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Abstract Background Arterial hypotension induced by general anesthesia is commonly identified as a risk factor of morbidity, especially neurological, after cardiac or noncardiac surgery in adults and children. Intraoperative hypotension is observed with sevoflurane anesthesia in children, in particular in neonates, infants younger than 6 months, and preterm babies. Ephedrine is commonly used to treat intraoperative hypotension. It is an attractive therapeutic, due to its dual action on receptors alpha and beta and its possible peripheral intravenous infusion. There are few data in the literature on the use of ephedrine in the context of pediatric anesthesia. The actual recommended dose of ephedrine (0.1 to 0.2 mg/Kg) frequently leads to a therapeutic failure in neonates and infants up to 6 months of age. The use of higher doses would probably lead to a better correction of hypotension in this population. The objective of our project is to determine the optimal dose of ephedrine for the treatment of hypotension after induction of general anesthesia with sevoflurane, in neonates and infants up to 6 months of age. Methods The ephedrine study is a prospective, randomized, open-label, controlled, dose-escalation trial. The dose escalation consists of 6 successive cohorts of 20 subjects. The doses studied are 0.6, 0.8, 1, 1.2, and 1.4 mg/kg. The dose chosen as the reference is 0.1 mg/kg, the actual recommended dose. Neonates and infants younger than 6 months, males and females, including preterm babies who undergo a surgery with general anesthesia inducted with sevoflurane were eligible. Parents of the subject were informed. Then, the subjects were randomized if presenting a decrease in mean blood pressure superior to 20% of their initial mean blood pressure (before induction of anesthesia), despite a vascular filling with sodium chloride 0.9%. The primary outcome is the success of the therapy defined as an mBP superior to 80% of the baseline mBP (prior to anesthesia) within 10 min post ephedrine administration. The subjects were followed-up for 3 days postanesthesia. Discussion This study is the first randomized, controlled trial intending to determine the optimal dose of ephedrine to treat hypotension in neonates and infants below 6 months old. Trial registration ClinicalTrials.gov NCT02384876 . Registered on March 2015.

Introduction There is a lack of objective evaluation with validated tools in school children with intellectual disability (ID). Standardized and validated tools, allowing children evaluations and follow-up, exist but are poorly used. Our action-study wishes to develop evaluation practices to better adapt to the specific needs of children with ID. Objectives We evaluated the multidimensional profiles (cognitive, adaptative and behavioral) of children with ID attending regular or adapted school system. Methods School children, aged 5 to 13 years old, with mild to moderate ID were enrolled in this French cohort study. The multidimensional evaluation consisted of a school evaluation grid proposed by the French educational system, a scale of school needs (GEVA-sco), an intellectual assessment (WISC IV), a behavior adaptative scale (Vineland II) and a behavior rating scale (the French Nisonger Child Behavior Rating Form (Nisonger CBRF)). The results of this multidimensional assessment were analyzed. Results Between November 2014 and June 2016, 121 children were enrolled, 3 children were lost to follow-up. Analysis was performed on 118 children. Seventy one (60.2 %) were male. Fifty-two (44.1%) were aged 6 to 9 years. Sixty-eight (57.6%) children were in regular schools and 50 (42.4%) in adapted schools. Children in regular schools had a higher mean IQ score (57.5) than children in adapted schools (43.5). The adaptative behavior profile of children in regular school is less severe than in children in adapted schools. Conclusions Multidimensional evaluations allow optimizing and personalizing support. Evaluation of adaptative behavior is more informative than cognitive profile which does not differentiate between children skills Disclosure No significant relationships.

Introduction Early screening of children at-risk to develop Autism Spectrum Disorder (ASD) needs to be improved to propose early interventions. This detection should allow diagnosis of ASD before the age of 3. An early screening performed at the general practitioner of the family should facilitate accessibility to diagnosis and a better collaboration between professionals. Objectives Our primary objective is to estimate the positive predictive value of an early detection kit composed of 2 questionnaires (First screening: M-CHAT-R/F™ + CSBS DP™-ITC) and a confirmation of the detection with a phone call by a neuropsychologist. Patients with confirmed positive M-CHAT-R/F™ and/or CSBS DP™-ITC scores are referred to a level 2 team for pre-diagnosis and diagnosis assessment. Methods The KitCAT study is a cohort study of 1,700 children aged 16 to 24 months seen in routine care in general or pediatric practices, or in nurseries and child care centers. Results Seven hundred and five children have already been enrolled in the study. Twenty nine patients, ie 4.1%, (with a confirmed positive M-CHAT-R/F™ and/or CSBS DP™-ITC scores) were referred to a level 2 team where a pre-diagnosis assessment was conducted by using the following test: ADI-R, ADOS 2, BLR, WPPSI-IV and Vineland II. The diagnosis of ASD (using the same test than the pre-diagnosis) was confirmed for the first two patients aged of 3. Conclusions The preliminary results confirm that the use of 2 questionnaires may optimize the reliability of the screening. A thousand children are still needed for the final analysis and further results are expected. Disclosure No significant relationships.

Background: Recent studies, including the TENSION trial, support the use of endovascular thrombectomy (EVT) in acute ischemic stroke with large infarct (Alberta Stroke Program Early Computed Tomography Score (ASPECTS) 3-5)., Objective: To evaluate the cost-effectiveness of EVT compared with best medical care (BMC) alone in this population from a German healthcare payer perspective., Methods: A short-term decision tree and a long-term Markov model (lifetime horizon) were used to compare healthcare costs and quality-adjusted life years (QALYs) between EVT and BMC. The effectiveness of EVT was reflected by the 90-day modified Rankin Scale (mRS) outcome from the TENSION trial. QALYs were based on published mRS-specific health utilities (EQ-5D-3L indices). Long-term healthcare costs were calculated based on insurance data. Costs (reported in 2022 euros) and QALYs were discounted by 3% annually. Cost-effectiveness was assessed using incremental cost-effectiveness ratios (ICERs). Deterministic and probabilistic sensitivity analyses were performed to account for parameter uncertainties., Results: Compared with BMC, EVT yielded higher lifetime incremental costs (€24 257) and effects (1.41 QALYs), resulting in an ICER of €17 158/QALY. The results were robust to parameter variation in sensitivity analyses (eg, 95% probability of cost-effectiveness was achieved at a willingness to pay of >€22 000/QALY). Subgroup analyses indicated that EVT was cost-effective for all ASPECTS subgroups., Conclusions: EVT for acute ischemic stroke with established large infarct is likely to be cost-effective compared with BMC, assuming that an additional investment of €17 158/QALY is deemed acceptable by the healthcare payer., Competing Interests: Competing interests: MB reports funding from the European Commission (European Union’s Horizon 2020 research and innovation programme, grant agreement No. 754640 – payments to the institution), and fees as consultant or lecturer from Novartis, Boehringer-Ingelheim, Guerbet, Seagen, and NeuroScios, all outside the submitted work. GT reports funding from the European Commission (European Union’s Horizon 2020 research and innovation programme, grant agreement No. 754640 – payments to the institution) for the TENSION trial, and fees as consultant or lecturer from Acandis, Alexion, Amarin, Bayer, Boehringer Ingelheim, BristolMyersSquibb/Pfizer, Daiichi Sankyo, Stryker, all outside the submitted work. The remaining authors have nothing to disclose., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Accurate endoscopic characterization of colorectal lesions is essential to predict histology and select the best treatment strategy but remains very difficult. Instead of the recommended endoscopic characterization, many gastroenterologists routinely perform biopsies of the lesion to propose endoscopic resection with or without R0 intent. The aim of this study was to determine which of endoscopic characterization or biopsies, either targeted (TB) or non-targeted (NTB), is the most effective to determine the best treatment strategy for colorectal neoplasia > 2 cm., Methods: We prospectively assessed the best strategy between endoscopic characterization and targeted or non-targeted biopsies, so that the proposed resection technique offered a level of quality of tumor resection adapted to the definitive histology of the lesion on R0-resected specimen., Results: 84 patients with 88 lesions were included. "Adequate treatment" was proposed by endoscopic characterization in 52.3 to 70.5% of cases, "under treatment" in 2.3 to 9.1% and "over treatment" in 20.5 to 45.5%. Two severe events were recorded. "Adequate treatment" was proposed by TB and NTB in respectively 72.7 and 69.3% of cases, "under treatment" in respectively 27.3 and 30.7% and no case of "over treatment" was reported. TB and NTB were ineffective to evaluate the depth of invasion in the submucosa and to differentiate superficial invasive from deep invasive adenocarcinomas., Conclusions: Biopsies-based strategies are unable to predict depth of cancer invasion and could be associated with a risk of under treatment of large colorectal lesions in near a third of the cases compared to only around 5% with endoscopic characterization. Endoscopic characterization could lead to over treatment, but mainly by endoscopic submucosal dissection with low morbidity. Characterization with the CONECCT classification could decrease the risk of under treatment and avoid surgeries for non-malignant colorectal lesions. Other endoscopic criteria should be determined to better characterize colorectal lesions and to improve the best adapted treatment for each lesion., Competing Interests: Declarations. Disclosures: Pierre Lafeuille, Emilien Daire, Jérôme Rivory, Florian Rostain, Jean-Christophe Saurin, Thomas Lambin, Frederic Moll, Tanguy Fenouil, Jérémie Jacques, Fabien Subtil and Mathieu Pioche have no competing interests to declare that are relevant to the content of this article., (© 2025. The Author(s).)

Introduction: Patients from low socioeconomic backgrounds are empirically considered more difficult to treat. The objectives were to evaluate low socioeconomic status of patients as a factor associated with increased treatment need and the correlation between socioeconomic status and dysmorphosis on one hand, and cooperation level on the other., Material and Methods: This was a retrospective comparative monocentric observational cohort study. Included subjects were under 16 years old at the time of orthodontic braces placement and were beneficiaries of the complémentaire santé solidaire (C2S) or not (non-C2S). Evaluated criteria included treatment need (IOTN-DHC), antero-posterior and vertical dysmorphosis (FMA, ANB, IMPA, I/F), and compliance. Fisher and Wilcoxon tests were performed. A 5% threshold was retained., Results: Overall, 173 patients were included and divided into two groups: C2S/non-C2S. Neither treatment need nor skeletal and alveolar-dental dysmorphosis are correlated with socioeconomic status. Cooperation is correlated with low socioeconomic status across all evaluated criteria: three times more bracket debondings, three times more remarks about failure to wear elastics, 1.25 times more missed appointments, ten times more treatment abandonments., Conclusion: It may not be dysmorphosis that makes orthodontic treatment of low socioeconomic status patients more difficult, but rather a lack of cooperation. This calls for clinical and policy interventions to increase patient involvement in treatment. Randomized trials are needed to corroborate the results.

Background: Glucose (GBT) and lactulose (LBT) breath tests have been recommended for the diagnosis of small intestinal bacterial overgrowth (SIBO). LBT may yield a higher prevalence of SIBO diagnosis, because of its limited small bowel absorption, and therefore colonic fermentation. The aim of this retrospective study was to confirm this hypothesis, in irritable bowel syndrome patients (IBS)., Methods: Among a cohort of 995 patients who underwent GBT or LBT, 287 with typical IBS according to Rome IV criteria, without past digestive surgery or significant medical comorbidities, were included., Results: 155 IBS patients underwent GBT, and 132 LBT (71% women, mean age 45±15, mean BMI: 22.6±4.3 kg/m 2 ). There were no difference between both groups in terms of demographics, IBS type and severity of symptoms. The prevalence of SIBO according to LBT was 47%, versus 4.5% only with GBT (p<0.001). The prevalence of methane values ≥ 10 ppm were similar in both groups (34%)., Conclusion: LBT is very frequently positive in IBS patients, as compared to GBT. The 2 tests are thus not interchangeable for the diagnosis of SIBO. Furthermore, the positivity of both tests was not correlated with symptoms, which may indicate a poor clinical interest of these tests in IBS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Background: Attention-deficit/hyperactivity disorder (ADHD) affects approximately 5% of children globally, with symptoms often persisting into adulthood. While pharmacological interventions are commonly employed for management, understanding the optimal dosing for efficacy and tolerability remains crucial. This study aims to conduct a dose-response network meta-analysis to estimate the efficacy of pharmacological treatments across different doses, aiming to inform clinical decision-making and improve treatment outcomes., Methods: This updated systematic review will include randomized controlled trials evaluating ADHD medication efficacy in children, adolescents, and adults. An updated search from a 2018 NMA will be conducted across multiple electronic databases with no language restrictions, using specific eligibility criteria focused on randomized controlled trials. The primary outcome will assess the severity of ADHD core symptoms, while secondary outcomes will consider treatment tolerability. A dose-response Bayesian hierarchical model will be used to estimate dose-response curves for each medication, identifying optimal dosing strategies., Discussion: With this dose-response network meta-analysis, we aim to better understand the dose-response relationship of pharmacological treatment in ADHD, which could help clinician to the identification of optimal doses., Systematic Review Registration: OSF https://doi.org/10.17605/OSF.IO/3MY4A ., (© 2024. The Author(s).)

In hospitalized children, height should be measured. When world health organization (WHO) height measurement gold standards is impossible, the ideal height estimation technique is still unclear. We conducted an international prospective study in eight different pediatric intensive care units to assess the accuracy, precision, practicability, safety, and inter-rater reliability of 12 different height estimation techniques, based on body segment measurement extrapolation, or other calculations using previous or projected heights. All extrapolation techniques were performed on each child, and later compared to their WHO gold standard heights. A total of 476 patients were enrolled. In the < 2-year subgroup, board length use and growth chart extrapolation performed best. In the ≥ 2-year subgroup, growth chart extrapolation and parents' report were the most accurate, followed by height measurement alongside the body with a tape measure. In both groups, body segment extrapolations were poorly predictive and showed mean bias and limits of agreement that varied a lot with age. Most body segment-based techniques presented with frequent measurement difficulties, but children's safety was rarely compromised. The inter-rater reliability of body segment measurement was low in the < 2-year subgroup.Conclusions: To accurately estimate height in hospitalized children, health care professionals should integrate the accuracy, precision, practicability, and reliability of each measurement technique to select the most appropriate one. Body segment-based techniques were the least accurate and should probably not be used. Simple techniques like growth chart extrapolation, or measurement alongside the body (and length board measurement in the youngest) should be implemented in daily practice.Trial Registration: The study protocol was registered (12 th April 2019) on the clinical-trial.gov website (NCT03913247)., (© 2024. The Author(s).)

Objectives: The COVID-19 pandemic led to the institution of public health measures in many countries which reduced respiratory infections. We aimed to identify and characterize changes in pediatric (<18 years) invasive pneumococcal disease (pIPD) in Portugal in 2018-2023., Methods: pIPD cases were identified by culture and molecular methods and stratified by age and serotype. When available the susceptibility of the isolates to antimicrobials was evaluated., Results: pIPD cases were markedly reduced in the last trimester of 2019-2020 and the entire 2020-2021 season. While 2021-2022 was in line with pre-pandemic seasons, in 2022-2023, the number of pIPD cases exceeded those found pre-pandemic. Molecular tests were responsible for identifying and serotyping 30% of cases, highlighting their importance in evaluating pIPD. Among the 316 pIPD cases, 37 different serotypes were detected, of which serotypes 3 (n = 85, 26.9%), 8 (n = 25, 7.9%), 10A (n = 21, 6.6%) and 24F (n = 20, 6.3%) were the most frequent. The post-pandemic serotype distribution reflected mostly pre-pandemic trends and the rebound was not driven by particular serotypes. We identified many vaccine failures, most (n = 37) representing serotype 3 infections. Penicillin non-susceptibility increased from 14% pre-pandemic to 29%, with serotype 24F becoming particularly significant., Conclusions: The higher number of cases of pIPD post-COVID-19 in Portugal raises the possibility of a higher burden of pneumococcal disease in Europe post-pandemic. The relatively stable serotype distribution and the current availability of the higher valency conjugate vaccines PCV15 and PCV20, potentially preventing a large proportion of pIPD (43% and 67%, respectively), offer an opportunity to control this increase., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: JM-C received research grants administered through his university and received honoraria for serving on the speakers bureaus of Pfizer and Merck Sharp and Dohme. MR received honoraria for serving on the speakers bureau of Pfizer and Merck Sharp and Dohme, for serving in expert panels of Merck Sharp and Dohme, support for attending meetings from Pfizer, and received research grants administered through his university from Merck Sharp and Dohme. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Assess the changes in post-traumatic stress disorder (PTSD), burnout, anxiety, depression, jobstrain, and isostrain levels over time among healthcare workers in emergency departments (EDs) after successive outbreaks of COVID-19. A prospective, multicenter study was conducted in 3 EDs and an emergency medical service. Healthcare workers who participated in our previous study were invited to participate in a follow-up 16 and 18 months and completed the questionnaires to assess symptoms of PTSD, burnout, anxiety, depression, jobstrain, and isostrain. Among the 485 healthcare workers asked to participate, 211 (43.5%) completed the survey at inclusion (122 were followed up at 3 months) and 59 participate to the follow-up study. At 16 months, 10.9% of healthcare workers had symptoms of PTSD and 17.4% at 18 months. At inclusion, 33.5% and 11.7% of healthcare workers had symptoms of anxiety and depression, respectively. A decrease in anxiety between inclusion and 16 months (p = 0.02) and an increase between 16 and 18 months (p = 0.009) was observed. At inclusion, 40.8% of all healthcare workers had symptoms of burnout. There was an increase in symptoms of burnout between inclusion and 18 months (p = 0.006). At inclusion, 43.2% and 29.5% of healthcare workers were exposed to jobstrain and isostrain, respectively. Jobstrain were higher among paramedics and administrative staff compared to physicians (p = 0.001 and p = 0.026, respectively). Successive outbreaks of COVID-19 led to long-term mental health consequences among ED healthcare workers that differed according to occupation. This must be taken into account to rethink the management of teams., (© 2024 The Author(s). Stress and Health published by John Wiley & Sons Ltd.)

Background: The ileocecal valve (ICV) is considered to be one of the most difficult locations for endoscopic submucosal dissection (ESD). The objective of this study was to evaluate the efficacy and safety of traction-assisted ESD in this situation., Methods: All patients who underwent traction-assisted ESD for an ICV lesion at three centers were identified from a prospective ESD database. En bloc and R0 rates were evaluated. Factors associated with non-R0 resection were explored., Results: 106 patients with an ICV lesion were included. The median lesion size was 50 mm (interquartile range 38-60) and 58.5% (62/106) invaded the terminal ileum. The en bloc and R0 resection rates were 94.3% and 76.4%, respectively. Factors associated with non-R0 resection were lesions covering ≥75% of the ICV (odds ratio [OR] 0.21. 95%CI 0.06-0.76; P=0.02), and involving the anal lip (OR 0.36, 95%CI 0.13-0.99; P=0.04) or more than two sites on the ICV (OR 0.27, 95%CI 0.07-0.99; P=0.03)., Conclusion: Traction-assisted ESD for treatment of ICV lesions was a safe and feasible option. Large lesions and anal lip involvement appeared to be factors predictive of difficulty., Competing Interests: C. Yzet is a consultant and lecturer for Abbvie, Takeda, Jansen, Amgen, and Galapagos. T. Wallenhorst has received honoraria for ESD training sessions from Olympus and Fujifilm, and lectures for Mayoli. J. Jacques has provided ESD training sessions for Olympus, Fuji, Erbe, Pentax Medical, and Lumendi, and lectures for Abbvie, Janssen, and Norgine. J. Rivory has received honoraria for training sessions in endoscopy and endoscopic resection from Olympus and Cook Medical. M. Schaefer has received honoraria for training session from Boston Scientific, and has received invitations to congresses from Olympus, Cook, Cousin Medical, Boston, Pentax, Abbvie, MSD, Amgen, and Norgine. M. Pioche has received honoraria for training sessions in endoscopy and endoscopic resection from Olympus, Cook Medical, Boston Scientific, and Pentax Medical; honoraria for training sessions in endoscopic characterization from Norgine and Provepharm; invitation to UEGW from AlfaSigma; and owns a patent for the Hospices Civils de Lyon IPEFIX device. M. Figueiredo, F. Rostain, L.J. Masgnaux, J. Grimaldi, R. Legros, P. Lafeuille, J. Albouys, and F. Subtil declare that they have no conflict of interest., (Thieme. All rights reserved.)

Study Objective: The present study is aimed at providing an assessment of the changes in burnout, job strain, isostrain, sleepiness, and fatigue levels over time and identifying factors associated with these symptoms among healthcare workers in French emergency departments (EDs). Method: We conducted a prospective, multicenter study in four EDs and an emergency medical service. Participants completed questionnaires at inclusion and at 90 days to assess burnout, job strain, isostrain, sleepiness, and fatigue. Results : A total of 211 respondents (43.5%) completed the questionnaires at inclusion. At the beginning of the study, 84 (40.8%) participants presented symptoms of burnout, 86 (43.2%) had symptoms of job strain, and 58 (29.4%) of isostrain. Forty-two (20.1%) healthcare workers presented symptoms of sleepiness, and 8 (3.8%) had symptoms of fatigue. We found that symptoms of burnout were more frequent for healthcare workers with a previous psychiatric history (55.3% vs. 39.1%, p = 0.02) and were lower among participants who had at least one dependent child (33.1% vs. 48.3%, p = 0.013). Symptoms of job strain were higher among administrative staff compared to physicians (55.6% vs. 28.7%, p = 0.01) and among healthcare workers with managerial responsibilities compared to those without (45.6% vs. 28.8%, p = 0.015). Symptoms of isostrain were higher among administrative staff (42.3%) compared to paramedics (34.1%) and physicians (19.8%, p = 0.026). Conclusion: We identified that potential factors associated with the emergence of symptoms of burnout and job strain are suggested, underlining several areas of improvement for the prevention against mental health disorders in the specific population of ED healthcare workers. Trial Registration: ClinicalTrials.gov identifier: NCT04383886., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Marion Douplat et al.)

Rationale: Central neuropathic pain resulting from spinal cord injury is notoriously debilitating and difficult to treat with few currently available treatments. A novel molecule with intrathecal administration: Ziconotide has been approved for treatment of refractory neuropathic pain in general. It acts as a presynaptic calcium channel blocker. A pilot study has shown its potential in SCI neuropathic pain patients., Objective: The aim of this study is to determine the long-term (6 months) efficacy of chronic intrathecal ziconotide for the treatment of neuropathic SCI pain., Study Design: Multicenter, Randomized, Comparative, Placebo controlled, Double blind clinical trial, with a crossover of random alternated periods of 6 months (placebo or ITZ) for a total of 15 months including a total of 44 patients., Study Population: • Patients with SCI of various etiologies exhibiting neuropathic pain refractory to non-invasive treatments. • > 18 years., Intervention: Intrathecal administration of ziconotide via an implanted pump., Study Outcomes: Primary study outcome Difference in pain intensity for all patients between effective treatment and placebo periods. Secondary study outcomes 1. Continuous evaluation of pain intensity. 2. Percentage of patients with at least 30% of pain reduction. 3. Satisfaction level of the patient pain relief. 4. Declarations of serious adverse events. 5. Duration and intensity of spontaneous and provoked pain. 6. Quality of life. 7. Patient global impression of change. 8. Quantification of daily dosages of analgesic drug intake. 9. Long term memory and neurocognitive effects. 10. Assessment of the patient's physical and emotional distress. NATURE AND EXTENT OF THE BURDEN AND RISKS ASSOCIATED WITH PARTICIPATION, BENEFIT, AND GROUP RELATEDNESS: Participation in this study is in accordance with current treatment protocols for SCI neuropathic pain in France therefore it proposes a treatment that would currently be considered regular practice even though no RCT evidence is yet available. The study gives patients the advantage of directly testing versus placebo a treatment that otherwise entails significant constraints. A Data Safety Monitoring board (DSMB) will be created for continuous safety analysis. Furthermore, patients will be followed in specialized pain centers offering the possibility of continuing their treatment after the study period., (© 2024. The Author(s).)

Introduction: The decisions of withholding or withdrawing life-sustaining treatments are difficult to make in the context of emergency departments (EDs) because most patients are unable to communicate. Relatives are thus asked to participate in the decision-making process, although they are unprepared to face such situations. We therefore aimed to develop a standardised intervention for announcing decisions of withholding or withdrawing life-sustaining treatments in EDs and assess the efficacy of the intervention on the stress of relatives., Methods and Analysis: The DISCUSS trial is a multicentre stepped-wedge cluster randomised study and will be conducted at nine EDs in France. A standardised intervention based on human simulation will be codesigned with partner families and implemented at three levels: the relatives, the healthcare professionals (HCP) and the EDs. The intervention will be compared with a control based on treatment as usual. A total of 538 families are planned to be included: 269 in the intervention group and 269 in the control group. The primary endpoint will be the symptoms of post-traumatic stress disorder (PTSD) at 90 days. The secondary endpoints will be symptoms of PTSD at 7 and 30 days, diagnosis of PTSD at 90 days and anxiety and depression scores at 7, 30 and 90 days. Satisfaction regarding the training, the assertiveness in communication and real-life stress of HCPs will be measured at 90 days., Ethics and Dissemination: This study was approved by the ethics committee Est III from Nancy and the French national data protection authority. All relatives and HCPs will be informed regarding the study objectives and data confidentiality. Written informed consent will be obtained from participants, as required by French law for this study type. The results from this study will be disseminated at conferences and in a peer-reviewed journal., Trial Registration Number: NCT06071078., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Long-term data showing the benefits of endovascular thrombectomy for stroke with large infarct are scarce. The TENSION trial showed the safety and efficacy of endovascular thrombectomy in patients with ischaemic stroke and large infarct at 90 days. We aimed to investigate the safety and efficacy at 12 months of endovascular thrombectomy in patients who were enrolled in the TENSION trial., Methods: TENSION was an open-label, blinded endpoint, randomised trial done at 40 hospitals across Europe and one hospital in Canada. We included patients (aged ≥18 years) with acute ischaemic stroke due to large vessel occlusion in the anterior circulation and who had a large infarct, as indicated by an Alberta Stroke Program Early Computed Tomographic Score (ASPECTS) of 3-5 on standard-of-care stroke imaging. We randomly assigned patients (1:1) to receive either endovascular thrombectomy with medical treatment or medical treatment only up to 12 h from stroke onset. The primary outcome was functional outcome across the entire range of the modified Rankin Scale at 90 days. Here, we report the prespecified 12-month follow-up analyses for functional outcome (using the simplified modified Rankin Scale questionnaire), quality of life (using the Patient-Reported Outcomes Measurement Information System 10-item [PROMIS-10] and EQ-5D questionnaires), post-stroke anxiety and depression (using the Patient Health Questionnaire-4 [PHQ-4]), and overall survival. Outcomes (except survival) were assessed in the intention-to-treat population; the survival analysis was based on treatment received. This trial is registered with ClinicalTrials.gov, NCT03094715, and is completed., Findings: We enrolled patients between July 17, 2018, and Feb 21, 2023, when the trial was stopped early for efficacy. 253 patients were randomly assigned, 125 (49%) to endovascular thrombectomy and 128 (51%) to medical treatment only. Median follow-up was 8·36 months (IQR 0·02-12·00). Endovascular thrombectomy was associated with a shift in the distribution of scores on the modified Rankin Scale towards better functional outcome at 12 months (adjusted common odds ratio 2·39 [95% CI 1·47-3·90]). Endovascular thrombectomy was also associated with a better quality of life compared with medical treatment only, as reflected by median scores on the EQ-5D questionnaire index (0·7 [IQR 0·4-0·9] vs 0·4 [0·2-0·7]), median scores for health status on the EQ-5D questionnaire visual analogue scale (50 [IQR 35-70] vs 30 [5-60]), and median global physical health scores on the PROMIS-10 questionnaire (T-score 39·8 [IQR 37·4-50·8] vs 37·4 [32·4-44·9]); although there was not enough evidence to suggest a difference between groups in global mental health scores on PROMIS-10 (41·1 [IQR 36·3-48·3] vs 38·8 [31·3-44·7]) or the numbers of patients reporting anxiety (13 [22%] of 58 vs 15 [42%] of 36) and depression (18 [31%] vs 18 [50%]) on PHQ-4. Overall survival was slightly better in the endovascular thrombectomy group compared with medical treatment only (adjusted hazard ratio 0·70 [95% CI 0·50-0·99])., Interpretation: In patients with acute ischaemic stroke from large vessel occlusion with established large infarct, compared with medical treatment only, endovascular thrombectomy was associated at 12 months after stroke with better functional outcome, quality of life, and overall survival. These findings suggest that the benefits of endovascular thrombectomy in patients with an ischaemic stroke and a large infarct are sustained in the long term and support the use of endovascular thrombectomy in these patients., Funding: European Union Horizon 2020 Research and Innovation Programme., Competing Interests: Declaration of interests MB reports funding from the European Union Horizon 2020 and Deutsche Forschungsgemeinschaft (payments to the institution); honoraria for lectures from Novartis, Boehringer Ingelheim, and Seagen; consulting fees from NeuroScios and Boehringer Ingelheim; and a role as Editor-in-Chief of Clinical Neuroradiology (Springer), outside the submitted work. JF reports funding from the European Commission; personal consulting fees from Acandis, Cerenovus, Medtronic, Microvention, Phenox, Roche, and Stryker; consulting at Philips (no payments); payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Penumbra and Tonbridge; support for attending meetings or travel from Medtronic and Penumbra; and stock or stock options from Tegus medical, eppdata, and Vastrax, outside the submitted work. JF also reports participation in a Data Safety Monitoring Board (DSMB) or Advisory Board at Phenox (personal fees) and Stryker (personal fees), and a role as past president of ESMINT. SB reports funding from the EU Horizon 2020 research and innovation programme (payments made to the institution; support for attending meetings or travel), outside the submitted work. AHA reports unrestricted research grants from Boehringer Ingelheim and honoraria for lectures from BMS/Pfizer, Teva, Roche, Abbvie, Lundbeck, Novartis, outside the submitted work. AHA also reports participation in Advisory Boards for MSD, BMS/Pfizer, Lundbeck, Lilly, and Abbvie. BF reports research grants from Carlos III Institute of Health (ISCIII), personal payment for educational lectures from Servicio Madrileño de Salud, payment to the institution for lectures from Euromedice, personal payment for educational lectures from Takeda, support for attending meetings from Daichii Sankyo, and receipt of materials for research from Abbot, outside the submitted work. MDH reports funding from Nil, a grant to the University of Calgary for the TEMPO-2 trial from Boehringer Ingelheim, a grant to the University of Calgary from Biogen, a grant to the University of Calgary for the ESCAPE-NA1 trial and ESCAPE-NEXT trial from NoNO, a grant to the University of Calgary for the ESCAPE-NA1 trial and ESCAPE-NEXT trial from the Canadian Institute for Health Research, a grant to the University of Calgary for the HERMES collaboration from Medtronic, and a grant to the University of Calgary for the QuICR Alberta Stroke Program; some of the funds were used for the ESCAPE-NA1 trial from Alberta Innovates. MDH also reports consulting fees from Sun Pharma Brainsgate (paid work for adjudication of clinical trial outcomes), US Patent 62/086,077 (licensed to Circle NVI), US Patent 10,916,346 (licensed to Circle NVI), and private stock ownership from Circle and PUreWeb, outside the submitted work. MDH reports participation as DSMC Chair of the RACECAT trial (end 2020), participation as DSMC Chair of the Oncovir Hiltonel trial (ongoing), participation as DSMC Chair of the DUMAS trial (ongoing), participation as DSMB member of the ARTESIA trial (ongoing), participation as DSMB member of the BRAIN-AF trial (ongoing), a role as President of the Canadian Neurological Sciences Federation (not for profit), and as Board Member of the Canadian Stroke Consortium (not for profit). AK reports grants from the European Commission for the TENSION study (payment to the institution), outside the submitted work. LP reports consulting fees from Balt, consulting fees from Microvention, consulting fees from Phenox, and support for attending meetings or travel for the TENSION investigator meeting (transport and accommodation was reimbursed by the organization), outside the submitted work. CZS reports grants from Health Research Foundation of Central Denmark Region, outside the submitted work. RAB reports speakers fees from Novo Nordisk and Beyer, outside the submitted work. HD reports financial compensation for the start-up fee and the obligatory payment to the hospital administration paid by the sponsor (Medical University Heidelberg) to the Clinical Division (no personal payments), personal consulting fees from Stryker, speakers honorary from Medtronic, and support for attending meetings or travel from Medtronic, outside the submitted work. HD also reports a role as past President of the Austrian Society of Interventional Radiology and past president Austrian Society of Neuroradiology. FD reports consulting fees from Cerenovus, Balt, Cerus Endovascular, and Microvention; payment for expert testimony from Cerenovus; and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Cerenovus, Stryker, Acandis, Asahi, Penumbra, Medtronic, Tonbridge, Inspire, and Q'Apel, outside the submitted work. FD also reports participation in a DSMB or Advisory Board at Cerenovus and Microvention and previous roles as Associate Editor for Journal of Interventional Surgery, Journal of Clinical Medicine, and Clinical Neuroradiology. FF reports consulting fees from eppdata and support for attending meetings or travel from Microvention, Medtronic, Cerebrovascular Research and Education Foundation, and Acandis, outside the submitted work. SG reports consulting fees from eppdata, outside the submitted work. CH reports consulting fees from Brainomix and lecture fees from Stryker, outside the submitted work. SH-J reports funding for data collection and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Terumo, outside the submitted work. MG reports research grants from Medtronic and Cerenovus (payments to the University of Calgary); royalties or licenses from Microvention (systems of intracranial access); personal consulting fees from Microvention, Medtronic, Stryker, Mentice, Philips, and Penumbra; and stock or stock options from Circle Neurovascular, outside the submitted work. FCK was chair of the German Stroke Registry (unpaid). RM reports payments for stroke lecture from TMC Academy, outside the submitted work. MM reports grants from Balt, Medtronic, MicroVention, and Stryker; consulting fees from Siemens; and support for attending meetings or travel from Europa Group, outside the submitted work. SM-H reports consulting fees from Terumo and Boston Scientific Corporation and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Terumo and Boston Scientific Corporation, outside the submitted work. NM reports provision of study materials, outside the submitted work. PP reports support for attending meetings or travel for the TENSION investigator meeting (transport and accommodation was reimbursed by the organisation), outside the submitted work. MP reports grants from the German Research Foundation, speaker honoraria unrelated from Merck Serono and Bayer, and support for attending meetings or travel from Merck Serono (travel reimbursement) and Bayer (travel reimbursement), outside the submitted work. VP reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Boehringer Ingelheim, Daichii Sankyo, AstraZeneca and BMS, and support for attending meetings or travel from NoNo (travel reimbursement). PAR reports consulting fees to the institution from Boehringer Ingelheim and Bayer, and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Boehringer Ingelheim, Bayer, Pfizer, and BMS (all made to the institution), outside the submitted work. ES reports grants from Hamburg Innovation and Hertie Foundation, outside the submitted work. DFV reports research grants from MicroVention, consulting fees from Medtronic, and paid lectures from Cerenovus/Johnson & Johnson, outside the submitted work. WW reports consulting fees to the institution from Abbvie, and consulting fees to the institution from BMS, GSK, and Servier, outside the submitted work. GT reports funding from the European Commission (EU Horizon 2020 research and innovation programme, payments to the institution); personal consulting fees from Acandis, AstraZeneca, Bayer, Boehringer Ingelheim, and Stryker; and personal payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Acandis, Alexion, Amarin, Bayer, Boehringer Ingelheim, BristolMyersSquibb/Pfizer, Daiichi Sankyo, Stryker, outside the submitted work. GT also reports participation as DSMB member for the TEA Stroke Trial (no payments) and ReSCInD trial (no payments), a role as speaker of the Commission for Cerebrovascular Diseases of the German Society of Neurology (no payments), and member of the Board of Directors of the European Stroke Organisation (no payments). All other declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.)