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Neural Correlates of taVNS: Scalp EEG and insular sEEG heartbeat evoked potentials modulation in an Epileptic patient case study
No full textHigh prevalence of antimicrobial resistance in rural Burkina Faso : assessment of risk factors for prevention and control
No full textIn Burkina Faso, from 2012 to 2018, extended-spectrum β-lactamase-Producing Escherichia coli (ESBL-EC) and Klebsiella pneumoniae (ESBL-KP) have been increasingly isolated from community-acquired invasive infections. This increase could be reflecting a high and increasing prevalence of faecal colonisation with these resistant bacteria in the community, as far as gut colonisation was identified as precursor to bloodstream infections. The overall objective of this thesis was therefore to assess the extent of these resistant bacteria in the community in rural Burkina Faso and to understand associated factors, in order to inform tailored infection prevention and control (IPC) interventions. Our data showed an estimated prevalence of faecal colonisation with ESBL-EC and ESBL-KP at 61.3% in rural Burkina Faso. This prevalence was higher during the rainy season compared to the dry season (70.2% vs 53.6%, p<0.001) and higher among study participants reporting not washing hands with soap before meals compared to those who did (62.5 vs 49.0%, p<0.001). In both bacteria, blaCTX-M-15 was the most prevalent (47.3% in E. coli and 19.9%; in K. pneumoniae) β-Lactamase genes. Plasmid-mediated quinolone resistance (PMQR) genes as qnr (48.1% in E. coli and 81.1% in K. pneumoniae), aac(6’)-ib-cr (21.2% in E. coli and 18.9% in K. pneumoniae) as well as OqxAB (5.8% in E. coli, and 78.4% in K. pneumoniae) were found along with β-Lactamase genes. In patients with severe acute febrile illness attending the Nanoro district hospital, 39.5% reported pre-hospital antibiotic use. This pre-hospital antibiotic use was significantly higher among patients referred from primary healthcare centers than among those who self-referred (54.0% vs 26.7%, p<0.001). Among all pre-hospital antibiotic use reported (424), Watch antibiotics were more frequently reported by referrals compared to self-referred patients (42.2% vs 28.1%, p=0.004). The investigations to understand the role of different healthcare providers and knowledge of antibiotics, showed that 33.5% healthcare were seeking outside healthcare facilities, including informal medicine vendors (47.7%), self-medication with left-over medicines kept at home (26.5%), medicine vendors in formal pharmacies (16.4%), traditional healers (9.4%) and only the latters (traditional healers) were not antibiotic dispensers. Reported reasons for seeking healthcare outside healthcare facilities included financial limitation, proximity to informal drug vendors, long waiting times at healthcare facilities and health professionals’ non-empathetic attitudes towards their patients. Antibiotics knowledge (only for illnesses of bacterial origin) was limited among healthcare professionals, very limited among medicines vendors in formal pharmacies, and non-existent among informal medicine vendors and the general community. While investigating antibiotic use by clinical presentation across all healthcare providers, we found that outpatient antibiotic use was more frequent after health center visits (54.8%, of which 16.5% Watch, n = 1249) than after visits to pharmacies (26.2%, 16.3% Watch, n = 328) and informal medicine vendors (26.9%, 50.0% Watch, n = 349). Across all healthcare providers, patients presenting with clinical presentations for which antibiotics were not recommended such as malaria, rhinopharyngitis, bronchitis, gastroenteritis, pain and wound were dispensed (Watch) antibiotics. Compliance with WHO’s AWaRe Antibiotic Book could have averted at least 68.4% of all Watch antibiotic use in outpatients at health centers. Community-wide, 2.9 DDD (95% CI 1.9–3.9) were used per 1000 adult inhabitants per day, health centers representing 89.7% of it. We concluded that the challenge of controlling antimicrobial resistance in such a setting should be multifaceted and combine both tailored antimicrobial stewardship (AMS) across all healthcare providers and the community to reduce antibiotic selective pressure and community-based hygiene interventions to break the cycle of transmission in order to mitigate and/or prevent spread. Antimicrobial stewardship program should be particularly intensified in health centers and should include dedicated education and awareness on AMR for healthcare workers, improved diagnostic tools to differentiate bacterial from non-bacterial infections, patient management algorithms based on the latest WHO recommendations for antibiotic prescription. At formal pharmacies, regulation on antibiotic sales should be strengthened, in combination with regular AMR awareness activities and monitoring to mitigate over-the-counter dispensing. At informal medicine vendors, AMR awareness programs should help self- restriction of Watch antibiotic sales. At community level, awareness activities should include risk behaviours leading to emergence and spread of resistant microorganisms in the community. Regarding community-based hygiene interventions, improving hand hygiene practices and enhancing sanitation can be effective steps toward mitigating the burden of antimicrobial resistance. Our studies were based on rigorous methodology. However, we are aware of some limitations that we have tried to overcome whenever possible. Regarding all questions on antibiotic use the last three months before the day of survey in the community, community members surveyed might have used medicine, not knowing whether it was an antibiotic or not. To mitigate response biases, we provided each fieldworker with any type of antibiotic available from the range of healthcare providers in the study area (Pharmacies in healthcare facilities, private pharmacies, informal medicine vendors). Once in the household, in case medicine use the last three months was reported, fieldworkers should ask the interviewed person to identify which one(s) among the batch of antibiotics they acknowledge having used. As well, selection of isolates for molecular characterization might have led to the absence of less phenotypically expressed genes. To mitigate this, we first divided all isolates into their different expressed phenotypic group (seven groups) and performed random selection among each group. In pre-hospital antibiotic use evaluation through patients attending the Nanoro district hospital, data was collected via a survey capturing use during the two weeks before consultation at the hospital, potentially underestimating actual use. Whenever possible, reported antibiotic use was verified from referral forms, patient medical files (healthcare booklet), and antibiotic packaging or blisters. During investigations on places of healthcare seeking the last three months, Participants may struggle to accurately recall where they sought healthcare, especially if multiple visits occurred. Minor illnesses visits may have been forgotten or misreported. Respondents may have also reported seeking care at formal healthcare facilities rather than informal or traditional healers, even if they used both, due to perceived judgment. Likewise, a severe illness or a visit closer to the time of the survey may be more easily recalled than earlier visits, which may lead to over reporting of recent experiences. To mitigate responses biases, we used a more or less short recall period (e.g. three months instead of six months). For each participant, field workers had to ask about symptoms or illnesses presented and for each of these illnesses, ask thereafter all the providers visited. Field workers also have to provide memory aid by recalling all healthcare providers in the surrounding. Visits were also crosschecked with medical records whenever possible. In the investigation of antibiotic use by clinical presentation across all healthcare providers, reported prevalence, means and proportions were corrected for clustering by healthcare provider, in two strata (Nanoro and Nazoanga), except for informal medicine stores, for which neither store nor health area were recorded to ensure confidentiality. Despite these limitations that we have tried to overcome as much as possible, this thesis reports robust findings that provide a full picture of population-level antimicrobial resistance in a rural setting of low-and Middle-income countries and the interconnected factors that may be underlying it, in order to set up tailored infection prevention and control interventions.(MED - Sciences médicales) -- UCL, 202
The Ultimate Upper Bound on the Injectivity Radius of the Stiefel Manifold
No full textWe exhibit conjugate points on the Stiefel manifold endowed with any member of the family of Riemannian metrics introduced by Hüper et al. [J. Geom. Mech., 13 (2021), pp. 55–72]. This family contains the well-known canonical and Euclidean metrics. An upper bound on the injectivity radius of the Stiefel manifold in the considered metric is then obtained as the minimum between the length of the geodesic along which the points are conjugate and the length of certain geodesic loops. Numerical experiments support the conjecture that the obtained upper bound is in fact equal to the injectivity radius
Bortezomib, melphalan, and prednisone with or without daratumumab in transplant-ineligible patients with newly diagnosed multiple myeloma (ALCYONE): final analysis of an open-label, randomised, multicentre, phase 3 trial.
No full textIn the phase 3 ALCYONE study, the addition of daratumumab to bortezomib, melphalan, and prednisone (D-VMP) significantly improved outcomes in transplant-ineligible patients with newly diagnosed multiple myeloma. Here, we present results from the final analysis of ALCYONE. ALCYONE was an international, multicentre, randomised, open-label, active-controlled, phase 3 trial in adults aged 18 years or older with newly diagnosed multiple myeloma who were ineligible for high-dose chemotherapy with autologous stem-cell transplantation, because of their age (≥65 years) or presence of substantial comorbidities, and had an Eastern Cooperative Oncology Group performance status of 0-2. Patients were enrolled between Feb 9, 2015, and July 14, 2016, and were randomly assigned (1:1) by randomly permuted blocks using an interactive web-based randomisation system to receive bortezomib, melphalan, and prednisone (VMP) alone or D-VMP, with randomisation stratified by International Staging System disease stage, geographical region, and age. Patients received up to nine 6-week cycles of subcutaneous bortezomib (1·3 mg/m of body surface area, twice per week on weeks 1, 2, 4, and 5 of cycle 1 and once weekly on weeks 1, 2, 4, and 5 of cycles 2-9), oral melphalan (9 mg/m, once daily on days 1-4 of each cycle), and oral prednisone (60 mg/m, once daily on days 1-4 of each cycle). Patients in the D-VMP group also received intravenous daratumumab at a dose of 16 mg/kg once weekly during cycle 1, once every 3 weeks in cycles 2-9, and once every 4 weeks thereafter until disease progression, unacceptably toxicity, or the end of study. The primary endpoint, progression-free survival, has been previously reported. The ALCYONE study has completed; presented here are final analyses for selected secondary endpoints related to overall survival, depth of response, subsequent therapy, and safety. The intention-to-treat population was the primary analysis population (including for overall survival), defined as all patients who were randomly assigned to study treatment. The safety population, consisting of patients who received any dose of study treatment, was used in safety analyses. This trial is registered with ClinicalTrials.gov, NCT02195479. In total, 706 patients were enrolled and randomly assigned to receive D-VMP (n=350) or VMP (n=356). Baseline characteristics were balanced between the two treatment groups; most participants were female (379 [54%] of 706 patients) and White (601 [85%] of 706 patients). At a median follow-up of 86·7 months (IQR 28·5-85·2), median overall survival was 83·0 months (95% CI 72·5-not estimable) with D-VMP versus 53·6 months (46·3-60·9) with VMP (hazard ratio [HR] 0·65 [95% CI 0·53-0·80]; p<0·0001). The most common grade 3 or 4 treatment-emergent adverse events were neutropenia (140 [40%] of 346 patients in the D-VMP group vs 138 [39%] of 354 patients in the VMP group), thrombocytopenia (120 [35%] vs 134 [38%]), and anaemia (63 [18%] vs 70 [20%]). Serious treatment-related adverse events occurred in 74 (21%) of 346 patients in the D-VMP group and 56 (16%) of 354 patients in the VMP group. Deaths due to treatment-related adverse events occurred in five (1%) of 346 patients in the D-VMP group (pneumonia, acute myocardial infarction, neuroendocrine tumour, tumour lysis syndrome, and acute respiratory failure) and three (1%) of 354 patients in the VMP group (acute myeloid leukaemia, pulmonary embolism, and bacterial pneumonia). With more than 7 years of follow-up, D-VMP continued to elicit clinical benefits in transplant-ineligible patients with newly diagnosed multiple myeloma, supporting the efficacy and safety of frontline daratumumab-based therapy in this patient population. Janssen Research & Development
Health status of adults exposed to severe acute malnutrition during childhood in the Eastern Democratic Republic of the Congo: the Lwiro cohort study
No full textBACKGROUND While most studies of adults with a history of severe acute malnutrition (SAM) focused on survival and long-term non-communicable diseases, few studies have examined community health. The aim of this study was to compare the overall health status and its predictors between adults with a history of SAM and healthy controls in the context of Eastern Democratic Republic of the Congo using the WHO Disability Assessment Schedule (WHODAS). METHODS We evaluated 257 adults in Eastern Democratic Republic of the Congo who were treated for SAM during childhood between 1988 and 2007. They were compared with 187 age-matched and sex-matched control adults living in the same community who had not been exposed to malnutrition as a child. The main outcome was the WHODAS summary score, measuring an individual’s health status in six domains of disability (household daily tasks, cognitive, mobility, self-care, social networks and social participation). A multivariable logistic regression model was used to identify the predictors of health status. RESULTS The median age of the participants in both groups was 20 years. The median (P25–P75) WHODAS score in SAM+ participants was 25.0 (14.6–33.3), whereas it was 8.3 (4.2–14.6) in SAM− participants (p<0.001). In five of the six disability domains (except individual self-care), SAM+ participants had significantly higher scores (poorer health) than SAM− participants. Consequently, 63% of SAM+ participants had a higher level of dependency compared with 16.6% of SAM− participants. Finally, being SAM+ was predictive of a higher WHODAS score (OR 8.6, 95% CI 5.4 to 13.6, p=0.002). In the multivariable logistic regression model, occupation, socioeconomic status and use of social networks, introduced separately in addition to SAM, remained significant but had no confounding effect on the association between SAM and WHODAS score. CONCLUSION SAM during childhood has deleterious consequences on the state of health during adulthood. It is imperative to implement interventions to prevent and treat SAM during childhood to maximise adult population health
Intestinal Microbiota Contributes to the Development of Cardiovascular Inflammation and Vasculitis in Mice.
No full textBACKGROUND: Alterations in the intestinal microbiota contribute to the pathogenesis of various cardiovascular disorders, but how they affect the development of Kawasaki disease (KD) an acute pediatric vasculitis, remains unclear. METHODS: We used the Lactobacillus casei cell wall extract (LCWE) murine model of KD vasculitis to assess the contribution of the intestinal microbiota to the development of vascular inflammation. We evaluated the severity of vasculitis in microbiota-depleted mice. 16S rRNA gene sequencing was used to characterize the fecal microbiome composition of LCWE-injected mice. Some groups of mice were orally treated with selected live or pasteurized bacteria, short-chain fatty acids, or Amuc_1100, the Toll-like receptor 2 signaling outer membrane protein from Akkermansia muciniphila, and their impact on vasculitis development was assessed. RESULTS: We report that depleting the gut microbiota reduces the development of cardiovascular inflammation in a murine model mimicking KD vasculitis. The development of cardiovascular lesions was associated with alterations in the intestinal microbiota composition and, notably, a decreased abundance of Akkermansia muciniphila and Faecalibacterium prausnitzii. Oral supplementation with either of these live or pasteurized individual bacteria or with short-chain fatty acids produced by them attenuated cardiovascular inflammation, as reflected by decreased local immune cell infiltrations. Treatment with Amuc_1100 also reduced the severity of vascular inflammation. CONCLUSIONS: This study reveals an underappreciated gut microbiota-cardiovascular inflammation axis in KD vasculitis pathogenesis and identifies specific intestinal commensals that regulate vasculitis in mice by producing metabolites or via extracellular proteins capable of enhancing and supporting gut barrier function
Le référé-liberté garantit la conservation de la biodiversité en tant que composante du droit à un environnement équilibré et respectueux de la santé : une lecture de l’ordonnance du 18 octobre 2024 du juge des référés du Conseil d’État français
No full textCet article analyse l'ordonnance du 18 octobre 2024 en référé-liberté du juge des référés du Conseil d’État français. Cette ordonnance confirmait celle du 4 octobre 2024 du juge des référés du Tribunal administratif de Toulouse suspendant l’exécution de l’arrêté du 27 septembre 2024 du préfet de l’Ariège en ce qu’il concernait la chasse aux lagopèdes alpins pour la campagne cynégétique 2024/2025 en se fondant sur le droit à un environnement équilibré et respectueux de la santé. Après avoir synthétisé l'affaire, cet article retrace brièvement le processus ayant conduit à l'acceptation de la justiciabilité du droit à un environnement sain en référé-liberté en France. Il met, enfin, en exergue la conception écocentrique de ce droit humain que l'ordonnance du 18 octobre 2024 affirme de manière tacite en considérant la conservation de la biodiversité comme une des composantes substantielles du droit à un environnement équilibré et respectueux de la santé
IJE - Practice Group Public Procurement Chronique de jurisprudence des chambres francophones du Conseil d’État en matière de marchés publics
No full textSur la base des arrêts de la VIe chambre (francophone) du Conseil d'État, la présentation porte sur les décisions clés de 2024 concernant l'organisation et l'attribution des marchés publics
