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Background: Pilot studies suggest potential effects of neck muscle vibration (NMV) and prism adaptation (PA) on postural balance disturbances related to spatial cognition., Objectives: To evaluate the effect of 10 sessions of NMV and/or PA on ML deviation. We used the mediolateral centre of pressure position (ML deviation) as a biomarker for spatial cognition perturbation, hypothesising that PA and NMV would improve ML deviation, with a potential synergistic impact when used together., Methods: We conducted a multicentre, single-blind, randomised controlled study. Participants within 9 months of a right-hemisphere supratentorial stroke and with less than 40% body weight supported on the paretic side in standing were randomised into 4 groups (PA, NMV, PA+NMV, or control)., Primary Outcome: ML deviation at Day 14., Secondary Outcomes: force platform data, balance abilities, autonomy, and ML deviation, measured just after the first session (Day 1), at Day 90, and Day 180. A generalised linear mixed model (GLMM) assessed intervention effects on these outcomes, adjusting for initial ML deviation and incorporating other relevant factors., Results: 89 participants were randomised and data from 80 participants, mean (SD) age 59.2 (10.2) years, mean time since stroke 94 (61) days were analysed. At Day 14, a weak time x group interaction (P = .001, omega-squared = 0.08) was found, with no significant between-group differences in ML deviation (P = .12) or in secondary outcomes (P = .08). Between-group differences were found on Day 1 (P = .03), Day 90 (P = .001) and Day 180 (P < .0001) regardless of age and stroke-related data. On Day 1, ML deviation improved in both the PA and NMV groups (P = .03 and P = .01). In contrast, ML deviation deteriorated in the NMV+PA group on Day 90 and Day 180 (P = .01 and P = .01)., Conclusions: The study found no evidence of any beneficial effects of repeated unimodal or combined sessions of NMV and/or PA on ML deviation after stroke., Trial Registration: ClinicalTrials.gov identifier NCT01677091., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier Masson SAS.)

Healthcare product procurement accounts for around 50% of the French healthcare system's greenhouse gas emissions. This lesson learned from the publication of the Shift Project's work in November 2021 has been a catalyst within the healthcare system, accelerating the consideration and implementation of actions aimed at reducing the environmental impact of the healthcare system, before, during and after care. In addition to their carbon footprint, healthcare products have a wide range of environmental impacts, including on water, air and soil, throughout their entire life cycle. We have chosen to divide this life cycle into four main stages: from research and development to production, distribution and market access, use and finally end-of-life management. Analysis of the regulatory framework at each stage and of existing initiatives described in the literature or by those in the field have structured and fuelled our thinking. We found that existing regulations focus exclusively on the health risk, with little or no consideration of the environmental risk, which is in itself a health risk. Furthermore, the implementation of certain structuring actions during the first 3 stages of the life cycle would make it possible to simplify or even eliminate the major problem of waste management associated with the end-of-life of healthcare products. With this in mind, we have produced 9 recommendations to ensure that the environmental impact of healthcare products is better taken into account throughout their life cycle., (Copyright © 2023 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.)

Background: The optimal right ventricular pacing site for patients requiring pacemaker implantation for permanent atrioventricular block is a matter of debate. Long-term right ventricular apical pacing has been associated with left ventricular ejection fraction impairment and heart failure. Right ventricular septal pacing has been proposed as an alternative., Aim: The aim of this randomized prospective multicentre trial was to compare left ventricular remodelling and outcomes between right ventricular apical and septal pacing after mid-term follow-up., Methods: Patients requiring pacemaker implantation for high-degree atrioventricular block were enrolled and randomized in a 1:1 fashion to receive a right ventricular apical or septal lead., Results: A total of 141 patients were included, 69 in the septal group and 72 in the apical group. Both groups exhibited similar left ventricular ejection fractions after 18 months of follow-up (septal 57.1±11.9% vs. apical 57.4±13.4%), and left ventricular ejection fraction variation was similar in the two groups at the end of follow-up (septal -1.5±13.2% vs. apical 0.3±13.3%). Additionally, left ventricular volume, quality of life and 6-minute walk distance were similar in the two groups. However, patients in the septal group were more likely to be asymptomatic, with a significantly lower concentration of N-terminal prohormone of brain natriuretic peptide. Lastly, lead position did not impact 18-month survival., Conclusion: Pacing from the right ventricular apex does not have any detrimental effect on left ventricular systolic function compared with septal pacing over an 18-month period., (Copyright © 2022. Published by Elsevier Masson SAS.)

Clinical research in outpatient healthcare, particularly in general practice, which is the first line of contact with the population, is now a public health issue. However, this type of research has specific characteristics that differentiate it from clinical research conducted in a hospital setting and requires an adaptation of its conditions of practice: in terms of organisation, the development of research in outpatient healthcare relies on the appropriation of its fundamentals by the investigators, which implies their presentation, upstream, from the initial cycle, and the participation of practitioners in training modules adapted to research in primary care, such as those already organised by several GIRCI (Groupement Inter régional de la Recherche Clinique et de l'Innovation [French Interregional Clusters for Clinical Research and Innovation]). To compensate for the fragmented nature of their location, on the model of the EMRCs (équipes mobiles de recherche clinique [mobile clinical research teams]) in oncology, mobile research teams should enable general medical practices to participate in clinical trials. This presupposes, on the one hand, the allocation of earmarked funding to ensure the sustainability of a base of dedicated personnel and, on the other hand, the impetus of a national dynamic through the setting up of a multi-organisation thematic institute for "research in primary care" associated, at the operational level, with a national scale investigation network supported by a platform of excellence. The use of digital tools and innovations (telemedicine; data collection via connected tools; e-consent; electronic signature) which make it possible to digitise and relocate all or part of the research procedures for both the participant and the investigation teams. An adaptation of the legal framework in order to bring the place of research closer to the patient and not the other way round, which means moving the equipment and investigations closer to the patient. Taking into account the acceptability of the patient, thus limiting the disruption that may be caused by his or her participation in a research protocol and motivating the practitioner by valuing his or her contribution and providing all the guarantees of scientific relevance and independence of practice. In view of the contextual analysis, positive feedback and the availability of organisational and digital support points facilitating the delocalisation and digitisation of the conduct of research activity as close as possible to the patient and his or her doctor, the round table concluded that opportunities exist today which favour the development of clinical research in general practice. It is important to seize this opportunity and make the most of it without delay., (Copyright © 2022. Published by Elsevier Masson SAS.)

Background: Diet strongly influences cardiovascular risk. Dietary evaluation is a major issue in cardiovascular prevention, but few simple tools are available. Our team previously validated a short food frequency questionnaire; a new version of this questionnaire (Cardiovascular Dietary Questionnaire 2 [CDQ-2]) is easier to complete and more reliable., Aims: To validate CDQ-2 in comparison with the original version, and to test its reproducibility., Methods: CDQ-2 has 17 closed-ended questions; it provides a global dietary score that is a combination of specific scores for saturated, monounsaturated and omega-3 fatty acids, and fruit and vegetables. CDQ-2 was validated against the original version in two groups, who completed both questionnaires: 99 patients with cardiovascular risk factors and 50 healthy subjects. Reproducibility was assessed with 27 health professionals who completed the questionnaire twice, with a 1-month interval., Results: The correlation coefficients of the scores between the two questionnaires ranged from 0.65 (monounsaturated fatty acids) to 0.93 (fruit and vegetables) (all P<0.001). The percentage of subjects classified in the same quartile by both questionnaires ranged from 56% (omega-3 fatty acids) to 78% (fruit and vegetables). The percentage of subjects classified in the same or adjacent quartile ranged from 91% to 99%. The intraclass correlation coefficients, which assessed reproducibility, ranged from 0.61 (fruit and vegetables) to 0.88 (saturated fatty acids) (P<0.001)., Conclusions: This new version of the short dietary questionnaire shows good reproducibility and correlations with the original version; use and reliability are improved, which makes CDQ-2 a valuable tool for cardiovascular prevention., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Good clinical practice (GCP) is an international ethical and scientific quality standard for the design, conduct, performance, monitoring, auditing, recording, analyses and reporting of clinical trials. Before the start of a clinical trial, investigators commit to perform the research in accordance with GCPs, regulatory dispositions and protocol. The sponsors are responsible for investigators' selection and for controlling their skills. Whereas industrial sponsors systematically require a certificate of GCP training, academic sponsors seem to be less demanding. We have carried out two surveys between April and June 2018. A first questionnaire was sent to the 40 French academic directions of clinical research and innovation in order to determine their requirements about the GCP training of the investigators participating in their trials. The second questionnaire was transmitted to physicians of the "Bretagne recherche clinique hospitalière network": Rennes, Saint-Malo, Saint-Brieuc, Vannes, Lorient and Pontivy hospitals, in order to determine the GCP certification rate, and their needs in terms of clinical research training. Twenty-eight (70%) directions of clinical research answered the first survey, among which 18 (64%) required systematically the investigators' GCP certification in case of category 1 interventional studies. This rate decreased for category 2 (50%) and non-interventional category 3 (18%) studies. A total of 345 physicians answered the second survey, among which 263 (76%) had already been clinical trial investigators. However, only 29% of all physicians and 54% of those who had been principal investigator were certified for GCP training. These results support the need for large campaigns of GCP training in public hospitals., (Copyright © 2020 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.)

Single-arm studies are sometimes used as pivotal studies but they have methodological limitations which prevent them from obtaining the high level of reliability as for a randomised controlled study which remains the gold standard in the evaluation of new treatments. The objective of this roundtable was to discuss the limitations of these single-arm studies, to analyse available and acceptable solutions in order to propose guidelines for their conduct and assessment. Single-arm studies themselves are intrinsically inappropriate for demonstrating the benefit of a new treatment because it is impossible to infer the benefit from a value obtained under treatment without knowing what it would have been in the absence of the new treatment. The implication is that comparison with other data is necessary. However this comparison has limitations due to (1) the post hoc choice of the reference used for comparison, (2) the confusion bias for which an adjustment approach is imperative and, (3) the other biases, measure and attrition among others. When these limitations are taken into account this should, first and foremost, lead to the conduct of externally controlled trials instead of single-arm trials as is proposed by the latest version of ICH E10. Moreover, the external control must be formalised in the study protocol with a priori selection of both the reference control and the formal method of comparison: test in relation to a standard, adjustment on individual data, a synthetic control group or matching-adjusted indirect comparisons (MAIC). Lastly, externally controlled studies must be restricted to situations where randomisation is infeasible. To be acceptable, these studies must be able to guarantee freedom from residual confusion bias, which is only truly acceptable if the observed effect is dramatic and the usual course of the disease is highly predicable., (Copyright © 2019. Published by Elsevier Masson SAS.)

Fifteen years after the completion of first human genome sequencing, the technique is almost a commodity but there is still little evidence of its usefulness as a diagnostic, prognostic or therapeutic tool. In France, the France genomics plan 2025 was launched in 2015 with the goal of integrating genomic tests into clinical practice and developing a National genomics network including industrial partnerships. Reflection on scientific applications and operational or societal issues is needed to make recommendations to help better associate Genomics and the medicine of tomorrow. In the perspective of personalized Evidence-based Medicine, studies with an appropriate methodological level to improve the definition of evidence should be promoted. The many operational challenges require the implementation of organisations and means to streamline the process of results reporting, and regulatory adaptations concerning the status of professions involved, the management of data generated, and the consent of patients. In parallel, genetic training for healthcare professionals and raising awareness on genetic tests for the public should be considered. The ethical stake should also be taken into account, especially on the participation of the patient in decisions concerning them and integrating the notion of uncertainty into the information given. The sociological effects on the experience and expectations of patients and the general population towards genomic medicine should also be evaluated to improve information, prevention and support for people. Finally, medico-economic studies must be conducted to inform policy-makers on the cost-effectiveness of complete genome sequencing for population health., (Copyright © 2018 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.)

Beyond the application of legal requirements, clinical trials must have a permanent approach of quality control. The clinical investigation centers (CICs) are academic structures of clinical research certified by the French National institute of health and medical research (Inserm) and whose functioning relies on recommendations of good practice. It is important to accompany this standardization of practices by the implementation of a quality management system. This article presents the process that enabled the CIC of Rennes to become certified ISO 9001 by French standards association (Afnor) certification in May, 2016. The application of the fundamental principles of the standard ISO 9001 in the domain of clinical research is approached. The problem of the perimeter for the certification and the related process mapping are exposed. The activities of methodology, management and analysis of clinical studies were chosen for the initial certification of the CIC of Rennes. The perspectives for the extension of the perimeter of certification are also approached at the end of article., (Copyright © 2018 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.)

Background: Radiofrequency ablation is an effective treatment for typical atrial flutter (AFL) but long-term results may be hampered by atrial fibrillation (AF)., Aims: To determine the incidence and predictors of AF during very long-term follow-up after radiofrequency ablation of typical AFL., Methods: From November 1998 to December 2000, patients who underwent successful radiofrequency ablation for cavotricuspid isthmus-dependent AFL in our centre were followed prospectively., Results: Of the 135 patients followed (mean age: 62+/-11 years), 69 (51%) had structural heart disease. Mean left ventricular ejection fraction was 52+/-11%. Patients were analysed according to preablation AF history: group 1 included patients with AFL (N=71); group 2 included patients with AFL and AF (N=64). During a median [interquartile range] follow-up of 7.8 [7.0-8.4] years, new-onset or recurrent AF was experienced by 99 (73%) patients: 44 (62%) in group 1 and 55 (86%) in group 2. Although most episodes occurred in the first 2 years postablation, AF prevalence increased continuously over time. Preablation AF history predicted AF occurrence (hazard ratio: 2.10, 95% confidence interval: 1.40-3.14; p=0.001), as did left atrial diameter (hazard ratio: 1.05 per 1 mm increase; 95% confidence interval: 1.02-1.08; p<0.001). AF evolved to become permanent in 24% of group 1 and 47% of group 2 patients (p=0.005)., Conclusion: During long-term follow-up, most patients will experience AF after ablation of typical AFL. Preablation AF history and left atrial enlargement predict postablation AF occurrence.

Background: Nutrition has a major influence after coronary events but long-term adherence to dietary advice is poorly evaluated., Aim: To evaluate if a cardiovascular rehabilitation programme including dietary counselling has a positive impact on adherence to dietary recommendations., Methods: Two groups of coronary patients were compared in an observational non-randomized study. Group I included 32 patients at the acute phase of a coronary syndrome and group II included 104 patients between six months and three years after completing a cardiovascular rehabilitation programme. The evaluation was performed with (1) a validated 14-item food frequency questionnaire (FFQ), which gives scores for the consumption of saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), Omega-6 and Omega-3 polyunsaturated fatty acids (PUFA), fruits and vegetables, and a global cardiovascular protective dietary score; and (2) biological markers., Results: SFA score was higher in group I vs II (7.4+/-2.8 vs 4.4+/-2.1, p<0.001) whereas Omega-3 PUFA (2.2+/-2.0 vs 4.7+/-2.1, p<0.001), fruit and vegetables score (3.3+/-1.4 vs 4.3+/-1.7, p=0.001) and global dietary score (-1.1+/-4.5 to 7.0+/-4.9, p<0.001) were higher in group II. The Omega-6:Omega-3 PUFA ratio was higher in group I (14.2+/-12.7 vs 6.3+/-5.4, p<0.001). Biological markers showed higher plasma contents of Omega-3 PUFA (4.05+/-1.70% vs 2.80+/-1.07%, p<0.001), folate (19.7+/-12.2 nmol/L vs 13.0+/-5.0 nmol/L, p<0.001) and vitamin C (7.60+/-3.99 mg/L vs 4.18+/-3.46 mg/L, p<0.001), and a higher erythrocyte membrane Omega-3 PUFA content (6.60+/-2.19% vs 5.38+/-2.17%, p=0.016) in group II vs I., Conclusion: Using a short FFQ, this study showed sustained improvement in dietary habits in patients with coronary heart disease who receive nutritional education during a cardiovascular rehabilitation programme.