Événements médicaux et comportementaux survenus chez des patients déclarant un traitement par prégabaline à la consultation d’entrée en milieu carcéral, suite à la décision d’équipe d’arrêter systématiquement un tel traitement : étude observationnelle descriptive par étude de dossiers dans les prisons d'Aiton et Chambéry

Pregabalin misuse is a growing public health issue in France, particularly in prisons. To date, there are no recommendations for withdrawal. This observational study was carried out following a decision by the medical team to systematically stop this treatment during the admission consultation in the Aiton and Chambéry prisons. Indeed, patients request such prescriptions, often outside the scope of the Marketing Authorisation (MA) and contest the medical decision to discontinue treatment. Between May 2021 and April 2023, patients declaring that they were taking Pregabalin at the time of their admission were included in the study. Data were collected on physical and behavioral events following withdrawal from Pregabalin, with a focus on serious events such as comitial seizure, death, hospitalization or emergency room consultation. Forty-six male patients were included, with an average age of 31.2 years. We found that 100% of patients had a substance use disorder. Observed practices were heterogeneous: treatment was weaned over a period of less than one month for 34 (74%) patients with different weaning protocols, including 29 (63%) patients for whom weaning was immediate. No serious events were observed. For 41 (89%) patients, the prescription was made outside the AMM. This observational study highlights that, in 46 patients reporting treatment with Pregabalin on admission to prison, systematic discontinuation of this treatment did not result in any serious medical or behavioral event. A larger-scale study is needed to consider generalizing this practice.Le mésusage de prégabaline est un enjeu de santé publique croissant, notamment en France, et particulièrement en milieu carcéral. Il n'existe pas, à ce jour, de recommandation pour le sevrage. Cette étude observationnelle a été réalisée à la suite d’une décision de l’équipe médicale d'arrêter ce traitement à la consultation d'entrée, de manière systématique dans les prisons d'Aiton et de Chambéry. En effet les patients sollicitent une telle prescription, souvent hors Autorisation de Mise sur le Marché (AMM) et contestent la décision médicale d’interruption du traitement. Les patients déclarant un traitement par prégabaline à leur consultation d’entrée ont été inclus entre mai 2021 et avril 2023, un recueil de données a été réalisé et relevait, dans le mois suivant la consultation d’entrée du patient, les événements physiques et comportementaux suite au sevrage de la prégabaline avec mise en avant des événements graves comme la survenue d’une crise comitiale, décès, hospitalisation ou consultation aux urgences. Quarante-six patients ont été inclus, de sexe masculin, avec une moyenne d’âge de 31,2 ans. Nous avons constaté que 100% des patients avaient un trouble lié à l’usage de substances. Les pratiques observées étaient hétérogènes : le traitement a été sevré sur une durée inférieure à un mois pour 34 (74%) patients avec des prises en charge différentes, dont 29 (63%) patients pour lesquels le sevrage était immédiat. Aucun événement grave n’a été observé. Pour 41 (89%) patients, la prescription était réalisée hors AMM. Cette étude observationnelle souligne que, chez 46 patients déclarant un traitement par prégabaline à l’admission en prison, l’arrêt systématique de ce traitement n’a pas entraîné d’événement médical ou comportemental grave. Une étude à plus large échelle est nécessaire afin d’envisager de généraliser cette pratique

Genomic and expression analysis of the vanG-like gene cluster of Clostridium difficile

Primary antibiotic treatment of Clostridium difficile intestinal diseases requires metronidazole or vancomycin therapy. A cluster of genes homologous to enterococcal glycopeptides resistance vanG genes was found in the genome of C. difficile 630, although this strain remains sensitive to vancomycin. This vanG-like gene cluster was found to consist of five ORFs: the regulatory region consisting of vanR and vanS and the effector region consisting of vanG, vanXY and vanT. We found that 57 out of 83 C. difficile strains, representative of the main lineages of the species, harbour this vanG-like cluster. The cluster is expressed as an operon and, when present, is found at the same genomic location in all strains. The vanG, vanXY and vanT homologues in C. difficile 630 are co-transcribed and expressed to a low level throughout the growth phases in the absence of vancomycin. Conversely, the expression of these genes is strongly induced in the presence of subinhibitory concentrations of vancomycin, indicating that the vanG-like operon is functional at the transcriptional level in C. difficile. Hydrophilic interaction liquid chromatography (HILIC-HPLC) and MS analysis of cytoplasmic peptidoglycan precursors of C. difficile 630 grown without vancomycin revealed the exclusive presence of a UDP-MurNAc-pentapeptide with an alanine at the C terminus. UDP-MurNAc-pentapeptide [D-Ala] was also the only peptidoglycan precursor detected in C. difficile grown in the presence of vancomycin, corroborating the lack of vancomycin resistance. Peptidoglycan structures of a vanG-like mutant strain and of a strain lacking the vanG-like cluster did not differ from the C. difficile 630 strain, indicating that the van G-like cluster also has no impact on cell-wall composition

Continuous positive airway pressure for respiratory support during COVID-19 pandemic: a frugal approach from bench to bedside

International audienceBackground We describe a frugal approach (focusing on needs, performance, and costs) to manage a massive influx of COVID-19 patients with acute hypoxemic respiratory failure (AHRF) using the Boussignac valve protected by a filter ("Filter Frugal CPAP", FF-CPAP) in and out the ICU.Methods (1) A bench study measured the impact of two filters with different mechanical properties on CPAP performances, and pressures were also measured in patients. (2) Non-ICU healthcare staff working in COVID-19 intermediate care units were trained with a video tutorial posted on a massive open online course. (3) A clinical study assessed the feasibility and safety of using FF-CPAP to maintain oxygenation and manage patients out of the ICU during a massive outbreak.Results: Bench assessments showed that adding a filter did not affect the effective pressure delivered to the patient. The resistive load induced by the filter variably increased the simulated patient's work of breathing (6-34%) needed to sustain the tidal volume, depending on the filter's resistance, respiratory mechanics and basal inspiratory effort. In patients, FF-CPAP achieved pressures similar to those obtained on the bench. The massive training tool provided precious information on the use of Boussignac FF-CPAP on COVID-19 patients. Then 85 COVID-19 patients with ICU admission criteria over a 1-month period were studied upon FF-CPAP initiation for AHRF. FF-CPAP significantly decreased respiratory rate and increased SpO(2). Thirty-six (43%) patients presented with respiratory indications for intubation prior to FF-CPAP initiation, and 13 (36%) of them improved without intubation. Overall, 31 patients (36%) improved with FF-CPAP alone and 17 patients (20%) did not require ICU admission. Patients with a respiratory rate > 32 breaths/min upon FF-CPAP initiation had a higher cumulative probability of intubation (p < 0.001 by log-rank test).Conclusion: Adding a filter to the Boussignac valve does not affect the delivered pressure but may variably increase the resistive load depending on the filter used. Clinical assessment suggests that FF-CPAP is a frugal solution to provide a ventilatory support and improve oxygenation to numerous patients suffering from AHRF in the context of a massive outbreak