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Brentuximab vedotin (BV)-bendamustine (90 or 120 mg/m2 day 1 and 2) every 28 days is an effective treatment for relapsed/refractory Hodgkin lymphoma (R/R HL) but associated to high toxicity especially for elderly patients. We conducted in St Louis Hospital, Paris, between 2015 and 2021 a retrospective single-center analysis of 44 patients with R/R HL treated with one-day BV-bendamustine (120 mg/m2) every 21 days. Sixteen percent of patients were ≥ 60 years old (yo). Seventy-three percent of patients received total number of cycles without interruption nor adaptation. No patient ≥ 70 yo required treatment interruption. Dose adjustment was necessary for 18% of patients. Infusion-related reaction (36%) occurred always at cycle 2 and was the only cause of treatment interruption. One febrile neutropenia, one non-documented septic shock, one pyelonephritis on transplanted kidney and one COVID complicated by cytopenias were reported. Sixteen percent patients presented a peripheral sensory neuropathy, 7% and 4% respectively grade 3-4 neutropenia and thrombocytopenia. Overall response was 84%, with 73% of complete remission. Median progression-free survival was of 19.8 months (95% CI 13.1-NR) and median overall survival was not reached with a median follow-up of 31 months. We suggest that one-day BV-bendamustine (120 mg/m2) ever 21 days is a safe and feasible treatment for R/R HL especially for elderly patients., (© 2024 John Wiley & Sons Ltd.)

Background: Factors associated with the appropriateness of antibiotic prescribing in primary care have been poorly explored. In particular, the impact of computerised decision-support systems (CDSS) remains unknown., Objectives: We aim at investigating the uptake of CDSS and its association with physician characteristics and professional activity., Methods: Since May 2022, users of a CDSS for antibiotic prescribing in primary care in France have been invited, when registering, to complete three case vignettes assessing clinical situations frequently encountered in general practice and identified as at risk of antibiotic misuse. Appropriateness of antibiotic prescribing was defined as the rate of answers in line with the current guidelines, computed by individuals and by specific questions. Physician's characteristics associated with individual appropriate antibiotic prescribing (< 50%, 50-75% and > 75% appropriateness) were identified by multivariate ordinal logistic regression., Results: In June 2023, 60,067 physicians had registered on the CDSS. Among the 13,851 physicians who answered all case vignettes, the median individual appropriateness level of antibiotic prescribing was 77.8% [Interquartile range, 66.7%-88.9%], and was < 50% for 1,353 physicians (10%). In the multivariate analysis, physicians' characteristics associated with appropriateness were prior use of the CDSS (OR = 1.71, 95% CI 1.56-1.87), being a general practitioner vs. other specialist (OR = 1.34, 95% CI 1.20-1.49), working in primary care (OR = 1.14, 95% CI 1.02-1.27), mentoring students (OR = 1.12, 95% CI 1.04-1.21) age (OR = 0.69 per 10 years increase, 95% CI 0.67-0.71)., Conclusion: Individual appropriateness for antibiotic prescribing was high among CDSS users, with a higher rate in young general practitioners, previously using the system. CDSS could improve antibiotic prescribing in primary care.

Background: During the first wave of the COVID-19 pandemic, a reduction in the number of newly diagnosed cases of lung cancer has been reported worldwide, often associated with a higher proportion of cases diagnosed at an advanced stage compared with previous years., Methods: Using the French National Hospital Database, we investigated incident lung cancer cases and their mortality during pandemic years 2020 and 2021, compared to predictions based on pre-pandemic years 2013-2019. Mortality was assessed up to 24 months following incidence date. Expected numbers of incident cases and all-cause deaths during the pandemic were estimated using Poisson regression models and survival was analyzed using Cox regressions., Results: The database included 397,092 incident lung cancer cases in total, 20 % of whom underwent thoracic surgery. During the first pandemic wave (March-June 2020), there were 12 % i.e., 1940 fewer incident lung cancer cases than the expected figure (16,325), while no significant difference was found thereafter. Survival at 6 and 24 months improved steadily from 2013 to 2019 and continued to improve during pandemic years 2020-2021. However, during the first wave, a slight excess mortality was observed compared with predictions based on pre-pandemic trends., Conclusions: The lower incidence observed during the first wave with no catch-up in the following periods could be explained by deaths among yet undiagnosed patients, either from COVID-19 or as a result of barriers to accessing healthcare. The excess mortality observed for both operated and non-operated patients may be attributable to delayed diagnosis, as well as to COVID-19-related deaths., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Author Christos Chouaïd received payments from: AZ, BI, GSK, Roche, Sanofi Aventis, BMS, MSD, Lilly, Novartis, Pfizer, Takeda, Bayer, Janssen, and Amgen If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Sleep and mood disorders are common in hemodialysis, but the effect of light therapy remains unknown in this population., Methods: We conducted a randomized, controlled, open-label pilot trial comparing two group of either 30 minutes of light therapy three times a week, or no exposure. The primary endpoint was change in sleep quality (PSQI) after five weeks of light therapy, with change in mood (DASS-21) as a secondary endpoint. We added the description of the same criteria in a prospective, non-randomized, real-life post-trial cohort., Study Results: We included 28 analyzable patients in the pilot study. Light therapy had no significant effect on PSQI reduction (p = 0.496). There was a trend towards a reduction in depression (-6.2 [95% CI, -12.5 to -0.05], p = 0.058). In the real-life cohort, out of 27 patients, 12 had a significant reduction in depression score (≥ 6 points)., Discussion: Light therapy performed in hemodialysis three times a week appears to have no effect on sleep quality, but could reduce depressive states. The technique is easy to implement, well tolerated and inexpensive. A multicenter randomized trial against the sham device will be needed to validate its effect on depression.

We show the value of real-time data generated by a computerized decision support system in primary care in strengthening pneumonia surveillance. The system showed a 66% (95% CI 64%-67%) increase in community-acquired pneumonia from 2018 to 2023 for the population of France, 1 month before a national alert was issued.

Background: Suboptimal use of antimicrobials is a driver of antimicrobial resistance in West Africa. Clinical decision support systems (CDSSs) can facilitate access to updated and reliable recommendations., Objective: This study aimed to assess contextual factors that could facilitate the implementation of a CDSS for antimicrobial prescribing in West Africa and Central Africa and to identify tailored implementation strategies., Methods: This qualitative study was conducted through 21 semistructured individual interviews via videoconference with health care professionals between September and December 2020. Participants were recruited using purposive sampling in a transnational capacity-building network for hospital preparedness in West Africa. The interview guide included multiple constructs derived from the Consolidated Framework for Implementation Research. Interviews were transcribed, and data were analyzed using thematic analysis., Results: The panel of participants included health practitioners (12/21, 57%), health actors trained in engineering (2/21, 10%), project managers (3/21, 14%), antimicrobial resistance research experts (2/21, 10%), a clinical microbiologist (1/21, 5%), and an anthropologist (1/21, 5%). Contextual factors influencing the implementation of eHealth tools existed at the individual, health care system, and national levels. At the individual level, the main challenge was to design a user-centered CDSS adapted to the prescriber's clinical routine and structural constraints. Most of the participants stated that the CDSS should not only target physicians in academic hospitals who can use their network to disseminate the tool but also general practitioners, primary care nurses, midwives, and other health care workers who are the main prescribers of antimicrobials in rural areas of West Africa. The heterogeneity in antimicrobial prescribing training among prescribers was a significant challenge to the use of a common CDSS. At the country level, weak pharmaceutical regulations, the lack of official guidelines for antimicrobial prescribing, limited access to clinical microbiology laboratories, self-medication, and disparity in health care coverage lead to inappropriate antimicrobial use and could limit the implementation and diffusion of CDSS for antimicrobial prescribing. Participants emphasized the importance of building a solid eHealth ecosystem in their countries by establishing academic partnerships, developing physician networks, and involving diverse stakeholders to address challenges. Additional implementation strategies included conducting a local needs assessment, identifying early adopters, promoting network weaving, using implementation advisers, and creating a learning collaborative. Participants noted that a CDSS for antimicrobial prescribing could be a powerful tool for the development and dissemination of official guidelines for infectious diseases in West Africa., Conclusions: These results suggest that a CDSS for antimicrobial prescribing adapted for nonspecialized prescribers could have a role in improving clinical decisions. They also confirm the relevance of adopting a cross-disciplinary approach with participants from different backgrounds to assess contextual factors, including social, political, and economic determinants., (©Nathan Peiffer-Smadja, Sophie Descousse, Elsa Courrèges, Audrey Nganbou, Pauline Jeanmougin, Gabriel Birgand, Séverin Lénaud, Anne-Lise Beaumont, Claire Durand, Tristan Delory, Josselin Le Bel, Elisabeth Bouvet, Sylvie Lariven, Eric D'Ortenzio, Issa Konaté, Marielle Karine Bouyou-Akotet, Abdoul-Salam Ouedraogo, Gisèle Affoue Kouakou, Armel Poda, Corinne Akpovo, François-Xavier Lescure, Aristophane Tanon. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 07.10.2024.)

Purpose: To compare the effectiveness and safety of cefazolin versus cloxacillin for the treatment of infective endocarditis (IE) due to methicillin-sensitive Staphylococci (MSS)., Methods: Data were retrospectively collected on patients treated for a definite MSS endocarditis who received cefazolin or cloxacillin for at least 10 consecutive days in six French hospitals between January-1 2014 and December-31 2020. The primary endpoint was treatment failure defined as a composite of death within 90 days of starting antibiotherapy, or embolic event during antibiotherapy, or relapse of IE within 90 days of stopping antibiotherapy. We used Cox regression adjusted for the inverse probability of treatment weighting of receiving cefazolin., Results: 192 patients were included (median age 67.8 years). IE was caused by S.aureus in 175 (91.1%) and by coagulase-negative staphylococci in 17 (8.9%). Ninety-four patients (48.9%) received cefazolin, and 98 (51%) received cloxacillin. 34 patients (34.7%) with cefazolin and 26 (27.7%) with cloxacillin met the composite primary endpoint, with no significant differences between groups (adjusted HR = 1.13, 95% CI 0.63 to 2.03). There were no significant differences in secondary efficacy endpoints or biological safety events., Conclusion: The effectiveness of cefazolin did not significantly differ from cloxacillin for the treatment of MSS endocarditis., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In a retrospective multicenter study of 575 patients with bloodstream infections or pneumonia due to wild-type AmpC β-lactamase-producing Enterobacterales, species with low in vitro mutation rates for AmpC derepression were associated with fewer treatment failures due to AmpC overproduction (adjusted hazard ratio, 0.5 [95% CI, .2-.9]). However, compared to cefepime/carbapenems, using third-generation cephalosporins as definitive therapy remained associated with this adverse outcome (15% vs 1%)., Competing Interests: Potential conflicts of interest. A. B. declares links of interest with Pfizer, Shionogi, Eumedica, Sanofi, Gilead, Astellas, Menarini, and Janssen for congress fees, symposia, or investigator in clinical studies. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Critically injured patients need rapid and appropriate hemostatic treatment, which requires prompt identification of trauma-induced coagulopathy (TIC) upon hospital admission. We developed and validated the performance of a clinical score based on prehospital resuscitation parameters and vital signs at hospital admission for early diagnosis of TIC., Methods: The score was derived from a level-1 trauma center registry (training set). It was then validated on data from two other level-1 trauma centers: first on a trauma registry (retrospective validation set), and then on a prospective cohort (prospective validation set). TIC was defined as a PT ratio  > 1.2 at hospital admission. Prehospital (vital signs and resuscitation care) and admission data (vital signs and laboratory parameters) were collected. We considered parameters independently associated with TIC in the score (binomial logistic regression). We estimated the score's performance for the prediction of TIC., Results: A total of 3489 patients were included, and among these a TIC was observed in 22% (95% CI 21-24%) of cases. Five criteria were identified and included in the TIC Score: Glasgow coma scale < 9, Shock Index > 0.9, hemoglobin < 11 g.dL -1 , prehospital fluid volume > 1000 ml, and prehospital use of norepinephrine (yes/no). The score, ranging from 0 and 9 points, had good performance for the identification of TIC (AUC: 0.82, 95% CI: 0.81-0.84) without differences between the three sets used. A score value < 2 had a negative predictive value of 93% and was selected to rule-out TIC. Conversely, a score value ≥ 6 had a positive predictive value of 92% and was selected to indicate TIC., Conclusion: The TIC Score is quick and easy to calculate and can accurately identify patients with TIC upon hospital admission., (© 2024. The Author(s).)

During the pandemic period, health care systems were substantially reorganized for managing COVID-19 cases. Corresponding consequences on persons with chronic diseases remain insufficiently documented. This observational cohort study investigated the direct and indirect impact of the pandemic period on the survival of kidney transplant recipients (KTR). Using the French National Health Data System, incident persons with end-stage kidney disease between 2015 and 2020, and who received a kidney transplant during this period were included and followed up from their transplantation date to December 31, 2021. The survival of KTR during the prepandemic and pandemic periods was investigated using Cox models with time-dependent covariates. There were 10 637 KTR included in the study, with 324 and 430 deaths observed during the prepandemic and pandemic periods, respectively. The adjusted risk of death during the pandemic period was similar to that observed during the prepandemic period (hazard ratio [HR] [95% confidence interval]: 0.92 [0.77-1.11]), COVID-19-related hospitalization was associated with an increased risk of death (HR: 10.62 [8.46-13.33]), and a third vaccine dose was associated with a lower risk of death (HR: 0.42 [0.30-0.57]). The pandemic period was not associated with an indirect higher risk of death in KTR with no COVID-19-related hospitalization., (Copyright © 2023 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: We investigated the mortality patterns of chronic obstructive pulmonary disease (COPD) patients in France relative to a control population, comparing year 2020 to pre-pandemic years 2017-2019. Methods: COPD patient and sex, age and residence matched control cohorts were created from the French National Health Data System. Survival was analyzed using Cox regressions and standardized rates. Results: All-cause mortality increased in 2020 compared to 2019 in the COPD population (+4%), but to a lesser extent than in the control population (+10%). Non-COVID-19 mortality decreased to a greater extent in COPD patients (-5%) than in the controls (-2%). Death rate from COVID-19 was twice as high in the COPD population relative to the control population (547 vs. 279 per 100,000 person-years). Conclusion: The direct impact of the pandemic in terms of deaths from COVID-19 was much greater in the COPD population than in the control population. However, the larger decline in non-COVID-19 mortality in COPD patients could reflect a specific protective effect of the containment measures on this population, counterbalancing the direct impact they had been experiencing., Competing Interests: Author CC received payments from: AZ, BI, GSK, Roche, Sanofi Aventis, BMS, MSD, Lilly, Novartis, Pfizer, Takeda, Bayer, Janssen, and Amgen. The remaining authors declare that they do not have any conflicts of interest., (Copyright © 2024 Poucineau, Khlat, Lapidus, Espagnacq, Chouaïd, Delory and Le Coeur.)

In primary care, urinary tract infections (UTIs) account for the majority of antibiotic prescriptions. Comments from microbiologists on interpreting the antimicrobial susceptibility testing (AST) profile for urinalysis were made to improve the prescription of antibiotics. We aimed to explore the added value of these comments on the quality of antibiotic prescribing by a superior double-blind digital randomized case-vignette trial among French general practitioners (GPs). One case vignette with (intervention) or without (control) a 'comment' after AST was randomly assigned to GPs. Among 815 participating GPs, 64.7% were women, at an average age of 37 years. Most (90.1%) used a computerized decision support system for prescribing antibiotics. Empirical antibiotic therapy was appropriate in 71.9% (95% CI, 68.8-75.0) of the cases, without differences between arms. The overall appropriateness of targeted antibiotic therapy (primary outcome) was not significantly increased when providing 'comments': 83.4% vs. 79.9% (OR = 1.26, 95% CI, 0.86-1.85). With the multivariate analysis, the appropriateness was improved by 2-folds (OR = 2.38, 95% CI, 1.02-6.16) among physicians working in healthcare facilities. Among digital-affine young general practitioners, the adjunction of a 'comment' by a microbiologist to interpret urinalysis in community-acquired UTIs did not improve the overall level of appropriateness of the targeted antibiotic.

Background: The optimal treatment regimen for infections caused by wild-type AmpC β-lactamase-producing Enterobacterales remains controversial. This study compared the outcomes of bloodstream infections (BSI) and pneumonia according to the type of definitive antibiotic therapy: third-generation cephalosporin (3GC), piperacillin ± tazobactam, cefepime or carbapenem., Methods: All cases of BSI and pneumonia caused by wild-type AmpC β-lactamase-producing Enterobacterales over 2 years in eight university hospitals were reviewed. Patients who received definitive therapy consisting of either a 3GC (3GC group), piperacillin ± tazobactam (piperacillin group), or cefepime or a carbapenem (reference group) were included in this study. The primary endpoint was 30-day all-cause mortality. The secondary endpoint was treatment failure due to infection by emerging AmpC-overproducing strains. Propensity-score-based models were used to balance confounding factors between groups., Results: In total, 575 patients were included in this study: 302 (52%) with pneumonia and 273 (48%) with BSI. Half (n=271, 47%) received cefepime or a carbapenem as definitive therapy, 120 (21%) received a 3GC, and 184 (32%) received piperacillin ± tazobactam. Compared with the reference group, 30-day mortality was similar in the 3GC [adjusted hazard ratio (aHR) 0.86, 95% confidence interval (CI) 0.57-1.31)] and piperacillin (aHR 1.20, 95% CI 0.86-1.66) groups. The likelihood of treatment failure was higher in the 3GC (aHR 6.81, 95% CI 3.76-12.4) and piperacillin (aHR 3.13, 95% CI 1.69-5.80) groups. The results were similar when stratifying the analysis on pneumonia or BSI., Conclusion: Treatment of included BSI or pneumonia caused by wild-type AmpC β-lactamase-producing Enterobacterales with 3GC or piperacillin ± tazobactam was not associated with higher mortality, but was associated with increased risk of AmpC overproduction leading to treatment failure compared with cefepime or a carbapenem., (Copyright © 2023 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

Transmission of SARS-CoV-2 in nursing homes is poorly documented. Using surveillance data of 228 European private nursing homes, we estimated weekly SARS-CoV-2 incidences among 21,467 residents and 14,371 staff members, compared to that in the general population, between August 3, 2020, and February 20, 2021. We studied the outcomes of "episodes of introduction" where one case was first detected and computed attack rates, reproduction ratio ( R ), and dispersion parameter ( k ). Out of 502 episodes of SARS-CoV-2 introduction, 77.1% (95%CI, 73.2%-80.6%) led to additional cases. Attack rates were highly variable, ranging from 0.4% to 86.5%. The R was 1.16 (95%CI, 1.11-1.22) with k at 2.5 (95%CI, 0.5-4.5). The timing of viral circulation in nursing homes did not mirror that in the general population ( p -values<0.001). We estimated the impact of vaccination in preventing SARS-CoV-2 transmission. Before vaccination's roll-out, a cumulated 5,579 SARS-CoV-2 infections were documented among residents and 2,321 among staff. Higher staffing ratio and previous natural immunization reduced the probability of an outbreak following introduction. Despite strong preventive measures, transmission likely occurred, regardless of building characteristics. Vaccination started on January 15, 2021, and coverage reached 65.0% among residents, and 42.0% among staff by February 20, 2021. Vaccination yielded a 92% reduction (95%CI, 71%-98%) of outbreak probability, and lowered R to 0.87 (95%CI, 0.69-1.10). In the post-pandemic era, much attention will have to be paid to multi-lateral collaboration, policy making, and prevention plans., Competing Interests: Conflict of interests The data provider (Colisee group) had no role in the study design, data analysis or data interpretation. PE-H and VK are employed by the Colisee group. The views expressed in this publication are those of the authors and not necessarily those of the Colisee group., (copyright: © 2022 Delory et al.)

Maternal effects are an important source of phenotypic variance, whereby females influence offspring developmental trajectory beyond direct genetic contributions, often in response to changing environmental conditions. However, relatively little is known about the mechanisms by which maternal experience is translated into molecular signals that shape offspring development. One such signal may be maternal RNA transcripts (mRNAs and miRNAs) deposited into maturing oocytes. These regulate the earliest stages of development of all animals, but are understudied in most insects. Here we investigated the effects of female internal (body condition) and external (time of season) environmental conditions on maternal RNA in the maturing oocytes and 24-h-old eggs (24-h eggs) of alfalfa leafcutting bees. Using gene expression and WGCNA analysis, we found that females adjust the quantity of mRNAs related to protein phosphorylation, transcriptional regulation, and nuclease activity deposited into maturing oocytes in response to both poor body condition and shorter day lengths that accompany the late season. However, the magnitude of these changes was higher for time of season. Females also adjusted miRNA deposition in response to seasonal changes, but not body condition. We did not observe significant changes in maternal RNAs in response to either body condition or time of season in 24-h eggs, which were past the maternal-to-zygotic transition. Our results suggest that females adjust the RNA transcripts they provide for offspring to regulate development in response to both internal and external environmental cues. Variation in maternal RNAs may, therefore, be important for regulating offspring phenotype in response to environmental change., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hagadorn, Hunter, DeLory, Johnson, Pitts-Singer and Kapheim.)