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Prevalence, management, health-care burden, and 90-day outcomes of prolonged mechanical ventilation in the paediatric intensive care unit (LongVentKids): an international, prospective, cross-sectional cohort study
No full textInternational audienc
Comment je fais… les bonnes mesures par échographie périnéale pour caractériser une incontinence urinaire
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Depressive symptoms in older adults are associated with changes in stress-related markers, functional connectivity and brain volume
No full textInternational audienceBackground Subclinical depressive symptoms increase the risk of developing Alzheimer’s disease (AD). The neurobiologicalmechanisms underlying this link may involve stress system dysfunction, notably related to the hippocampuswhich is particularly sensitive to AD. We aimed to investigate the links between blood stress markers and changesin brain regions involved in the stress response in older adults with or without subclinical depressive symptoms.Methods This cross-sectional study was conducted using baseline data from the Age-Well trial. Cognitively unimpaired(CU) older adults with (DepS; n = 73) or without (NoDepS; n = 58) subclinical depressive symptoms (definedusing the 15-item Geriatric Depression Scale) were included in the analyses. Blood cortisol, epinephrine and norepinephrinewere measured; as well as the resting-state functional connectivity (rs-FC) between, and gray matter (GM)volume of, the hypothalamus, hippocampus and hippocampal subfields. Blood stress markers levels and neuroimagingmeasures were compared between groups; then regression analyses were conducted between these measures.Results DepS participants showed higher plasma epinephrine levels, which was associated with greater rs-FCbetween the CA1 and Subiculum hippocampal subfields and the hypothalamus. Lower GM volume in the CA1and DG/CA2-3–4 subfields was also found in DepS. No between-group differences were observed for blood cortisoland norepinephrine.Conclusions Our findings show that subclinical depressive symptoms are associated with increased sympatho-adrenomedullaryaxis activity, together with lower GM volume in a hippocampal subfield (i.e., CA1) particularly sensitiveto AD. While causation cannot be inferred, these results suggest that screening and treating subclinical depressivesymptoms in CU older adults could reduce AD risk.Trial registration ClinicalTrials.gov Identifier: NCT02977819, Registration Date: 2016–11-25
Association between education level and disability progression in patients with multiple sclerosis in France
No full textInternational audienceBackground: Studies have reported an association between socioeconomic status and disability progression in multiple sclerosis (MS), but findings using the pre-MS individual socioeconomic status are missing. Objective: The objective was to investigate the association between education level and disability progression. Methods: All Observatoire Français de la Sclérose en Plaques (OFSEP) patients with MS clinical onset over 1960–2014, and aged ⩾25 years at MS onset were included. Education level was classified into four categories from low (primary/secondary school) to very high (master/doctoral degree). Time from MS onset to EDSS 4.0 was studied using flexible parametric survival models adjusted for age, period, and center, and stratified by phenotype (relapsing multiple sclerosis (RMS) and primary progressive multiple sclerosis (PPMS)) and sex. Results: A total of 11,586 patients were included (women/men ratio = 2.5; age = 36.7 ± 8.6 years; follow-up duration 16.7 ± 9.3 years; 86.4% RMS). For women with RMS, the risk of reaching the outcome at 5 years was inversely associated with the education level (Hazard Ratio medium: 0.74 (0.63–0.87), high: 0.51 (0.43–0.62), very high: 0.39 (0.30–0.50) vs low). Results were similar for men. In PPMS, the risk was significantly different between the extreme groups (very high vs low) for women (0.45 (0.28–0.75)) and men (0.54 (0.32–0.91)), but no gradient was evident. Conclusion: Our study showed a strong association between education level and disability progression, regardless of sex and phenotype
National impact of a constraining regulatory framework on pregabalin dispensations in France, 2020–2022
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Switching From Dupilumab to Tralokinumab or Janus Kinase Inhibitors in Cases of Ocular and/or Facial Adverse Events in Patients With Atopic Dermatitis: A Multicenter Retrospective Study
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Methodological expectations for demonstration of health product effectiveness by observational studies
No full textInternational audienceThe issue of assessing the effectiveness of health technologies (drugs, devices, etc.) through observational studies is becoming increasingly important as registration and market access agencies consider them in their evaluation process. In this context, observational studies must be able to provide real demonstrations of a level of reliability comparable to those produced by the conventional randomized controlled trial (RCT) approach. The objective of the roundtable was to establish the acceptability criteria for an observational study (non-randomized, non-interventional study) to be able to provide these demonstrations, and possibly serve as a confirmatory study for registration and market access authorities, the construction of therapeutic strategies or the development of recommendations. In order to do this, the study must be a real confirmatory study respecting the hypothetical-deductive approach and guaranteeing the absence of HARKing and p-hacking by attesting to the establishment of a protocol and a statistical analysis plan, recorded before any inferential analysis. It must also be part of a formalized approach to causal inference and demonstrate that it correctly identifies the causal estimand sought. The study should ensure that there is no residual confusion bias by taking into account all confounding factors affecting the comparison, which should be determined by a formal approach (such as a graphical causality approach, DAGs). Residual confusion bias diagnoses by forgery and nullification analysis should be non-existent. The study shall be at low risk of bias, in particular selection bias, among others by using a target test emulation design. Overall type I error risk should be strictly controlled. The absence of selective publication of results and selection bias should be ensured
Alitretinoin is not a suitable treatment for the majority of chronic hand eczema patients
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Should We Transplant Candidates With a Positive SARS-CoV-2 RT-PCR Test?
No full textInternational audienceBackground. It remains unclear whether physicians should accept transplantation offers for candidates with a positive SARS-CoV-2 reverse transcription polymerase chain reaction test due to the potential risk of severe infection after initiating immunosuppressive therapy. Methods. A multicenter observational study was conducted in 19 French solid organ transplantation units. Patients on the waiting list for liver or kidney transplants who had a positive SARS-CoV-2 reverse transcription polymerase chain reaction nasopharyngeal swab at the time of transplantation were recorded. Results. Sixty-five patients were included. The recipients were predominantly men (n = 40; 62%) with a mean age of 55.4 y (SD = 16.5). On the day of transplantation, 2 patients exhibited symptoms compatible with COVID-19. The majority of patients (n = 55; 85%) underwent thoracic imaging, with only 3 patients showing imaging results compatible with COVID-19. Ten patients (28%) had a cycle threshold value <30. Anti–SARS-CoV-2 spike protein serology within 3 mo before transplantation was available for 36 patients; only 2 patients were seronegative. Due to COVID-19, physicians adapted the immunosuppressive therapy for 16 patients (25%). Specific antiviral therapy was used for 15 patients (23%), primarily remdesivir (n = 12). Overall, the majority of patients did not receive any adjustment of immunosuppressive therapy or antiviral treatment (n = 36; 55%). The outcomes were generally favorable even for patients with the lowest cycle threshold values, indicating a high viral load. Four patients died during follow-up, although none of these deaths were attributable to COVID-19. Conclusions. Transplantation appears to be safe for patients who are asymptomatic or have mild symptoms, reassuring thoracic imaging, and a history of anti–SARS-CoV-2 infection and/or immunization
E4F1 coordinates pyruvate metabolism and the activity of the elongator complex to ensure translation fidelity during brain development
No full textInternational audiencePyruvate metabolism defects lead to severe neuropathies such as the Leigh syndrome (LS) but the molecular mechanisms underlying neuronal cell death remain poorly understood. Here, we unravel a connection between pyruvate metabolism and the regulation of the epitranscriptome that plays an essential role during brain development. Using genetically engineered mouse model and primary neuronal cells, we identify the transcription factor E4F1 as a key coordinator of AcetylCoenzyme A (AcCoA) production by the pyruvate dehydrogenase complex (PDC) and its utilization as an essential co-factor by the Elongator complex to acetylate tRNAs at the wobble position uridine 34 (U 34 ). E4F1-mediated direct transcriptional regulation of Dlat and Elp3, two genes encoding key subunits of the PDC and of the Elongator complex, respectively, ensures proper translation fidelity and cell survival in the central nervous system (CNS) during mouse embryonic development. Furthermore, analysis of PDH-deficient cells highlight a crosstalk linking the PDC to ELP3 expression that is perturbed in LS patients