For critically ill patients requiring continuous renal replacement therapy, regional citrate anticoagulation is the preferred strategy to maintain extracorporeal circuit patency. Current clinical practice relies on two citrate-based protocols, with the widely used but complex 4% trisodium citrate solution posing a hypernatraemia risk and haemofiltration replacement fluid of sodium citrate offering procedural simplification and a more physiological electrolyte profile. Direct prospective comparison of their circuit lifespan efficacy is currently unavailable.

This single-centre, prospective, open-label, parallel-group randomised controlled trial will be conducted in China. 90 patients will be enrolled and randomly assigned (1:1) to receive anticoagulation with either citrate-based haemofiltration replacement fluid or 4% trisodium citrate solution, with all patients undergoing a standardised continuous venovenous haemofiltration protocol. The primary outcome is circuit lifespan, with a non-inferiority margin set at 2.43 hours. Secondary outcomes include the 72-hour circuit survival probability, duration of hospitalisation, and all-cause mortality rates at 28 and 90 days. The primary analysis will follow the intention-to-treat principle.

The study protocol has been approved by the Biomedical Research Ethics Committee of West China Hospital, Sichuan University (Approval No. (2025)1157). Any subsequent amendments must be submitted to the same ethics committee for further review and approval prior to implementation. Furthermore, the findings of this trial will be disseminated through presentations at relevant national and international conferences and via publication in peer-reviewed scientific journals.

Chinese Clinical Trial Registry ChiCTR2500106991.

Physician burnout is a global crisis compromising healthcare sustainability and patient safety. Balint groups, a structured case-based discussion intervention focusing on the doctor-patient relationship, are increasingly used to mitigate this distress. However, existing evidence regarding their efficacy remains fragmented. This systematic review and meta-analysis aims to evaluate the effectiveness of Balint groups in reducing physician burnout and improving secondary psychological outcomes, while also assessing implementation characteristics.

We will search MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Web of Science, CINAHL, PsycINFO and major Chinese databases (China National Knowledge Infrastructure, Wanfang Data and SinoMed) from inception to 31 May 2026, supplemented by grey literature and trial registries. The formal search has not yet commenced and is planned to begin on protocol publication. We will include both randomised controlled trials (RCTs) and non-randomised studies of interventions (non-randomised trials (NRTs), including non-controlled before-after studies) that evaluate Balint groups for practising physicians. The primary outcome is the change in burnout severity, with priority given to the emotional exhaustion subscale of the Maslach Burnout Inventory; however, data from other validated tools, such as the Oldenburg Burnout Inventory, will also be extracted and synthesised if reported. Secondary outcomes include stress and anxiety as psychological comorbidities closely associated with burnout, and job satisfaction, adherence and medical errors as its downstream occupational consequences. Two reviewers will independently screen studies, extract data and assess risk of bias using the Cochrane RoB 2.0 tool for RCTs and the Effective Public Health Practice Project tool for NRTs. Data synthesis will be conducted separately for RCTs (between-group effects) and NRTs (within-group effects) using random-effects models. Heterogeneity will be explored via subgroup analyses (eg, career stage) and, where data permit, meta-regression. The certainty of evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation approach.

Ethical approval is not required as this study synthesises primary data from published research. Findings will be disseminated through a peer-reviewed journal publication and conference presentations to inform interventions for physician well-being.

CRD420251142526.

Quality collaboratives improve quality of care at the hospital and collaborative levels, but less is understood about how such efforts affect patient-level disparities. This study evaluated how a quality improvement (QI) effort (increasing multiarterial grafting during coronary artery bypass grafting (CABG)) translated into populations which historically receive lower-quality care (females and patients of low socioeconomic status).

Retrospective cohort study.

All non-federal hospitals in the state of Michigan that perform cardiac surgery and participate in a statewide collaborative database (n=33).

Patients undergoing first-time, isolated CABG receiving at least two bypass grafts from 2011 to 2022 were identified.

Association of sex and socioeconomic status with multiarterial grafting was evaluated across the study period. The distressed community index (DCI), a socioeconomic ranking (0—not distressed, 100—severely distressed), was matched to the patient’s zip code. Hierarchical regression modelling was performed to associate DCI and sex with multiarterial grafting, incorporating patient factors and hospital and surgeon effects. A sex-surgery year and DCI-surgery year interaction term was performed to assess the change in the rate of multiarterial grafting.

A total of 40 322 patients underwent CABG at 33 centres with a median age of 66 years and 24% were female. The rate of multiarterial grafting was 15%, although lower among females (10% vs 17%) and the highest (vs lowest) DCI quartile (14% vs 18%). After risk adjustment, females were less likely to receive multiarterial grafting (OR_adj 0.51 (95% CI 0.45 to 0.58), padj 0.35 per 10-point increase (95% CI 0.24 to 0.51), p0.05).

Despite a large overall increase in multiarterial grafting due to QI efforts, females and patients with low socioeconomic status had lower rates of multiarterial grafting. QI efforts should be evaluated both overall and among patients who historically receive lower quality care to improve quality and equity.

Pathologic myopia (PM) is a leading cause of irreversible blindness worldwide, yet effective therapeutic interventions remain limited. Although repeated low-level red light (RLRL) therapy has demonstrated significant efficacy in controlling myopia progression among children, its application in patients with PM remains unexplored. This study aims to evaluate the regulatory effects of RLRL on choroidal vascular density and thickness in patients with PM and verify its safety and efficacy in delaying the progression of fundus atrophic lesions.

This is a prospective, randomised, controlled trial enrolling 158 patients with PM aged 18–55 years. Participants will be randomised (1:1) to an intervention group or a control group. The intervention group will receive light-emitting diode–based RLRL therapy (wavelength, 660 nm; power density, 65 mW/cm²) administered two times daily for 3 min per session, 5 days per week, over a 12-month period. The control group will receive a sham treatment (power density, 5 mW/cm²) following an identical schedule. The primary outcome measure is the change in choroidal vascular density and choroidal vessel volume index at 12 months.

This study has been approved by the Ethics Review Committee of Shanghai Eye Disease Prevention and Treatment Centre (EC-20250506-04). This study will be conducted in adherence to the approved protocol, Good Clinical Practice and the Declaration of Helsinki. The study results will be submitted to a peer-reviewed journal and presented at both local and international congresses.

NCT07312214

Early screening of non-alcoholic fatty liver disease (NAFLD) is critical for early diagnosis and management. The disease was renamed and its diagnostic criteria revised as metabolic-associated FLD (MAFLD) in 2020 and further updated to metabolic dysfunction-associated steatotic liver disease (MASLD) in 2023. This study evaluated the predictive performance and clinical feasibility of non-invasive diagnostic indicators across the NAFLD, MAFLD and MASLD diagnostic criteria.

Cross-sectional study.

Health Management Centre in China.

A total of 5810 participants aged ≥18 years were enrolled. Individuals with missing laboratory data, imaging results or self-reported information were excluded.

Disease-specific indicators included Fatty Liver Index (FLI), Hepatic Steatosis Index and Zhejiang University index (ZJU). Non-disease-specific indicators included lipid accumulation product (LAP), Visceral Adiposity Index and the Triglyceride and Glucose Index. Subgroup analysis was performed by gender and Body Mass Index (BMI).

The area under the receiver operating characteristic curve (AUROC) for all six non-invasive indicators exceeded 0.7. FLI showed the optimal predictive performance across the three criteria (NAFLD-AUROC: 0.802, MAFLD-AUROC: 0.847 and MASLD-AUROC: 0.811), with comparable performance observed for ZJU (0.797, 0.838 and 0.809, respectively). Pairwise z-tests demonstrated a significant difference between FLI and ZJU for MAFLD (p0.05). Subgroup analyses revealed that ZJU performed better in males (NAFLD-AUROC: 0.790, MAFLD-AUROC: 0.839 and MASLD-AUROC: 0.803), while FLI was superior in females (NAFLD-AUROC: 0.832, MAFLD-AUROC: 0.838 and MASLD-AUROC: 0.838) and in participants who were overweight (NAFLD-AUROC: 0.709, MAFLD-AUROC: 0.765 and MASLD-AUROC: 0.709). LAP exhibited the highest predictive efficacy in the normal BMI subgroup (NAFLD-AUROC: 0.758, MAFLD-AUROC: 0.804 and MASLD-AUROC: 0.796).

FLI exhibited the highest predictive efficacy across all diagnostic criteria, and ZJU showed comparable performance. Considering diagnostic accuracy and clinical practicality, ZJU is recommended as a favourable, non-invasive tool for population-based screening in the Chinese population.

Status epilepticus (SE) in adults is a serious neurological emergency that can lead to high morbidity and mortality rates. Although functional outcomes are often assessed using general scoring systems, limited data on health-related quality of life (HRQoL) in patients admitted to intensive care units (ICUs) are still limited. Furthermore, comprehensive evaluations of patient-reported physical, cognitive, mental health and psychological outcomes are lacking in this population. POSEIDON 2 aims to assess HRQoL and cognitive, physical and psychological impairments at 3 and 12 months after ICU discharge following SE and quantify caregiver burden.

POSEIDON 2 is a prospective, multicentre, longitudinal study conducted in 19 French ICUs. The study combines data from the SE ICTAL Registry with data from patients who survived admission to the ICU for SE, who will be recruited for the study. The study also includes patient-reported outcome (PRO) data collected 3 (M3) and 12 (M12) months after discharge from the ICU using validated instruments. The Zarit scale will be used to measure the burden on caregivers at M3 and M12. The primary endpoint is the prevalence of overall HRQOL impairment at M3 and M12, as defined by dichotomous scores on the physical and mental components of the 36-Item Short Form Health Survey compared with those of the general population. Secondary endpoints include domain-specific impairments, such as cognitive function, dependence, mental health and patient experiences. The sample size has been calculated based on an estimated prevalence of 75% for HRQoL impairment, with a planned sample size of 140 patients.

The POSEIDON 2 study protocol received ethical approval from the ethics committee ‘Comité de Protection des Personnes Ouest VI’ on 5 October 2023 (#2023-A01223-42). The study is conducted in accordance with the Declaration of Helsinki, Good Clinical Practice and the regulatory requirements of France. Written informed consent is obtained from participants, who are able to decline participation or withdraw from the study at any time. Findings will be disseminated through publication in peer-reviewed journals and presentations at scientific conferences.

NCT06100978.

To assess the association between ambient ozone (O₃) exposure and semen quality among men with unhealthy behaviours and low income.

A case-control study was conducted from February 2024 to January 2025, in which male participants aged 18–45 years were recruited from Foshan, and following propensity score matching, a total of 820 participants were included in the final analysis.

The evaluated the association between O₃ exposure during the 70–90 days, 10–14 days, 0–9 days and 0–90 days prior to semen collection and semen quality using stepwise conditional logistic regression analyses, and restricted cubic splines were incorporated into the models.

O₃ exposure during the 70–90 days and 0–90 days preceding semen sample collection was significantly associated with an increased risk of low semen quality, with ORs of 1.020 (95% CI 1.003 to 1.039) and 1.056 (95% CI 1.008 to 1.108), respectively. Additionally, O₃ exposure during the 0–90-days period showed a significant positive association with abnormal sperm concentration. A non-linear relationship between O₃ exposure and sperm concentration was also observed. Notably, O₃ exposure during the 0–9 days before semen collection was inversely associated with the risk of low semen quality. Subgroup analyses across age, lifestyle factors and socioeconomic strata revealed no significant effect modifications.

This study found that O₃ exposure during the 70–90 days and 0–90 days before sampling was associated with reduced semen quality in men with unhealthy behaviours and low income.

To investigate the potential long-term impacts of adult growth hormone deficiency (GHD).

Observational, retrospective matched cohort.

UK Clinical Practice Research Datalink (CPRD) Aurum database of primary care records with linkage to deprivation, secondary care and mortality data.

Adults registered with CPRD between 31/03/2002 and 29/03/2021. Individuals with GHD were exact matched up to 1:4 with unaffected controls on sex, age group (by decade) and general practice with propensity score matching on age, ethnicity and deprivation.

Mortality, cardiovascular disease (CVD), osteoporosis, fractures, depression, time off work and unemployment were investigated using Cox proportional hazards modelling.

1573 adults with GHD were matched to 6234 unaffected controls. Median follow-up was 5.2 years for cases (IQR 2.2, 10.6) and 5.1 years for controls (IQR 2.2, 10.3). Adult GHD was associated with an increased risk of premature mortality (adjusted HR (aHR) 1.61; 95% CI 1.27, 2.03), CVD (aHR 2.38; 95% CI 1.84 to 3.07) and osteoporosis (aHR 4.03; 95% CI 2.88 to 5.65), but there was no evidence for an increased risk of fractures. A higher rate of depression (aHR 1.72; 95% CI 1.23 to 2.40) and unemployment (aHR 2.06; 95% CI 1.56 to 2.71) was also seen in adults with GHD, although there was no evidence for increased time off work.

GHD in adults is associated with increased risk of premature mortality, CVD, osteoporosis, depression and socioeconomic challenges such as unemployment. Timely diagnosis, appropriate treatment and comprehensive support are critical to mitigating these adverse outcomes.

Clinical trials have produced inconclusive results regarding the optimal glucose range for a patient with sepsis in the intensive care unit (ICU) receiving insulin treatment.

To investigate the optimal glucose range in patients with sepsis in the ICU independent of confounding covariates.

Targeted trial emulation of glucose ranges using causal inference targeted maximum likelihood estimation and longitudinal mixed-effects models combined with survival models.

Single-centre, academic referral hospital in Boston, Massachusetts, USA.

Adults fulfilling sepsis 3 criteria with at least three glucose readings and insulin treatment from the Medical Information Mart for Intensive Care (MIMIC)-IV database (2008–2019).

Five predefined glucose distributions with means at 100, 130, 160 (baseline), 190 and 220 mg/dL mimicking current guidelines’ recommendations (140–180 mg/dL).

The primary outcome was in-hospital mortality. Modified counterfactual treatment-policy risks across distinct time-weighted glucose ranges were estimated.

Of 73 181 eligible patients, 8002 patients with a median age of 66 years (41% women, 67% white ethnicity, 57% diabetes) were included. There was a U-shaped curve between glucose range and mortality in patients without diabetes, but overall, this association was not significant (mean glucose at 100 mg/dL with 21% mortality and mean glucose at 220 mg/dL with 26% mortality, p-for-trend 0.26). Mortality was lowest at 17%, with mean glucose between 130 and 160 mg/dL. Hypoglycaemic events (

Our data suggest a U-shaped association of glucose and mortality with an optimal average glucose between 160 and 190 mg/dL. These results confirm current guideline recommendations. Together with recent results from randomised controlled trials, intensivists should aim for a liberal glucose range in most patients.

to describe the evolution of anxiety during the COVID-19 pandemic in France and to assess whether it differed according to pre-existing alcohol misuse.

A prospective longitudinal study.

A French online cohort: CONFINS. Data has been collected since the first lockdown in April–May 2020 until January 2022.

1868 participants being at least 18 years of age and who had been confined in France by government measures.

The primary outcome was anxiety, measured through Generalised Anxiety Disorder – seven items (GAD-7). Its association with alcohol misuse (defined using AUDIT-C score) was estimated using segmented linear mixed models. Interactions with gender and perceived loneliness at baseline were evaluated.

Of the 1868 included participants, 729 responded to at least one follow-up questionnaire (median follow-up time: 46 weeks). We identified 58% as having pre-existing alcohol misuse. Alcohol misuse was significantly associated with an increased GAD-7 score starting at the second lockdown in women (β=0.30; p=0.014) and in participants having a high perceived loneliness (β=0.59; p=0.011).

Pre-existing alcohol misuse appeared to be a risk factor for anxiety during the COVID-19 pandemic, particularly for women and those with high perceived loneliness. Mental health support should be proposed to these vulnerable groups in the event of a future health crisis.

To evaluate the impact of various antihypertensive drugs on secondary stroke prevention in a real-life setting.

Nationwide historic cohort study.

French healthcare system data (SNDS).

Adults hospitalised for ischaemic stroke between 2014 and 2015 were followed up until December 2021 and stratified based on the presence of atrial fibrillation (AF).

Risk of stroke recurrence was assessed using a time-dependent Cox cause-specific model accounting for changes in drug exposure. We also investigated the risk of major adverse cardiovascular events (MACE) or all-cause death. Models were adjusted on stroke characteristics, coprescriptions and co-morbidities, at inclusion and across follow-up.

Among 54 764 patients without AF (median age 71; 46% women) and 17 960 with AF (median age 79; 51% women), stroke recurrence occurred in 11% and 13%, respectively. In non-AF patients, reduced recurrence risk was associated only with use of calcium channel blockers (adjusted HR (aHR) 0.91, 95% CI 0.86 to 0.97), thiazide diuretics (aHR 0.90, 95% CI 0. 83 to 0.97), loop diuretics (aHR 0.86, 95% CI 0.77 to 0.95) and potassium-sparing agents (aHR 0.83, 95% CI 0.70 to 0.98). In AF patients, only potassium-sparing agents (aHR 0.82, 95% CI 0.69 to 0.99) were associated with reduced recurrence risk. All antihypertensive drugs, apart from loop diuretics, were associated with a reduced risk of MACE or all-cause death.

In this large cohort, only diuretics and calcium channel blockers were associated with a reduced risk of recurrent stroke. Most antihypertensive drugs, however, may be more effective in overall cardiovascular prevention.

China has continued to improve tuberculosis (TB) control in the past decade; however, the sudden outbreak of COVID-19 hindered this progress. As a province with a large population and frequent international exchanges, Guangdong has been seriously affected by COVID-19. This study aimed to understand the effect of COVID-19 on TB detection in Guangdong based on the autoregressive integrated moving average (ARIMA) model.

Time-series study.

Guangdong, China.

We used the ARIMA model to quantify the effect of COVID-19 by comparing reported cases during the COVID-19 pandemic with predicted cases under a counterfactual scenario of no COVID-19 pandemic. After model evaluation, we chose ARIMA (0,1,2)(0,1,1)₁₂ as the prediction model. We also highlighted that there were three emergency response periods in which the responses and public responses to COVID-19 varied.

During the pandemic period, the average annual TB notification rate was 57.95/100 000, which decreased by 27.97% compared with the pre-pandemic period. Although it decreased by 6.17% on average annually in the pre-pandemic period, it decreased by 14.92% in 2020 as compared with 2019, but only decreased by 0.34% in 2021 as compared with 2020. The results of the ARIMA model showed that the number of reported cases in 2020 decreased by 6.62% compared with that of the predicted cases, but this decreased by 0.42% only in 2021. The most seriously affected period was the second-level emergency response period in 2020, when the relative difference between reported and predicted cases reached the peak (–16.43%). The least affected period was the third-level emergency response period of 2021, the reported cases recovered and exceeded the predicted cases, with a gap of 0.77%.

TB detection in Guangdong had generally declined during the COVID-19 pandemic, which might be related to the movement restrictions, diverted resources and patients’ concerns. This decline would lead to the delay or even interruption of diagnosis and treatment, which would cause the regression of TB control. To improve TB detection, it is important for stakeholders to take consorted effort during public health emergencies.

Hypertension and depression frequently co-occur, complicating patient management and worsening outcomes. This scoping review aims to systematically map non-pharmacological interventions for managing comorbid hypertension and depression, providing insights into current practices and guiding future research.

Following the Joanna Briggs Institute guidelines and Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews standards, a comprehensive search was conducted across multiple databases, including PUBMED, Embase, PsycINFO, CINAHL, Cochrane Library, Chinese Biomedical Literature Database and Chinese National Knowledge Infrastructure, covering the literature from January 2004 to December 2023. Studies were selected based on predefined inclusion criteria focusing on non-pharmacological or complex interventions. Data extraction was performed using the Template for Intervention Description and Replication checklist to ensure detailed and structured summaries of each intervention.

Fifteen quantitative studies were included, most of which were pilot randomised control trials, pre-post studies and with generally small sample sizes (20 to 2365). Interventions were categorised into integrated and coordinated care, behavioural and psychological interventions and physical and lifestyle interventions. Delivery methods varied, with most interventions being face-to-face, while a few used digital platforms such as mobile apps and telephone support. Disease-level and patient-level outcomes were mainly reported, while only three examined system-level outcomes. 13 of 15 included studies showed positive results in managing comorbidity. The variability in follow-up periods (ranging from 1 week to 12 months) and measurement instruments across studies limited the ability to draw consistent long-term conclusions.

This scoping review highlights the role of psychosocial and non-pharmacological interventions, particularly collaborative/integrated care and behavioural therapies, in managing comorbid hypertension and depression. These interventions consistently improve depressive symptoms, with mixed effects on blood pressure control. Further research is needed to standardise core outcomes and evaluate the long-term effectiveness and scalability of these interventions.

Atrial fibrillation (AF) constitutes a growing public health challenge. Consequently, the exploration of modifiable risk factors is essential for advancing AF prevention and management. While obstructive sleep apnoea is established as a risk factor for AF recurrence following catheter ablation, and its treatment with continuous positive airway pressure therapy reduces recurrence rates, the influence of non-sleep apnoea-related sleep indicators remains unclear. This systematic review aims to elucidate the association between these non-sleep apnoea-related sleep indicators and AF recurrence to inform optimised management strategies.

A comprehensive search will be performed in databases, including PubMed, Embase, the Cochrane Library, Chinese National Knowledge Infrastructure, VIP Database and Wanfang Data, covering publications from database inception to 27 August 2024. Study selection will be performed independently by two reviewers using predefined eligibility criteria, with the screening process documented in a referred Reporting Items for Systematic Review and Meta-Analysis-compliant flow diagram. Data will be extracted using standardised forms and risk of bias of included studies will be assessed with the Risk Of Bias In Non-randomised Studies-of Interventions tool. Non-sleep apnoea-related sleep indicators, including sleep duration, sleep quality, sleep latency, sleep efficiency, REM (Rapid Eye Movement)/NREM (Non-Rapid Eye Movement), etc, serve as exposure factors. The primary outcome is defined as AF recurrence, whereas the secondary outcome comprises quality of life measures among AF patients. Should sufficient data be available, a meta-analysis will be performed using appropriate statistical methods; otherwise, a narrative synthesis will be conducted.

This study uses publicly available data, so ethical approval is not required. The findings will be disseminated through peer-reviewed journals and scholarly platforms to inform clinical practice and future research.

CRD42024607124.

Low back pain (LBP) is the leading contributor to disability globally. It has a substantial impact on the lives of those who experience it, and places considerable economic burden on healthcare systems. Despite these impacts, and the consistency of guideline recommendations, many individuals do not receive recommended LBP management. Structural barriers to accessing timely, evidence-based care, as well as public uncertainty about where to seek appropriate management, can influence the care individuals receive. Telephone and digitally based helplines assist to overcome many traditional barriers to accessing care and offer a scalable platform to improve the delivery of guideline recommended management for LBP. However, uptake of such services can be limited without targeted promotion and patient-centred design. This project aims to codesign, implement and evaluate an upgraded component of an existing Australian helpline service, tailored for people with back pain and supported by a media awareness campaign. This protocol outlines the codesign process, implementation and planned evaluation of the helpline.

This protocol uses three complementary frameworks—an iterative codesign process, the Practical Robust Implementation Sustainability Model, and the Reach, Effectiveness, Adoption, Implementation and Maintenance framework—to guide the codesign and development, implementation and evaluation of an upgraded helpline for people with LBP. The codesign process involves key stakeholders, including consumers and clinicians, to inform the development and implementation of both the upgraded helpline service and the media campaign to raise awareness and uptake of the helpline. Data sources will include a pre–post cohort of helpline service users, routinely collected service data (eg, monthly call rate) and health system data to evaluate the broader population level impact (eg, rates of emergency department presentations for LBP in the Australian region targeted by the media campaign). Implementation evaluation will include Reach, Effectiveness, Adoption, Implementation and Maintenance as well as internal and external environmental factors that influence the success of these outcome measures.

The project was approved by the University of Sydney’s Human Research Ethics Committee (HE001081). This project involves collaboration with consumers, clinicians and other stakeholders to interpret, translate and disseminate research findings to relevant audiences.