Prior Reperfusion Strategy Does Not Modify Outcome in Early Versus Late Start of Anticoagulants in Patients With Ischemic Stroke: Prespecified Subanalysis of the Randomized Controlled ELAN Trial

Stroke, Ahead of Print. BACKGROUND:Early initiation of direct oral anticoagulants (DOACs) in patients with nonvalvular atrial fibrillation and acute ischemic stroke is beneficial and safe. Whether prior acute reperfusion therapy modifies the treatment effect of early versus late DOAC initiation is unknown.METHODS:For this post hoc analysis of the multicenter, randomized controlled ELAN trial (Early Versus Late Initiation of Direct Oral Anticoagulants in Post-Ischaemic Stroke Patients With Atrial Fibrillation), all participants with data concerning reperfusion treatment were included. The primary outcome was the composite outcome of recurrent ischemic stroke, symptomatic intracranial hemorrhage, major extracranial bleeding, systemic embolism, or vascular death within 30 days. Patients were divided into 4 groups based on prior reperfusion therapy: no treatment, intravenous thrombolysis (IVT), endovascular treatment (EVT), or IVT combined with EVT. We performed logistic regression adjusted for age, hypertension, infarct location/size, pre-modified Rankin Scale, NIHSS, and hemorrhagic transformation, including the interaction term between treatment groups (early versus late DOAC) and reperfusion strategy.RESULTS:We included 1973 of 2013 (98%) patients of the ELAN trial population, with a median age of 77 (71–84) years and of whom 899 (46%) were female. Of them, 1015 (51%) underwent no prior reperfusion treatment, 519 (26%) IVT, 190 (10%) EVT, and 249 (13%) IVT+EVT. We did not identify an interaction for any of the outcome events between prior reperfusion therapy and timing of DOAC initiation. Rates were numerically lower in the early DOAC-initiated group for the following: no reperfusion therapy, 17 (3.3%) versus 24 (4.8%; adjusted odds ratio, 0.69 [95% CI, 0.36–1.28]); EVT, 1 (1.2%) versus 7 (6.4%; adjusted odds ratio, 0.25 [95% CI, 0.03–1.21]); and EVT+IVT, 3 (2.4%) versus 4 (3.3%; adjusted odds ratio, 0.76 [95% CI, 0.17–3.23]). In patients who had received IVT, the rates were 3% (n=8) in the early group versus 2% (n=5) in the late group (adjusted odds ratio, 1.52 [95% CI, 0.52–4.84]).CONCLUSIONS:Prior reperfusion therapy does not modify the effect of early versus late DOAC initiation on clinical outcomes in patients with atrial fibrillation and acute ischemic stroke.REGISTRATION:URL:https://www.clinicaltrials.gov; Unique identifier: NCT03148457.

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What proportion of people have long-term pain after total hip or knee replacement? An update of a systematic review and meta-analysis

Objectives
To update our previous systematic review to synthesise latest data on the prevalence of long-term pain in patients who underwent total hip replacement (THR) or total knee replacement (TKR). We aim to describe the prevalence estimates and trends in this review.

Design
Systematic review and meta-analysis.

Data sources
Update searches were conducted in MEDLINE and Embase databases from 1 January 2011 to 17 February 2024. Citation tracking was used to identify additional studies.

Eligibility criteria
We included prospective cohort studies reporting long-term pain after THR or TKR at 3, 6, 12 and 24 months postoperative.

Data extraction and synthesis
Two reviewers independently identified studies as eligible. One reviewer conducted data extraction, checked by a second reviewer. The risk of bias assessment was performed using Hoy’s checklist. Bayesian, random-effects meta-analysis was used to synthesise the results.

Results
For TKR, 68 studies with 89 time points, including 598 498 patients, were included. Multivariate meta-analysis showed a general decrease in pain proportions over time: 21.9% (95% CrI 15.6% to 29.4%) at 3 months, 14.1% (10.9% to 17.9%) at 6 months, 12.6% (9.9% to 15.9%) at 12 months and 14.6% (9.5% to 22.4%) at 24 months. Considerable heterogeneity, unrelated to examined moderators, was indicated by substantial prediction intervals in the univariate models. Substantial loss to follow-up and risk of bias led to low confidence in the results. For THR, only 11 studies were included, so it was not possible to describe the trend. Univariate meta-analysis estimated 13.8% (8.5% to 20.1%) and 13.7% (4.8% to 31.0%) of patients experiencing long-term pain 6 and 12 months after THR, respectively, though concerns in risk of bias results reduced confidence in these findings.

Conclusions
Our review suggests that approximately 22% of patients report pain 3 months post-TKR, with 12%–15% experiencing long-term pain up to 2 years. At least 14% report pain 6–12 months after THR. Given the prevalence of chronic postsurgical pain, implementing existing and developing new preventive and management strategies is crucial for optimal patient outcomes.

PROSPERO registration number
CRD42023475498.

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Neuromodulation through brain stimulation-assisted cognitive training in patients with post-chemotherapy subjective cognitive impairment (Neuromod-PCSCI) after breast cancer: study protocol for a double-blinded randomised controlled trial

Introduction
Breast cancer is the most common form of cancer in women. A considerable number of women with breast cancer who have been treated with chemotherapy subsequently develop neurological symptoms such as concentration and memory difficulties (also known as ‘chemobrain’). Currently, there are no validated therapeutic approaches available to treat these symptoms. Cognitive training holds the potential to counteract cognitive impairment. Combining cognitive training with concurrent transcranial direct current stimulation (tDCS) could enhance and maintain the effects of this training, potentially providing a new approach to treat post-chemotherapy subjective cognitive impairment (PCSCI). With this study, we aim to investigate the effects of multi-session tDCS over the left dorsolateral prefrontal cortex in combination with cognitive training on cognition and quality of life in women with PCSCI.

Methods and analysis
The Neuromod-PCSCI trial is a monocentric, randomised, double-blind, placebo-controlled study. Fifty-two women with PCSCI after breast cancer therapy will receive a 3-week tDCS-assisted cognitive training with anodal tDCS over the left dorsolateral prefrontal cortex (target intervention), compared with cognitive training plus sham tDCS (control intervention). Cognitive training will consist of a letter updating task. Primary outcome will be the performance in an untrained task (n-back task) after training. In addition, feasibility, safety and tolerability, as well as quality of life and performance in additional untrained tasks will be investigated. A follow-up visit will be performed 1 month after intervention to assess possible long-term effects. In an exploratory approach, structural and functional MRI will be acquired before the intervention and at post-intervention to identify possible neural predictors for successful intervention.

Ethics and dissemination
Ethical approval was granted by the ethics committee of the University Medicine Greifswald (BB236/20). Results will be available through publications in peer-reviewed journals and presentations at national and international conferences.

Trial registration number
ClinicalTrials.gov; NCT04817566, registered on 26 March 2021.

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Stepped wedge cluster randomised controlled trial to assess the impact of a decision support tool for physical restraint use in intensive care units (ARBORea Study): a study protocol

Introduction
Intensive care units (ICUs) manage patients with or likely to have one or more life-threatening acute organ failures that might require the use of invasive supportive therapies. The use of physical restraint is frequent, with rates up to 50%, and usually initiated to maintain patient safety especially if the patient is agitated. Physical restraints have been associated with delirium, post-traumatic stress disorder and physical injuries while restricting patients’ individual freedom. Moreover, the incidence of invasive therapeutic devices’ self-removal by patients might not be decreased by physical restraint use. No recommendation is available concerning ICU patients and physical restraint management, despite being a daily practice. The main objective is to evaluate whether a strategy aimed at decreasing physical restraint use in ICU patients with that of a strategy based on routine and subjective caregivers’ decision is safe and efficient.

Methods and analysis
ARBORea is a multicentre randomised, stepped-wedge trial testing an innovative, dedicated web-based, multiprofessionally developed, experts validated, nursing management strategy in comparison with standard care. The primary outcome is physical restraint use rate (effectiveness) measured at least every 8 hours and incidents’ rate (tolerance) defined as the rate of incidents attributable to non-compliance, corresponding to the deterioration or self-removal of critical devices, a fall or self-aggressive or heteroaggressive behaviours. Planned enrolment is 4000 ICU adult participants at 20 French academic and non-academic centres. Safety and long-term outcomes will be evaluated.

Ethics and dissemination
Trial results will be reported according to the Consolidated Standards of Reporting Trials 2010 guidelines. Findings will be published in peer-reviewed journals and presented at local, national and international meetings and conferences to publicise and explain the research to clinicians, commissioners and service users. The trial is funded by the French Ministry of Health and has been approved by the French local ethics committee (Comité de Protection des Personnes Sud-Ouest et Outre-Mer 2, Toulouse, France with registration number: 2020-A02904-35).

Trial registration number
(ClinicalTrials.gov) NCT04957238 on 12 July 2021 before first inclusion in study.

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Enhancing dyadic outcomes of stroke survivors and caregivers: protocol for a randomised controlled trial

Introduction
Stroke is a leading cause of death and disability worldwide. Stroke survivors and their caregivers often face profound social isolation and various participation restrictions, resulting in frustration and adverse health outcomes. Dyad-focused interventions, which address both survivor and caregiver needs, are essential during the transition process. However, few interventions equally prioritise the outcomes of both survivors and caregivers. This study aims to evaluate the efficacy of a newly developed dyad-focused strategy training intervention in enhancing participation among stroke survivors and their caregivers.

Methods and analysis
This study employs a single-blind, parallel-group randomised controlled trial with allocation concealment and assessor blinding. We aim to enrol 138 stroke survivor-caregiver dyads, randomly assigned in a 1:1 ratio to either the experimental intervention group or the control group. Both groups will receive their usual rehabilitation plus 45–60 min sessions of the intervention twice weekly for a total of 12 sessions. Outcome measures, including the Participation Measure-3 Domains, 4 Dimensions, General Self-Efficacy Scale and Activity Measure for Post-Acute Care, will be collected at baseline, post-intervention and at 3-month, 6-month and 12-month follow-ups. Data will be analysed using multiple linear regression and mixed-effects regression models. Qualitative indepth interviews with participants, caregivers and therapists will be conducted post intervention, transcribed and thematically analysed.

Ethics and dissemination
Ethics approval was obtained from the Ethics Committee of Taipei Medical University (approval number: N202203083), National Taiwan University Hospital (approval number: 202207096RINA) and Taipei Tzu Chi Hospital (approval number: 11 M-107). Findings will be disseminated through presentations at scientific conferences and publications in peer-reviewed journals.

Trial registration number
NCT05571150; Preresults.

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Impact of perioperative esketamine on the perioperative neurocognitive dysfunction: a systematic review and meta-analysis of randomised controlled studies

Objectives
The effect of esketamine on perioperative neurocognitive dysfunction (PND) remains controversial. This systematic review and meta-analysis aimed to evaluate the impact of perioperative esketamine administration on PND.

Design
Systematic review and meta-analysis.

Data sources
PubMed, EMBASE, Web of Science and Cochrane Library were searched from their inception to 25 April 2024.

Eligibility criteria for selecting studies
We included the randomised controlled trials (RCTs) that compared single or continuous intravenous infusion of esketamine to saline among adult surgical patients without pre-existing neurocognitive disorders.

Data extraction and synthesis
Two reviewers independently extracted pertinent information from the included studies. Risk of bias was assessed using Cochrane’s risk of bias criteria. Risk ratios (RRs) and their corresponding 95% CIs were synthesised using a random-effects model. The overall evidence quality was appraised using the Grading of Recommendations Assessment, Development and Evaluation framework.

Results
10 RCTs were included in our meta-analysis, involving 854 surgical patients. Perioperative esketamine was associated with a reduced risk of postoperative delirium (POD) (relative risk (RR): 0.46, 95% CI: 0.30 to 0.71, p

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Augmentation of trauma-focused psychotherapy for post-traumatic stress disorder: a protocol for a systematic review and meta-analysis

Introduction
Despite the established status of trauma-focused psychotherapy (TFP) as a first-line treatment for post-traumatic stress disorder (PTSD), a substantial proportion of individuals do not achieve clinically significant improvement or discontinue treatment. Exploring augmentation strategies to enhance treatment outcomes is essential to reduce the overall burden PTSD puts on individuals and society. This protocol outlines a systematic review and meta-analysis of randomised controlled trials (RCTs) evaluating the efficacy of non-pharmacological augmentation strategies in addition to TFP for PTSD treatment.

Methods and Analysis
We comprehensively searched PubMed, Embase, CENTRAL, PTSDpubs, PsycArticles, PsycINFO, PSYNDEX and CINAHL for RCTs without restrictions on publication dates or languages in October 2024. Study screening is currently ongoing. Additionally, we will perform forward and backward searches of the included studies and relevant reviews. Two reviewers will independently screen and select studies, extract data and assess the risk of bias. We will conduct a narrative review to qualitatively synthesise data and a meta-analysis to quantitatively compare the treatment efficacy of augmented TFP with TFP alone or TFP plus placebo. Primary outcomes will be both symptom severity and response rates. The secondary outcome will be dropout rates. We will explore sources of between-study heterogeneity and potential moderators through subgroup and meta-regression analyses. We will assess the overall quality of the included studies with the Grading of Recommendations Assessment, Development, and Evaluation system.

Ethics and dissemination
Ethical approval is not required. We intend to publish results in a peer-reviewed journal and provide materials and data through the Open Science Framework.

PROSPERO registration number
CRD42024549435.

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Intracellular L-PGDS–Derived 15d-PGJ2 Inhibits CaMKII Through Lipoxidation to Alleviate Cardiac Ischemia/Reperfusion Injury

Circulation, Ahead of Print. BACKGROUND:Myocardial ischemia/reperfusion (I/R) injury is a substantial challenge to the management of ischemic heart disease, the leading cause of mortality worldwide. Arachidonic acid (AA) is a prominent polyunsaturated fatty acid in the human body and plays an important role in various physiological and pathological conditions. AA metabolic enzymes determine AA levels; however, currently there is no comprehensive analysis of AA enzymes in cardiac I/R injury.METHODS:The profiling of AA metabolic enzymes was analyzed with the RNA sequencing transcriptome data from the mouse heart tissues with I/R injury. Cultured neonatal and adult rat ventricular myocytes, human embryonic stem cell–derived cardiomyocytes, and in vivo mouse I/R models were used to confirm the role of L-PGDS (lipocalin-type prostaglandin D2 synthase)/15d-PGJ2 in I/R injury. A biotin-tagged 15d-PGJ2 analog combined with liquid chromatography–tandem mass spectrometry was used to identify the downstream signaling of L-PGDS/15d-PGJ2.RESULTS:Based on the transcriptome data and experimental validations, L-PGDS, together with its downstream metabolite 15d-PGJ2, was downregulated in cardiac tissue with I/R injury. Functionally, L-PGDS overexpression mitigates myocardial I/R injury, whereas knockdown exacerbates the damage. Supplementation of 15d-PGJ2 alleviated I/R injury. Mechanistically, 15d-PGJ2 covalently bound to the Ca2+/CaMKII (calmodulin protein kinase II) and induced lipoxidation of its cysteine 495 (CaMKII-δ9) to dampen the formation of CaMKII oligomers and alleviate its overactivation, consequently ameliorating cardiomyocyte death and cardiac injury.CONCLUSIONS:Our study uncovered L-PGDS/15d-PGJ2/CaMKII signaling as a new mechanism underlying I/R-induced cardiomyocyte death. This provides new mechanistic insights and therapeutic targets for myocardial I/R injury and subsequent heart failure. We also showed that lipoxidation is a new post-translational modification type for CaMKII, deepening our understanding of the regulation of its activity.

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SUMMIT MAX: A randomized trial of the super large bore HiPoint Reperfusion System versus Vecta System for aspiration thrombectomy

Stroke, Ahead of Print. Background:Rapid and complete recanalization is a primary goal in the endovascular treatment of large vessel occlusion stroke. The effectiveness and safety of super large bore aspiration catheters (.088” inner diameter) for the treatment of large vessel occlusion stroke have not been demonstrated in a randomized trial.Methods:SUMMIT MAX was a prospective, randomized, controlled, open label clinical trial of patients with ICA and MCA M1 occlusions, comparing the super large bore HiPoint Reperfusion system (Route 92 Medical) to the Vecta Aspiration system (Stryker Neurovascular) (NCT05018650). We hypothesized that the effectiveness and safety of the HiPoint reperfusion system was non-inferior (12.5% non-inferiority margin) to the Vecta Aspiration system. The primary effectiveness endpoint was successful reperfusion, defined as mTICI ≥ 2b as adjudicated by an independent core lab, using only the assigned study device, with any use of a non-study device prior to or following use of study device defined as failure. The primary safety endpoint was symptomatic intracranial hemorrhage (sICH) within 24h (-8/+24) post-procedure.Results:There were 250 patients enrolled of whom 166 met criteria for the modified intent-to-treat population: 89 in HiPoint and 77 in Vecta. The median age was 69; 54.2% were female. Successful reperfusion with any adjunctive therapy counted as a failure was 77.5% (69/89) in the HiPoint group versus 50.6% (39/77) in the Vecta group (p

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Antimicrobial prophylaxis for endourological procedures in Jordanian hospitals: a multi-centre qualitative study

Objectives
To explore urologists’ perceptions of barriers to, and facilitators of, adherence to international antimicrobial prophylaxis (AP) guidelines for endourological procedures in Jordan and to identify strategies to optimise guideline-concordant AP prescribing.

Design
The present study is a qualitative study undertaken through semi-structured interviews and inductive thematic analysis. Study results are reported per Consolidated Criteria for Reporting Qualitative Research.

Setting
Secondary and tertiary care across multiple public, private and academic hospitals in Jordan.

Participants
Nineteen practising urologists (all male; median age 32 years, IQR 8; nine residents, 10 specialists) who routinely prescribe AP for endourological procedures. Participants were recruited via convenience snowball sampling and interviewed until thematic saturation was reached.

Interventions
Not applicable.

Primary and secondary outcome measures
The main outcomes were themes describing perceived barriers to guideline adherence and potential facilitators to support appropriate AP use.

Results
Participants identified several barriers: (1) patient level, strong expectations for antibiotics post-procedure and concerns about procedure-site hygiene; (2) clinician level, fear of postoperative infections and litigation, lack of familiarity with updated guidance and doubts about applying international guidelines locally; (3) system level, hierarchical prescribing dynamics, referral communication gaps, high workloads and time pressures, and concerns over sterilisation practices. Facilitators included targeted professional training and regular guideline updates for urologists, development of local AP guidelines informed by local resistance data, enhanced patient education campaigns and active involvement of clinical pharmacists in preoperative antibiotic review and auditing.

Conclusions
Urologists in Jordan face multifaceted barriers to AP guideline adherence. Future stewardship programmes can use insights from this study to develop locally tailored guidelines, targeted clinician training and pharmacist-led audits. Pilot testing with metrics such as prescribing rates, guideline concordance, antibiotic consumption and postoperative infection incidence will be essential to validate their impact before wider implementation.

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Effect of Baduanjin on postoperative activity tolerance, lung function and negative emotions in patients with lung cancer: a protocol for systematic review and meta-analysis

Introduction
Patients who have undergone lung cancer surgery often experience reduced exercise tolerance, impaired lung function and increased negative emotions such as anxiety and depression. Baduanjin, a traditional Chinese mind-body exercise, has shown benefits in improving exercise tolerance and lung function in populations with chronic diseases. However, evidence on the effectiveness of Baduanjin for post-lung cancer surgery patients remains limited. This study aims to systematically assess the impact of Baduanjin on exercise tolerance, lung function and emotional well-being in these patients.

Methods and analysis
We will conduct a comprehensive search of PubMed, the Cochrane Library, China National Knowledge Infrastructure, Chinese Biomedical Literatures database, Wangfang database and China Science and Technology Journal Database (VIP) to identify randomised controlled trials (RCTs) assessing Baduanjin in postoperative lung cancer patients. The primary outcome measure will be the 6-minute walk test distance. We will assess the risk of bias in included RCTs using the bias risk assessment form from the Cochrane Collaboration Handbook. This protocol follows the Preferred Reporting Items for Systematic Reviews and Meta-analyses Protocols 2015 guidelines.

Ethics and dissemination
Ethical approval is not required as no primary data are collected. The results will be presented at scientific conferences or submitted to a peer-reviewed scientific journal.

PROSPERO registration number
CRD42024570196.

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Changes in medical student attendance at in-person teaching sessions: a systematic review

Introduction
The COVID-19 pandemic has had a significant impact on medical education, with many institutions shifting to online learning to ensure the safety of students and staff. However, there appears to be a decline in in-person attendance at medical schools across the UK and worldwide following the relaxation of social distancing rules and the reinstatement of in-person teaching. Importantly, this trend was also observed before the pandemic. While reflected within the literature, there is currently no systematic review describing these changes. We aim to find out how medical students’ attendance is changing as documented within the literature and its impact on their educational outcomes.

Methods
This systematic review followed the guidelines of the Centre of Research and Dissemination, Moose and Preferred Reporting Items for Systematic Reviews and Meta-Analyses. We searched the major databases of Medline via Ovid, Embase via Ovid, Scopus, Web of Science, British Education Index via EBSCOhost and ERIC via EBSCOhost in September 2023. Two reviewers independently screened each paper and extracted the data, with a third reviewer for dispute resolution. All studies reporting on medical students from various universities, both graduate and undergraduate, and describing changes in attendance and/or students’ educational outcomes were included. Risk of bias in individual studies was assessed using the Agency for Healthcare Research and Quality tool. A narrative synthesis of the findings from all included studies was done.

Results
12 papers were included in the analysis. Primary aim: Of the eight papers that measured attendance data over more than one academic year, only one paper demonstrated a statistically significant decrease while one paper demonstrated a statistically significant increase in attendance over the observational period. Other papers either did not perform statistical tests or did not demonstrate statistical significance. Secondary aims: Most papers showed a general positive correlation between attendance and educational outcomes. No studies explicitly explored reasons for changes in attendance seen. Only one paper outlined a possible strategy to address changes in attendance, a mandatory attendance policy, which has mixed outcomes.

Discussion
Despite widespread anecdotally reported attendance decline post-COVID-19, overall, there was no consistent change in attendance noted. However, there was a large heterogeneity in the studies included. Further research is required to elucidate trends in attendance and its impact on medical education.

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Perioperative SARS-CoV-2 infection and postoperative complications: a single-centre retrospective cohort study in China

Objective
To explore the association between perioperative SARS-CoV-2 infection and the postoperative complications during the breakout of the Omicron epidemic wave.

Design
Observational retrospective cohort study. Multivariable logistic regression was performed to explore the association between the duration from surgery to COVID-19 diagnosis and the likelihood of postoperative complications.

Setting
A general hospital in China.

Participants
7927 patients aged 18 years and older who underwent surgical treatment between 1 December 2022 and 28 February 2023.

Primary outcome measures
The outcome was a composite of postoperative adverse events that occurred within the initial 30 postoperative days.

Results
Of all patients, 420 (11.76%) experienced postoperative complications. Compared with No COVID-19, preoperative COVID-19 within 1 week (pre-1w) exhibited a high risk of postoperative complications (adjusted OR (aOR), 2.67; 95% CI 1.50 to 4.78), followed by patients with pre-2w (aOR, 2.14; 95% CI 1.20 to 3.80). For patients with postoperative COVID-19 within 1 week (post-1w), the aOR was 2.48 (95% CI 1.48 to 4.13), followed by patients with post-2w (aOR 1.95; 95% CI 1.10 to 3.45), and those with post-3w (aOR 2.25; 95% CI 1.27 to 3.98). The risks of postoperative complications decreased roughly with the increase of the time interval between the surgery date and SARS-CoV-2 infection. Stratification analyses suggested that perioperative COVID-19 increased the risk of postoperative complications in older patients, smokers, those with comorbidities or experiencing moderate or severe COVID-19 symptoms.

Conclusions
Our findings reveal a significant time-dependent relationship between perioperative COVID-19 and postoperative complications, highlighting the importance of tailored preoperative risk evaluations, enhanced postoperative surveillance, and the implementation of effective postoperative COVID-19 prevention measures.

Trial registration number
ChiCTR2300072473.

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Risk prediction model for difficulty in weaning from mechanical ventilation in critically ill patients: results from a multicentre retrospective study

Objectives
We aimed to establish a diagnostic system using retrospective data to predict difficult wean from mechanical ventilation.

Design
A multicentre retrospective study

Setting
Five tertiary hospitals from China.

Participants
Critically ill patients received mechanical ventilation between January 2018 and December 2022.

Primary and secondary outcome measures
The primary endpoint was success weaning from mechanical ventilation ( >48 hours), reintubation or death, whichever occurred first.

Results
Among 1365 initially screened patients, 703 patients (median age: 69 years; 63.02% male) were included. From 42 factors, 22 (p≤0.10) were identified for multivariate analysis. Subsequently, the lung injury score, brain natriuretic peptide level at 24 hours, 24 hour fluid balance, use of dexmedetomidine, spontaneous breathing trial (continuous positive airway pressure vs other) and endotracheal tube reinsertion were included in the predictive model. The area under the curve value was 0.8888 (95% CI: 0.8382, 0.9394). The sensitivity, specificity, positive predictive value, negative predictive value, accuracy, likelihood ratio (LR)+ and LR– were 0.7559, 0.875, 0.9746, 0.3608, 0.7721, 6.0743 and 0.279, respectively. We established a nomogram model based on the optimal model.

Conclusions
A model with six factors was established to predict difficult wean from mechanical ventilation in critically ill patients. However, the model should be verified in future well-designed studies before being extended to other populations.

Trial registration
ChiCTR1900021432. Registered on February 21, 2019; Post-results.

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Prevalence of common mental disorders and sleep disorder among adolescents and young adults with HIV: a systematic review and meta-analysis

Objective
Adolescents and young adults (AYA) with HIV are a population at high risk of experiencing mental issues and sleep disorder. We aim to summarise the global prevalence and risks of depression, anxiety, post-traumatic stress disorder (PTSD) and sleep disorder among AYA with HIV.

Design
Systematic review and meta-analysis.

Data sources
PubMed, Web of Science, Embase and PsycINFO were searched from inception to 3 August 2024.

Eligibility criteria
Observational studies reporting the prevalence of depression, anxiety, PTSD or sleep disorder among AYA with HIV and published in English were included. Reviews, case reports, conference papers, notes, editorials and non-observational research were excluded.

Data extraction and synthesis
Titles, abstracts and full texts were reviewed and screened, and data were independently extracted. A modified Newcastle-Ottawa Quality Assessment Scale (NOS) was used to evaluate study quality. Heterogeneity was assessed by I2 statistics, and subgroup analysis was performed to identify the source of heterogeneity. The pooled prevalence and the risks of depression, anxiety, PTSD and sleep disorder by comparison with HIV-uninfected peers were measured with random-effects and fixed-effects models. Publication bias was examined using Egger’s correlation tests and funnel plot. The Grading of Recommendations Assessment, Development and Evaluation was used to assess the certainty of evidence.

Results
56 articles were included in the final analysis. According to the modified NOS, 13 (23.2%) studies were considered good, 38 (67.9%) were satisfactory and 5 (8.9%) were unsatisfactory. 51 studies including 21 735 AYA with HIV contributed data for the pooled prevalence of depression (28%, 95% CI 24% to 32%, I2=98.68%; low certainty evidence); 21 studies including 8021 cases contributed data for the pooled prevalence of anxiety (22%, 95% CI 17% to 27%, I2=98.35%; low certainty evidence); 9 studies including 3691 cases contributed data for the pooled prevalence of PTSD (12%, 95% CI 8% to 17%, I2=95.60%; low certainty evidence); and 4 studies including 1909 cases contributed data for the pooled prevalence of sleep disorder (51%, 95% CI 31% to 70%, I2=98.37%; low certainty evidence). Compared with AYA without HIV, those with HIV had a higher risk of depression (OR=2.67, 95% CI 1.63 to 5.90, I2=84.0%), anxiety (OR=1.89, 95% CI 1.32 to 2.69, I2=50.3%), PTSD (OR=1.58, 95% CI 1.23 to 2.04, I2=40.1%) and sleep disorder (OR=2.11, 95% CI 1.51 to 2.95, I2=0.0%). A subgroup analysis found that studies conducted in Asia had a lower prevalence of depression (21.7% vs 29.6%, p

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Protocol for the economic evaluation of the Care for Adolescents who Received Information 'Bout Outcomes, 2nd iteration (CARIBOU-2) non-randomised, cluster-controlled trial of an integrated care pathway for depression in adolescents

Introduction
Depressive disorders in adolescents are highly prevalent and debilitating and are a risk factor for self-harm and death by suicide. In the context of recovery from the COVID-19 pandemic, strained healthcare resources are compounded by an increased demand for treatment services for adolescents with depression. The objective of this study protocol is to delineate the proposed economic evaluation of an integrated care pathway for depression in adolescents within the Care for Adolescents who Received Information ‘Bout Outcomes, 2nd iteration (CARIBOU-2) non-randomised, cluster-controlled trial.

Methods and analysis
Two economic evaluations of the CARIBOU-2 trial (n=300) will be conducted—a cost-effectiveness analysis and a cost-utility analysis. In the cost-effectiveness analysis, we will examine the primary clinical outcome of the trial, change in the Mood and Feelings Questionnaire total score. In the cost-utility analysis, the clinical outcome will be quality-adjusted life-years, a generic measure of health burden. Data on the resources and respective costs required to deliver the intervention will be collected by the research team. Data on resource use post-intervention will be obtained from a mix of administrative data holdings and self-report; relevant unit costs will be obtained from existing data sources. The outcome of both economic evaluations will be the incremental cost-effectiveness ratio. Relevant sensitivity analyses will be undertaken, and cost-effectiveness acceptability curves will be produced to characterise any sources of uncertainty in the analysis. Equity considerations will also be examined, where relevant.

Ethics and dissemination
Ethical approval for the larger CARIBOU-2 trial, including the economic evaluation, has been obtained by the Centre for Addiction and Mental Health as well as site-level ethics boards (019/2021; Centre for Addiction and Mental Health). All participants will provide informed consent for their data to be analysed and reported. The results of the main trial and the economic evaluation will be submitted for publication in a peer-reviewed journal and shared with relevant policy makers across Canada.

Trial registration number
NCT05142683.

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