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Summary: Background: Although immunomodulators have established benefit against the new coronavirus disease (COVID-19) in general, it is uncertain whether such agents improve outcomes without increasing the risk of secondary infections in the specific subgroup of previously immunocompromised patients. We assessed the effect of immunomodulators on outcomes of immunocompromised patients hospitalized for COVID-19. Methods: The protocol was prospectively registered with PROSPERO (CRD42022335397). MEDLINE, Cochrane Central Register of Controlled Trials and references of relevant articles were searched up to 01-06-2022. Authors of potentially eligible randomized controlled trials were contacted to provide data on immunocompromised patients randomized to immunomodulators vs control (i.e., placebo or standard-of-care). Findings: Eleven randomized controlled trials involving 397 immunocompromised patients hospitalized for COVID-19 were included. Ten trials had low risk of bias. There was no difference between immunocompromised patients randomized to immunomodulators vs control regarding mortality [30/182 (16.5%) vs 41/215 (19.1%); RR 0.93, 95% CI 0.61–1.41; p = 0.74], secondary infections (RR 1.00, 95% CI 0.64–1.58; p = 0.99) and change in World Health Organization ordinal scale from baseline to day 15 (weighed mean difference 0.27, 95% CI -0.09–0.63; p = 0.15). In subgroup analyses including only patients with hematologic malignancy, only trials with low risk of bias, only trials administering IL-6 inhibitors, or only trials administering immunosuppressants, there was no difference between comparators regarding mortality. Interpretation: Immunomodulators, compared to control, were not associated with harmful or beneficial outcomes, including mortality, secondary infections, and change in ordinal scale, when administered to immunocompromised patients hospitalized for COVID-19. Funding: Hellenic Foundation for Research and Innovation.

Background: Chorioamnionitis is recognized as a major consequence of preterm premature rupture of membranes (PPROM), and a frequent cause of neonatal morbidity and mortality. The association between fetal heart rate (FHR) and chorioamnionitis remains unclear., Objectives: The aim of this study was to evaluate the dynamics of FHR in a PPROM population at the approach of delivery according to the presence or absence of chorioamnionitis., Materials & Methods: 120 pregnant women with PPROM between 26 and 34 weeks' gestation were enrolled in this multicenter prospective unblinded study. All participants were fully informed of the study's objectives. 39 of the 120 patients were included in the analysis of FHR recordings. The analysis consisted of extracting features from computerized FHR analysis (cFHR) and fetal heart rate variability analysis (FHRV) in the temporal, frequency and nonlinear domains. Then, each set of features was analyzed separately using the multiple factor analysis, where three groups were defined as the feature set for days 0, -1 and -2 prior to birth. The distances between the global projection and the projections for each day were computed and used in the ROC analysis to distinguish chorioamnionitis from non-chorioamnionitis group., Results: The results showed that there were significant differences in certain features between populations with and without chorioamnionitis. The distinction between the two populations reached an area under the curve (AUC) of only 37% [34-40] for cFHR features and 63% [59-66] for time-domain FHRV features when comparing all stages of chorioamnionitis to non-chorioamnionitis subjects. When only stage 3 chorioamnionitis was compared to non-chorioamnionitis patients, the AUC reached 90% [88-93] for nonlinear-domain and 84% [82-87] for time-domain FHRV features, whereas it was limited to 71% [68-74] using cFHR features., Conclusion: The present study suggests that the HRV features are more reliable for diagnosing chorioamnionitis than cFHR, and that the assessment of features dynamics over several days is an interesting tool for detecting chorioamnionitis. Further study should be carried out on a larger sample to confirm these findings, improve the diagnostic performance of chorioamnionitis and help clinicians decide on delivery criteria., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Taoum et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Studies with negative results are less likely to be published than others, potentially leading to publication bias. Introduced in 2000, trial registration could have participated in decreasing the proportion of unpublished studies. We assessed the proportion of negative randomized controlled trials (RCT) over the last 20 years. We searched Medline for RCT published in 2000, 2005, 2010, 2015, and 2020 in the British Medical Journal, the Journal of the American Medical Association, the Lancet, and the New England Journal of Medicine. The primary endpoint was the proportion of negative (final comparison on the primary study-endpoint without statistical significance or favoring the control arm) studies published in 2000 and 2020. Factors independently associated with the publication of negative studies were identified using multivariable analysis. A total of 1,542 studies were included. The proportion of negative RCT significantly increased between 2000 and 2020 (from 27.6% to 37.4%; P = 0.01), however, the trend over time was not significant (P = 0.203). In multivariable analysis, the following factors were associated with a higher proportion of published negative studies: superiority (P < 0.001), two-group trials (P < 0.001), number of patients ≥510 (P < 0.001), cardiology trials (P = 0.003), emergency/critical care trials (P < 0.001), obstetrics trials (P = 0.032), surgery trials (P = 0.006), pneumology trials (P = 0.029). Exclusive industry funding was associated with a lower proportion of published negative studies (P < 0.001). The proportion of published negative studies in 2020 was higher only when compared to 2000. During the two decades, no trend was noticeable. There is no clear relationship between trial registration and the publication of negative results over time., (© 2025 The Author(s). Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

This study aimed to assess the feasibility of applying two recent phase I meta-analyses methods to protein kinase inhibitors (PKIs) developed in oncology and to identify situations where these methods could be both feasible and useful. This ancillary study used data from a systematic review conducted to identify dose-finding studies for PKIs. PKIs selected for meta-analyses were required to have at least five completed dose-finding studies involving cancer patients, with available results, and dose escalation guided by toxicity assessment. To account for heterogeneity caused by various administration schedules, some studies were divided into study parts, considered as separate entities in the meta-analyses. For each PKI, two Bayesian random-effects meta-analysis methods were applied to model the toxicity probability distribution of the recommended dose and to estimate the maximum tolerated dose (MTD). Meta-analyses were performed for 20 PKIs including 96 studies corresponding to 115 study parts. The median posterior probability of toxicity probability was below the toxicity thresholds of 0.20 for 70% of the PKIs, even if the resulting credible intervals were very wide. All approved doses were below the MTD estimated for the minimum toxicity threshold, except for one, for which the approved dose was above the MTD estimated for the maximal threshold. The application of phase I meta-analysis methods has been feasible for the majority of PKI; nevertheless, their implementation requires multiple conditions. However, meta-analyses resulted in estimates with large uncertainty, probably due to limited patient numbers and/or between-study variability. This calls into question the reliability of the recommended doses., (© 2024 The Author(s). Research Synthesis Methods published by John Wiley & Sons Ltd.)

Background: The way that pain is assessed in the PACU could impact on postoperative pain and analgesic consumption. However, there is currently no evidence to support this speculation. The authors hypothesised that using a comfort scale reduces postoperative opioid consumption when compared with a standard numerical rating scale (NRS) to evaluate pain in the PACU., Methods: In this cluster-randomised trial, patients were assessed using either a comfort scale (comfort group) or a pain NRS (NRS group). The primary outcome was the opioid consumption in the PACU. The main secondary outcomes were postoperative pain, nausea and vomiting, length of stay in the PACU, and satisfaction., Results: Of 885 randomised patients, 860 were included in the analysis. Opioid consumption in the PACU was comparable in the comfort and NRS groups (median [interquartile range [IQR] 0 (0-5) vs 0 (0-6); P=0.2436), irrespective of the type of surgical procedure. The majority of patients did not need any postoperative opioid (59% in the comfort group and 56% in the NRS group, P=0.2260). There was no difference in postoperative pain, nausea and vomiting, time to reach an Aldrete score ≥9 after extubation, and global satisfaction., Conclusions: Using a comfort scale to assess pain in the PACU did not spare any opioid compared with use of a standard NRS. Further studies focusing on patients at risk of increased postoperative opioid consumption are necessary., Clinical Trial Registration: NCT05234216., (Copyright © 2024 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Background: Pilot studies suggest potential effects of neck muscle vibration (NMV) and prism adaptation (PA) on postural balance disturbances related to spatial cognition., Objectives: To evaluate the effect of 10 sessions of NMV and/or PA on ML deviation. We used the mediolateral centre of pressure position (ML deviation) as a biomarker for spatial cognition perturbation, hypothesising that PA and NMV would improve ML deviation, with a potential synergistic impact when used together., Methods: We conducted a multicentre, single-blind, randomised controlled study. Participants within 9 months of a right-hemisphere supratentorial stroke and with less than 40% body weight supported on the paretic side in standing were randomised into 4 groups (PA, NMV, PA+NMV, or control)., Primary Outcome: ML deviation at Day 14., Secondary Outcomes: force platform data, balance abilities, autonomy, and ML deviation, measured just after the first session (Day 1), at Day 90, and Day 180. A generalised linear mixed model (GLMM) assessed intervention effects on these outcomes, adjusting for initial ML deviation and incorporating other relevant factors., Results: 89 participants were randomised and data from 80 participants, mean (SD) age 59.2 (10.2) years, mean time since stroke 94 (61) days were analysed. At Day 14, a weak time x group interaction (P = .001, omega-squared = 0.08) was found, with no significant between-group differences in ML deviation (P = .12) or in secondary outcomes (P = .08). Between-group differences were found on Day 1 (P = .03), Day 90 (P = .001) and Day 180 (P < .0001) regardless of age and stroke-related data. On Day 1, ML deviation improved in both the PA and NMV groups (P = .03 and P = .01). In contrast, ML deviation deteriorated in the NMV+PA group on Day 90 and Day 180 (P = .01 and P = .01)., Conclusions: The study found no evidence of any beneficial effects of repeated unimodal or combined sessions of NMV and/or PA on ML deviation after stroke., Trial Registration: ClinicalTrials.gov identifier NCT01677091., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier Masson SAS.)

Background: We assessed the prognostic value of serological humoral markers measured one month after the last dose of the primary COVID-19 vaccine course for predicting the risk of severe acute respiratory syndrome coronavirus 2 SARS-CoV-2 infection over the following six months in specific populations., Methods: ANRS0001SCOV-POPART is a French nationwide multicenter prospective observational cohort study assessing the immune response to Covid-19 vaccines routinely administered to 11 subgroups of patients with chronic disease and a control group. Participants from the ANRS0001S COV-POPART were included if they received at least two doses of Covid-19 vaccine for the primary vaccine course, had measurements of anti-Spike, anti-receptor binding domain (RBD) IgG-specific or neutralizing antibodies one month after the end of the primary vaccine course, without being infected by SARS-CoV-2 before the measurement. SARS-CoV-2 infections defined by a positive PCR/antigenic test or seroconversion to detectable anti nucleocapsid antibodies were evaluated until the first COVID-19 booster injection. Cox proportional hazards models taking into account interval-censored data were implemented to estimate the association between each antibody level and the risk of SARS-CoV-2 infection. Predictive performances were evaluated by the area under the receiving operating characteristic curve (AUROC)., Results: Two thousand five hundred seventy adults from a specific population and 1,123 from the control group were included. The cumulative probabilities of SARS-CoV-2 infections at five months after serological measurement were 6.0% 95% confidence interval: [5.0; 7.9] and 10.1% 95% confidence interval: [8.3; 11.9], respectively. Higher levels of anti-Spike IgG antibody were associated with a lower risk of SARS-CoV-2 infections in the control group, but not in the specific populations. Among the specific populations, AUROC were 74.5%, 74.9%, and 72.4% for anti-Spike IgG, anti-RBD IgG, and neutralizing antibodies, respectively. AUROC were superior in the specific populations, 82.0%, 81.2%, and 81.4% for anti-Spike IgG, anti-RBD IgG, and neutralizing antibodies, respectively., Conclusions: Vaccine-induced antibody response after the primary course of Covid-19 infection only moderately discriminated between participants developing a SARS-CoV-2 infection during the Omicron wave., Trial Registration: NCT04824651 (first posted: 2021-04-01)., (© 2024. The Author(s).)

Background: Sepsis is a leading cause of death and serious illness that requires early recognition and therapeutic management to improve survival. The quick-SOFA score helps in its recognition, but its diagnostic performance is insufficient. To develop a score that can rapidly identify a community acquired septic situation at risk of clinical complications in patients consulting the emergency department (ED)., Methods: We conducted a monocentric, prospective cohort study in the emergency department of a university hospital between March 2016 and August 2018 (NCT03280992). All patients admitted to the emergency department for a suspicion of a community-acquired infection were included. Predictor variables of progression to septic shock or death within the first 90 days were selected using backward stepwise multivariable logistic regression to develop a clinical score. Receiver operating characteristic (ROC) curves were constructed to determine the discriminating power of the area under the curve (AUC). We also determined the threshold of our score that optimized the performance required for a sepsis-worsening score. We have compared our score with the NEWS-2 and qSOFA scores., Results: Among the 21,826 patients admitted to the ED, 796 patients were suspected of having community-acquired infection and 461 met the sepsis criteria; therefore, these patients were included in the analysis. The median [interquartile range] age was 72 [54-84] years, 248 (54%) were males, and 244 (53%) had respiratory symptoms. The clinical score ranged from 0 to 90 and included 8 variables with an area under the ROC curve of 0.85 (confidence interval [CI] 95% 0.81-0.89). A cut-off of 26 yields a sensitivity of 88% (CI 95% 0.79-0.93), a specificity of 62% (CI 95% 57-67), and a negative predictive value of 95% (CI 95% 91-97). The area under the ROC curve for our score was 0.85 (95% CI, 0.81-0.89) versus 0.73 (95% CI, 0.68-0.78) for qSOFA and 0.66 (95% CI, 0.60-0.72) for NEWS-2., Conclusions: Our study provides an accurate clinical score for identifying septic patients consulting the ED early at risk of worsening disease. This score could be implemented at admission., (© 2024. The Author(s).)

Healthcare product procurement accounts for around 50% of the French healthcare system's greenhouse gas emissions. This lesson learned from the publication of the Shift Project's work in November 2021 has been a catalyst within the healthcare system, accelerating the consideration and implementation of actions aimed at reducing the environmental impact of the healthcare system, before, during and after care. In addition to their carbon footprint, healthcare products have a wide range of environmental impacts, including on water, air and soil, throughout their entire life cycle. We have chosen to divide this life cycle into four main stages: from research and development to production, distribution and market access, use and finally end-of-life management. Analysis of the regulatory framework at each stage and of existing initiatives described in the literature or by those in the field have structured and fuelled our thinking. We found that existing regulations focus exclusively on the health risk, with little or no consideration of the environmental risk, which is in itself a health risk. Furthermore, the implementation of certain structuring actions during the first 3 stages of the life cycle would make it possible to simplify or even eliminate the major problem of waste management associated with the end-of-life of healthcare products. With this in mind, we have produced 9 recommendations to ensure that the environmental impact of healthcare products is better taken into account throughout their life cycle., (Copyright © 2023 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.)

Background: Worldwide, chronic obstructive pulmonary disease (COPD) remains largely underdiagnosed., Aim: To assess whether the use of Global Initiative for Chronic Obstructive Lung Disease (GOLD) questions and COPD coordination, either alone or combined, would detect new COPD cases in primary care., Design and Setting: GPs in Brittany, France, systematically enrolled patients aged 40-80 years over a 4-month period in this French multicentre cluster randomised controlled study., Method: GPs were randomly allocated to one of four groups: control (standard of care), GOLD questions (adapted from symptoms and risk factors identified by GOLD), COPD coordination, and GOLD questions with COPD coordination. New cases of COPD were those confirmed by spirometry: post-bronchodilator forced expiratory volume in 1 second over forced vital capacity of <0.7., Results: In total, 11 430 consultations were conducted by 47 GPs, who enrolled 3162 patients who did not have prior diagnosed asthma or COPD. Among these, 802 (25%) were enrolled in the control, 820 (26%) in the GOLD questions, 802 (25%) in the COPD coordination, and 738 (23%) in the GOLD questions with COPD coordination groups. In the control group, COPD was not evoked, and no spirometry was prescribed. All new cases of COPD diagnosed ( n = 24, 0.8%) were in the intervention groups, representing 6.8% of patients who performed spirometry. Statistically significantly more new cases of COPD were detected with COPD coordination ( P = 0.01)., Conclusion: Interventions that can be easily implemented, such as the GOLD questions and COPD coordination, can identify new cases of COPD. Studies are needed to identify the most appropriate case-finding strategies for GPs to detect COPD in primary care for each country., (© The Authors.)

Objective: Ischemic stroke is a major health issue. Currently, the relationship between dietary patterns and the occurrence of cardiovascular diseases including stroke is established, but the effect of systematic dietary intervention on dietary changes in ischemic stroke patients is unknown. Our objective was to compare changes in the dietary pattern of ischemic stroke patients who received a systematic diet intervention with changes in the dietary pattern of ischemic stroke patients who did not receive a systematic dietary intervention during their hospitalization., Methods: In this before-and-after study, two groups of patients with ischemic stroke were compared: Group 1 included 34 patients admitted with an ischemic stroke without a systematic dietray intervention; Group 2 included 34 patients admitted with an ischemic stroke with a systematic dietary intervention. Dietary patterns were assessed by a validated food frequency questionnaire of 19 questions (from a previously validated questionnaire of 14 questions), at the onset of stroke and at 6 months after stroke. This questionnaire allows the calculation of different scores as follows: global food score, saturated fatty acids score (SFA), unsaturated fatty acids score (UFA), fruit and vegetable score, and alcohol score., Results: Score changes were more important in group 2 than in group 1 for the global food score (7.4 ± 7 vs. 1.9 ± 6.7, p = 0.0013), the fruit and vegetable score (2 ± 2.6 vs. 0.6 ± 2.2, p = 0.0047), and the UFA score (1.8 ± 2.7 vs. 0.1 ± 3.3, p = 0.0238), whereas no significant differences were observed for the SFA score (-3.9 ± 4.9 vs. -1.6 ± 6, p = 0.1779) and the alcohol score (-0.4 ± 1.5 vs. -0.3 ± 1.1, p = 0.6960)., Conclusion: This study showed that systematic dietary intervention during hospitalization improves the dietary patterns of ischemic stroke patients. The impact on the recurrence of ischemic stroke or cardiovascular events after dietary pattern changes needs to be studied., 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 Besseau, Sartori, Larnier, Paillard, Laviolle and Mahé.)

Background: After heart transplantation, calcineurin inhibitors (CNI) (cyclosporin A and tacrolimus) are key immunosuppressive drugs to prevent graft rejection. Whole-blood concentration (C blood )-guided therapeutic drug monitoring (TDM) is systematically performed to improve graft outcomes. However, some patients will still experience graft rejection and/or adverse events despite CNI C blood within the therapeutic range. Other pharmacokinetic parameters, such as the intragraft, or intracellular concentration at the CNI site of action could refine their TDM. Nonetheless, these remain to be explored. The objective of the INTRACAR study was to describe the relationship between whole blood, intragraft, and intracellular CNI concentrations as well as their efficacy in heart transplant recipients (HTR)., Methods: In a cohort of HTR, protocol endomyocardial biopsies (EMB) were collected to assess rejection by anatomopathological analysis. Part of the EMB was used to measure the intragraft concentrations of CNI (C EMB ). C blood and the concentration inside peripheral blood mononuclear cells, (C PBMC ), a cellular fraction enriched with lymphocytes, were also monitored. Concentrations in the 3 matrices were compared between patients with and without biopsy-proven acute rejection (BPAR)., Results: Thirty-four HTR were included, representing nearly 100 pharmacokinetic (PK) samples for each CNI. C blood , C EMB , and C PBMC correlated for both CNI. BPAR was observed in 74 biopsies (39.6%) from 26 patients (76.5%), all except one was of low grade. None of the PK parameters (C blood , C EMB , C PBMC , C EMB/blood , and C PBMC/blood ) was associated with BPAR., Conclusions: In this cohort of well-immunosuppressed patients, no association was observed for any of the PK parameters, including C blood , with the occurrence of BPAR. However, a trend was noticed for the C EMB and C EMB/blood of cyclosporin A. Further studies in higher-risk patients may help optimize the use of C EMB and C PBMC for CNI TDM in HTR., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: We aimed to investigate the 1-month humoral response to two or three doses of a messenger RNA coronavirus disease 2019 (COVID-19) vaccine as a primary vaccination regimen in specific populations compared with that in healthy adults., Methods: Agence Nationale Recherche contre le Sida (ANRS)0001S-COV-POPART (NCT04824651) is a French nation-wide, multi-centre, prospective, observational cohort study assessing the immune response to COVID-19 vaccines routinely administered to 11 sub-groups of patients with chronic conditions and two control groups. Patients and controls who received at least two vaccine doses and whose results 1 month after the second dose were available were included. The humoral response was assessed 1 month after the first, second and third doses (if applicable) based on the percentage of responders (positive for anti-Spike severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] IgG antibodies), geometric means of anti-Spike SARS-CoV-2 IgG antibodies (enzyme-linked immunosorbent assay) and proportion of participants with anti-SARS-CoV-2-specific neutralizing antibodies (in vitro neutralization assay for the original SARS-CoV-2 strain). All analyses were centralized., Results: We included 4091 participants in this analysis: 2979 participants from specific sub-populations and 1112 controls. Only 522 (17.5%) participants from the specific populations received three doses as a primary vaccination regimen. Patients living with human immunodeficiency virus, cancer and diabetes had high percentages of responders after two doses, whereas patients with solid organ transplants, allogeneic hematopoietic stem cell transplants and hypogammaglobulinaemia had the lowest percentage of responders (35.9% [95% CI, 29.2-43.0], 57.4% [95% CI, 48.1-66.3] and 77.1% [95% CI, 65.6-86.3], respectively). In those who received the third dose, the percentage of responders reached 54.2% (95% CI, 42.9-65.2) (vs. 32.3% [95% CI, 16.7-51.4] after 2 doses) among those with solid organ transplants and 73.9% (95% CI, 58.9-85.7) (vs. 56.1% [95% CI, 46.2-65.7] after 2 doses) among those with hematopoietic stem cell transplants. Similar results were found with anti-SARS-CoV-2-specific neutralizing antibodies., Conclusions: A lower humoral response to COVID-19 vaccines was observed in the specific populations compared with that in the controls. The third dose of this vaccine in the primary regimen had a positive effect on the percentages of patients who developed anti-Spike IgG antibodies and specific neutralizing antibodies., (Copyright © 2022 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Because of a narrow therapeutic index and a wide inter- and intra-patient variability, therapeutic drug monitoring of the immunosuppressant drug tacrolimus (TAC) based on whole-blood concentrations (C blood ) is mandatory in solid organ transplant recipients. Using peripheral blood mononuclear cells concentrations (C PBMC ) could improve patient outcomes. The poor correlation between C blood and C PBMC makes hypothesize that drug transporters are implicated in the intracellular accumulation of TAC. The aim of this work was therefore to clinically study: i) the role of genetic variants and ii) the effect of mRNA and protein expression of 4 drug transporters on the TAC C PBMC/blood ratio. In addition, functional in vitro experiments were performed to mechanistically validate the clinical observations. Genetic variants of ABCB1/P-gp and SLC28A3/CNT3 did not influence TAC C PBMC in liver transplant recipients (LTR). ABCC2/MRP2 at the mRNA level; ABCB1/P-gp, SLC28A3/CNT3 and SLC29A1/ENT1 at the protein level; correlated with the C PBMC/blood in kidney and LTR. In vitro results suing transporter-expressing cells confirmed that TAC is substrate of P-gp but not MRP2, whereas experiments remained inconclusive for CNT3 and ENT1. In conclusion, the genetic-transcription-protein-functional approach presented in this work provides new insights in the understanding of TAC transport at the T lymphocyte plasma membrane., Competing Interests: Declaration of competing interest Gwendal Coste's Ph.D. has been partly funded by Astellas Pharma. Florian Lemaitre has been invited to participation in congresses by Chiesi and Sandoz., (Copyright © 2022 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.)

Objective: The aim of the study was to evaluate the impact of the use of a reinforced stapler (RS) during distal pancreatectomy (DP) on postoperative outcomes., Background: DP remains associated with significant postoperative morbidity owing to pancreatic fistula (PF). To date, there is no consensus on the management of the pancreatic stump. The use of an RS potentially represents a simple way to decrease the rate of PF., Methods: The REPLAY study (NCT03030170) is a prospective, multicenter, randomized study. Patients who underwent DP were randomized (1:1 ratio) in 2 groups for the use of a standard stapler (SS) or an RS to close remnant pancreatic parenchyma. The primary endpoint was the rate of overall PF. Secondary endpoints included severity of PF, length of hospital stay, overall morbidity, and rate of readmission for a PF within 90 days. Participants were blinded to the procedure actually carried out., Results: A total of 199 were analyzed (SS, n=99; RS, n=100). One patient who did not undergo surgery was excluded. Baseline characteristics were comparable in both groups. The rate of overall PF was higher in RS group (SS: 67.7%, RS: 83%, P =0.0121), but the rate of clinically relevant PF was similar (SS: 11.1%, RS: 14%, P =0.5387). Mean length of total hospital stay, readmission for PF, postoperative morbidity, and mortality at 90 days were similar., Conclusion: The results of this randomized clinical trial did not favor the use of RS during DP to reduce the rate of PF., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Under-representation of women in high academic and medical positions is reported in many countries. This study aims to compare degrees and careers between men and women tenured as Full Professors of Medicine in recent years in France., Methods: We identified all new tenured French Full Professors between 2017 and 2021 and collected the publicly available data (gender, year of birth, curriculum) from the Bibliographic Agency for Higher Education, a public institution under the aegis of the Ministry for Higher Education Research and Innovation. The primary outcome was the gender difference in age appointment of Full Professors. Secondary outcomes were gender differences in career development., Results: Among 820 Full Professors, only 266 (32.4%) were women. They were tenured at a later age than men (43.7 vs 42.4 years, p<0.001), while they graduated for the MD (29.5 vs 29.9 years, p<0.005) or PhD (35.3 vs 36.0 years, p<0.05) several months earlier. Women were also more often Associate Professors than men before becoming Full Professors (67.3% vs 59.2%, p<0.05).  Before achieving Full professor tenure, the average delay is longer for women from MD graduation (14.6 vs 12.5 years), PhD graduation (8.7 vs 6.4 years), or Associate Professor nomination (7.5 vs 5.5 years), with a difference of 2.2, 2.4 and 2.0 years respectively (p<0.001 for all comparisons)., Conclusion: Gender inequalities remain in regards to access to Full Professor status, the highest position in the medical fields., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Background: In sepsis, neutrophil respiratory bursts participate in endothelium damage, the first step to multiple organ failure. In plasma two antioxidant selenoenzymes, which protect the endothelium, decrease: selenoprotein-P, and to a lesser extent glutathione peroxidase (GPX3). Sodium selenite (Na 2 SeO 3 ) is a Se donor, but also an oxidant chemotherapy drug depending on its concentration. In a previous published study, Na 2 SeO 3 continuous infusion in septic shock patients at a pharmacological dose of 4 mg 1 Se/day on day-1, followed by a high nutritional dose of 1 mg Se/day during 9 days, showed no beneficial effect on weaning of catecholamine nor on survival. In this ancillary study, we report clinical and biological effects of such continuous infusion of Na 2 SeO 3. METHODS: This was a multicenter, placebo-controlled, double-blind study on 60 patients. Na 2 SeO 3 or placebo in continuous infusion as described above. Evolution with time of plasma Se, selenoprotein-P, GPX3, Organ dysfunction (sequential organ failure assessment SOFA scores, including PaO2/FiO2, for respiratory failure, and plasma lactate) and quality of life at 6 months (by SF36 scores) were analyzed using two-way (time, treatment) non-parametric repeated-measures analysis of variance (Friedman test)., Main Results: At baseline, plasma Se was about a quarter of reference values. From baseline to day-4 plasma Se, selenoprotein-P and GPX3 significantly increased by 3.9, 2.7 and 1.8 respectively in the Na 2 SeO 3 group as compared with placebo and remained elevated by 2.3, 2.7 and 2.1 at day-14 respectively (p < 0.001). Na 2 SeO 3 did not affect global and organ by organ SOFA Scores and plasma lactate concentration at day-1 and later up to day-14. The evolution of PaO2/FiO2 until day-14 was similar in the two groups. Quality of life in the surviving patients at 6 months was similar between the two groups., Conclusion: Continuous infusion of Na 2 SeO 3 at 4 mg Se at day-1 seems to have neither beneficial nor toxic effect at day-1 or later and induces a late increase of selenoprotein-P at day-4. Preclinical studies are required to confirm the use of Na 2 SeO 3 as a cytotoxic drug against neutrophils and protection of the endothelium by selenoprotein-P., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Background: Although effective mRNA vaccines for SARS-CoV-2 infection have been deployed worldwide, their interchangeability could facilitate the scale-up of vaccination programs. The objective of the trial was to assess whether the immune response induced by a heterologous SARS-CoV-2 mRNA primo vaccination is non-inferior to that of a homologous mRNA vaccination., Methods: We conducted a multicenter, randomized, open-label trial in adults 18 years of age and older who received a first dose of SARS-CoV-2 mRNA vaccine. Participants were randomly assigned in a 1:1 ratio to receive a second dose of BNT162b2 or mRNA-1273, 28 to 49 days after the first dose. Randomization was stratified on the vaccine received at the first vaccination. The primary endpoint was the anti-spike IgG antibodies titer measured 28 days after the second vaccine dose. This study is registered with ClinicalTrials.gov, Trial, NCT04900467., Findings: Of the 414 randomized participants recruited from May 28 to July 2, 2021, 390 were included in the per protocol analysis: 94 participants in group 1 (BNT162b2/BNT162b2), 96 in group 2 (BNT162b2/mRNA-1273), 97 in group 3 (mRNA-1273/mRNA-1273), and 103 in group 4 (mRNA-1273/BNT162b2). The geometric mean titers ratios of anti-spike IgG antibodies for each heterologous regimen relative to the corresponding homologous regimen were 1·37 (two-sided 95% CI, 1·10 to 1·72) in the groups 1 and 2 and 0·67 (two-sided 95% CI, 0·55 to 0·82) in the groups 3 and 4. Levels of neutralizing antibodies to the main circulating SARS-Cov-2 viral strains were higher with the vaccine regimen containing mRNA-1273. Participants who received mRNA-1273 as a second dose experienced a higher rate of local adverse reactions and general symptoms than those who received BNT162b2 ( p  < 0·0001)., Interpretation: The two SARS-CoV-2 mRNA vaccines could be used with flexibility for the second dose of COVID-19 primo vaccination. Tolerance remains good regardless of vaccine sequence although mRNA-1273 was more reactogenic., Funding: French Ministries of Solidarity and Health and Research. BNT162b2 was provided by Pfizer/BioNTech. mRNA-1273 was provided by Moderna., Competing Interests: OL reports grant from French ministry of health and grants or contracts from Pfizer, Sanofi-Pasteur, GSK, MSD, AstraZeneca and Janssen. CJ reports fees for boardmembership from AstraZeneca, Pfizer and MSD. TS reports grant from DGOS (French Ministry of health), AstraZeneca, Bayer, Novartis, Sanofi, Boehringer, Daiichi Sankyo, Eli Lilly, GSK and personal fees for boardmembership and consulting from various pharmaceutical companies, including AstraZeneca, Sanofi, Bayer, Ablative Solutions and 4 Living Biotech. KL reports personal fees from Gilead, MSD, Janssen, ViiV, Spikimm and fees for development of educational presentations from Janssen, Gilead, MSD, Sobi, and Chiesi. PL reports personal fees for board membership from Pfizer, Janssen, AstraZeneca, MSD, Viiv, GSK, consultancy and travel accommodation from Pfizer. EBN has received grant pending from Sanofi Pasteur and fees for board membership from Pfizer, and Janssen. MB reports travels grants from various pharmaceutical companies, including Pfizer, Novex, Janssen. XDL reports research grant from INSERM., (© 2022 The Authors.)

Background: Transparency and reproducibility are expected to be normative practices in clinical trials used for decision-making on marketing authorisations for new medicines. This registered report introduces a cross-sectional study aiming to assess inferential reproducibility for main trials assessed by the European Medicines Agency., Methods: Two researchers independently identified all studies on new medicines, biosimilars and orphan medicines given approval by the European Commission between January 2017 and December 2019, categorised as 'main studies' in the European Public Assessment Reports (EPARs). Sixty-two of these studies were randomly sampled. One researcher retrieved the individual patient data (IPD) for these studies and prepared a dossier for each study, containing the IPD, the protocol and information on the conduct of the study. A second researcher who had no access to study reports used the dossier to run an independent re-analysis of each trial. All results of these re-analyses were reported in terms of each study's conclusions, p-values, effect sizes and changes from the initial protocol. A team of two researchers not involved in the re-analysis compared results of the re-analyses with published results of the trial., Results: Two hundred ninety-two main studies in 173 EPARs were identified. Among the 62 studies randomly sampled, we received IPD for 10 trials. The median number of days between data request and data receipt was 253 [interquartile range 182-469]. For these ten trials, we identified 23 distinct primary outcomes for which the conclusions were reproduced in all re-analyses. Therefore, 10/62 trials (16% [95% confidence interval 8% to 28%]) were reproduced, as the 52 studies without available data were considered non-reproducible. There was no change from the original study protocol regarding the primary outcome in any of these ten studies. Spin was observed in the report of one study., Conclusions: Despite their results supporting decisions that affect millions of people's health across the European Union, most main studies used in EPARs lack transparency and their results are not reproducible for external researchers. Re-analyses of the few trials with available data showed very good inferential reproducibility., Trial Registration: https://osf.io/mcw3t/., (© 2022. The Author(s).)

Background: The optimal right ventricular pacing site for patients requiring pacemaker implantation for permanent atrioventricular block is a matter of debate. Long-term right ventricular apical pacing has been associated with left ventricular ejection fraction impairment and heart failure. Right ventricular septal pacing has been proposed as an alternative., Aim: The aim of this randomized prospective multicentre trial was to compare left ventricular remodelling and outcomes between right ventricular apical and septal pacing after mid-term follow-up., Methods: Patients requiring pacemaker implantation for high-degree atrioventricular block were enrolled and randomized in a 1:1 fashion to receive a right ventricular apical or septal lead., Results: A total of 141 patients were included, 69 in the septal group and 72 in the apical group. Both groups exhibited similar left ventricular ejection fractions after 18 months of follow-up (septal 57.1±11.9% vs. apical 57.4±13.4%), and left ventricular ejection fraction variation was similar in the two groups at the end of follow-up (septal -1.5±13.2% vs. apical 0.3±13.3%). Additionally, left ventricular volume, quality of life and 6-minute walk distance were similar in the two groups. However, patients in the septal group were more likely to be asymptomatic, with a significantly lower concentration of N-terminal prohormone of brain natriuretic peptide. Lastly, lead position did not impact 18-month survival., Conclusion: Pacing from the right ventricular apex does not have any detrimental effect on left ventricular systolic function compared with septal pacing over an 18-month period., (Copyright © 2022. Published by Elsevier Masson SAS.)

Background: Tivozanib (Fotivda) is an anti-angiogenic tyrosine kinase inhibitor that was denied access to the US market by the Food and Drug Administration (FDA). In contrast, it was granted approval by the European Medicines Agency (EMA) for the treatment of Renal Cell Carcinoma in adults. Given the conflicting decisions from these regulatory agencies, the objectives of the following study are (i) to critically review the evidence supporting the approval of tivozanib; (ii) to analyse the dissemination of this evidence in the literature by way of a citation analysis., Methods: Pivotal trials were searched by two independent reviewers using Medline, Cochrane Library, ClinicalTrials.gov and the European Public Assessment Report. The risk of bias for each trial was then inductively assessed. Articles citing any of these trials were identified using Web of Sciences. Finally, the quality of the citations was evaluated by two independent reviewers according to standard data extraction methods., Results: The search for primary evidence identified two pivotal studies: TIVO-1 upon which the FDA and the EMA decisions were based, and TIVO-3 which was conducted after the agencies' decisions had been issued. The TIVO-1 trial presented several limitations that compromised causal inference, in relation to (i) design (absence of blinding, inappropriate comparator, and one-way crossover), (ii) poor internal consistency in the results for the primary endpoint, (iii) a discrepancy between a benefit observed for progression-free survival (HR: 0.80, 95% CI [0.64-0.99]) and the absence of difference for overall survival (HR: 1.25, 95% CI [0.95 - 1.62]). Our citation search protocol identified 229 articles that cited TIVO-1 in the 7 years following its publication, among which 151 (65.9%) citing articles discussing efficacy. Presence of spin was identified in 64 (42.4%) of these 151 citing articles, and 39 (25.8%) additional articles citing results without providing enough elements to interpret the TIVO-1 results., Conclusion: EMA's approval was based on a single pivotal trial presenting critical limitations, rendering the results from the trial potentially inconclusive. The broad dissemination of TIVO-1 results in the scientific literature may have been affected by spin or results were presented in an inadequate critical manner., (© 2022. The Author(s).)

Background: It is speculated that the anesthetic strategy during endovascular therapy for stroke may have an impact on the outcome of the patients. The authors hypothesized that conscious sedation is associated with a better functional outcome 3 months after endovascular therapy for the treatment of stroke compared with general anesthesia., Methods: In this single-blind, randomized trial, patients received either a standardized general anesthesia or a standardized conscious sedation. Blood pressure control was also standardized in both groups. The primary outcome measure was a modified Rankin score less than or equal to 2 (0 = no symptoms; 5 = severe disability) assessed 3 months after treatment. The main secondary outcomes were complications, mortality, reperfusion results, and National Institutes of Health Stroke Scores at days 1 and 7., Results: Of 351 randomized patients, 345 were included in the analysis. The primary outcome occurred in 129 of 341 (38%) of the patients: 63 (36%) in the conscious sedation group and 66 (40%) in the general anesthesia group (relative risk, 0.91 [95% CI, 0.69 to 1.19]; P = 0.474). Patients in the general anesthesia group experienced more intraoperative hypo- or hypertensive episodes, while the cumulative duration was not different (mean ± SD, 36 ± 31 vs. 39 ± 25 min; P = 0.079). The time from onset and from arrival to puncture were longer in the general anesthesia group (mean difference, 19 min [i.e., -00:19] [95% CI, -0:38 to 0] and mean difference, 9 min [95% CI, -0:18 to -0:01], respectively), while the time from onset to recanalization was similar in both groups. Recanalization was more often successful in the general anesthesia group (144 of 169 [85%] vs. 131 of 174 [75%]; P = 0.021). The incidence of symptomatic intracranial hemorrhage was similar in both groups., Conclusions: The functional outcomes 3 months after endovascular treatment for stroke were similar with general anesthesia and sedation. Our results, therefore, suggest that clinicians can use either approach., (Copyright © 2022, the American Society of Anesthesiologists. All Rights Reserved.)

Background: Patients with severe COVID-19 have emerged as a population at high risk of invasive fungal infections (IFIs). However, to our knowledge, the prevalence of IFIs has not yet been assessed in large populations of mechanically ventilated patients. We aimed to identify the prevalence, risk factors, and mortality associated with IFIs in mechanically ventilated patients with COVID-19 under intensive care., Methods: We performed a national, multicentre, observational cohort study in 18 French intensive care units (ICUs). We retrospectively and prospectively enrolled adult patients (aged ≥18 years) with RT-PCR-confirmed SARS-CoV-2 infection and requiring mechanical ventilation for acute respiratory distress syndrome, with all demographic and clinical and biological follow-up data anonymised and collected from electronic case report forms. Patients were systematically screened for respiratory fungal microorganisms once or twice a week during the period of mechanical ventilation up to ICU discharge. The primary outcome was the prevalence of IFIs in all eligible participants with a minimum of three microbiological samples screened during ICU admission, with proven or probable (pr/pb) COVID-19-associated pulmonary aspergillosis (CAPA) classified according to the recent ECMM/ISHAM definitions. Secondary outcomes were risk factors of pr/pb CAPA, ICU mortality between the pr/pb CAPA and non-pr/pb CAPA groups, and associations of pr/pb CAPA and related variables with ICU mortality, identified by regression models. The MYCOVID study is registered with ClinicalTrials.gov, NCT04368221., Findings: Between Feb 29 and July 9, 2020, we enrolled 565 mechanically ventilated patients with COVID-19. 509 patients with at least three screening samples were analysed (mean age 59·4 years [SD 12·5], 400 [79%] men). 128 (25%) patients had 138 episodes of pr/pb or possible IFIs. 76 (15%) patients fulfilled the criteria for pr/pb CAPA. According to multivariate analysis, age older than 62 years (odds ratio [OR] 2·34 [95% CI 1·39-3·92], p=0·0013), treatment with dexamethasone and anti-IL-6 (OR 2·71 [1·12-6·56], p=0·027), and long duration of mechanical ventilation (>14 days; OR 2·16 [1·14-4·09], p=0·019) were independently associated with pr/pb CAPA. 38 (7%) patients had one or more other pr/pb IFIs: 32 (6%) had candidaemia, six (1%) had invasive mucormycosis, and one (<1%) had invasive fusariosis. Multivariate analysis of associations with death, adjusted for candidaemia, for the 509 patients identified three significant factors: age older than 62 years (hazard ratio [HR] 1·71 [95% CI 1·26-2·32], p=0·0005), solid organ transplantation (HR 2·46 [1·53-3·95], p=0·0002), and pr/pb CAPA (HR 1·45 [95% CI 1·03-2·03], p=0·033). At time of ICU discharge, survival curves showed that overall ICU mortality was significantly higher in patients with pr/pb CAPA than in those without, at 61·8% (95% CI 50·0-72·8) versus 32·1% (27·7-36·7; p<0·0001)., Interpretation: This study shows the high prevalence of invasive pulmonary aspergillosis and candidaemia and high mortality associated with pr/pb CAPA in mechanically ventilated patients with COVID-19. These findings highlight the need for active surveillance of fungal pathogens in patients with severe COVID-19., Funding: Pfizer., Competing Interests: Declaration of interests J-PG reports personal fees from Gilead and grants and personal fees from Pfizer, outside of the submitted work. ED reports grants and non-financial support from Merck Sharp & Dohme and Gilead and non-financial support from Pfizer and Astellas, outside of the submitted work. AF reports personal fees and non-financial support from Merck Sharp & Dohme, grants from Janssen, personal fees and non-financial support from Gilead, and non-financial support from Pfizer, outside of the submitted work. C-EL reports personal fees from Carmat, Merck, BioMérieux, Brahms (part of Thermo Fisher Scientific), Bayer Healthcare, and Faron, outside of the submitted work. FraB reports grants from Astellas, personal fees from Merck Sharp & Dohme, and non-financial support from Pfizer, Merck Sharp & Dohme, and Astellas, outside of the submitted work. J-FT reports personal fees from Pfizer, Merck, Astellas, and Gilead, outside of the submitted work. FP reports non-financial support from Gilead and Pfizer, outside of the submitted work. EmC reports personal fees from Gilead, Baxter, and Sanofi-Genzyme, outside of the submitted work. AA reports personal fees from Pfizer and Gilead, outside of the submitted work. MC reports grants from Pfizer, outside of the submitted work. JuM reports non-financial support from Gilead, outside of the submitted work. SE reports grants, personal fees, and non-financial support from Aerogen and Fisher & Paykel, outside of the submitted work. GV reports grants and personal fees from BioMérieux and grants from SOS Oxygène and Janssen, outside of the submitted work. JeM reports grants from Pfizer and Gilead, outside of the submitted work. J-RZ reports grants and personal fees from Merck Sharp & Dohme and personal fees from Novartis and Pfizer, outside of the submitted work. M-EB reports grants from Pfizer during the conduct of the study; grants and non-financial support from Gilead and Pfizer, and non-financial support from Merck Sharp & Dohme, outside of the submitted work. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Clinical research in outpatient healthcare, particularly in general practice, which is the first line of contact with the population, is now a public health issue. However, this type of research has specific characteristics that differentiate it from clinical research conducted in a hospital setting and requires an adaptation of its conditions of practice: in terms of organisation, the development of research in outpatient healthcare relies on the appropriation of its fundamentals by the investigators, which implies their presentation, upstream, from the initial cycle, and the participation of practitioners in training modules adapted to research in primary care, such as those already organised by several GIRCI (Groupement Inter régional de la Recherche Clinique et de l'Innovation [French Interregional Clusters for Clinical Research and Innovation]). To compensate for the fragmented nature of their location, on the model of the EMRCs (équipes mobiles de recherche clinique [mobile clinical research teams]) in oncology, mobile research teams should enable general medical practices to participate in clinical trials. This presupposes, on the one hand, the allocation of earmarked funding to ensure the sustainability of a base of dedicated personnel and, on the other hand, the impetus of a national dynamic through the setting up of a multi-organisation thematic institute for "research in primary care" associated, at the operational level, with a national scale investigation network supported by a platform of excellence. The use of digital tools and innovations (telemedicine; data collection via connected tools; e-consent; electronic signature) which make it possible to digitise and relocate all or part of the research procedures for both the participant and the investigation teams. An adaptation of the legal framework in order to bring the place of research closer to the patient and not the other way round, which means moving the equipment and investigations closer to the patient. Taking into account the acceptability of the patient, thus limiting the disruption that may be caused by his or her participation in a research protocol and motivating the practitioner by valuing his or her contribution and providing all the guarantees of scientific relevance and independence of practice. In view of the contextual analysis, positive feedback and the availability of organisational and digital support points facilitating the delocalisation and digitisation of the conduct of research activity as close as possible to the patient and his or her doctor, the round table concluded that opportunities exist today which favour the development of clinical research in general practice. It is important to seize this opportunity and make the most of it without delay., (Copyright © 2022. Published by Elsevier Masson SAS.)

Fluoroquinolones efficacy depend on both the drug exposure and the level of drug resistance of the bacteria responsible for the infection. Specifically for the Staphylococcus species, which is the microorganism mainly involved in osteoarticular infections (OAI), in-vitro data reported that an AUC/MIC ratio above 115 h maximizes drug efficacy. However, data on OAI patients are lacking and a simple approach to access AUCs is still a clinical issue. We conducted a prospective, single-center study in 30 OAI patients hospitalized in the Rennes University Hospital to model ofloxacin pharmacokinetics and to define a limited sampling strategy (LSS) suitable for ofloxacin and levofloxacin treatments. Modeling was conducted with the Monolix software. The final model was externally validated using levofloxacin data. Monte-Carlo simulations were used to evaluate the probability of target attainment (PTA) of different dosing regimens. Two hundred and ninety-seven (297) ofloxacin concentrations were available for the pharmacokinetic modeling. Ofloxacin pharmacokinetics was best described using a bicompartmental model with a first order elimination, and a transit compartment model absorption. CKD-EPI and sex explained half of ofloxacin pharmacokinetic variability. For LSS, the 0, 1 h and 3 h sampling scheme resulted in the best approach both for BID and TID dosages (R 2 adjusted = 91.1% and 95.0%, outliers = 4.8% and 5.0%, respectively). PTA allows choosing the best drug and dosage according to various hypotheses. A simple 3-sample protocol (pre-dose, 1 h after intake and 3 h after intake) to estimate ofloxacin and levofloxacin AUC allows optimal drug dosage for the treatment of osteoarticular infections., (Copyright © 2021. Published by Elsevier Masson SAS.)

Background: Diet strongly influences cardiovascular risk. Dietary evaluation is a major issue in cardiovascular prevention, but few simple tools are available. Our team previously validated a short food frequency questionnaire; a new version of this questionnaire (Cardiovascular Dietary Questionnaire 2 [CDQ-2]) is easier to complete and more reliable., Aims: To validate CDQ-2 in comparison with the original version, and to test its reproducibility., Methods: CDQ-2 has 17 closed-ended questions; it provides a global dietary score that is a combination of specific scores for saturated, monounsaturated and omega-3 fatty acids, and fruit and vegetables. CDQ-2 was validated against the original version in two groups, who completed both questionnaires: 99 patients with cardiovascular risk factors and 50 healthy subjects. Reproducibility was assessed with 27 health professionals who completed the questionnaire twice, with a 1-month interval., Results: The correlation coefficients of the scores between the two questionnaires ranged from 0.65 (monounsaturated fatty acids) to 0.93 (fruit and vegetables) (all P<0.001). The percentage of subjects classified in the same quartile by both questionnaires ranged from 56% (omega-3 fatty acids) to 78% (fruit and vegetables). The percentage of subjects classified in the same or adjacent quartile ranged from 91% to 99%. The intraclass correlation coefficients, which assessed reproducibility, ranged from 0.61 (fruit and vegetables) to 0.88 (saturated fatty acids) (P<0.001)., Conclusions: This new version of the short dietary questionnaire shows good reproducibility and correlations with the original version; use and reliability are improved, which makes CDQ-2 a valuable tool for cardiovascular prevention., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Introduction: Women are under-represented in senior academic and hospital positions in many countries. The authors aim to assess the place and the evolution of all appointed female and male health practitioners' working in French public Hospitals., Materials and Methods: Data of this observational study were collected from the National Management Centre (Centre National de Gestion) from 2015 up to January 1, 2020. First, the authors described demographic characteristics and specialties of all appointed medicine, pharmacy, and dentistry doctors' working as Hospital Practitioners, Associate Professors, and Full Professors in French General and University-affiliated Hospitals in 2020. Then, they retrospectively reported the annual incidence of new entrance according to gender and professional status from 1999 to 2019 thanks to the appointment date of all practitioners in activity between 2015 and 2020., Results: In 2020, 51 401 appointed practitioners (49.7% of female) were in activity in French public hospitals with a large majority being medical doctors (92.4%) compared to pharmacists (6%) and dentists (1.6%). Women represented 52.5% of the Hospital Practitioners, 48.6% of the Associate Professors, and 22.0% of the Full Professors (p < 0.001). There were disparities between the rates of female Full Professors in medicine (20.6%), pharmacy (36.1%), and dentistry (44.3%, p < 0.001). Women were appointed Hospital Practitioners and Associate Professors earlier than men (respectively 37.1 versus 38.8 years, p < 0.001 and 36.1 versus 36.5 years, p = 0.04), and at a later age among Full Professors (43.7 versus 41.9 years, p < 0.001). Compared to men, the annual proportion of appointed women varied significantly between 1999 and 2019 from 47.6% to 60.4% for Hospital Practitioners, from 50.0% to 44.6% for Associate Professors, and from 11.2% to 33.3% for Full Professors (p < 0.001 for trend)., Conclusions: Although more and more women occupy positions in French hospitals, there is still a gender gap regarding access to Full Professor status in medicine and pharmacy, but not in dentistry. The disparity in numbers makes comparison difficult. Despite a trend towards gender equality during the last twenty years, it has not yet been achieved regarding access to the highest positions., Competing Interests: The authors have declared that no competing interests exist.

Objective: Male sex is one of the determinants of severe coronavirus diseas-e-2019 (COVID-19). We aimed to characterize sex differences in severe outcomes in adults with diabetes hospitalized for COVID-19., Methods: We performed a sex-stratified analysis of clinical and biological features and outcomes (i.e. invasive mechanical ventilation (IMV), death, intensive care unit (ICU) admission and home discharge at day 7 (D7) or day 28 (D28)) in 2380 patients with diabetes hospitalized for COVID-19 and included in the nationwide CORONADO observational study (NCT04324736)., Results: The study population was predominantly male (63.5%). After multiple adjustments, female sex was negatively associated with the primary outcome (IMV and/or death, OR: 0.66 (0.49-0.88)), death (OR: 0.49 (0.30-0.79)) and ICU admission (OR: 0.57 (0.43-0.77)) at D7 but only with ICU admission (OR: 0.58 (0.43-0.77)) at D28. Older age and a history of microvascular complications were predictors of death at D28 in both sexes, while chronic obstructive pulmonary disease (COPD) was predictive of death in women only. At admission, C-reactive protein (CRP), aspartate amino transferase (AST) and estimated glomerular filtration rate (eGFR), according to the CKD-EPI formula predicted death in both sexes. Lymphocytopenia was an independent predictor of death in women only, while thrombocytopenia and elevated plasma glucose concentration were predictors of death in men only., Conclusions: In patients with diabetes admitted for COVID-19, female sex was associated with lower incidence of early severe outcomes, but did not influence the overall in-hospital mortality, suggesting that diabetes mitigates the female protection from COVID-19 severity. Sex-associated biological determinants may be useful to optimize COVID-19 prevention and management in women and men.