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Abstract Background Over the past three decades, our understanding of sleep apnea in women has advanced, revealing disparities in pathophysiology, diagnosis, and treatment compared to men. However, no real-life study to date has explored the relationship between mask-related side effects (MRSEs) and gender in the context of long-term CPAP. Methods The InterfaceVent-CPAP study is a prospective real-life cross-sectional study conducted in an apneic adult cohort undergoing at least 3 months of CPAP with unrestricted mask-access (34 different masks, no gender specific mask series). MRSE were assessed by the patient using visual analog scales (VAS). CPAP-non-adherence was defined as a mean CPAP-usage of less than 4 h per day. The primary objective of this ancillary study was to investigate the impact of gender on the prevalence of MRSEs reported by the patient. Secondary analyses assessed the impact of MRSEs on CPAP-usage and CPAP-non-adherence depending on the gender. Results A total of 1484 patients treated for a median duration of 4.4 years (IQ25–75: 2.0–9.7) were included in the cohort, with women accounting for 27.8%. The prevalence of patient-reported mask injury, defined as a VAS score ≥ 5 (p = 0.021), was higher in women than in men (9.6% versus 5.3%). For nasal pillow masks, the median MRSE VAS score for dry mouth was higher in women (p = 0.039). For oronasal masks, the median MRSE VAS score for runny nose was higher in men (p = 0.039). Multivariable regression analyses revealed that, for both women and men, dry mouth was independently and negatively associated with CPAP-usage, and positively associated with CPAP-non-adherence. Conclusion In real-life patients treated with long-term CPAP, there are gender differences in patient reported MRSEs. In the context of personalized medicine, these results suggest that the design of future masks should consider these gender differences if masks specifically for women are developed. However, only dry mouth, a side effect not related to mask design, impacts CPAP-usage and non-adherence. Trial Registration: InterfaceVent is registered with ClinicalTrials.gov (NCT03013283).First registration date is 2016–12-23.

Summary: Background: Patients with obesity are at high-risk of extubation failure. Discrepancies were found in the results of recent randomized controlled trials (RCTs) regarding the roles of noninvasive ventilation (NIV), high flow nasal cannula (HFNC) and conventional oxygen therapy (COT) to prevent extubation failure in critically ill patients with obesity. Methods: In this systematic review and network meta-analysis, we searched MEDLINE, Cochrane Center Register of Controlled Trials and Web of Science from 1 January 1998 to 1 July 2024 for RCTs evaluating noninvasive respiratory support therapies (NIV, HFNC, COT, NIV + HFNC) after extubation in critically ill adults with obesity. Primary outcome was reintubation at day 7. Secondary outcome was 28-day mortality. We generated pooled risk ratios (RR) and numbers needed to treat (NNT). We rated risk of bias using the Cochrane risk-of-bias 2.0 tool. The study was registered with PROSPERO (CRD 42022308995). Findings: In seven RCTs including 1933 patients, NIV + HFNC (RR 0.36 [95% confidence interval (CI) 0.16–0.82], NNT = 10 [95% CI 7–33]) and NIV (RR 0.45 [95% CI 0.23–0.88], NNT = 11 [95% CI 8–50]) but not HFNC (RR 0.79 [95% CI 0.40–1.59]) reduced reintubation at day 7, compared to COT. Compared to HFNC, NIV + HFNC (RR 0.46 [95% CI 0.23–0.90], NNT = 14 [95% CI 10–77]) but not NIV (RR 0.57 [95% CI 0.32–1.02]) reduced reintubation at day 7. Compared to HFNC, both NIV (RR 0.31 [95% CI 0.13–0.74], NNT = 15 [95% CI 12–40]) and NIV + HFNC (RR 0.30 [95% CI 0.10–0.89], NNT = 15 [95% CI 11–90]) reduced 28-day mortality. Interpretation: The results suggest that compared to COT and HFNC, NIV alone or with HFNC reduces reintubation in critically ill patients with obesity after extubation. Compared to HFNC, NIV alone or with HFNC reduces mortality. The number needed to treat with NIV or NIV + HFNC to avoid one death was 15. These findings support the application of NIV to mitigate extubation failure in critically ill adults with obesity. Funding: None.

Introduction Biologics provide significant benefits in asthma, reducing exacerbations and symptoms. Some biologics have shown promising results in small subgroups of patients with chronic obstructive pulmonary disease (COPD) and frequent exacerbations. Nevertheless, real-life data on the size of the COPD target population remain scarce.Methods We analysed the characteristics of COPD and coexisting asthma and COPD patients included in the prospective multicentre, French COhort of BRonchial obstruction and Asthma, between 2008 and 2023 and evaluated the number of patients who could correspond to the inclusion criteria of randomised controlled trials evaluating various biologics targeting interleukin 33 (IL-33) (-receptor), IL-5 (-receptor), IL-4Rα or TSLP, in routine clinical practice.Results Among 434 COPD patients, only 21.7% met inclusion criteria for at least one biologic. Among patients with asthma, 54 (3.5%) had coexisting features of COPD in terms of age, smoking status and airflow obstruction and met inclusion criteria for at least one biologic. Notably, these patients were predominantly female, with worse lung function. Globally, the target chronic airway diseases population of the eagerly awaited biologics remains limited to a small part (ie, 1.3%–8%, depending on the biologic).Conclusion In a real-life COPD and asthma population (including asthmatic patients with features of COPD), the proportion of patients satisfying selection criteria applied in randomised controlled trials assessing the efficacy of biologics remains limited to less than 10% of the whole population.

Abstract Background The objective was to compare sevoflurane, a volatile sedation agent with potential bronchodilatory properties, with propofol on respiratory mechanics in critically ill patients with COPD exacerbation. Methods Prospective study in an ICU enrolling critically ill intubated patients with severe COPD exacerbation and comparing propofol and sevoflurane after 1:1 randomisation. Respiratory system mechanics (airway resistance, PEEPi, trapped volume, ventilatory ratio and respiratory system compliance), gas exchange, vitals, safety and outcome were measured at inclusion and then until H48. Total airway resistance change from baseline to H48 in both sevoflurane and propofol groups was the main endpoint. Results Sixteen patients were enrolled and were sedated for 126 h(61–228) in the propofol group and 207 h(171–216) in the sevoflurane group. At baseline, airway resistance was 21.6cmH2O/l/s(19.8–21.6) in the propofol group and 20.4cmH2O/l/s(18.6–26.4) in the sevoflurane group, (p = 0.73); trapped volume was 260 ml(176–290) in the propofol group and 73 ml(35–126) in the sevoflurane group, p = 0.02. Intrinsic PEEP was 1.5cmH2O(1–3) in both groups after external PEEP optimization. There was neither early (H4) or late (H48) significant difference in airway resistance and respiratory mechanics parameters between the two groups. Conclusions In critically ill patients intubated with COPD exacerbation, there was no significant difference in respiratory mechanics between sevoflurane and propofol from inclusion to H4 and H48.

Abstract Delayed cerebral ischemia (DCI) after aneurysmal subarachnoid haemorrhage (aSAH) is a singular pathological entity necessitating early diagnostic approaches and both prophylactic and curative interventions. This retrospective before-after study investigates the effects of a management strategy integrating perfusion computed tomography (CTP), vigilant clinical monitoring and standardized systemic administration of milrinone on the occurrence of delayed cerebral infarction (DCIn). The $${\text{"before"}}$$ "before" period included 277 patients, and the $${\text{"after"}}$$ "after" one 453. There was a higher prevalence of Modified Fisher score III/IV and more frequent diagnosis of vasospasm in the $${\text{"after"}}$$ "after" period. Conversely, the occurrence of DCIn was reduced with the $${\text{"after"}}$$ "after" management strategy (adjusted OR 0.48, 95% CI [0.26; 0.84]). Notably, delayed ischemic neurologic deficits were less prevalent at the time of vasospasm diagnosis (24 vs 11%, $$p=0.001$$ p = 0.001 ), suggesting that CTP facilitated early detection. In patients diagnosed with vasospasm, intravenous milrinone was more frequently administered (80 vs 54%, $$p

Background: The understanding of risk factors related to severe anaphylaxis is key to implementing prevention strategies. We present the first French population-based nine-year anaphylaxis hospitalization study evaluating specific trends and factors related to severe anaphylaxis (SA), to support identification of phenotypes at-risk. Methods: This study used descriptive data from the French hospitalization database for the years 2012–2021, and included all patients hospitalized with anaphylaxis using International Classification of Diseases (ICD)-10 codes listed as a primary diagnosis. SA were cases that either required a hospitalization in intensive care units or resulted in death. Potential risk factors were identified according to corresponding ICD codes, available as secondary data during the patient's hospitalization. Results: The average hospitalization rate of all cases of anaphylaxis (SA and non-SA) was 1.34/100,000/year, and rate of admissions for SA was 0.08/100,000/year. Among the 5463 SA, 37.7% had unspecified coding label, when trigger was not identified. For SA cases in which trigger was identified, most were related to drugs (45.6%), followed by food (9.3%) and insect sting (7.2%). Overall, admissions due to anaphylaxis (SA and non-SA) were more frequent in males (57%). However, when the trigger was drugs, the proportion was significantly higher in females. For children aged 5–9 years, the most common trigger for SA was food. Patients for which SA was triggered by insect stings were identified exclusively in the 10–14 years age group. Chronic spontaneous urticaria was associated with insect sting-induced anaphylaxis, regardless of the severity. Angioedema was associated with all causes of SA. Cases of anaphylaxis presenting with urticaria and angioedema included cases with identified and unidentified triggers. Asthma and a personal history of allergy were associated with drug- and food-induced anaphylaxis. Conclusion: This is the first study to provide data on severe phenotypes of anaphylaxis in France. Data presented is key to the implementation of public health actions and preventive strategies to improve quality care.

Objectives (1) To assess the progression of ultrasonography-detected synovitis in a cohort of patients with rheumatoid arthritis (RA) in remission during 1 year of follow-up (2) to evaluate the ability of consecutive examinations of ultrasonography to predict relapse (R) or radiographic progression (RP) at 1 year.Methods Patients with RA (2010 American College of Rheumatology-European Alliance of Associations for Rheumatology criteria) in clinical remission (Disease Activity Score in 28 joints (DAS28)0.6 or DAS28-CRP>3.2 and any modification of disease-modifying anti-rheumatic drugs or glucocorticoids defined relapse. Univariate and multivariate Cox regression analyses were used to evaluate factors associated with R/RP at 1 year.Results PDUS was detected in 75 (65.2%), 66, 60, 46 and 29 of the 115 patients with RA at baseline and at months 3, 6, 9 and 12, respectively. 58 (50.4%) patients exhibited persistent PDUS. After 1 year, 22/85 (25.9%) experienced relapse and 12 (14.1%) showed RP. On multivariate analysis, factors predicting R/RP at 1 year were persistent PDUS (HR=2.98, p=0.014) and an increase in DAS28-CRP level at the visit before relapse (HR=4.36, p=0.004).Conclusion Persistent PDUS during follow-up, rather than at baseline, predicted worse outcome at 1 year and requires careful monitoring.

BackgroundEnvironmental and behavioral factors are responsible for 12.6 million deaths annually and contribute to 25% of deaths and chronic diseases worldwide. Through the One Health initiative, the World Health Organization and other international health organizations plan to improve these indicators to create healthier environments by 2030. To meet this challenge, training primary care professionals should be the priority of national policies. General practitioners (GPs) are ready to become involved but need in-depth training to gain and apply environmental health (EH) knowledge to their practice. In response, we designed the Primary Care Environment and Health (PCEH) online course in partnership with the Occitanie Regional Health Agency in France. This course was used to train GP residents from the Montpelier-Nimes Faculty of Medicine in EH knowledge. The course was organized in 2 successive parts: (1) an asynchronous e-learning modular course focusing on EH knowledge and tools and (2) 1 day of face-to-face sessions. ObjectiveThis study assessed the impact of the e-learning component of the PCEH course on participants’ satisfaction, knowledge, and behavior changes toward EH. MethodsThis was a pilot before-and-after study. Four modules were available in the 6-hour e-learning course: introduction to EH, population-based approach (mapping tools and resources), clinical cases, and communication tools. From August to September 2021, we recruited first-year GP residents from the University of Montpellier (N=130). Participants’ satisfaction, knowledge improvements for 19 EH risks, procedure to report EH risks to health authorities online, and behavior change (to consider the possible effects of the environment on their own and their patients’ health) were assessed using self-reported questionnaires on a Likert scale (1-5). Paired Student t tests and the McNemar χ2 test were used to compare quantitative and qualitative variables, respectively, before and after the course. ResultsA total of 74 GP residents completed the e-learning and answered the pre- and posttest questionnaires. The mean satisfaction score was 4.0 (SD 0.9) out of 5. Knowledge scores of EH risks increased significantly after the e-learning course, with a mean difference of 30% (P

Abstract Background In studies prior to lung-protective ventilation, liver cirrhosis in acute respiratory distress syndrome (ARDS) was associated with high mortality rates. Since patients with cirrhosis have been excluded from many trials on ARDS, their outcome when treated with lung-protective ventilation is unclear. The objectives were to assess whether cirrhosis is associated with mortality in ARDS and trends over time in mortality and severity. Methods We conducted a retrospective analysis of a prospective observational cohort conducted in a 20-bed tertiary ICU from October 2003 to December 2021. All consecutive adult critically ill patients with ARDS were included. ARDS was defined by the Berlin criteria. The primary outcome was 90 day mortality, assessed with Kaplan–Meier curves and multivariate Cox analysis. Time trends were assessed on 90 day mortality, Sequential Organ-Function Assessment score (SOFA) and non-hepatic SOFA. Ventilation settings were compared between patients with and without cirrhosis. Results Of the 7155 patients screened, 863 had a diagnosis of ARDS. Among these ARDS patients, 157(18%) had cirrhosis. The overall 90 day mortality was of 43% (378/863), 57% (90/157) in patients with cirrhosis and 41% (288/706) in patients without cirrhosis (p

Abstract Heatwaves affect human health and should be more and more frequent because of global warming and could lead to increase mortality in general population, especially regarding cardiovascular mortality. During the summer 2019, Europe experienced a strong episode of heatwave. Telemonitoring of patients with heart failure (HF) provide an elegant tool to monitor closely the weights, and we assumed to be able to assess our hypothesis through a nationwide telemonitoring system. Here, we hypothesize that (i) there will be a change in patients' weight during the heatwave and (ii) that the telemonitoring would enable us to follow these changes. The change in weight would be a surrogate for clinical worsening (with or without decompensated HF). Briefly, 1420 patients with a median age of 73.0 years and mean weight of 78.1 kg have been included in this analysis. The relationship between temperature and weight is very strong (P

Background & Aims: Liver transplantation (LT) is a last resort treatment for patients at high risk of mortality from end-stage liver disease. Over the past years, alcohol-associated liver disease has become the most frequent indication for LT in the world. The outcomes of LT for alcohol-associated liver disease are good, but return to alcohol use is detrimental for medium-term survival because of cancer development, cardiovascular events, and recurrent alcohol-associated cirrhosis. Several strategies have been developed to prevent return to alcohol use during the pre- or post-LT period, but there are no specific recommendations. Therefore, the main objective of this study was to investigate if the integration of an addiction team in a LT unit affected the rate of severe alcohol relapse after LT. The secondary objectives were to assess the effects of addiction follow up on cardiovascular events, cancer, and overall survival. Methods: This study was a retrospective comparison between centres with or without addiction monitoring. Results: The study included 611 patients of which 79.4% were male with a mean age of 55.4 years at the time of LT, 190 were managed by an integrated addiction team. The overall alcohol relapse rate was 28.9% and the rate of severe relapse was 13.0%. Patients with addiction follow-up had significantly less frequent severe alcohol relapse than those in the control group (p = 0.0218). Addiction follow up (odds ratio = 0.19; p = 0.001) and age at LT (odds ratio = 1.23; p = 0.02) remained significantly associated with post-LT cardiovascular events. Conclusions: Our study confirms the benefits of integrating an addiction team to reduce return to alcohol use after LT. Clinical Trials registration: This study is registered at ClinicalTrials.gov (NCT 04964687). Impact and implications: The main indication for liver transplantation is alcohol-associated cirrhosis. There are currently no specific recommendations on the addiction monitoring of transplant candidates, although severe return to alcohol use after liver transplantation has a negative impact on long-term survival of patients. In this study, we explored the impact of a systematic addiction intervention on the return to alcohol use rates. In our transplantation centre, we demonstrated the interest of an addiction follow up to limit the severe alcohol relapses rate. This information should be further investigated in prospective studies to validate these data.

IntroductionThe worldwide rate of preterm birth (PTB) has been increasing over the last two decades. COVID-19 lockdowns provide a unique opportunity to assess the effects of socioenvironmental and lifestyle factors on premature birth and birth weight. We explored the effects of COVID-19 lockdowns on the PTB rate and birth weight at a nationwide scale in France until one year after their occurrence.Material and MethodsThis national retrospective observational study evaluated the rate of PTB and birth weight in France from January 2016 to December 2020. Data were obtained from the national Programme Médicalisé des Systèmes d'Information database. The rates of global and sub-categories of PTB were tested. The birth weight was studied before and after lockdown for all live births, for term and premature neonates, and for each category of low birth weight (LBW) by a stratified analysis.ResultsData from 2,949,372 births from January 2016 to December 2019, including 228,857 PTB, were compared to those of 699,344 births and 51,886 PTB from January to December 2020. The national rate of PTB decreased significantly from 7.7% to 7.3%, when compared with the 2016–2019 period. This decrease was persistent up to 9 months later. It was observed only for moderate PTB, whereas very PTB and extremely PTB remained stable. The national mean birth weight for full-term babies increased after the lockdown and was still observable up to 8 months later (+0.16%, p

Introduction When both severe metabolic acidemia (pH equal or less than 7.20; PaCO2 equal or less than 45 mm Hg and bicarbonate concentration equal or less than of 20 mmol/L) and moderate-to-severe acute kidney injury are observed, day 28 mortality is approximately 55%–60%. A multiple centre randomised clinical trial (BICARICU-1) has suggested that sodium bicarbonate infusion titrated to maintain the pH equal or more than 7.30 is associated with a higher survival rate (secondary endpoint) in a prespecified stratum of patients with both severe metabolic acidemia and acute kidney injury patients. Whether sodium bicarbonate infusion may improve survival at day 90 (primary outcome) in these severe acute kidney injury patients is currently unknown.Methods and analysis The sodium bicarbonate for the treatment of severe metabolic acidosis with moderate or severe acute kidney injury in the critically ill: a randomised clinical trial (BICARICU-2) trial is an investigator-initiated, multiple centre, stratified, parallel-group, unblinded trial with a computer-generated allocation sequence and an electronic system-based randomisation. After randomisation, the intervention group will receive 4.2% sodium bicarbonate infusion to target a plasma pH equal or more than 7.30 while the control group will not receive sodium bicarbonate. The primary outcome is the day 90 mortality. Main secondary outcomes are organ support dependences.Ethics and dissemination The trial has been approved by the appropriate ethics committee (CPP Nord Ouest, Rouen, France, 25 April 2019, number: 19.03.15.72446). Informed consent is required. If sodium bicarbonate improves day 90 mortality, it will become part of the routine care.Trial registration number NCT04010630.

Key messages Electronic relaxation therapies are effective supportive care tools for improving stressful symptoms in ICU patients. Effectiveness depends on the type of symptom and the characteristics of the devices. Overall discomfort and adrenergic stress response are more significantly improved by virtual reality using a synthetic imagined world than using a real world or music therapy alone.

Introduction Readiness to be freed from ventilatory support can be evaluated by spontaneous breathing trial (SBT) assessing the patient’s ability to sustain respiratory effort after extubation. Current SBT practices are heterogenous and there are few physiological studies on the topic. The objective of this study is to assess which SBT best reproduces inspiratory effort to breathe after extubation depending on the patient’s illness.Methods and analysis This will be a multicentre randomised cross-over physiological study, in a large population, in the era of modern intensive care units using last generation modern ventilators. Each included patient will perform three 15-minute SBTs in a random order: pressure support ventilation (PSV) level of 7 cmH2O with positive end expiratory pressure (PEEP) level of 0 cmH2O, PSV 0 cmH2O with PEEP 0 cmH2O and T-piece trial. A rest period of baseline state ventilation will be observed between the SBTs (10 min) and before extubation (30 min). Primary outcome will be the inspiratory muscle effort, reflected by pressure time product per minute (PTPmin). This will be calculated from oesophageal pressure measurements at baseline state, before and after each SBT and 20 min after extubation. Secondary outcomes will be PTPmin at 24 hours and 48 hours after extubation, changes in physiological variables and respiratory parameters at each step, postextubation respiratory management and the rate of successful extubation. One hundred patients with at least 24 hours of invasive mechanical ventilation will be analysed, divided into five categories of critical illness: abdominal surgery, brain injury, chest trauma, chronic obstructive pulmonary disease and miscellaneous (pneumonia, sepsis, heart disease).Ethics and dissemination The study project was approved by the appropriate ethics committee (2019-A01063-54, Comité de Protection des Personnes TOURS - Région Centre - Ouest 1, France). Informed consent is required, for all patients or surrogate in case of inability to give consent.Trial registration number NCT04222569.

Introduction How cardiorespiratory function changes following the surgical correction of pectus excavatum (PE) often gives mixed results, with meta-analyses demonstrating no benefit in terms of pulmonary function but improvement in cardiac function. Functional responses may depend on type of surgery, follow-up time and/or the patient’s presurgical functional status, and debate persists on the purely aesthetic nature of such surgery. The aim of this protocol is to analyse data describing lung function and incremental exercise testing before vs after the surgical correction of PE.Methods and analysis A historical-prospective before–after surgical correction of PE cohort will be constituted. Historical inclusions are recruited during follow-up visits at approximately 12, 24, 36 or 48 months following a prior surgery (with presurgical data mined from patient records). Prospective inclusions are recruited during presurgical work-ups and followed for 1 year following surgery. The data collected include spirometry, incremental exercise testing, body mass index, body composition, questionnaires targeting general health status, self-esteem and body image. Any complications due to surgery are also described.The primary outcome is oxygen pulse during incremental exercise testing, and 44 data points are required to demonstrate a moderate postsurgical change (ie, a Cohen’s effect of d=0.5). Wilcoxon signed-rank tests or t-tests for paired data will be used for before–after comparisons (with false discovery rate corrections for secondary analyses).Ethics and dissemination This study will be conducted according to the principles of the Declaration of Helsinki (as revised in 2013) and was approved by a randomly assigned, independent, ethics committee (Comité de Protection des Personnes Sud-Méditerranée II, reference number: 218 B21) as per French law on 6 July 2018. Informed, written consent for study participation is required of all study candidates prior to enrolment. Results will be published in an international peer-reviewed journal.Trial registration number NCT03770390; Clinicaltrials.gov.

Abstract Background Whether sepsis-associated diaphragm dysfunction may improve despite the exposure of mechanical ventilation in critically ill patients is unclear. This study aims at describing the diaphragm function time course of septic and non-septic mechanically ventilated patients. Methods Secondary analysis of two prospective observational studies of mechanically ventilated patients in whom diaphragm function was assessed twice: within the 24 h after intubation and when patients were switched to pressure support mode, by measuring the endotracheal pressure in response to bilateral anterior magnetic phrenic nerve stimulation (Ptr,stim). Change in diaphragm function was expressed as the difference between Ptr,stim measured under pressure support mode and Ptr,stim measured within the 24 h after intubation. Sepsis was defined according to the Sepsis-3 international guidelines upon inclusion. In a sub-group of patients, the right hemidiaphragm thickness was measured by ultrasound. Results Ninety-two patients were enrolled in the study. Sepsis upon intubation was present in 51 (55%) patients. In septic patients, primary reason for ventilation was acute respiratory failure related to pneumonia (37/51; 73%). In non-septic patients, main reasons for ventilation were acute respiratory failure not related to pneumonia (16/41; 39%), coma (13/41; 32%) and cardiac arrest (6/41; 15%). Ptr,stim within 24 h after intubation was lower in septic patients as compared to non-septic patients: 6.3 (4.9–8.7) cmH2O vs. 9.8 (7.0–14.2) cmH2O (p = 0.004), respectively. The median (interquartile) duration of mechanical ventilation between first and second diaphragm evaluation was 4 (2–6) days in septic patients and 3 (2–4) days in non-septic patients (p = 0.073). Between first and second measurements, the change in Ptr,stim was + 19% (− 13–61) in septic patients and − 7% (− 40–12) in non-septic patients (p = 0.005). In the sub-group of patients with ultrasound measurements, end-expiratory diaphragm thickness decreased in both, septic and non-septic patients. The 28-day mortality was higher in patients with decrease or no change in diaphragm function. Conclusion Septic patients were associated with a more severe but reversible impaired diaphragm function as compared to non-septic patients. Increase in diaphragm function was associated with a better survival.

Abstract Background Non-inferiority trials are becoming increasingly popular in public health and clinical research. The choice of the non-inferiority margin is the cornerstone of such trials. Most of the time, the non-inferiority margin is fixed and constant, determined from historical trials as a fraction of the effect of the reference intervention. But in some circumstances, there may some uncertainty around the reference treatment that one would like to account for when performing the hypothesis testing. In this case, the non-inferiority margin is not fixed in advance and depends on the reference intervention estimate. Hence, the uncertainty surrounding the non-inferiority margin should be accounted for in statistical tests. In this work, we explore how to perform the non-inferiority test for a continuous variable with a flexible margin. Methods We have proposed in this study, two procedures for the non-inferiority test with a flexible margin for continuous endpoints. The proposed test procedures are based on a test statistic and confidence interval approaches respectively. Simulations have been used to assess the performances and properties of the proposed test procedures. An application was done on a real-world clinical data, to assess the efficacy of clinical monitoring alone versus laboratory and clinical monitoring in HIV-infected adult patients. Results Basically, for both proposed methods, the type I error estimate was not dependent on the values of the reference treatment. In the test statistic approach, the type 1 error rate estimate was approximatively equal to the nominal value. It has been found that the confidence interval level determined approximatively the level of significance. For a given nominal type I error α, the appropriate one- and two-sided confidence intervals should be with levels 1−α and 1−2α, respectively. Conclusions Based on the type I error rate and power estimates, the proposed non-inferiority hypothesis test procedures had good performances and were applicable in practice. Trial registration ClinicalTrials.gov NCT00301561. Registered on March 13, 2006, url: https://clinicaltrials.gov/ct2/show/NCT00301561 .

Abstract Background Whether the COVID-19 pandemic impacts Positive Airway Pressure (PAP) adherence over the long-term is unknown and only preliminary short-term data have been reported. Methods With the aim of describing the impact of the first and second waves of COVID-19 on PAP adherence during 2020 in France, we designed a cross-sectional study of Sleep-Apnea (SA)-patients under PAP telemonitoring. To examine PAP adherence in adult SA patients, we assessed de-identified data from a non-profit healthcare provider database during the period January 1, 2019 to December 31, 2020. Included patients met the following criteria: (i) PAP-treated for at least 4 months before January 1, 2019 and with continuous PAP during both 2019 and 2020; (ii) ≥ 360 daily PAP telemonitored data per year. For PAP adherence, data were collected using the PAP-software. Results 8477/10482 patients were finally included in the analysis [72.4% male, median age 70 years (IQ25–75: 61–77], 25.6%

Background Obstructive sleep apnea syndrome is a common sleep-breathing disorder associated with adverse health outcomes including excessive daytime sleepiness, impaired quality of life and is well-established as a cardiovascular risk factor. Continuous positive airway pressure is the reference treatment, but its cardiovascular and metabolic benefits are still debated. Combined interventions aiming at improving patient's lifestyle behaviours are recommended in guidelines management of obstructive sleep apnea syndrome but adherence decreases over time and access to rehabilitation programmes is limited. Telerehabilitation is a promising approach to address these issues, but data are scarce on obstructive sleep apnea syndrome. Methods The aim of this study is to assess the potential benefits of a telerehabilitation programme implemented at continuous positive airway pressure initiation, compared to continuous positive airway pressure alone and usual care, on symptoms and cardiometabolic risk factors of obstructive sleep apnea syndrome. This study is a 6-months multicentre randomized, parallel controlled trial during which 180 obese patients with severe obstructive sleep apnea syndrome will be included. We will use a sequential hierarchical criterion for major endpoints including sleepiness, quality of life, nocturnal systolic blood pressure and inflammation biological parameters. Discussion m-Rehab obstructive sleep apnea syndrome is the first multicentre randomized controlled trial to examine the effectiveness of a telerehabilitation lifestyle programme in obstructive sleep apnea syndrome. We hypothesize that a telerehabilitation lifestyle intervention associated with continuous positive airway pressure for 6 months will be more efficient than continuous positive airway pressure alone on symptoms, quality of life and cardiometabolic risk profile. Main secondary outcomes include continuous positive airway pressure adherence, usability and satisfaction with the telerehabilitation platform and medico-economic evaluation. Trial registration Clinicaltrials.gov Identifier: NCT05049928. Registration data: 20 September 2021

Introduction Therapeutic education for patients with asthma has been shown to reduce asthma morbidity. The high availability of smart phones provides the opportunity to furnish patient training via specifically designed chatbot applications. The goal of this protocol is to perform a first pilot comparison of traditional face to face versus chatbot-guided patient therapeutic education programmes for patients with asthma.Methods and analysis Eighty adult patients with a physician-confirmed diagnosis of asthma will be enrolled in a two-parallel-arm, randomised (1:1) controlled pilot trial. A single-Zelen consent procedure is deployed to first enrol all participants in the comparator arm, that is, the standard patient therapeutic education programme at the University Hospitals of Montpellier, France. This means of patient therapeutic education is based on reoccurring interviews and discussion with qualified nursing staff as per usual care. Following baseline data acquisition, randomisation will be performed. Those patients randomised to the comparator arm will not be informed of the second arm. Those patients randomised to the experimental arm will be proposed access to a specifically designed chatbot (Vik-Asthme) as the second tested means of patient training (refusals continue with standard training, though analysed as intention to treat). The primary outcome is change in the total Asthma Quality of Life Questionnaire score at the end of follow-up (6 months). Secondary outcomes cover asthma control, spirometry, general health status, programme adherence and burden for medical staff, exacerbations and medical resource use (medications, consults, emergency visits, hospitalisation and intensive care).Ethics and dissemination This study (‘AsthmaTrain’ protocol version 4–20220330) has been approved by the Committee for the Protection of Persons Ile-de-France VII on 28 March 2022 (reference number 21.03617.000059). Enrolment began on 24 May 2022. Results will be published in international peer-reviewed journals.Trial registration number NCT05248126.

Background: Drug hypersensitivity reaction (DHR) to iodinated radiocontrast media (iRCM) is reported in 1%–3% of injections. Risk assessment of patients with suspicion of DHR to iRCM relies solely on clinical phenotyping and drug allergy workup. Using a novel unsupervised TwoStep cluster analysis, we aimed to identify prototypic patterns within a large cohort of patients evaluated for a potential iRCM DHR. Methods: A retrospective study was conducted using data from the Drug Allergy and Hypersensitivity Database of the Allergy Unit, University Hospital of Montpellier, Montpellier, France. All referred patients during February 2001 to December 2019 with suspicion of iRCM DHR with either confirmed positive or confirmed negative skin tests were included in the analysis. Results: A total of 1439 patients were evaluated. The chronology of the index reaction was immediate and nonimmediate in 77.1% and 22.4%, respectively. Cluster analysis categorized the total study population in 5 clusters. Cluster 1 compiled all nonimmediate and cluster 2–5 almost all immediate reactors. Cluster 1 and 2 had recent reactions (

(1) Background: We have previously shown that sputum rheology can discriminate between patients with COPD and other muco-obstructive lung diseases, and that it is correlated with mucin content and sputum eosinophilia. We now hypothesize that it could be a more-accurate guide than clinical evaluation for the prescription of azithromycin to prevent exacerbations of COPD and to reduce exposure to antibiotics; (2) Methods: “COPD CaRhe” is a multicentric, randomized, controlled trial comparing outcomes in two parallel arms (36 vs. 36 patients). Patients will be recruited in the university hospitals of Montpellier, Bordeaux, and Toulouse, in France, and they should have a diagnosis of COPD with frequent exacerbations (≥3/year). Enrollment will occur during a routine visit to a respiratory department, and follow-up visits will occur every 3 months for a period of 1 year. At each visit, a 3-month prescription of azithromycin will be provided to those patients who obtain a score of 39 on a rheological assessment of sputum, depending upon their randomization group. The primary outcome will be the number of exacerbations of COPD; (3) Discussion: By using sputum rheology, the COPD CaRhe study may provide clinicians with an objective biomarker to guide the prescription of azithromycin while reducing the cumulative exposure to macrolides.

Age estimation in juveniles is a critical procedure in judicial cases for verification of imputability or for civil reasons when adopting children. Several methods based both on skeletal and dental growth have been performed and applied on different populations; nevertheless, few articles have compared different methods in order to test their reliability in different conditions and age ranges, and this is a clear obstacle in the creation of common guidelines for age estimation in the living. A comparison of five dental methods (Anderson, Ubelaker, Schour and Massler, Gustafson and Koch, Demirjian) and one skeletal method (Greulich a Pyle atlas) was performed on a population of 94 children aged between 0 and 8 years. Results showed that, whereas under 2 years all the methods have the same inaccuracy, over 2 years the diagram methods, such as Schour and Massler and Ubelaker’s revised one, have a lower error range than the most frequently used Greulich and Pyle atlas and Demirjian method. Schour and Massler, Gustafson and Koch, and Ubelaker methods showed, respectively, a mean error amounting to 0.40, 0.53, and 0.56 years versus the 0.74 and 0.88 years given by Demirjian and the Greulich and Pyle atlas. An in-depth analysis of the potential of several methods is necessary in order to reach a higher adherence of age estimation with the complexity of growth dynamics.

Objectives. The current guidelines still do not include specific recommendations on the use of subvalvular repair (SV-r) for treatment of ischemic mitral regurgitation (IMR). Therefore, the objective of our study was to evaluate the clinical impact of mitral regurgitation (MR) recurrence and ventricular remodeling on long-term outcomes after SV-r combined with restrictive annuloplasty (RA-r). Methods. We performed a subanalysis of the papillary muscle approximation trial, studying 96 patients with severe IMR and coronary artery disease undergoing restrictive annuloplasty alongside subvalvular repair (SV-r + RA-r group) or restrictive annuloplasty alone (RA-r group). We analyzed treatment failure differences, the influence of residual MR, left ventricular remodeling, and clinical outcomes. The primary endpoint was treatment failure (composite of death; reoperation; or recurrence of moderate, moderate-to-severe, or severe MR) within 5 years of follow-up after the procedure. Results. A total of 45 patients showed failure of the treatment within 5 years, of which 16 patients underwent SV-r + RA-r (35.6%) and 29 underwent RA-r (64.4%, p = 0.006). Patients with significant residual MR presented with a higher rate of all-cause mortality at 5 years compared with trivial MR (HR 9.09, 95% CI 2.08–33.33, p = 0.003). MR progression occurred earlier in the RA-r group, as 20 patients in the RA-r group vs. 6 in SV-r + RA-r group had a significant MR 2 years after surgery (p = 0.002). Conclusions. RA-r remains a surgical mitral repair technique with an increased risk of failure and mortality at 5 years compared with SV-r. The rates of recurrent MR are higher, and recurrence occurs earlier, with RA-r alone compared to SV-r. The addition of the subvalvular repair increases the durability of the repair, thus extending all of the benefits of preventing MR recurrence.