Exploration analytique des intoxications par les pesticides

Du fait du nombre croissant d'intoxications par les pesticides, il est important de développer des méthodes performantes permettant l'identification et le dosage des molécules appartenant à l'ensemble des classes de pesticides. Dans ce but, nous avons développé une méthode de dosage originale et sensible de 61 pesticides dans les matrices biologiques. Cette méthode utilise une procédure d'extraction solide/liquide sur support polymérique (HLB and MCX) OASIS®. Le couplage chromatographie en phase gazeuse/spectrométrie de masse (GC/MS) est utilisé pour les pesticides volatils (organophosphorés, organochlorés, phtalimides, uraciles) et un couplage chromatographie en phase liquide/spectrométrie de masse (LC/MS) pour les pesticides polaires et thermolabiles (carbamates, benzimidazoles). L'acquisition est réalisée en mode fragmentométrique (SIM). Les rendements d'extraction varient selon la nature des pesticides dosés, mais restent satisfaisants pour l'ensemble des pesticides. Les limites de détection (LOD) et les limites de quantification (LOQ) sont réparties entre 2,5 et 20 ng/ml et de 5 à 50 ng/ml. La linéarité a été étudiée entre les différentes LOQ et 1000 ng/ml pour tous les pesticides étudiés. Les résultats sont reproductibles et répétables, avec une bonne précision et une bonne justesse. Des exemples d'intoxication permettent de montrer l'intérêt diagnostique de ces méthodes : deux cas d'intoxication mortelle à l'endosulfan et au carbofuran ; trois autres d'intoxication aiguë au parathion-éthyle, à la bifenthrine et à l'aldicarbe

Long-term outcome and safety of prolonged bedaquiline treatment for multidrug-resistant tuberculosis

for the French MDR-TB Management Group9International audienceBedaquiline, a recently approved drug for the treatment of multidrug-resistant tuberculosis (MDR-TB), is recommended for a duration of 24 weeks. There are scarce data on patients treated with this drug outside clinical trials.All MDR-TB patients who started treatment from January 1, 2011 to December 31, 2013 and received ≥30 days of bedaquiline were included in a multicentre observational cohort.Among 45 MDR-TB patients, 53% harboured isolates resistant to both fluoroquinolones and second-line injectables, and 38% harboured isolates resistant to one of these drug classes. Median bedaquiline treatment duration was 361 days and 33 patients (73%) received prolonged (>190 days) bedaquiline treatment. Overall, 36 patients (80%) had favourable outcome, five were lost to follow-up, three died, and one failed and acquired bedaquiline resistance. No cases of recurrence were reported. Severe and serious adverse events were recorded in 60% and 18% of patients, respectively. Values of Fridericia-corrected QT interval (QTcF) >500 ms were recorded in 11% of patients, but neither arrhythmias nor symptomatic cardiac side-effects occurred. Bedaquiline was discontinued in three patients following QTcF prolongation. No significant differences in outcomes or adverse events rates were observed between patients receiving standard and prolonged bedaquiline treatment.Bedaquiline-containing regimens achieved favourable outcomes in a large proportion of patients. Prolonged bedaquiline treatment was overall well tolerated in this cohort

A national platform for Covid-19 vaccine studies recruitment in France: Covireivac volunteer’s characteristics

During the Covid-19 pandemic, the urgent need for safe and effective vaccines has led to many vaccine trials, implying fast and extensive recruitment of volunteers. In France, until 2020, vaccine clinical research participants were usually recruited locally, through center-based pools of volunteers, and local communication plans. Covireivac is a French public online platform launched on 10/01/2020 that enables national, large-scale recruitment of volunteers for Covid-19 vaccine studies. On the Covireivac website, all adult participants registered online, gave their informed consent, and filled out two online forms with information on their identity, health status (comorbidities, treatments), and known exposure to SARS-CoV-2. Since July 2021, volunteers could mention if their children are interested in participating in a Covid-19 vaccine trial. The objective of this work is to describe Covireivac's volunteer characteristics registered from 10/01/2020 to 11/02/2022. To identify independent volunteer characteristics associated with a period of registration we performed a multivariate logistic regression. Among 54,424 registrations, 52,391 (96%) were analysed; 61% were male (n = 31,893), median age was 50 y; 13% (n = 6586) were healthcare workers. At registration, 15,879 volunteers (33%) reported at least one comorbidity, among whom 16% (n = 7349) were obese and 17% (n = 8346) had hypertension. Most volunteers registered during the first month (n = 35,876, 66%). The Covireivac platform allowed quick and large recruitment of potential volunteers for Covid-19 vaccine trials and could be used on a larger scale for vaccine trials in France. It could facilitate recruitment in vaccine trials and provide sponsors with better visibility of the recruitment capacities of clinical research centers

Hypogonadism: A neglected comorbidity in young and middle-aged HIV-positive men on effective combination antiretroviral therapy

International audienceObjective: Male hypogonadism is poorly characterized in young-to-middle-aged people with HIV (PWH). We used a reliable free testosterone assay to assess the prevalence and predictive factors for male hypogonadism in PWH on effective combined antiretroviral therapy (cART).Design:A French cross-sectional study from January 2013 to June 2016.Methods:We included HIV-1-infected men aged between 18 and 50years with HIV loads of 50 RNA copies/ml or less, on effective cART for at least 6 months. Hypogonadism was defined, according to guidelines, as a mean calculated serum free testosterone concentration less than 70pg/ml (Vermeulen equation). Sociodemographic, anthropo-metric, bone-densitometry, hormonal, immunovirological, metabolic, and therapeutic parameters were collected. The IIEF-5, HAM-D, and AMS scales, respectively, assessed erectile function, depression, and quality of life.Results:Overall, 240 patients were enrolled, 231 were analyzed. Low free testosterone concentrations (<70pg/ml) were recorded in 20 patients (8.7%), and were exclusively of secondary origin. In multivariable analysis, the risk factors predictive of male hypogonadism were age more than 43 years [adjusted odds ratio (aOR) 3.17, 95% confidence interval (95% CI) 1.02-9.86;P = 0.04], total fat percentage more than 19% (aOR3.5, 95% CI 1.18-10.37; P = 0.02), and treatment including efavirenz (aOR3.77, 95% CI 1.29-10.98;P=0.02). A nadir CD4+ T-cell count more than 200 cells/μl (aOR 0.22, 95% CI 0.07-0.65;P < 0.01) were protective.Conclusion:Male hypogonadism remains common in young-to-middle-aged PWH with stably suppressed viral replication. Treatment including efavirenz, being over 43 years old, and having a total body fat percentage greater than 19% could be used as criteria for identifying PWH at risk. Early screening for male hypogonadism might improve care by identifying patients requiring testosterone replacement. Copyrigh

A French cohort for assessing COVID-19 vaccine responses in specific populations

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Safety and immunogenicity of a measles-vectored SARS-CoV-2 vaccine candidate, V591 / TMV-083, in healthy adults: results of a randomized, placebo-controlled Phase I study

International audienceBackground V591 (TMV-083) is a live recombinant measles vector-based vaccine candidate expressing a pre-fusion stabilized SARS-CoV-2 spike protein.Methods We performed a randomized, placebo-controlled Phase I trial with an unblinded dose escalation and a dou- ble-blind treatment phase at 2 sites in France and Belgium to evaluate the safety and immunogenicity of V591. Ninety healthy SARS-CoV-2 sero-negative adults (18-55 years of age) were randomized into 3 cohorts, each compris- ing 24 vaccinees and 6 placebo recipients. Participants received two intramuscular injections of a low dose vaccine (1 £ 105 median Tissue Culture Infectious Dose [TCID50]), one or two injections of a high dose vaccine (1 £ 106 TCID50), or placebo with a 28 day interval. Safety was assessed by solicited and unsolicited adverse events. Immuno- genicity was measured by SARS-CoV-2 spike protein-binding antibodies, neutralizing antibodies, spike-specific T cell responses, and anti-measles antibodies. ClinicalTrials.gov, NCT04497298.Findings Between Aug 10 and Oct 13, 2020, 148 volunteers were screened of whom 90 were randomized. V591 showed a good safety profile at both dose levels. No serious adverse events were reported. At least one treatment- related adverse event was reported by 15 (20.8%) participants receiving V591 vs. 6 (33.3%) of participants receiving placebo. Eighty-one percent of participants receiving two injections of V591 developed spike-binding antibodies after the second injection. However, neutralizing antibodies were detectable on day 56 only in 17% of participants receiv- ing the low dose and 61% receiving the high dose (2 injections). Spike-specific T cell responses were not detected. Pre-existing anti-measles immunity had a statistically significant impact on the immune response to V591, which was in contrast to previous results with the measles vector-based chikungunya vaccine.Interpretation While V591 was generally well tolerated, the immunogenicity was not sufficient to support further development

Prevention and management of VZV infection during pregnancy and the perinatal period

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Immunogenicity and Safety of Beta-Adjuvanted Recombinant Booster Vaccine

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Cardiac Adverse Events and Remdesivir in Hospitalized Patients with Coronavirus Disease 2019 (COVID-19): A Post Hoc Safety Analysis of the Randomized DisCoVeRy Trial

International audienceBackground We aimed to evaluate the cardiac adverse events (AEs) in hospitalized patients with Coronavirus Disease 2019 (COVID-19) receiving remdesivir plus standard of care (SoC) compared to SoC alone (control), as an association was noted in some cohort studies and disproportionality analyses of safety databases. Methods This post-hoc safety analysis is based on data from the multicenter, randomized, open-label, controlled DisCoVeRy trial in hospitalized patients with COVID-19 (NCT04315948). Any first AE occurring between randomization and day 29 in the modified intention-to-treat (mITT) population randomized to either remdesivir or control group was considered. Analysis was performed using Kaplan-Meier survival curves and Kaplan-Meier estimates were calculated for event rates. Results Cardiac AEs were reported in 46 (11.2%) of 410 and 48 (11.3%) of 423 patients in the mITT population (n = 833) enrolled in the remdesivir and control groups, respectively. The difference between both groups was not significant (HR 1.0, 95% CI 0.7-1.5, p = 0.98), even when evaluating serious and non-serious cardiac AEs separately. The majority of reports in both groups were of arrhythmic nature (remdesivir, 84.8%; control, 83.3%) and were associated with a favorable outcome. There was no significant difference between remdesivir and control groups in the occurrence of different cardiac AE subclasses, including arrhythmic events (HR 1.1, 95% CI: 0.7-1.7, p = 0.68). Conclusions Remdesivir treatment was not associated with an increased risk of cardiac AEs, whether serious or not, and regardless of AE severity, compared to control, in patients hospitalized with moderate or severe COVID-19. This is consistent with the results of other randomized controlled trials and meta-analyses