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  • New
  • Research Article
  • 10.1136/bmjopen-2025-101593
Efficacy and safety of microbiota-targeted therapeutics in autoimmune and inflammatory rheumatic diseases: protocol for a systematic review and meta-analysis of randomised controlled trials.
  • Dec 14, 2025
  • BMJ open
  • Maja Skov Kragsnaes + 35 more

An abnormal composition of gut bacteria along with alterations in microbial metabolites and reduced gut barrier integrity has been associated with the pathogenesis of chronic autoimmune and inflammatory rheumatic diseases (AIRDs). The aim of the systematic review, for which this protocol is presented, is to evaluate the clinical benefits and potential harms of therapies targeting the intestinal microbiota and/or gut barrier function in AIRDs to inform clinical practice and future research. This protocol used the reporting guidelines from the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocol. We will search Embase (Ovid), Medline (Ovid) and the Cochrane Library (Central) for reports of randomised controlled trials of patients diagnosed with an AIRD. Eligible interventions are therapies targeting the intestinal microbiota and/or gut barrier function including probiotics, synbiotics, faecal microbiota transplantation, live biotherapeutic products and antibiotics with the intent to modify disease activity in AIRDs. The primary outcome of the evidence synthesis will be based on the primary endpoint of each trial. Secondary efficacy outcomes will be evaluated and selected from the existing core domain sets of the individual diseases and include the following domains: disease control, patient global assessment, physician global assessment, health-related quality of life, fatigue, pain and inflammation. Harms will include the total number of withdrawals, withdrawals due to adverse events, number of patients with serious adverse events, disease flares and deaths. A meta-analysis will be performed for each outcome domain separately. Depending on the type of outcome, the quantitative synthesis will encompass both ORs and standardised mean differences with corresponding 95% CIs. No ethics approval will be needed for this systematic review. We will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to disseminate the study results through a peer-reviewed publication. CRD42025644244.

  • New
  • Research Article
  • 10.1136/bmjopen-2025-105683
Development and validation of a case identification algorithm for hand trauma patients using health administrative data and the epidemiology of hand trauma in a universal healthcare system.
  • Dec 14, 2025
  • BMJ open
  • Chloe R Wong + 8 more

Our primary objectives were (1) to develop and validate an administrative data algorithm for the identification of hand trauma cases using clinical diagnoses documented in medical records as the reference standard and (2) to estimate the incidence of hand trauma in a universal public healthcare system from 1993 to 2023 using a population-based research cohort constructed using a validated case identification algorithm. A population-based retrospective validation study. Ontario, Canada, from 2022 to 2023 (validation) and from 1993 to 2023 (estimation). Our reference standard was the known hand trauma status of 301 patients (N=147 with hand trauma) who presented to an urban tertiary-care hand trauma centre in Toronto, Ontario. (1) The sensitivity, specificity, positive and negative predictive values of the optimal algorithm to identify hand trauma using provincial health administrative data and (2) age-standardised and sex-standardised incidence rates of hand trauma among men and women, by age, and by area of patient residence. The optimal algorithm had a sensitivity of 73.8% (95% CI 66.6% to 81.0%), specificity of 80.1% (95% CI 73.8% to 86.5%), positive predictive value of 78.1% (95% CI 71.2% to 85.0%) and negative predictive value of 76.1% (95% CI 69.5% to 82.7%). Over the study period, the age-standardised and sex-standardised incidence of hand trauma increased from 384 to 530 per 100 000. The greatest increase was observed in males and individuals aged 0-19 and 80+, with higher incidence rates in Southern compared with Northern Ontario. Our algorithm enabled identification of hand trauma cases using health administrative data suitable for population-level surveillance and health services research, revealing a rising burden of hand trauma from 1993 to 2023. These findings can support improved surveillance, resource allocation and care delivery for this public health problem.

  • New
  • Research Article
  • 10.1136/bmjopen-2024-098420
Microsimulation modelling to predict the burden of CKD and the cost-effectiveness of timely CKD screening in Belgium: results from the Inside CKD study.
  • Dec 14, 2025
  • BMJ open
  • Rucha Vadia + 10 more

Inside CKD aims to assess the burden of chronic kidney disease (CKD) and the cost-effectiveness of screening programmes in Belgium. Microsimulation-based modelling. Data derived from national statistics and key literature from Belgium. Virtual populations of ≥10 million individuals, representative of Belgian populations of interest, were generated based on published data and cycled through the Inside CKD model. Baseline input data included age, estimated glomerular filtration rate (eGFR), urine albumin-creatinine ratio (UACR) and CKD status. Outcomes included the clinical and economic burden of CKD during 2022-2027 and the cost-effectiveness of two different CKD screening programmes (one UACR measurement and two eGFR measurements or only two eGFR measurements, followed by renin-angiotensin-aldosterone system inhibitor treatment in newly diagnosed eligible patients). The economic burden estimation included patients diagnosed with CKD stages 3-5; the screening cost-effectiveness estimation included patients aged ≥45 years with no CKD diagnosis and high-risk subgroups (with cardiovascular disease, hypertension, type 2 diabetes or aged ≥65 years). Between 2022 and 2027, CKD prevalence is estimated to remain stable and substantial at approximately 1.66 million, with 69.9% undiagnosed. The total healthcare cost of patients diagnosed with CKD is expected to remain stable at approximately €2.15 billion per year. The one UACR, two eGFR measurement screening programme was cost-effective in all populations, with an incremental cost-effectiveness ratio of €3623 per quality-adjusted life year (QALY) gained in those aged ≥45 years, well below the estimated willingness-to-pay threshold of €43 839 per QALY gained. Without changes to current practice, the disease burden of CKD in Belgium is predicted to remain substantial over the next few years. This highlights the need for timely diagnosis of CKD and demonstrates that, in line with guideline recommendations, implementing a CKD screening programme involving UACR and eGFR measurements followed by treatment would be cost-effective.

  • New
  • Research Article
  • 10.1136/bmjopen-2025-107906
Multilayer low-stretch bandage combined with conventional rehabilitation to promote functional recovery after knee surgery: study protocol for a prospective, single-blind, randomised controlled trial.
  • Dec 14, 2025
  • BMJ open
  • Xiaofeng Han + 5 more

Patients undergoing anterior cruciate ligament reconstruction (ACLR) and patellar fracture frequently present with substantial pain, swelling and inflammation. These pathophysiological changes not only intensify postoperative pain but also compromise the intra-articular environment via mechanical compression and localised microcirculatory deficits, thereby impeding recovery. Conventional interventions for postoperative swelling, such as cryotherapy and physical agent modalities, are commonly applied yet exhibit limited efficacy. Multilayer low-stretch bandage (MLB), with its gradient compression properties, has recently demonstrated superior swelling control and functional restoration; however, existing research primarily assesses short-term outcomes and lacks a systematic analysis across the postoperative continuum-acute, subacute and chronic phases-as well as long-term follow-up. This study therefore employs a multi-temporal intervention design and extended follow-up to evaluate the effectiveness of MLB in managing swelling, modulating pain and enhancing long-term knee function and activities of daily living across different recovery stages. The findings aim to furnish high-level evidence for knee rehabilitation protocols, refine clinical practice and ultimately improve patient quality of life. This prospective, single-blind, randomised controlled trial will enrol 36 patients following ACLR and patellar fracture. Participants will be allocated at a 1:1 ratio through computerised randomisation to either an experimental group receiving MLB plus conventional rehabilitation, or a control group receiving conventional rehabilitation alone. The study spans 12 weeks, with follow-up assessments scheduled at baseline (T0), 4 weeks (T1), 8 weeks (T2) and 12 weeks (T3). Outcome measures comprise the Hospital for Special Surgery (HSS) Knee Rating Score, affected limb oedema regression rate, Visual Analogue Scale (VAS) pain score, knee range of motion, quadriceps and hamstring muscle strength, centre of pressure (COP) displacement parameters, proprioceptive testing, the 36-Item Short Form Health Survey (SF-36) and the Holden Walking Function Classification. A subsequent 1-year follow-up will assess long-term efficacy and patient satisfaction, while adverse events are strictly monitored throughout the entire study period. Adherence to Consolidated Standards of Reporting Trials guidelines is maintained, and a single-blind design ensures that both participants and assessors remain unaware of group assignments. This trial aims to establish an evidence-based foundation for optimising postoperative rehabilitation in this patient population. Ethical approval for the study was obtained from the Medical Ethics Committee of Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School (2025-0141-01). The results of the study will be published in a peer-reviewed medical journal. ClinicalTrials.gov chiCTR2500100566. Registration date is 10 April 2025.

  • New
  • Research Article
  • 10.1136/bmjopen-2025-100792
High-dose intermittent theta burst stimulation targeting the individualised frontoparietal cognitive network for post-stroke cognitive impairment: protocol for a randomised sham-controlled trial in China.
  • Dec 14, 2025
  • BMJ open
  • Kaiyue Han + 8 more

Cognitive impairment is a common consequence after stroke. Intermittent theta burst stimulation (iTBS) has emerged as a promising cognitive therapy. However, traditional iTBS typically employs lower doses and one-size-fits-all stimulation targets, which may not fully capitalise on the potential of this therapy and warrants further evaluation for both efficacy and safety. This study aims to evaluate the efficacy and safety of high-dose iTBS targeting the individualised frontoparietal cognitive network (FCN) identified by precision functional neuroimaging for post-stroke cognitive impairment (PSCI). This is a prospective, double-blind, sham-controlled, parallel-group randomised controlled trial. 60 eligible participants with PSCI will be randomly assigned (1:1) to an active iTBS or a sham-controlled group. The active group will receive high-dose iTBS (3600 pulses/day) at 80% resting motor threshold targeting the left individualised FCN, guided by a real-time neuronavigation system. The sham group will follow identical procedures using a sham coil. Both groups will also undergo conventional computerised cognitive training. The intervention will be administered on workdays over a period of 3 weeks, totalling 15 workdays. The primary outcome is the change in Montreal Cognitive Assessment scores from baseline to immediately post-treatment. Secondary outcomes include long-term change in global cognition, activities of daily living and specific cognitive domains (assessed by a comprehensive neuropsychological battery covering memory, attention, executive function and language), as well as mood. Assessments occur at baseline, post-treatment and 3-month follow-up. Safety outcomes, specifically the number of adverse events related to iTBS, will be monitored and recorded throughout the trial. This study has been approved by the Medical Ethics Committee of the China Rehabilitation Research Center. The results of this study will be published in peer-reviewed scientific journals and disseminated at academic conferences. NCT05953415.

  • New
  • Research Article
  • 10.1136/bmjopen-2025-108713
Impact of atherosclerotic cardiovascular disease on mortality in ICU sepsis patients: a retrospective MIMIC-IV cohort study.
  • Dec 14, 2025
  • BMJ open
  • Yu-Cheng Chang + 3 more

Evaluation of the impact of atherosclerotic cardiovascular disease (ASCVD), particularly polyvascular disease, on 30-day and 365-day mortality among intensive care unit (ICU) patients diagnosed with sepsis. Retrospective cohort study. This study was conducted using data from the Medical Information Mart for Intensive Care IV, a publicly available critical care database from a tertiary care hospital in the US. A total of 7895 adult ICU patients with sepsis were included between 2008 and 2022. Among them, 3314 (41.97%) had ASCVD, defined by International Classification of Diseases (ICD) codes for coronary artery disease, peripheral artery disease or stroke. The primary outcomes were all-cause mortality at 30 and 365 days following ICU admission. ASCVD patients with a greater number of disease beds tend to be male, older, have lower body mass index, heart rates, mean blood pressure, respiratory rate and temperature, compared with non-ASCVD patients. Before propensity-score matching, patients with ASCVD (3314) had significantly higher 30-day (29.21% vs 24.14%, p<0.001) and 365-day mortality (30.81% vs 25.67%, p<0.001) compared with those without ASCVD (4581). Multivariate Cox regression analysis identified ASCVD as an independent predictor of 30-day (HR: 1.166, 95% CI 1.046 to 1.300, p=0.006), indicating a 16.6% higher risk of death within 30 days. For 365-day mortality, ASCVD patients had an HR of 1.168 (95% CI 1.051 to 1.298, p=0.004), reflecting a 16.8% increased risk of death within a year. Mortality risk increased incrementally with the number of involved vascular beds, especially in patients with three disease beds who exhibited the highest risk. Our findings reveal that in sepsis patients with ASCVD as a continuous variable, each additional bed increased the 30-day and 365-day mortality risk by 13.1% and 13.9%. ASCVD significantly increases the mortality risk in ICU patients with sepsis. Integrated management of sepsis and ASCVD-using targeted interventions such as tailored pharmacotherapy and risk factor modification-may reduce mortality and morbidity in this high-risk population.

  • New
  • Research Article
  • 10.1136/bmjopen-2025-112676
Sleep problems and associated risk factors among physicians in Bangladesh: a protocol for systematic review and meta-analysis of observational cross-sectional studies.
  • Dec 14, 2025
  • BMJ open
  • Mantaka Rahman + 8 more

Sleep problems are an escalating global health concern, with prevalence estimates ranging from 8.3% to 45%. Physicians are disproportionately affected, with rates around 44% compared with 36% in the general population. In Bangladesh, reported rates range from 32% to 58%, with physicians being particularly vulnerable. Poor sleep among physicians is strongly linked to burnout, medical errors and increased mental health risks. Despite these serious implications, existing evidence from Bangladesh remains fragmented and inconsistent, limiting its utility for health policy and workforce interventions. This review therefore seeks to generate reliable pooled prevalence estimates and identify key determinants of sleep problems among Bangladeshi physicians. The research team will search the PubMed, Scopus, Web of Science, EMBASE, PsycInfo, ProQuest Medical, CINAHL, Google Scholar and BanglaJOL electronic and regional databases following Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines for published studies from inception until 1 August 2025, using truncated and phrase-searched keywords, relevant medical subject headings and citation chaining from grey literature. Observational cross-sectional studies published within the predefined timeframe, using validated assessment tools, and published in English or other major international languages will be prioritised for inclusion. Review papers, case reports, case series, intervention studies, commentaries, preprints, meeting abstracts, protocols, unpublished articles and letters will be excluded. Two independent reviewers will screen the retrieved papers using the Rayyan web-based application, with any disagreements resolved by a third reviewer. Quantitative estimates of sleep problems, including prevalence, duration, quality and associated risk factors among Bangladeshi physicians will be extracted. A narrative synthesis and meta-analysis will be performed to assess the pooled prevalence using a random effects meta-analysis model. Forest and funnel plots will be generated for visualisation. Heterogeneity will be assessed using the I 2 statistic, with sensitivity or subgroup analysis conducted as required. The quality of included studies will be evaluated using Joanna Briggs Institute critical appraisal tools for observational study designs. All statistical analysis will be conducted using Jamovi V2.7.6, R V4.3.2 'meta' packages and GraphPad Prism V9.0.2. This review will synthesise evidence from existing published literature. While completing the findings, the findings will be submitted to an international peer-reviewed journal and disseminated through conferences, policy forums and stakeholders' networks to inform future research and interventions. CRD420251123294.

  • New
  • Research Article
  • 10.1136/bmjopen-2025-108243
Effects of transcutaneous electrical nerve stimulation on cognitive function and upper limb motor function in people with chronic stroke: a study protocol for a randomised controlled trial.
  • Dec 14, 2025
  • BMJ open
  • Nga Huen Chan + 1 more

Cognitive impairment and upper limb impairment are common complications following stroke, but rehabilitation interventions targeting post-stroke cognitive and upper limb motor deficits remain understudied. Transcutaneous electrical nerve stimulation, including transcutaneous vagus nerve stimulation (tVNS) and transcutaneous spinal cord stimulation (tSCS), can potentially alleviate cognitive impairment and promote motor recovery. Although tVNS and tSCS may facilitate neuroplasticity following stroke, their effects on cognitive and upper limb motor outcomes have not been sufficiently studied. Therefore, the proposed clinical trial will investigate the effects of tVNS and tSCS on cognitive function and upper limb motor function in people with chronic stroke. A three-arm sham-controlled single-blind parallel-group randomised controlled trial will be performed with people with chronic stroke. All participants (n=90) will be randomly allocated to receive 18 sessions of intervention with different stimulation protocols (tVNS, tSCS and sham stimulation) at a 1:1:1 ratio. All participants will receive upper limb exercises concurrent with the corresponding stimulation protocols for 45 min in each session, three sessions per week, for 6 weeks. The primary outcomes will be the Montreal Cognitive Assessment and Fugl-Meyer Assessment for Upper Extremity. The secondary outcomes will be the Rivermead Behavioural Memory Test, Digit Span Test, Trail Making Test, Wolf Motor Function Test, maximum isometric voluntary contraction of the elbow, muscle stiffness of the elbow extensor and flexor, Arm Activity Measure, Oxford Participation and Activity Questionnaire and 12-item Short-Form Survey. All outcomes will be assessed at baseline, after 9 and 18 sessions of the intervention, and 1 month after the cessation of the intervention. Ethical approval has been obtained from the Human Subjects Ethics Committee of The Hong Kong Polytechnic University (HSEARS20221011002). The results yielded from this study will be submitted for publication in peer-reviewed journals and at international conferences. NCT05615610.

  • New
  • Research Article
  • 10.1136/bmjopen-2025-099698
Implementing recommended falls prevention practices for older patients in hospitals in England: a realist evaluation.
  • Dec 14, 2025
  • BMJ open
  • Natasha Alvarado + 9 more

To explore why there is variation in implementation of multifactorial falls prevention practices that are recommended to reduce falls risks for older patients in hospital. Mixed method, realist evaluation. Three older persons and three orthopaedic wards in acute hospitals in England. Healthcare professionals, including nurses, therapists and doctors (n=40), and patients aged 65 and over, and carers (n=31). We examined mechanisms hypothesised to underpin the implementation of multifactorial falls risk assessment and multidomain, personalised prevention plans. We developed an explanation detailing that how contextual factors supported or constrained implementation of recommended falls prevention practices. Nurses led delivery of falls risk assessment and prevention planning using their organisation's electronic health records (EHR) to guide and document these practices. Implementation of recommended practices was influenced by (1) organisational EHR systems that differed in falls risk assessment items they included, (2) competing priorities on nurse time that could reduce falls risk assessment to a tick box exercise, encourage 'blanket' rather than tailored interventions and that constrained nurse time with patients to personalise prevention plans and (3) established but not recommended falls prevention practices, such as risk screening, that focused multidisciplinary communication on patients screened as at high risk of falls and that emphasised nursing, rather than Multidisciplinary Team (MDT), responsibility for preventing falls through constant patient supervision. To promote consistent delivery of multifactorial falls prevention practices, and to help ease the nursing burden, organisations should consider how electronic systems and established ward-based practices can be reconfigured to support greater multidisciplinary staff and patient and carer involvement in modification of individual falls risks.

  • New
  • Research Article
  • 10.1136/bmjopen-2025-099468
Association between the continuum of maternal healthcare services and child immunisation in East Africa: a propensity score matching analysis.
  • Dec 14, 2025
  • BMJ open
  • Alemayehu Kasu Gebrehana + 9 more

To assess the association between the maternal continuum of healthcare and child immunisation in East Africa using propensity score matching (PSM). Cross-sectional study using Demographic and Health Survey data. This study was conducted in East African countries. This study included a weighted sample of 13 488 women with children aged 12-23 months. Child immunisation was the outcome variable of this study. The PSM estimates indicate that the average treatment effect on the treated for complete child immunisation was 0.0583, meaning that children of mothers who received a complete maternal continuum of care had a 5.83% higher probability of being fully immunised compared with children of mothers with incomplete care. Expressed relative to the treated group's mean, this corresponds to a 7.48% increase. Additionally, our results indicated that the population average treatment effect was 0.0629. This means that, on average, a complete continuum of maternal healthcare increases the probability of full child immunisation by approximately 6.29% across the entire population. The study highlights that children whose mothers receive comprehensive maternal healthcare are more likely to complete their childhood immunisations. This finding underscores the need to integrate immunisation services into maternal healthcare programmes to enhance vaccination coverage and promote better child health. To maximise this connection, improving access to maternal healthcare, especially in underserved regions, is crucial, along with ensuring that immunisation is a regular part of maternal care.