaluate the PRADO-IC program based on the hypotheses provided by health authorities., Methods and Results: The PRADOC study is a multicenter, controlled, randomized, open-label, mixed-method trial of the transition program PRADO-IC versus usual management in patients hospitalized with heart failure (standard of care group; NCT03396081). A total of 404 patients were recruited between April 2018 and May 2021. The mean patient age was 75 years (±12 years) in both groups. The 2 groups were well balanced regarding severity indices. At discharge, patients homogeneously received the recommended drugs. There was no difference between groups regarding hospitalizations for acute heart failure at 1 year, with 24.60% in the standard of care group and 25.40% in the PRADO-IC group during the year following the index hospitalization (hazard ratio, 1.04 [95% CI, 0.69-1.56]; P =0.85) or cardiovascular mortality (hazard ratio, 0.67 [95% CI, 0.34-1.31]; P =0.24)., Conclusions: The PRADO-IC has not significantly improved clinical outcomes, though a trend toward reduced cardiovascular mortality is evident. These results will help in understanding how transitional care programs remain to be integrated in pathways of current patients, including telemonitoring, and to better tailor individualized approaches., Registration: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT03396081.

Context: Objective Structured Clinical Examinations (OSCEs) are an increasingly popular evaluation modality for medical students. While the face-to-face interaction allows for more in-depth assessment, it may cause standardization problems. Methods to quantify, limit or adjust for examiner effects are needed., Methods: Data originated from 3 OSCEs undergone by 900-student classes of 5 th - and 6 th -year medical students at Université Paris Cité in the 2022-2023 academic year. Sessions had five stations each, and one of the three sessions was scored by consensus by two raters (rather than one). We report OSCEs' longitudinal consistency for one of the classes and staff-related and student variability by session. We also propose a statistical method to adjust for inter-rater variability by deriving a statistical random student effect that accounts for staff-related and station random effects., Results: From the four sessions, a total of 16,910 station scores were collected from 2615 student sessions, with two of the sessions undergone by the same students, and 36, 36, 35 and 20 distinct staff teams in each station for each session. Scores had staff-related heterogeneity (p<10 -15 ), with staff-level standard errors approximately doubled compared to chance. With mixed models, staff-related heterogeneity explained respectively 11.4%, 11.6%, and 4.7% of station score variance (95% confidence intervals, 9.5-13.8, 9.7-14.1, and 3.9-5.8, respectively) with 1, 1 and 2 raters, suggesting a moderating effect of consensus grading. Student random effects explained a small proportion of variance, respectively 8.8%, 11.3%, and 9.6% (8.0-9.7, 10.3-12.4, and 8.7-10.5), and this low amount of signal resulted in student rankings being no more consistent over time with this metric, rather than with average scores (p=0.45)., Conclusion: Staff variability impacts OSCE scores as much as student variability, and the former can be reduced with dual assessment or adjusted for with mixed models. Both are small compared to unmeasured sources of variability, making them difficult to capture consistently., (© 2024. The Author(s).)

Background: Practice-based research is one of the levers identified by the World Health Organization (WHO) to strengthen primary health care. The scaling of health and social care innovations has the potential to reduce inequities in health and to expand the benefits of effective innovations. It is now rapidly gaining the attention of decision-makers in health and social care, particularly in high-income countries. To meet the challenge of declining numbers of primary care physicians in France, Multi-professional Healthcare Centers (MHC) were created to bring together medical and paramedical professionals. They are a source of innovation in meeting the health challenges facing our populations. Specific methodology exists to identify health innovations and assess their scalability. A working group, including end-users and specialists, has adapted this methodology to the French context and the University department of general practice of Montpellier-Nîmes (France) launched a pilot study in Occitanie, a French region., Objective: To identify and evaluate the scalability of innovations produced in pluri-professional healthcare centers in the Occitanie region., Methods: A pilot, observational, cross-sectional study was carried out. The SPRINT Occitanie study was based on a questionnaire with two sections: MHC information and the modified Innovation Scalability Self-Administered Questionnaire (ISSaQ), version 2020. The study population was all 279 MHC in the Occitanie region., Results: 19.3% (54) of MHC in the Occitanie region, responded fully or incompletely to the questionnaire. Four out of 5 U-MHCs were represented. Five MHC presented multiple innovations. The average per MHC was 1.94 (± 2.4) innovations. 26% of them (n = 9) had high scalability, 34% (n = 12) medium scalability and 40% (n = 14) low scalability. The main innovation represented (86%) were healthcare program, service, and tool., Conclusions: In our cross-sectional study, a quarter of the innovations were highly scalable. We were able to demonstrate the importance of MHC teams in working on primary care research through the prism of innovations. Primary-care innovations must be detected, evaluated, and extracted to improve their impact on their healthcare system., (© 2024. The Author(s).)

Introduction: Long-term oxygen therapy (LTOT) is reported to improve survival in patients with chronic respiratory failure. We aimed to describe effectiveness, burden, and cost of illness of patients treated with portable oxygen concentrators (POC) compared to other LTOT options., Methods: This retrospective comparative analysis included adult patients with chronic respiratory insufficiency and failure (CRF) upon a first delivery of LTOT between 2014 and 2019 and followed until December 2020, based on the French national healthcare database SNDS. Patients using POC, alone or in combination, were compared with patients using stationary concentrators alone (aSC), or compressed tanks (CTC) or liquid oxygen (LO2), matched on the basis of age, gender, comorbidities, and stationary concentrator use., Results: Among 244,719 LTOT patients (mean age 75 ± 12, 48% women) included, 38% used aSC, 46% mobile oxygen in the form of LO2 (29%) and POC (18%), whereas 9% used CTC. The risk of death over the 72-month follow-up was estimated to be 13%, 15%, and 12% lower for patients in the POC group compared to aSC, CTC, and LO2, respectively. In the POC group yearly mean total costs per patient were 5% higher and 4% lower compared to aSC and CTC groups, respectively, and comparable in the LO2 group. The incremental cost-effectiveness ratio (ICER) of POC was €8895, €6288, and €13,152 per year of life gained compared to aSC, CTC, and LO2, respectively., Conclusion: Within the POC group, we detected an association between higher mobility (POCs autonomy higher than 5 h), improved survival, lower costs, and ICER - €6 238, compared to lower mobility POCs users., (© 2024. The Author(s).)

Aims: Evaluating the benefit of telemonitoring in heart failure (HF) management in real-world settings is crucial for optimizing the healthcare pathway. The aim of this study was to assess the association between a 6-month application of the telemonitoring solution Chronic Care Connect™ (CCC) and mortality, HF hospitalizations, and associated costs compared with standard of care (SOC) in patients with a diagnosis of HF., Methods and Results: From February 2018 to March 2020, a retrospective cohort study was conducted using the largest healthcare insurance system claims database in France (Système National des Données de Santé) linked to the CCC telemonitoring database of adult patients with an ICD-10-coded diagnosis of HF. Patients from the telemonitoring group were matched with up to two patients from the SOC group based on their high-dimensional propensity score, without replacement, using the nearest-neighbour method. A total of 1358 telemonitored patients were matched to 2456 SOC patients. The cohorts consisted of high-risk patients with median times from last HF hospitalization to index date of 17.0 (interquartile range: 7.0-66.0) days for the telemonitoring group and 27.0 (15.0-70.0) days for the SOC group. After 6 months, telemonitoring was associated with mortality risk reduction (hazard ratio [HR] 0.71, 95% confidence interval [CI] 0.56-0.89), a higher risk of first HF hospitalization (HR 1.81, 95% CI 1.55-2.13), and higher HF healthcare costs (relative cost 1.38, 95% CI 1.26-1.51). Compared with the SOC group, the telemonitoring group experienced a shorter average length of overnight HF hospitalization and fewer emergency visits preceding HF hospitalizations., Conclusion: The results of this nationwide cohort study highlight a valuable role for telemonitoring solutions such as CCC in the management of high-risk HF patients. However, for telemonitoring solutions based on weight and symptoms, consideration should be given to implement additional methods of assessment to recognize imminent worsening of HF, such as impedance changes, as a way to reduce mortality risk and the need for HF hospitalizations. Further studies are warranted to refine selection of patients who could benefit from a telemonitoring system and to confirm long-term benefits in high-risk and stable HF patients., (© 2024 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Data are limited on the relationship between ovarian cancer surgery volume and outcomes in France., Methods: For this retrospective, population-based study, patients with ovarian cancer that was diagnosed between January 1, 2012 and December 31, 2016 were identified from the French National Health Data System (SNDS). Hospitals were classified in function of their ovarian cancer surgery volume. Patient, tumor, hospital, and hospital stay characteristics also were evaluated. The hospital procedure volume effect on 5-year overall survival (OS) and recurrence-free survival (RFS) was determined with Cox-proportional hazards models., Results: This study included 8429 patients and 53.4% underwent cytoreductive surgery in hospitals with procedure volume < 20 cases/year. The 5-year OS rates were 63% and 60% in hospitals with procedure volume ≥ 20 and < 20 cases/year (p = 0.02). In multivariate analysis, OS and RFS were significantly increased when surgery was performed in hospitals doing ≥ 20 surgeries/year (vs. < 20) (hazard ratio HR = 1.18, 95% CI = 1.08-1.29 and HR = 1.10, 95% CI = 1.03-1.17). In the volume subgroup analysis, a difference was observed mainly between hospitals with < 10 surgeries/year and the other hospitals (HR = 1.27, 95% CI = 1.14-1.41 and HR = 1.14, 95% CI = 1.05-1.23). The patients' age and comorbidities, tumor stage, and hospital stay (duration, first cytoreduction surgery) were associated with OS., Conclusions: Ovarian cancer surgery volume ≥ 20 cases/year was significantly associated with improved OS and RFS but only with a limited clinical benefit. The biggest differences in OS and RFS were observed between hospitals with procedure volume < 10 cases/year and all the other hospitals., (© 2024. Society of Surgical Oncology.)

Sex-based differences in obesity-related hepatic malignancies suggest the protective roles of estrogen. Using a preclinical model, we dissected estrogen receptor (ER) isoform-driven molecular responses in high-fat diet (HFD)-induced liver diseases of male and female mice treated with or without an estrogen agonist by integrating liver multi-omics data. We found that selective ER activation recovers HFD-induced molecular and physiological liver phenotypes. HFD and systemic ER activation altered core liver pathways, beyond lipid metabolism, that are consistent between mice and primates. By including patient cohort data, we uncovered that ER-regulated enhancers govern central regulatory and metabolic genes with clinical significance in metabolic dysfunction-associated steatotic liver disease (MASLD) patients, including the transcription factor TEAD1. TEAD1 expression increased in MASLD patients, and its downregulation by short interfering RNA reduced intracellular lipid content. Subsequent TEAD small molecule inhibition improved steatosis in primary human hepatocyte spheroids by suppressing lipogenic pathways. Thus, TEAD1 emerged as a new therapeutic candidate whose inhibition ameliorates hepatic steatosis., (© 2024. The Author(s).)

Background : Acute heart failure (AHF) represents a leading cause of unscheduled hospital stays, frequent rehospitalisations, and mortality worldwide. The aim of our study was to develop a bedside prognostic tool, a multivariable predictive risk score, that is useful in daily practice, thus providing an early prognostic evaluation at admission and an accurate risk stratification after discharge in patients with AHF. Methods : This study is a subanalysis of the STADE HF study, which is a single-centre, prospective, randomised controlled trial enrolling 123 patients admitted to hospital for AHF. Here, 117 patients were included in the analysis, due to data exhaustivity. Regression analysis was performed to determine predictive variables for one-year mortality and/or rehospitalisation after discharge. Results : During the first year after discharge, 23 patients died. After modellisation, the variables considered to be of prognostic relevance in terms of mortality were (1) non-ischaemic aetiology of HF, (2) elevated creatinine levels at admission, (3) moderate/severe mitral regurgitation, and (4) prior HF hospitalisation. We designed a linear model based on these four independent predictive variables, and it showed a good ability to score and predict patient mortality with an AUC of 0.84 (95%CI: 0.76-0.92), thus denoting a high discriminative ability. A risk score equation was developed. During the first year after discharge, we observed as well that 41 patients died or were rehospitalised; hence, while searching for a model that could predict worsening health conditions (i.e., death and/or rehospitalisation), only two predictive variables were identified: non-ischaemic HF aetiology and previous HF hospitalisation (also included in the one-year mortality model). This second modellisation showed a more discrete discriminative ability with an AUC of 0.67 (95% C.I. 0.59-0.77). Conclusions : The proposed risk score and model, based on readily available predictive variables, are promising and useful tools to assess, respectively, the one-year mortality risk and the one-year mortality and/or rehospitalisations in patients hospitalised for AHF and to assist clinicians in the management of patients with HF aiming at improving their prognosis.

Background: Exergaming has been proposed to improve gait and balance disorders in Parkinson's disease (PD) patients. We aimed to assess the efficacy of a home-based, tailored, exergaming training system designed for PD patients with dopa-resistant gait and/or balance disorders in a controlled randomized trial., Methods: We recruited PD patients with dopa-resistant gait and/or balance disorders. Patients were randomly assigned (1:1 ratio) to receive 18 training sessions at home by playing a tailored exergame with full-body movements using a motion capture system (Active group), or by playing the same game with the computer's keyboard (Control group). The primary endpoint was the between-group difference in the Stand-Walk-Sit Test (SWST) duration change after training. Secondary outcomes included parkinsonian clinical scales, gait recordings, and safety., Results: Fifty PD patients were enrolled and randomized. After training, no significant difference in SWST change was found between groups (mean change SWST duration [SD] -3.71 [18.06] s after Active versus -0.71 [3.41] s after Control training, p = 0.61). Some 32% of patients in the Active and 8% in the Control group were considered responders to the training program (e.g., SWST duration change ≥2 s, p = 0.03). The clinical severity of gait and balance disorders also significantly decreased after Active training, with a between-group difference in favor of the Active training (p = 0.0082). Home-based training induced no serious adverse events., Conclusions: Home-based training using a tailored exergame can be performed safely by PD patients and could improve gait and balance disorders. Future research is needed to investigate the potential of exergaming., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)