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Dupilumab in atopic-dermatitis-like eczema associated with inborn errors of immunity: A nationwide study
No full textInternational audienc
Dentists’ Knowledge, Attitudes, and Practices Regarding Molar Incisor Hypomineralization (MIH): A French Survey
No full textInternational audienceIntroduction: With an estimated 878 million cases worldwide in 2015, molar incisor hypomineralization(MIH) is a growing issue. Early detection and management require knowledge and application of goodclinical practices. The aim of the study was to evaluate the knowledge, attitudes, and practices of Frenchdentists regarding MIH.Method: A self-administered questionnaire was distributed to different groups of practitioners between 30January and 27 March 2023, including members of the French dental practice-based research network,members of the social network “French pediatric dentists,” and members of the professional social networkLinkedIn (LinkedIn, Sunnyvale, California, United States). The data from 311 questionnaires were analyzed.Results: Around 277 (89%) practitioners were familiar with MIH, 180 (58%) were perfectly aware of theclinical features of MIH, and 193 (62%) reported being able to clinically identify MIH. Nearly 100% (310) ofdentists cited “environmental pollutants” as the most frequent etiological factor. Glass ionomer is the mostused restorative material.Conclusion: Education regarding MIH must be improved among dentists to correctly detect, treat, or referpatients. It would seem useful to carry out an MIH prevalence study in France
CT-3DFlow : Leveraging 3D Normalizing Flows for Unsupervised Detection of Pathological Pulmonary CT scans
No full textUnsupervised pathology detection can be implemented by training a model on healthy data only and measuring the deviation from the training set upon inference, for example with CNN-based feature extraction and one-class classifiers, or reconstruction-score-based methods such as AEs, GANs and Diffusion models. Normalizing Flows (NF) have the ability to directly learn the probability distribution of training examples through an invertible architecture. We leverage this property in a novel 3D NF-based model named CT-3DFlow, specifically tailored for patient-level pulmonary pathology detection in chest CT data. Our model is trained unsupervised on healthy 3D pulmonary CT patches, and detects deviations from its log-likelihood distribution as anomalies. We aggregate patches-level likelihood values from a patient's CT scan to provide a patient-level 'normal'/'abnormal' prediction. Out-of-distribution detection performance is evaluated using expert annotations on a separate chest CT test dataset, outperforming other state-of-the-art methods
Antimicrobial susceptibility and epidemiological types of Legionella pneumophila human isolates from Italy (1987–2020)
No full textInternational audienceObjectives: Although antimicrobial resistance has not yet emerged as an overarching problem for Legionella pneumophila ( L. pneumophila ) infection, the description of clinical and environmental strains resistant to fluoroquinolones and macrolides is a cause of concern. This study aimed to investigate the antimicrobial susceptibility of L. pneumophila human isolates in Italy.Methods: A total of 204 L. pneumophila clinical isolates were tested for sensitivity to 9 antibiotics using the broth microdilution assay (BMD). All isolates were typed by sequence-based typing, and Legionella pneumophila serogroup 1 (Lp1) isolates by monoclonal antibody subgrouping. Minimum inhibitory concentration (MIC) data were correlated with the possible source of infection and geographical distribution. The presence of the lpeAB efflux pump genes was also investigated. The genome sequences of a subpopulation of isolates showing reduced susceptibility to azithromycin were also analysed. Results: The L. pneumophila isolates did not show significant resistance to the tested antibiotics, although a trend toward reduced sensitivity to azithromycin was observed in a subpopulation of 46 strains, most of which belonged to sequence type 1 (ST1), the second most widespread ST in Italy. An amplicon of the expected size overlapping the lpeAB genes was obtained only in the 46-subpopulation above mentioned. In 4 of the 46 isolates, sequencing analysis showed the occurrence of amino-acid substitutions already described in other strains. No further mutation was found .Conclusions: The presence of L. pneumophila strains with reduced susceptibility or resistance to azithromycin should be monitored to predict future trends and suggest to physicians a combined therapy with fluoroquinolones when a poor response to azithromycin is observed
Acromegaly Disease Control Maintained After Switching From Injected Somatostatin Receptor Ligands to Oral Paltusotine
No full textInternational audienceAbstract Context Paltusotine is a nonpeptide selective somatostatin receptor 2 agonist in development as once-daily oral treatment for acromegaly. Objective To evaluate the efficacy and safety of paltusotine in the treatment of patients with acromegaly previously controlled with injected somatostatin receptor ligands (SRLs). Methods This phase 3, randomized, double-blind, placebo-controlled trial enrolled adults with acromegaly who had IGF-I ≤1.0 times the upper limit of normal (×ULN) while receiving a stable dose of depot octreotide or lanreotide. Patients were switched from injected SRLs and randomized to receive paltusotine or placebo orally for 36 weeks. The primary endpoint was proportion of patients maintaining IGF-I ≤1.0× ULN. Secondary endpoints were change in IGF-I level, change in Acromegaly Symptom Diary score, and maintenance of mean 5-sample GH <1.0 ng/mL. Results The primary endpoint was met: 83.3% (25/30) of patients receiving paltusotine and 3.6% (1/28) receiving placebo maintained IGF-I ≤1.0× ULN (odds ratio, 126.53; 95% CI, 13.73->999.99; P < .0001). Paltusotine was also superior to placebo for all secondary endpoints: mean (± SE) change in IGF-I of 0.04 ± 0.09× ULN vs 0.83 ± 0.1× ULN (P < .0001); mean (± SE) change in Acromegaly Symptom Diary score of −0.6 ± 1.5 vs 4.6 ± 1.6 (P = .02); mean GH maintained at <1.0 ng/mL in 20/23 (87.0%) vs 5/18 (27.8%) patients (odds ratio, 16.61; 95% CI, 2.86-181.36; P = .0003). The most common adverse events were acromegaly symptoms and gastrointestinal effects characteristic of SRLs. Conclusion Replacement of injected SRLs by once-daily oral paltusotine was effective in maintaining both biochemical and symptom control in patients with acromegaly and was well tolerated
Prognosis Associated with Complete Pathological Response Following Neoadjuvant Treatment for PancreaTic AdenOcarciNOma in the FOFLIRINOX Era: the Multicenter TONO Study
No full textInternational audienceBackground: The use of multiagent FOLFIRINOX chemotherapy for pancreatic adenocarcinoma in a neoadjuvant setting has been associated with an increased rate of complete pathological response (CPR) after surgery. This study investigated the long-term outcomes of patients with CPR in a multicenter setting to identify prognostic factors for overall survival (OS) and recurrence-free survival (RFS).Methods: This retrospective cohort study examined biopsy-proven pancreatic adenocarcinomas with CPR after neoadjuvant chemotherapy or chemoradiotherapy and surgery, between January 2006 and December 2023 across 22 French and 2 Belgian centers. Cox analyses were used to identify prognostic factors of OS and RFS.Results: There were 101 patients with CPR after chemotherapy (n = 58, 57.4%) and chemoradiotherapy (n = 43, 42.6%) followed by surgery. Neoadjuvant FOLFIRINOX was used in 90% of patients. The median OS after surgery was 177 months (95% confidence interval (CI) 58.9-177 months) with 1-, 3-, 5-, and 10-year OS rates of 93%, 75%, 63%, and 51%, respectively. The median RFS was 67.8 months (95% CI:34.4-NR) with 1-, 3-, 5-, and 10-year RFS rates of 83%, 58%, 54%, and 49%, respectively. The multivariate Cox analysis of OS and RFS showed that preoperative radiotherapy was an independent negative prognostic factor for OS (hazard ratio (HR) 2.51; 95% CI 1.00-6.30; p = 0.03) and RFS (HR 2.62; 95% CI 1.27-5.41; p = 0.009).Conclusions: Complete pathologic response after neoadjuvant treatment is associated with remarkable long-term survival that is usually not seen after the resection of pancreatic adenocarcinomas. One-third of the patients still experienced disease recurrence, which was more common in those receiving preoperative chemoradiotherapy
P0621 Effectiveness and Safety of Induction Therapy with Upadacitinib for the Treatment of Perianal Crohn’s Disease : Real-World Data from a GETAID Multicentre Cohort Study
No full textInternational audienceBackground Upadacitinib has demonstrated efficacy as an induction treatment for Crohn’s disease (CD)1, and a post hoc analysis of phase 3 randomized, placebo-controlled trials has shown its efficacy in perianal fistulizing CD (pCD)2. However, real-world data in this setting remain limited. Methods From September 2022 to September 2024, all consecutive patients with CD treated with once-daily upadacitinib 45 mg in 32 French and Belgian GETAID centres were retrospectively included. Clinical remission (absence of draining pus including with pressure for fistulas and no anal ulcers for primary lesions, as per local physician’s judgement, with no need for new dedicated medical treatment for perianal lesions (antibiotics and/or topics), or surgical treatment) and clinical response (an improvement of at least 50% of ulcers or fistulas by physician’s assessment) were assessed at week 12. Univariate and multivariable analyses were performed to identify predictors of clinical response. Results Among the 243 patients treated, 54 (22.2%) had active perianal Crohn’s disease (pCD) at the time of induction. This group included 43 patients (81.0%) with fistulizing disease and 11 (19.0%) with isolated anal ulcers. Median age was 38 (IQR, 29.0-45.8) years, 28 (51.9%) were men, and 9 (17.0%) were active smokers. All had been previously exposed to at least one advanced therapy (median number: 4, IQR [3-5]), and 25 (47.2%) had undergone prior perianal surgery (Table 1). By week 12, clinical response was achieved in 37 patients (68.5%, n=37/54), and clinical remission in 10 patients (n=10/54, 18.5%). Among patients with fistulizing pCD, 29 patients (67.4%, n=29/43) achieved clinical response, while 6 (14.0%, n=6/43) achieved remission. Among patients with primary perianal CD, complete remission of ulcers was observed in 4 (n=4/11, 36.4%) (Figure 1). In multivariate analysis, penetrating phenotype (OR=14.8, 95%CI: 1.6-381.9, p=0.04) was associated with higher rates of clinical response at W12 while the number of prior biologics did not influence clinical response (OR = 1.63, 95% CI: 0.47-5.79; p = 0.47). Fifteen adverse events (AEs) occurred in 13 (24.1%) patients, including 5 (9.3%) serious AEs, all 5 cases corresponding to CD exacerbation. At week 12, 7 (13%) patients discontinued upadacitinib, all due to lack of efficacy. Conclusion In this real-world cohort of highly refractory CD patients, upadacitinib induction resulted in a clinical response of perianal CD in two-third of patients. References 1.Loftus EV, Panés J, Lacerda AP, et al. Upadacitinib Induction and Maintenance Therapy for Crohn’s Disease. N Engl J Med. 2023;388(21):1966-1980. doi:10.1056/NEJMoa2212728 2. Colombel JF, Lacerda AP, Irving PM, et al. Efficacy and Safety of Upadacitinib for Perianal Fistulizing Crohn’s Disease: A Post Hoc Analysis of 3 Phase 3 Trials. Clin Gastroenterol Hepatol. 2024;0(0)
Association between education level and access to disease-modifying treatment in patients with multiple sclerosis in France
No full textThe author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Research grant from Eugène Devic EDMUS Foundation against MS, in partnership with the ARSEP FoundationInternational audienceBackground: We hypothesized that differences in access to disease-modifying treatments (DMTs) could explain the association between socioeconomic status and disability progression in multiple sclerosis (MS). Objective: This study aimed to analyze the association between education level and DMT use in France. Methods: All patients from OFSEP network with MS onset over 1996–2014 and aged ⩾ 25 years at onset were included. Three time-to-event outcomes were investigated using flexible parametric survival regression models: time from MS onset to first DMT (any) and to platform therapy, and time from platform therapy to switch to high-efficacy therapy. Results: Overall, 7563 patients were included (mean follow-up 12.6 ± 5.9 years). The percentages of patients aged less than 40 years at MS onset and who initiated treatment before the age of 40 years were significantly higher in the groups with a higher education level. The time-to-event outcomes showed no major difference in DMT practices according to education level, except for women who had a significantly shorter time to DMT initiation in medium to very high education level groups versus low, at 5 years from MS clinical onset. Conclusion: Our results suggest that the association between education level and MS disability progression does not solely reflect different therapeutic practices, particularly in men
Association of Burnout and Intention‐To‐Leave the Job With Objective Nursing Workload and Nursing Working Environment: A Cross‐Sectional Study Among Intensive Care Nurses
No full textInternational audienceAim - The objectives of this study were to determine the prevalence of burnout risk and intention-to-leave among intensive care unit (ICU) nurses and analyse the association of these with workload and work environment. Design - A cross-sectional survey of nurses working in ICUs was conducted in France between 15 January 2024 and 15 April 2024 alongside a longitudinal assessment of workload during the same period. Methods - ICU nurse workload was assessed using the Nursing Activities Score (NAS). The risk of burnout was assessed using the Maslach Burnout Inventory scale and intention-to-leave the hospital was assessed with a binary question. A total of 1271 nurses working in 61 intensive care units completed the questionnaire and 14,134 NAS per patient and 1885 NAS per nurse were included in the study. Results - The median overall of burnout by hospital site was 64.7% [P25: 53.3-P75: 72.7] for the broad definition and a median of 20.7% [13.3-27.3] of ICU nurses reported an intent-to-leave their job. The median overall NAS score per nurse was 135.9% [121.4-156.9] and the prevalence of NAS scores exceeding 100% per nurse was 73.9% [62.8-80.3]. A significant association was found between nurses working in an ICU with a better work environment and all dimensions of burnout as well as the intention-to-leave the job. A prevalence in the hospital site of NAS scores exceeding 100% per nurse below the median was associated with a lower burnout (OR = 0.69, 95% CI: 0.50-0.88 for broad definition) and intention-to-leave the job (OR = 0.68, 95% CI: 0.50-0.92). Conclusion - This study found significant associations between burnout and the intention to leave the job for nurses in ICUs, mainly due to a better work environment and, to a lesser extent, a lower workload for nurses. Implications for the profession and/or patient care - In an era of nurse shortages and absenteeism, it is crucial for institutions to retain their nursing staff. Our results should encourage hospital managers to take action to improve the ICU work environment and keep ICU workloads manageable to decrease burnout and the intention-to-leave the job among ICU nurses. Reporting method - This article follows the STROBE guidelines for the reporting of cross-sectional studies. Patient or public contribution - No patient or public contribution
