Les correspondances des Antilles au XVIIIe siècle, entre affaires familiales et affaires économiques

During the 18th century, the departure for the American colonies caused a break with the original environment, forced and definitive for Africans and more or less voluntary and lasting for Europeans. For the latter, the installation did not necessarily imply a complete break with loved ones who remained in mainland France. Emotional ties and mutual interests encouraged them to maintain exchanges despite the distance. Personal and family success was closely linked to the mobilization and maintenance of family, friendly and professional networks. Epistolary relations thus constituted a valuable tool for French settlers and traders. The numerous private letters still preserved allow historians to reconstruct the networks of relationships formed on both sides of the Atlantic and open a window on the importance of overseas links in the realization of colonial projects. The studies proposed here thus reveal in all their richness the existence of “Atlantic families” and the views on colonial slave societies.Au cours du XVIIIe siècle, le départ pour les colonies d'Amérique provoquait une coupure franche avec l’environnement d’origine, forcée et définitive pour les Africains et plus ou moins volontaire et durable pour les Européens. Pour ces derniers, l’installation n’impliquait pas nécessairement une rupture complète avec les proches restés en métropole. Les liens affectifs et les intérêts mutuels incitaient à maintenir des échanges malgré la distance. La réussite personnelle et plus largement familiale passait étroitement par la mobilisation et l’entretien des réseaux familiaux, amicaux et professionnels. Les relations épistolaires ont ainsi constitué un outil précieux pour les colons et négociants français. Les nombreuses lettres privées qui sont parvenues jusqu’à nous permettent aux historiens de reconstituer les réseaux de relations formés de part et d’autre de l’Atlantique et ouvrent une fenêtre sur l’importance des liens ultra-marins dans la réalisation des projets coloniaux. Les études de ce dossier révèlent ainsi dans toute leur richesse l’existence de « familles atlantiques » et les regards portés sur les sociétés coloniales

Epistolary correspondence between the Antilles and France in the 18th century: between family affairs and economic affairs

Au cours du XVIIIe siècle, le départ pour les colonies d'Amérique provoquait une coupure franche avec l’environnement d’origine, forcée et définitive pour les Africains et plus ou moins volontaire et durable pour les Européens. Pour ces derniers, l’installation n’impliquait pas nécessairement une rupture complète avec les proches restés en métropole. Les liens affectifs et les intérêts mutuels incitaient à maintenir des échanges malgré la distance. La réussite personnelle et plus largement familiale passait étroitement par la mobilisation et l’entretien des réseaux familiaux, amicaux et professionnels. Les relations épistolaires ont ainsi constitué un outil précieux pour les colons et négociants français. Les nombreuses lettres privées qui sont parvenues jusqu’à nous permettent aux historiens de reconstituer les réseaux de relations formés de part et d’autre de l’Atlantique et ouvrent une fenêtre sur l’importance des liens ultra-marins dans la réalisation des projets coloniaux. Les études de ce dossier révèlent ainsi dans toute leur richesse l’existence de « familles atlantiques » et les regards portés sur les sociétés coloniales.During the 18th century, the departure for the American colonies caused a break with the original environment, forced and definitive for Africans and more or less voluntary and lasting for Europeans. For the latter, the installation did not necessarily imply a complete break with loved ones who remained in mainland France. Emotional ties and mutual interests encouraged them to maintain exchanges despite the distance. Personal and family success was closely linked to the mobilization and maintenance of family, friendly and professional networks. Epistolary relations thus constituted a valuable tool for French settlers and traders. The numerous private letters still preserved allow historians to reconstruct the networks of relationships formed on both sides of the Atlantic and open a window on the importance of overseas links in the realization of colonial projects. The studies proposed here thus reveal in all their richness the existence of “Atlantic families” and the views on colonial slave societies

SORL1 rare variants: a major risk factor for familial early-onset Alzheimer’s disease

International audienceThe SORL1 protein plays a protective role against the secretion of the amyloid β peptide, a key event in the pathogeny of Alzheimer's disease. We assessed the impact of SORL1 rare variants in early-onset Alzheimer's disease (EOAD) in a case-control setting. We conducted a whole exome analysis among 484 French EOAD patients and 498 ethnically matched controls. After collapsing rare variants (minor allele frequency ≤1%), we detected an enrichment of disruptive and predicted damaging missense SORL1 variants in cases (odds radio (OR)=5.03, 95% confidence interval (CI)=(2.02-14.99), P=7.49.10(-5)). This enrichment was even stronger when restricting the analysis to the 205 cases with a positive family history (OR=8.86, 95% CI=(3.35-27.31), P=3.82.10(-7)). We conclude that predicted damaging rare SORL1 variants are a strong risk factor for EOAD and that the association signal is mainly driven by cases with positive family history

Implementation of a centralized pharmacovigilance system in academic pan‐European clinical trials : experience from EU‐Response and conect4children consortia

Setting-up a high quality, compliant and efficient pharmacovigilance (PV) system in multi-country clinical trials can be more challenging for academic sponsors than for companies. To ensure the safety of all participants in academic studies and that the PV system fulfils all regulations, we set up a centralized PV system that allows sponsors to delegate work on PV. This initiative was put in practice by our Inserm-ANRS MIE PV department in two distinct multinational European consortia with 19 participating countries: conect4children (c4c) for paediatrics research and EU-Response for Covid-19 platform trials. The centralized PV system consists of some key procedures to harmonize the complex safety processes, creation of a local safety officer (LSO) network and centralization of all safety activities. The key procedures described the safety management plan for each trial and how tasks were shared and delegated between all stakeholders. Processing of serious adverse events (SAEs) in a unique database guaranteed the full control of the safety data and continuous evaluation of the risk-benefit ratio. The LSO network participated in efficient regulatory compliance across multiple countries. In total, there were 1312 SAEs in EU-Response and 83 SAEs in c4c in the four trials. We present here the lessons learnt from our experience in four clinical trials. We managed heterogeneous European local requirements and implemented efficient communication with all trial teams. Our approach builds capacity for PV that can be used by multiple academic sponsors

Severity of COVID-19 and survival in patients with rheumatic and inflammatory diseases: data from the French RMD COVID-19 cohort of 694 patients

International audienceObjectives: There is little known about the impact of SARS-CoV-2 on patients with inflammatory rheumatic and musculoskeletal diseases (iRMD). We examined epidemiological characteristics associated with severe disease, then with death. We also compared mortality between patients hospitalised for COVID-19 with and without iRMD.Methods: Individuals with suspected iRMD-COVID-19 were included in this French cohort. Logistic regression models adjusted for age and sex were used to estimate adjusted ORs and 95% CIs of severe COVID-19. The most significant clinically relevant factors were analysed by multivariable penalised logistic regression models, using a forward selection method. The death rate of hospitalised patients with iRMD-COVID-19 (moderate-severe) was compared with a subset of patients with non-iRMD-COVID-19 from a French hospital matched for age, sex, and comorbidities.Results: Of 694 adults, 438 (63%) developed mild (not hospitalised), 169 (24%) moderate (hospitalised out of the intensive care unit (ICU) and 87 (13%) severe (patients in ICU/deceased) disease. In multivariable imputed analyses, the variables associated with severe infection were age (OR=1.08, 95% CI: 1.05-1.10), female gender (OR=0.45, 95% CI: 0.25-0.80), body mass index (OR=1.07, 95% CI: 1.02-1.12), hypertension (OR=1.86, 95% CI: 1.01-3.42), and use of corticosteroids (OR=1.97, 95% CI: 1.09-3.54), mycophenolate mofetil (OR=6.6, 95% CI: 1.47-29.62) and rituximab (OR=4.21, 95% CI: 1.61-10.98). Fifty-eight patients died (8% (total) and 23% (hospitalised)). Compared with 175 matched hospitalised patients with non-iRMD-COVID-19, the OR of mortality associated with hospitalised patients with iRMD-COVID-19 was 1.45 (95% CI: 0.87-2.42) (n=175 each group).Conclusions: In the French RMD COVID-19 cohort, as already identified in the general population, older age, male gender, obesity, and hypertension were found to be associated with severe COVID-19. Patients with iRMD on corticosteroids, but not methotrexate, or tumour necrosis factor alpha and interleukin-6 inhibitors, should be considered as more likely to develop severe COVID-19. Unlike common comorbidities such as obesity, and cardiovascular or lung diseases, the risk of death is not significantly increased in patients with iRMD

Severity of COVID-19 and survival in patients with rheumatic and inflammatory diseases: data from the French RMD COVID-19 cohort of 694 patients

International audienceObjectives: There is little known about the impact of SARS-CoV-2 on patients with inflammatory rheumatic and musculoskeletal diseases (iRMD). We examined epidemiological characteristics associated with severe disease, then with death. We also compared mortality between patients hospitalised for COVID-19 with and without iRMD.Methods: Individuals with suspected iRMD-COVID-19 were included in this French cohort. Logistic regression models adjusted for age and sex were used to estimate adjusted ORs and 95% CIs of severe COVID-19. The most significant clinically relevant factors were analysed by multivariable penalised logistic regression models, using a forward selection method. The death rate of hospitalised patients with iRMD-COVID-19 (moderate-severe) was compared with a subset of patients with non-iRMD-COVID-19 from a French hospital matched for age, sex, and comorbidities.Results: Of 694 adults, 438 (63%) developed mild (not hospitalised), 169 (24%) moderate (hospitalised out of the intensive care unit (ICU) and 87 (13%) severe (patients in ICU/deceased) disease. In multivariable imputed analyses, the variables associated with severe infection were age (OR=1.08, 95% CI: 1.05-1.10), female gender (OR=0.45, 95% CI: 0.25-0.80), body mass index (OR=1.07, 95% CI: 1.02-1.12), hypertension (OR=1.86, 95% CI: 1.01-3.42), and use of corticosteroids (OR=1.97, 95% CI: 1.09-3.54), mycophenolate mofetil (OR=6.6, 95% CI: 1.47-29.62) and rituximab (OR=4.21, 95% CI: 1.61-10.98). Fifty-eight patients died (8% (total) and 23% (hospitalised)). Compared with 175 matched hospitalised patients with non-iRMD-COVID-19, the OR of mortality associated with hospitalised patients with iRMD-COVID-19 was 1.45 (95% CI: 0.87-2.42) (n=175 each group).Conclusions: In the French RMD COVID-19 cohort, as already identified in the general population, older age, male gender, obesity, and hypertension were found to be associated with severe COVID-19. Patients with iRMD on corticosteroids, but not methotrexate, or tumour necrosis factor alpha and interleukin-6 inhibitors, should be considered as more likely to develop severe COVID-19. Unlike common comorbidities such as obesity, and cardiovascular or lung diseases, the risk of death is not significantly increased in patients with iRMD