Francis Guillemin’s research while affiliated with University of Lorraine and other places

With existing chronic diseases such as rheumatic and musculoskeletal diseases (RMDs), in the last three decades, there has been a significant increase in the burden of musculoskeletal diseases with an increase in disability-adjusted life years. RMDs, including inflammatory arthritis and osteoarthritis, encompass a significant burden in the world and result in an increase in disability-adjusted life years. Effective pharmacological treatments are available for IA, but not for OA in which non-pharmacological interventions are recommended. In addition to current disease management, a healthy lifestyle, including exercise and diet, should be promoted in those with RMDs. This chapter gives an overview of the association between exercise and diet on disease progression in people with IA and OA based on the international EULAR 2021 recommendations on lifestyle factors. The chapter discusses research and knowledge gaps and how to promote lifestyle factors in clinical practice.

Background There is a need to improve knowledge of the health-related quality of life (HRQoL) in the post-heart transplantation (HTx) period and the factors affecting it. This qualitative study aimed to identify the most important domains of HRQoL for heart transplant recipients and the factors that impact it. Methods This was a qualitative study across 5 geographically diverse large HTx centers in France from July 2022 to January 2023. We gathered a purposive sample of individuals who had undergone HTx. A face-to-face semi-structured interview guide was used for individual interviews. All interviews were audio-recorded and transcribed verbatim. Results A total of 14 individuals (10 men) were interviewed. The data analysis led to the development of 8 main themes (with sub-themes) that were relevant to participants: HRQoL perception (mental health, physical capacity, symptoms and comorbidities), participants? experience during the HTx process, immunosuppressive treatments, relationship with the healthcare team, external and internal resources, socio-economic aspects and feelings about the donor. Recipients, spontaneously made connections between these themes. Conclusions Heart transplant recipients had diverse perceptions of their HRQoL in the post-HTx period. The rich variety of themes identified from the review highlights that recipients have a complex HRQoL profile which is not currently captured by standard HRQoL tools that are commonly employed. These aspects should be taken into account in the clinical follow-up and in the selection of the most appropriate Patient Reported Outcome Measures (PROMs).

Sports coaches play a key role on sports participants’ health, due to the informal educational dimension inherent to sport, but feel limited in terms of health promotion (HP) implementation in their practices. The aim of this systematic mapping review is to identify coaches’ HP skills, which are already used in daily practice, and which they need to acquire, as well as leverages and barriers to their use. Based on PRISMA-P guidelines, six databases were searched using keywords close to sport coaching and skill and health. Inclusion criteria were 1) targeting organized grassroots sport coaches, 2) peer review English original articles, 3) discussing coaches’ skills. Among the 2485 studies found, 56 were included based on a double-blind selection. Analysis included: thematic coding of skills, followed by a categorization based on health determinants (social, environmental, economic and organizational) mobilized and an analysis of the types of health (social, physical and psychological) affected. Results identified ten coach's HP skills: sport participant management, health support, education, evaluation, motivation, cooperation, prevention, communication, role modeling and self-management. These skills are mostly targeting sport participant psychological health. Barriers included coaches’ own definition of the boundaries of their role, pressure from sport participants’ relatives. Leverages to skills use were self-confidence, attending training, getting experience, increasing knowledge or adhering to guidelines. Coaches’ HP skills are close both internal (e.g., self-management, role modeling) and external (in relations to sport participants or partners) and target mostly psychological health.

Background We investigate whether the National Institutes of Health Stroke Scale (NIHSS) at 24 hours could serve as a primary outcome in acute ischemic stroke trials, and whether combining 90‐day modified Rankin Scale (mRS) and 24‐hour NIHSS in a hierarchical outcome could enhance detection of treatment effect, using endovascular treatment (EVT) as an exemplary study intervention. Methods This was a post hoc analysis of pooled data from 7 randomized EVT trials. Twenty‐four‐hour NIHSS as a surrogate outcome for 90‐day mRS was assessed in a causal mediation model. A 7‐point ordinal NIHSS score was generated by grouping 24‐hour NIHSS, including death as a separate category (“ordinal” NIHSS). EVT effect sizes and sample sizes required for detecting EVT benefit with 80% power were compared when using granular 24‐hour NIHSS, ordinal 24‐hour NIHSS, 90‐day mRS, and a hierarchical outcome (win ratio) that combines 90‐day mRS and 24‐hour NIHSS. Results A total of 1720 patients were included. Twenty‐four‐hour NIHSS mediated the association between EVT and 90‐day mRS and met criteria for a useful surrogate outcome. Effect sizes were highest and sample sizes required to detect EVT benefit smallest for the win ratio approach (228), followed by 90‐day mRS (240) and ordinal 24‐hour NIHSS (242). In patients with baseline NIHSS <10 and ≥25, ordinal 24‐hour NIHSS resulted in the highest effect size. Conclusions Twenty‐four‐hour NIHSS is a useful surrogate outcome for 90‐day mRS in patients with acute ischemic stroke undergoing EVT, with a similar EVT effect size compared with 90‐day mRS. It could potentially enhance detection of EVT benefit in patients with very low or high baseline NIHSS. An ordered hierarchical outcome could improve detection of EVT treatment effect.

Background: Prior studies have demonstrated that the incidence of stroke and rate of infarct progression varies across the 24-hour cycle and that circadian rhythm is associated with the brain’s response to reperfusion and neuroprotection. However, the pathophysiology of this variation is poorly understood. In this study we assessed changes in collateral status with time of day as a possible mechanism behind this variation. Methods: Using data from the 7 randomized EVT trials in the HERMES collaboration, patients with analyzable baseline CT angiograms were selected. Presenting collateral status on CTAs was rated using the Regional Collateral Score (rCS). The effect of time of onset (last known well) and time of scan on collateral status was assessed. Time of day was analyzed as: 1) binary day-night (23:00–06:59/07:00–22:59); 2) 4-hour intervals (23:00–02:59/03:00–06:59/07:00–10:59/11:00–14:59/15:00–18:59/19:00–22:59) and 3) a continuous variable as per Consortium International pour la Recherche Circadienne sur l’AVC recommendations. Results: Among 1250 patients with LVOs, 1086 (86.9%) had daytime and 164 (13.1%) had night-time stroke onset. Baseline demographic and clinical features of patients that differed (Table 1) were night-time onset patients were younger (62.0 vs 67.1 years), less often had highly severe (NIHSS>16) deficits (43.6% vs 56.3%), had longer onset-to-arrival (186 vs 122 minutes), and longer onset-to-imaging (218 vs 159 minutes). In multivariable analysis, categorizing based on last known well time, there were no significant difference in rCS score by night vs day (7.5±2.0 vs 7.4±2.3 p=0.99) or by 4-hour intervals (7.8±1.9 vs 7.3±2.1 vs 7.4±2.2 vs 7.5±2.2 vs 7.5±2.3 vs 7.1±2.4 p=0.24) (Figure 1). Similarly, categorizing by scan time, there were no significant differences in rCS score by night vs day (7.3±2.3 vs 7.4±2.2 p=0.60) or by 4-hour intervals (7.2±2.4 vs 7.6±2.0 vs 7.3±2.2 vs 7.4±2.1 vs 7.5±2.3 vs 7.6±2.3 p=0.22) (Figure 1). The relationship between continuous time and rCS mapped by LOESS regression also did not indicate substantial rCS variation with time of onset (Figure 2). Conclusion: Our study does not demonstrate a strong relationship between time of day and regional collateral score. This was at least partially driven by a ceiling effect as most patients had good collateral scores. Further studies to identify patient and imaging characteristics that may explain the relationship between circadian variation of stroke outcomes are needed.

Background: We investigate whether the NIHSS at 24 hours could serve as an alternative primary outcome measure in acute ischemic stroke trials, and whether combining 90-day modified Rankin Score (mRS) and 24-hour NIHSS in a hierarchical outcome could enhance detection of treatment effect, using EVT as an exemplary study intervention. Methods: Post-hoc analysis from the HERMES collaboration that pooled data from 7 randomized controlled EVT trials. Validity of 24-hour NIHSS as a surrogate outcome for 90-day mRS was assessed in a causal mediation model (Figure 1). A 7-point ordinal NIHSS score was generated by grouping 24-hour NIHSS, including death as a separate category (“ordinal” NIHSS). EVT effect sizes and sample sizes required for detecting EVT benefit with 80% power were compared when using granular 24-hour NIHSS, ordinal 24-hour NIHSS, 90-day mRS, and hierarchical outcome (win-ratio) that combines 90-day mRS and 24-hour NIHSS. Subgroup analyses were performed in patients with baseline NIHSS<10 and ≥25. Results: A total of 1720 patients were included. Median 90-day mRS in the EVT/control arms was 3.0(IQR:1.0-4.0)/4.0(IQR:2.0-5.0) and median 24-hour NIHSS was 9.0(IQR:3.0-17.0)/14.0(IQR:7.5-19.0), see Figure 2. 24-hour NIHSS mediated the association between EVT and 90-day mRS and met the criteria for a surrogate outcome. Effect sizes were highest and sample sizes required to detect EVT benefit smallest for the win ratio approach (228), followed by 90-day mRS(240) and ordinal 24-hour NIHSS(242), see Table 1. In subgroup analyses of patients with baseline NIHSS<10 and≥25, ordinal 24-hour NIHSS resulted in the highest effect size/ smallest sample size. Conclusion: 24-hour NIHSS may be a valid surrogate outcome for 90-day mRS in acute ischemic stroke patients undergoing EVT, with a similar EVT effect size compared to 90-day mRS. It could potentially enhance detection of EVT benefit in patient subgroups with very low or very high baseline NIHSS. Combining 90-day mRS and 24-hour NIHSS in an ordered hierarchical could improve detection of EVT treatment effect compared to 90-day mRS.

Integrating genomic medicine into healthcare systems is a health policy challenge that requires continuously transferring scientific advances into clinics and ensuring equal access for patients. France was one of the first countries to integrate genome sequencing into clinical practice at a nationwide level, with the ambition to provide more accurate diagnostics and personalized treatments. Since 2016, the French government has invested €239M in the 2025 French Genomic Medicine Initiative (PFMG2025) which has so far focused on patients with rare diseases (RD), cancer genetic predisposition (CGP) and cancers. PFMG2025 has addressed numerous challenges to set up an operational organizational framework. As of December the 31st 2023, 12,737 results were returned to prescribers for RD/CGP patients (median delivery time: 202 days, diagnostic yield: 30.6%) and 3109 for cancer patients (median delivery time: 45 days). PFMG2025’s future priorities encompass ensuring economic sustainability, strengthening links with research, empowering patients and practitioners, and fostering collaborations with European partners. Funding As of December the 31st 2023, €239M have been invested by the French government.