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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.

Abstract Background Critical care randomized controlled trials (RCTs) are often published in high-impact journals, whether general journals [the New England Journal of Medicine (NEJM), The Lancet, the Journal of the American Medical Association (JAMA)] or critical care journals [Intensive Care Medicine (ICM), the American Journal of Respiratory and Critical Care Medicine (AJRCCM), Critical Care Medicine (CCM)]. As rejection occurs in up to 97% of cases, it might be appropriate to assess pre-submission probability of being published. The objective of this study was to develop and internally validate a simplified score predicting whether an ongoing trial stands a chance of being published in high-impact general journals. Methods A cohort of critical care RCTs published between 1999 and 2018 in the three highest impact medical journals (NEJM, The Lancet, JAMA) or the three highest impact critical care journals (ICM, AJRCCM, CCM) was split into two samples (derivation cohort, validation cohort) to develop and internally validate the simplified score. Primary outcome was journal of publication assessed as high-impact general journal (NEJM, The Lancet, JAMA) or critical care journal (ICM, AJRCCM, CCM). Results A total of 968 critical care RCTs were included in the predictive cohort and split into a derivation cohort (n = 510) and a validation cohort (n = 458). In the derivation cohort, the sample size (P value

Abstract Aims Optimizing medical cardiac treatment for sleep apnoea (SA) in patients with chronic heart failure and reduced ejection fraction (HFrEF) is an expert Grade C recommendation based on six studies encompassing a total of 67 patients only. Whether sacubitril–valsartan (SV), a cornerstone of HFrEF medical treatment, impacts SA is unknown and requires evaluation. Methods and results The ENTRESTO‐SAS trial is a six‐centre, prospective, open‐label real‐life cohort study (NCT02916160). Ambulatory patients eligible for SV (i.e. HFrEF adults who remain symptomatic despite optimal treatment) were evaluated before and after 3 months of SV (including nocturnal ventilatory polygraphy); 118 patients were final analysed [median age was 66 (IQ25–75: 56–73) years, 81.4% male, 36.5% New York Heart Association III–IV, N‐terminal pro‐B‐type natriuretic peptide level of 1564 (701–3376) ng/L, left ventricular ejection fraction of 30 (25–34)%, 60.7% ischaemic HFrEF, 97.5% initially treated with angiotensin‐converting enzyme inhibitors or angiotensin II receptor blockers, 83.9% with beta‐blockers, 64.4% with mineralocorticoid receptor antagonists, and 74.6% with diuretics]. Three groups were defined according to initial central/obstructive apnoea–hypopnoea indices (AHIs): G1 (n = 49, AHIcentral ≥ 5/h and AHIobstructive

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 (

Abstract Background The course of chronic obstructive pulmonary disease (COPD) is punctuated by exacerbations, most often of infectious origin, responsible for many intensive care unit (ICU) and intermediate care unit (IMCU) admissions. Our objective was to study in-hospital mortality during severe COPD exacerbations in ICU and IMCU based on the performance of bronchoscopy. Methods A retrospective analysis was carried out on stays in ICUs for COPD exacerbation from the French Programme for the Medicalisation of Information Systems databases for the years 2014 and 2015. Propensity score matching of stays made it possible to constitute two comparable groups on the factors of excess mortality described in the literature (age, sex, SAPS 2, type of admission and bronchial tumour). Results We identified 14,491 stays for COPD exacerbation in ICUs, 2586 of which received a bronchoscopy. Mortality was significantly higher in the fibroscopy group (31.32% versus 19.8%). After propensity score matching, we found an excess of mortality in the intervention group (OR = 1.749 [1.516–2.017]) associated with a significantly longer length of stay. The main diagnoses associated with an increased risk of death were pulmonary embolism (OR = 3.251 [1.126–9.384]), bacterial pneumonia (OR = 1.906 [1.173–3.098]) and acute respiratory failure (OR = 1.840 [1.486–2.278]). Conclusions Performing bronchoscopy during ICU hospitalisations for severe COPD exacerbations was associated with increased mortality. This increased mortality appears to be related to a bias in patient selection with a procedure reserved for patients with the adverse course.

Abstract Background Transcranial sonography is a point-of-care tool recommended in intensive care units (ICU) to monitor brain injured patients. Objectives of the study was to assess feasibility and reliability of the third ventricle (V3) diameter measurement using transcranial sonography (TCS) compared to brain computed-tomography (CT), the gold standard measurement, and to measure the TCS learning curve. Design: prospective study, in a 16-bed neurological ICU in an academic hospital. Every consecutive brain injured adult patient, who required a brain CT and TCS monitoring were included. The V3 diameter was blindly measured by TCS and CT. Intraclass correlation coefficient (ICC) and Bland–Altman plot were used to assess the reliability and agreement between TCS and CT V3 measurements. Diagnosis performance of the V3 diameter using TCS to detect hydrocephalus was measured. Absolute difference between V3 measurement by residents and experts was measured consecutively to assess the learning curve. Results Among the 100 patients included in the study, V3 diameter could be assessed in 87 patients (87%) from at least one side of the skull. Both temporal windows were available in 70 patients (70%). The ICC between V3 diameter measured by TCS and CT was 0.90 [95% CI 0.84–0.93] on the right side, and 0.92 [0.88–0.95] on the left side. In Bland–Altman analysis, mean difference, standard deviation, 95% limits of agreement were 0.36, 1.52, − 2.7 to 3.3 mm, respectively, on the right side; 0.25, 1.47, − 2.7 to 3.1 mm, respectively, on the left side. Among the 35 patients with hydrocephalus, V3 diameters could be measured by TCS in 31 patients (89%) from at least one side. Hydrocephalus was, respectively, excluded, confirmed, or inconclusive using TCS in 35 (40%), 25 (29%) and 27 (31%) of the 87 assessable patients. After 5 measurements, every resident reached a satisfactory measurement compared to the expert operator. Conclusion TCS allows rapid, simple and reliable V3 diameter measurement compared with the gold standard in neuro-ICU patients. Aside from sparing irradiating procedures and transfers to the radiology department, it may especially increase close patient monitoring to detect clinically occult hydrocephalus earlier. Further studies are needed to measure the potential clinical benefit of this method. Trial registration: ClinicalTrials.gov ID: NCT02830269.

Abstract Background Pulmonary rehabilitation (PR) improves exercise capacity, health-related quality of life (HRQoL) and dyspnea in chronic obstructive pulmonary disease (COPD) patients. Maintenance programs can sustain the benefits for 12 to 24 months. Yet, the long-term effects (> 12 months) of pragmatic maintenance programs in real-life settings remain unknown. This prospective cohort study assessed the yearly evolution in the outcomes [6-min walking distance (6MWD), HRQoL, dyspnea] of a supervised self-help PR maintenance program for COPD patients followed for 5 years. The aim was to assess the change in the outcomes and survival probability for 1 to 5 years after PR program discharge in COPD patients following a PR maintenance program supported by supervised self-help associations. Methods Data were prospectively collected from 144 COPD patients who followed a pragmatic multidisciplinary PR maintenance program for 1 to 5 years. They were assessed yearly for 6MWD, HRQol (VQ11) and dyspnea (MRC). The 5-year survival probability was compared to that of a control PR group without a maintenance program. A trajectory-based cluster analysis identified the determinants of long-term response. Results Maintenance program patients showed significant PR benefits at 4 years for 6MWD and VQ11 and 5 years for MRC. The 5-year survival probability was higher than for PR patients without PR maintenance. Two clusters of response to long-term PR were identified, with responders being the less severe COPD patients. Conclusions This study provides evidence of the efficacy of a pragmatic PR maintenance program in a real-life setting for more than 3 years. In contrast to short-term PR, long-term PR maintenance appeared more beneficial in less severe COPD patients.

Abstract Background For some patients, Continuous Positive Airway Pressure (CPAP) remains an uncomfortable therapy despite the constant development of technological innovations. To date, no real life study has investigated the relationship between mask related side-effects (MRSEs) and CPAP-non-adherence (defined as

Abstract Background Veno-arterial extracorporeal life support (VA-ECLS) results in cardiopulmonary shunting with reduced native cardiac output (NCO). Low NCO occurrence is common and associated with risk of thromboembolic and pulmonary complications. Practical tools for monitoring NCO during VA-ECLS would therefore be valuable. Pulse pressure (PP) and end-tidal carbon dioxide (EtCO2) are known to be related to cardiac output. We have designed a study to test whether PP and EtCO2 were efficient for the monitoring of NCO during VA-ECLS. Methods In this prospective single-center observational study, patients who underwent a VA-ECLS for cardiogenic shock from January 2016 to October 2017 were included, provided low NCO was suspected by a PP

Abstract Backgrounds To explain the excess cardiovascular mortality observed in the SERVE-HF study, it was hypothesized that the high-pressure ASV default settings used lead to inappropriate ventilation, cascading negative consequences (i.e. not only pro-arrythmogenic effects through metabolic/electrolyte abnormalities, but also lower cardiac output). The aims of this study are: i) to describe ASV-settings for long-term ASV-populations in real-life conditions; ii) to describe the associated minute-ventilations (MV) and therapeutic pressures for servo-controlled-flow versus servo-controlled-volume devices (ASV-F Philips®-devices versus ASV-V ResMed®-devices). Methods The OTRLASV-study is a cross-sectional, 5-centre study including patients who underwent ASV-treatment for at least 1 year. The eight participating clinicians were free to adjust ASV settings, which were compared among i) initial diagnosed sleep-disordered-breathing (SBD) groups (Obstructive-Sleep-Apnea (OSA), Central-Sleep-Apnea (CSA), Treatment-Emergent-Central-Sleep-Apnea (TECSA)), and ii) unsupervised groups (k-means clusters). To generate these clusters, baseline and follow-up variables were used (age, sex, body mass index (BMI), initial diagnosed Obstructive-Apnea-Index, initial diagnosed Central-Apnea-Index, Continuous-Positive-Airway-Pressure used before ASV treatment, presence of cardiopathy, and presence of a reduced left-ventricular-ejection-fraction (LVEF)). ASV-data were collected using the manufacturer’s software for 6 months. Results One hundred seventy-seven patients (87.57% male) were analysed with a median (IQ25–75) initial Apnea-Hypopnea-Index of 50 (38–62)/h, an ASV-treatment duration of 2.88 (1.76–4.96) years, 61.58% treated with an ASV-V. SDB groups did not differ in ASV settings, MV or therapeutic pressures. In contrast, the five generated k-means clusters did (generally described as follows: (C1) male-TECSA-cardiopathy, (C2) male-mostly-CSA-cardiopathy, (C3) male-mostly-TECSA-no cardiopathy, (C4) female-mostly-elevated BMI-TECSA-cardiopathy, (C5) male-mostly-OSA-low-LVEF). Of note, the male-mostly-OSA-low-LVEF-cluster-5 had significantly lower fixed end-expiratory-airway-pressure (EPAP) settings versus C1 (p = 0.029) and C4 (p = 0.007). Auto-EPAP usage was higher in the male-mostly-TECSA-no cardiopathy-cluster-3 versus C1 (p = 0.006) and C2 (p

Abstract Background Patient skepticism concerning medical innovations can have major consequences for current public health and may threaten future progress, which greatly relies on clinical research. The primary objective of this study is to determine the variables associated with patient acceptation or refusal to participate in clinical research. Specifically, we sought to evaluate if distrust in pharmaceutical companies and associated psychosocial factors could represent a recruitment bias in clinical trials and thus threaten the applicability of their results. Methods This prospective, multicenter survey consisted in the administration of a self-questionnaire to patients during a pulmonology consultation. The 1025 questionnaires distributed collected demographics, socio-professional and basic health literacy characteristics. Patients were asked to rank their level of trust for pharmaceutical companies and indicate their willingness to participate in different categories of research (pre or post marketing, sponsored by an academic institution or pharmaceutical company). Logistic regression was used to determine factors contributing to “trust” versus “distrust” group membership and willingness to participate in each category of research. Results One thousand patients completed the survey, corresponding to a response rate of 97.5%. Data from 838 patients were analyzed in this study. 48.3% of respondents declared that they trusted pharmaceutical companies, while 35.5% declared distrust. Being female (p = 0.042), inactive in the employment market(p = 0.007), and not-knowing the name of one’s disease(p = 0.010) are factors related to declared distrust. Distrust-group membership is associated with unwillingness to participate in certain categories of trials such as pre-marketing and industry-sponsored trials. Conclusion Distrust in pharmaceutical companies is associated with a specific patient profile and with refusal to participate in certain subcategories of trials. This potential recruitment bias may explain the under-representation of certain categories of patients such as women in pre-marketing drug trials.

Abstract Background Low back pain is highly prevalent and a major source of disability worldwide. Spa therapy is frequently used to treat low back pain, but the associated level of evidence for efficacy is insufficient. To fill this knowledge gap, this protocol proposes an appropriately powered, prospective, evaluator-blinded, multi-centre, two-parallel-arm, randomised (1:1), controlled trial that will compare spa therapy in addition to usual care including home exercise (UCHE) versus UCHE alone for the treatment of chronic low back pain. Methods Eligible patients (anticipated sample size of 358) will have had low back pain for more than 3 months and scores for pain greater than 40 mm on a visual analogue scale (VAS). Following initial consent for UCHE and baseline evaluations, patients are randomised (1:1) to UCHE alone, or UCHE plus spa therapy (18 days of mud packs, underwater massages, showers and water exercises under medical supervision). Patients in the latter arm will be requested to sign an additional consent form as per Zelen randomisation. Follow-up visits will occur at approximately months 1, 6 and 12 and (along with baseline assessments) will cover changes over time in VAS pain scores, the impact of lower back pain on daily life (the Rolland and Morris Disability Questionnaire (RMDQ)), inappropriate fears and beliefs about lower back pain (the fear, avoidance, belief questionnaire (FABQ)), general quality of life (the Euroqol Group 5 dimension, 5 level questionnaire (EQ-5D-5 L)), Patient Acceptable Symptom State (PASS), consumption of analgesic drugs and nonsteroidal anti-inflammatory drugs (NSAIDs), and overall state of health. Health resource use and days of sick leave (and subsequently the associated costs) will also be recorded. The primary outcome is the presence/absence of a clinically relevant change (improvement of at least 30%) in the VAS score for pain at 6 months. Discussion Despite the fact that previous, rather dated recommendations encourage spa therapy for the treatment of low back pain, the current literary corpus is methodologically poor. This protocol has been designed to provide results spanning a thorough range of outcomes at the highest evidence level possible. Trial registration ClinicalTrials.gov: NCT03910023 . Registered on 10 April 2019.

Abstract Background Muscle weakness following critical illness is the consequence of loss of muscle mass and alteration of muscle quality. It is associated with long-term disability. Ultrasonography is a reliable tool to quantify muscle mass, but studies that evaluate muscle quality at the critically ill bedside are lacking. Shear wave ultrasound elastography (SWE) provides spatial representation of soft tissue stiffness and measures of muscle quality. The reliability and reproducibility of SWE in critically ill patients has never been evaluated. Methods Two operators tested in healthy controls and in critically ill patients the intra- and inter-operator reliability of the SWE using transversal and longitudinal views of the diaphragm and limb muscles. Reliability was calculated using the intra-class correlation coefficient and a bootstrap sampling method assessed their consistency. Results We collected 560 images. Longitudinal views of the diaphragm (ICC 0.83 [0.50–0.94]), the biceps brachii (ICC 0.88 [0.67–0.96]) and the rectus femoris (ICC 0.76 [0.34–0.91]) were the most reliable views in a training set of healthy controls. Intra-class correlation coefficient for inter-operator reproducibility and intra-operator reliability was above 0.9 for all muscles in a validation set of healthy controls. In critically ill patients, inter-operator reproducibility and intra-operator 1 and 2 reliability ICCs were respectively 0.92 [0.71–0.98], 0.93 [0.82–0.98] and 0.92 [0.81–0.98] for the diaphragm; 0.96 [0.86–0.99], 0.98 [0.94–0.99] and 0.99 [0.96–1] for the biceps brachii and 0.91 [0.51–0.98], 0.97 [0.93–0.99] and 0.99 [0.97–1] for the rectus femoris. The probability to reach intra-class correlation coefficient greater than 0.8 in a 10,000 bootstrap sampling for inter-operator reproducibility was respectively 81%, 84% and 78% for the diaphragm, the biceps brachii and the rectus femoris respectively. Conclusions SWE is a reliable technique to evaluate limb muscles and the diaphragm in both healthy controls and in critically ill patients. Trial registration The study was registered (ClinicalTrial NCT03550222).

(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.

BackgroundObesity is a major public health issue. Combining exercise training, nutrition, and therapeutic education in metabolic rehabilitation (MR) is recommended for obesity management. However, evidence from randomized controlled studies is lacking. In addition, MR is associated with poor patient adherence. Mobile health devices improve access to MR components. ObjectiveThe aim of this study is to compare the changes in body composition, anthropometric parameters, exercise capacity, and quality of life (QOL) within 12 weeks of patients in the telerehabilitation (TR) program to those of usual care patients with obesity. MethodsThis was a parallel-design randomized controlled study. In total, 50 patients with obesity (BMI>30 kg/m²) were included in a TR group (TRG) or a usual care group (UCG) for 12 weeks. Patients underwent biometric impedance analyses, metabolic exercise tests, actimetry, and QOL and satisfaction questionnaires. The primary outcome was the change in fat mass at 12 weeks from baseline. Secondary outcomes were changes in body weight, metabolic parameters, exercise capacity, QOL, patients’ adhesion, and satisfaction. ResultsA total of 49 patients completed the study. No significant group × time interaction was found for fat mass (TRG: mean 1.7 kg, SD 2.6 kg; UCG: mean 1.2 kg, SD 2.4 kg; P=.48). Compared with the UCG, TRG patients tended to significantly improve their waist to hip ratios (TRG: −0.01 kg, SD 0.04; UCG: +0.01 kg, SD 0.06; P=.07) and improved QOL physical impact (TRG: +21.8, SD 43.6; UCG: −1.2, SD 15.4; P=.005). Significant time effects were observed for body composition, 6-minute walk test distance, exercise metabolism, sedentary time, and QOL. Adherence (95%) and satisfaction in the TRG were good. ConclusionsIn adults with obesity, the TR program was not superior to usual care for improving body composition. However, TR was able to deliver full multidisciplinary rehabilitation to patients with obesity and improve some health outcomes. Given the patients’ adherence and satisfaction, pragmatic programs should consider mobile health devices to improve access to MR. Further studies are warranted to further establish the benefits that TR has over usual care. Trial RegistrationClinicalTrials.gov NCT03396666; http://clinicaltrials.gov/ct2/show/NCT03396666

Objectives The role of health-related quality of life (HRQoL) and psychological variables in pulmonary arterial hypertension (PAH) progression remains poorly quantified. We aimed to investigate the relationship between disease progression in PAH patients and HRQoL and psychological characteristics. Methods A 3-year longitudinal cohort was initiated. Patients with stable PAH (groups I–IV ineligible for angioplasty/endarterectomy) were included (n=55). Standard clinical variables, including invasive haemodynamic parameters, were prospectively recorded. A battery of questionnaires was used to characterise the psychological status of patients upon study initiation, and HRQoL was quantified using the SF-36 Questionnaire every 3 months for 24 months, and then again at 36 months. Guideline-defined disease progression and progression-free survival were recorded for 36 months. Measurements and main results Psychological distress was highly prevalent at baseline. The Physical Component Summary (PCS) and the Mental Component Summary (MCS) of the HRQoL were poor (PCS=37.13±8.18; MCS=42.42±10.88) but stable over 3 years of follow-up. Among PCS subscales, Physical Functioning (PF) (p=0.012) was identified as being independently associated with disease progression (Cox survival model), along with mean pulmonary arterial pressure (p=0.003) and cardiac output (p=0.005). Depression was the unique independent psychological characteristic associated with PF (p=0.0001). Conclusions PAH patients have poor HRQoL. In addition to already known criteria related to disease severity, the HRQoL PF subscale is independently associated with disease progression in PAH. This may be explained by depression.

Abstract Chronic obstructive pulmonary disease (COPD) is associated with exercise intolerance and limits the functional gains in response to exercise training in patients compared to sedentary healthy subjects (SHS). The blunted skeletal muscle angiogenesis previously observed in COPD patients has been linked to these limited functional improvements, but its underlying mechanisms, as well as the potential role of oxidative stress, remain poorly understood. Therefore, we compared ultrastructural indexes of angiogenic process and capillary remodelling by transmission electron microscopy in 9 COPD patients and 7 SHS after 6 weeks of individualized moderate-intensity endurance training. We also assessed oxidative stress by plasma-free and esterified isoprostane (F2-IsoP) levels in both groups. We observed a capillary basement membrane thickening in COPD patients only (p = 0.008) and abnormal variations of endothelial nucleus density in response to exercise training in these patients when compared to SHS (p = 0.042). COPD patients had significantly fewer occurrences of pericyte/endothelium interdigitations, a morphologic marker of capillary maturation, than SHS (p = 0.014), and significantly higher levels of F2-IsoP (p = 0.048). Last, the changes in pericyte/endothelium interdigitations and F2-IsoP levels in response to exercise training were negatively correlated (r = − 0.62, p = 0.025). This study is the first to show abnormal capillary remodelling and to reveal impairments during the whole process of angiogenesis (capillary creation and maturation) in COPD patients. Trial registration NCT01183039 & NCT01183052, both registered 7 August 2010 (retrospectively registered).

Abstract Background Intensive care unit (ICU)-acquired weakness (ICU-AW) and ICU-acquired diaphragm dysfunction (ICU-DD) occur frequently in mechanically ventilated (MV) patients. It is unknown whether they have different risk factors and different impacts on outcome. This study was designed to (1) describe the respective risk factors associated with ICU-AW and severe ICU-DD and (2) evaluate the respective impact of ICU-AW and severe ICU-DD on outcome. Methods Post hoc analysis of two prospective cohort studies conducted in two ICUs. In patients mechanically ventilated for at least 24 h undergoing a first spontaneous breathing trial, severe ICU-DD was defined as diaphragm twitch pressure

Abstract Backgrounds As a consequence of the increased mortality observed in the SERVE-HF study, many questions concerning the safety and rational use of ASV in other indications emerged. The aim of this study was to describe the clinical characteristics of ASV-treated patients in real-life conditions. Methods The OTRLASV-study is a prospective, 5-centre study including patients who underwent ASV-treatment for at least 1 year. Patients were consecutively included in the study during the annual visit imposed for ASV-reimbursement renewal. Results 177/214 patients were analysed (87.57% male) with a median (IQ25–75) age of 71 (65–77) years, an ASV-treatment duration of 2.88 (1.76–4.96) years, an ASV-usage of 6.52 (5.13–7.65) hours/day, and 54.8% were previously treated via continuous positive airway pressure (CPAP). The median Epworth Scale Score decreased from 10 (6–13.5) to 6 (3–9) (p 45% in 92.7% of patients. Associated comorbidities/etiologies were cardiac in nature for 75.7% of patients (neurological for 12.4%, renal for 4.5%, opioid-treatment for 3.4%). 9.6% had idiopathic central-sleep-apnea. 6.2% of the patients were hospitalized the year preceding the study for cardiological reasons. In the 6 months preceding inclusion, night monitoring (i.e. polygraphy or oximetry during ASV usage) was performed in 34.4% of patients, 25.9% of whom required a subsequent setting change. According to multivariable, logistic regression, the variables that were independently associated with poor adherence (ASV-usage ≤4 h in duration) were TECSA group versus CSA group (p = 0.010), a higher Epworth score (p = 0.019) and lack of a night monitoring in the last 6 months (p

Abstract Background Whereas telemedicine usage is growing, the only clinical algorithm for Continuous Positive Airway Pressure (CPAP) adherence management is that stipulated by the 2013 American Thoracic Society (ATS). The capacity of the latter to predict non-adherence in long-term CPAP-treated patients has not been validated. Methods Patients from the prospective real-life InterfaceVent study (NCT03013283, study conducted in an adult cohort undergoing at least 3 months of CPAP) and eligible for ATS algorithm usage were analysed. The residual device Apnea–Hypopnea-Index (AHIflow) and High Large Leak (HLL) thresholds proposed in the ATS algorithm were evaluated for predicting adherence (i.e. AHIflow > 10/h, HLLs 95th > 24 L/min for ResMed® devices and ResMed® nasal mask, HLLs 95th > 36 l/min for ResMed® devices and ResMed® oronasal masks, HLLs > 1 h for Philips® devices and HHLs > 60 l/min for Fisher & Paykel® devices). Adherence was defined according to the 2013 ATS algorithm (i.e. CPAP use > 4 h/j for at least 70% of days). Results 650/1484 patients eligible for ATS algorithm usage were analysed (15.38% non-adherent, 74% male with a median (IQ25–75) age of 68 (61–77) years, a body mass index of 30.8 (27.7–34.5) kg/m2, an initial AHI of 39 (31–55) events/h, and CPAP-treatment-duration of 5.1 (2.2–7.8) years). Logistic regression analysis demonstrated no significant relationship between the ATS proposed AHIflow or HLL thresholds and non-adherence. Complementary ROC curve analysis failed to determine satisfactory AHIflow and HLL thresholds. Conclusion When managing non-adherence in long-term CPAP-treated patients, our data do not validate absolute AHIflow or HLL thresholds in general. Trial registration The INTERFACE-VENT study is registered on ClinicalTrials.gov (Identifier: study (NCT03013283).

Introduction To date, continuous positive airway pressure (CPAP) remains the cornerstone of obstructive sleep apnoea treatment. CPAP data describing residual sleep-disordered breathing events (ie, the CPAP-measured apnoea–hypopnoea indices (AHI-CPAPflow)) is difficult to interpret because it is an entirely different metric than the polysomnography (PSG) measured AHI gold standard (AHI-PSGgold). Moreover, manufacturer definitions for apnoea and hypopnoea are not only different from those recommended for PSG scoring, but also different between manufacturers. In the context of CPAP initiation and widespread telemedicine at home to facilitate sleep apnoea care, there is a need for concrete evidence that AHI-CPAPflow can be used as a surrogate for AHI-PSGgold.Methods and analysis No published systematic review and meta-analysis (SRMA) has compared the accuracy of AHI-CPAPflow against AHI-PSGgold and the primary objective of this study is therefore to do so using published data. The secondary objectives are to similarly evaluate other sleep disordered breathing indices and to perform subgroup analyses focusing on the inclusion/exclusion of central apnoea patients, body mass index levels, CPAP device brands, pressure titration modes, use of a predetermined and fixed pressure level or not, and the impact of a 4% PSG desaturation criteria versus 3% PSG on accuracy. The Preferred Reporting Items for SRMA protocols statement guided study design. Randomised controlled trials and observational studies of adult patients (≥18 years old) treated by a CPAP device will be included. The CPAP intervention and PSG comparator must be performed synchronously. PSGs must be scored manually and follow the American Academy of Sleep Medicine guidelines (2007 AASM criteria or more recent). To assess the risk of bias in each study, the Quality Assessment of Diagnostic Accuracy Studies 2 tool will be used.Ethics and dissemination This protocol received ethics committee approval on 16 July 2020 (IRB_MTP_2020_07_2020000404) and results will be disseminated via peer-reviewed publications.PROSPERO/Trial registration numbers CRD42020159914/NCT04526366; Pre-results

During pregnancy the formation of alloreactive anti-human leukocyte antigen (HLA) antibodies are a major cause of acute rejection in organ transplantation and of adverse effects in blood transfusion. The purpose of the study was to identify maternal HLA class Ib genetic factors associated with anti-HLA allo-immunization in pregnancy and the degree of tolerance estimated by IgG4 expression. In total, 86 primiparous women with singleton pregnancies were included in the study. Maternal blood samples and umbilical cord samples were collected at delivery. Clinical data were obtained. Maternal blood serum was screened for HLA class I and II antibodies, identification of Donor Specific Antibody (DSA), activation of complement measured by C1q and IgG4 concentrations. Mothers were genotyped for HLA class Ib (HLA-E, -F and -G). Anti-HLA class I and II antibodies were identified in 24% of the women. The maternal HLA-E*01:06 allele was significantly associated with a higher fraction of anti-HLA I immunization (20.0% vs. 4.8%, p = 0.048). The maternal HLA-G 3’-untranslated region UTR4-HLA-G*01:01:01:05 haplotype and the HLA-F*01:03:01 allele were significantly associated with a low anti-HLA I C1q activation (16.7% vs. 57.1%, p = 0.028; 16.7% vs. 50.0%, p = 0.046; respectively). Both HLA‑G and HLA-F*01:03:01 showed significantly higher levels of IgG4 compared with the other haplotypes. The results support an association of certain HLA class Ib alleles with allo-immunization during pregnancy. Further studies are needed to elucidate the roles of HLA-E*01:06, HLA-F*01:03 and HLA‑G UTR4 in reducing the risk for allo-immunization.

BackgroundPatients affected with aneurysmal subarachnoid hemorrhage (aSAH) often require intensive care, and then present distinctive outcome from less severe patients. We aimed to specify their long-term outcome and to identify factors associated with poor outcome.MethodsWe conducted a retrospective study in a French university hospital intensive care unit. Patients with aSAH requiring mechanical ventilation hospitalized between 2010 and 2015 were included. At least one year after initial bleeding, survival and degree of disability were assessed using the modified Rankin Scale (mRS) via telephone interviews. A multivariable logistic regression analysis was performed to determine independent factors associated with poor outcome defined as mRS≥3.ResultsTwo-hundred thirty-six patients were included. Among them, 7 were lost to follow-up, and 229 were analyzed: 73 patients (32%) had a good outcome (mRSConclusionAmong aSAH patients requiring assisted ventilation, two-third of them survived at one year, and one-third showed good long-term outcome. As it appears as an independant factor associated with poor outcome, DCI shoud retain particular attention in future studies beyond angiographic vasospasm.

Introduction Tracheal intubation is one of the most daily practiced procedures performed in intensive care unit (ICU). It is associated with severe life-threatening complications, which can lead to intubation-related cardiac arrest. Using a preshaped endotracheal tube plus stylet may have potential advantages over endotracheal tube without stylet. The stylet is a rigid but malleable introducer which fits inside the endotracheal tube and allows for manipulation of the tube shape; to facilitate passage of the tube through the laryngeal inlet. However, some complications from stylets have been reported including mucosal bleeding, perforation of the trachea or oesophagus and sore throat. The use of a stylet for first-attempt intubation has never been assessed in ICU and benefit remains to be established.Methods and analysis The endotracheal tube plus stylet to increase first-attempt success during orotracheal intubation compared with endotracheal tube alone in ICU patients (STYLETO) trial is an investigator-initiated, multicentre, stratified, parallel-group unblinded trial with an electronic system-based randomisation. Patients will be randomly assigned to undergo the initial intubation attempt with endotracheal tube alone (ie,without stylet, control group) or endotracheal tube + stylet (experimental group). The primary outcome is the proportion of patients with successful first-attempt orotracheal intubation. The single, prespecified, secondary outcome is the incidence of complications related to intubation, in the hour following intubation. Other outcomes analysed will include safety, exploratory procedural and clinical outcomes.Ethics and dissemination The study project has been approved by the appropriate ethics committee ‘Comité-de-Protection-des-Personnes Nord-Ouest3-19.04.26.65808 Cat2 RECHMPL19_0216/STYLETO2019-A01180-57’”. Informed consent is required. The results will be submitted for publication in a peer-reviewed journal and presented at one or more scientific conferences. If combined use of endotracheal tube plus stylet facilitates tracheal intubation of ICU patients compared with endotracheal tube alone, its use will become standard practice, thereby decreasing first-attempt intubation failure rates and, potentially, the frequency of intubation-related complications.Trial registration details ClinicalTrials.gov Identifier: NCT04079387; Pre-results.

Introduction Recurrent vasovagal syncope (VVS) is associated with decreased quality-of-life and frequent use of emergency services. The evidence base for causality, diagnostic procedures and potential VVS treatments is poor. Scattered observations in the literature suggest a link between respiratory disturbances during sleep and VVS. Empirical observations lead us to further hypothesise that the appropriate management of sleep apnoea syndrome (SAS) may help resolve comorbid recurrent VVS in certain patients. We therefore designed this pilot study to provide a framework for the observation of changes in outcomes accompanying the deployment of SAS treatments in patients with VVS.Methods and analysis This is a multicentre, registry-based study whose primary objective is to evaluate the effect of SAS management on the number of syncope/presyncope episodes in a population suffering from both VVS and SAS. To this effect, syncope rates prior to the treatment of SAS will be compared with those occurring after the initiation of the latter. In addition, yearly assessments will collect data for echocardiography, polysomnography, Holter monitoring, table tilt tests, multiple sleep latency tests, SAS management parameters and questionnaires describing fatigue, depression and quality-of-life. Sixty patients will be included with a minimum follow-up period of 12 months. The primary analysis will use comparisons of centrality for paired data to describe the changes in syncope rates before versus after the initiation of SAS management. Longitudinal data will be analysed using mixed models with patients set as a random effect. Subgroup analyses will be performed for SAS-treatment adherence and efficacy.Ethics and dissemination The VVS-SAS registry was approved by an ethics committee (Comité pour la Protection des Personnes Ile-de-France VI, Reference number CPP/2-18) in accordance with French law. The princeps publication will present before–after SAS management results and longitudinal analyses.Trial registration number NCT04294524. Pre-results.