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☐ ☆ ✇ BMJ Open

Pragmatic, open-label, multicentre, randomised controlled trial to guide initial therapy for immune checkpoint inhibitor-induced inflammatory arthritis comparing standard of care (prednisolone) to adalimumab without glucocorticoids: REACT trial protocol

Por: Fisher · B. A. · Rowe · A. · Hodson · C. · Wilkhu · M. · Williams · E. · Turner · E. · Allard · A. · Blake · T. · Bombardieri · M. · Cope · A. P. · Dubey · S. · Mankia · K. · Malley · T. · Moore · O. · Payne · M. · Plummer · R. · Tilby · M. · Tillett · T. · Wong · E. · Wu · Y. · Filer · A. · Pra — Marzo 3rd 2026 at 13:40
Introduction

Immune checkpoint inhibitors (ICIs) have revolutionised cancer treatment through targeted disruption of the physiological pathways that maintain tissue tolerance, but which are co-opted by cancers to evade immunosurveillance. Thus, the resultant T-cell activity often causes immune-related adverse events including immune checkpoint inhibitor-induced inflammatory arthritis (ICI-IA). ICI-IA results in functional impairment that frequently persists, even after ICI discontinuation, with substantial quality-of-life impacts for cancer survivors.

A high-quality body of evidence to guide ICI-IA management remains an unmet need. Pharmacological treatment may be prolonged, typically begins with non-specific immunosuppression, including systemic steroids, and is usually only rationalised to more targeted therapy in resistant cases. Moreover, retrospective data suggest the high dose glucocorticoids sometimes used in new-onset ICI-IA may be associated with worse cancer outcomes.

Tumour necrosis factor (TNF) inhibition strategies are well established with excellent efficacy and safety profiles in ‘spontaneous’ inflammatory arthritides including rheumatoid and psoriatic arthritis. Mechanistic evidence from ex vivo and murine studies also supports the utility of anti-TNF therapy for steroid-refractory cases of ICI-IA. Although good clinical responses have been reported in this setting, the REACT trial (REmission induction of Arthritis caused by Cancer ImmunoTherapy) aims to provide randomised and robust clinical evidence for deploying targeted therapy earlier in ICI-IA management. It will test whether up-front anti-TNF therapy can more effectively and quickly control symptoms, reduce glucocorticoid exposure, prevent early ICI discontinuation and increase the frequency of drug-free ICI-IA remission.

Methods and analysis

REACT is a prospective, multicentre, open-label, superiority, two-arm, randomised controlled clinical trial to guide initial therapy for patients with ICI-IA. The trial will compare the current standard of care (initial prednisolone; Arm A) with the anti-TNF drug, adalimumab without glucocorticoids (Arm B).

The primary outcome is glucocorticoid-free arthritis remission rate at 24 weeks where remission is defined as: (i) No use of systemic or intra-articular glucocorticoids (except when used for adrenal insufficiency) within 4 weeks prior to assessment at 24 weeks; and (ii) absence of synovitis on clinical examination.

Ethics and dissemination

The protocol was approved by East Midlands—Leicester South Research Ethics Committee on 31-Oct-2024 (Ref: 24/EM/0202). Participants are required to provide written informed consent. The results of this trial will be disseminated through national and international presentations and peer-reviewed publications.

Trial registration number

ISRCTN18217497.

☐ ☆ ✇ BMJ Open

Mapping the evidence on dietary acculturation post-migration among Indian immigrants in Australia, Canada, New Zealand and the UK: a scoping review protocol

Por: Bachani Singh · S. · George · M. S. · Upton · P. · Knight-Agarwal · C. R. — Marzo 3rd 2026 at 13:40
Introduction

Indian immigrants experience significant dietary acculturation post-migration, shifting from traditional diets to more westernised eating patterns influenced by socioeconomic and environmental factors. This transition, often marked by increased processed food consumption and reduced intake of traditional staples, contributes to elevated risks of obesity and type 2 diabetes. Despite the growing Indian diaspora in Australia, Canada, New Zealand and the UK, the evidence on their dietary acculturation remains limited.

Methods and analysis

This review will adopt the Joanna Briggs Institute (JBI) methodology for scoping reviews. A three-step search strategy will be applied across databases including MEDLINE (via PubMed), CINAHL, Scopus and Web of Science. Google Scholar will be used as a supplementary search tool to identify additional relevant studies. The search will include peer-reviewed studies and grey literature published in English between 1 January 2000 and 22 May 2025. First-generation Indian immigrants of all ages will be included, while second-generation immigrants, refugee populations and studies linked to non-communicable disease interventions will be excluded. Screening will be conducted in Covidence by two independent reviewers, with discrepancies resolved by a third reviewer. Data will be extracted using a standard JBI tool, charted in tabular form, and synthesised narratively and thematically.

Ethics and dissemination

As this review will use published and publicly available data, formal ethics approval is not required. Findings will be disseminated through peer-reviewed publication, conference presentations and community engagement.

☐ ☆ ✇ BMJ Open

Effect of the English National Enhanced Service on weight management referral rate: an interrupted time-series analysis

Por: Haffner · S. J. P. · Stevens · R. J. · Amies-Cull · B. · Heath · L. · Bankhead · C. · Aveyard · P. · Jebb · S. A. — Marzo 3rd 2026 at 13:40
Objectives

To assess the impact of a National Enhanced Service (NES) incentive for weight management that financially rewarded practices for each eligible patient referred to a weight management programme.

Design

Interrupted time-series analysis to examine the rate of weight management referral and weight management advice.

Setting

Primary healthcare records from January 2018 to December 2024 in the Oxford Clinical Informatics Digital Hub, covering 8.3 million patients in 1198 primary care clinics around England.

Interventions

NES payments to practices for weight management were introduced in April 2021.

Results

The rate of referral increased from 1 referral per 1000 patients per month before the incentive to around 4 referrals per 1000 patients per month afterwards. There was no evidence that the increase differed by age, gender, ethnic group or socioeconomic status. The occurrence of weight management advice was unchanged by the introduction of the NES and was at least three times more common than referral to weight management services.

Conclusions

The NES was associated with a fourfold increase in referrals to weight management services. However, clinicians are much more likely to offer advice rather than a referral to a weight management programme. There is a clear opportunity to improve outcomes for patients by encouraging greater use of referrals to effective weight management services in place of advice.

☐ ☆ ✇ BMJ Open

Performance validation of an artificial intelligence-assisted chest radiograph algorithm for incidental pulmonary nodule detection in Malaysian healthcare facilities: a multicentre cross-sectional study protocol

Por: Megat Ramli · P. N. · Ahmad · N. · Aizuddin · A. N. · Abdul Hamid · Z. — Marzo 3rd 2026 at 13:40
Introduction

Incidental pulmonary nodules (IPNs) are commonly encountered on chest radiographs (CXRs) performed for routine clinical indications and may represent early manifestations of significant pulmonary pathology, including lung cancer. While low-dose CT screening has mortality benefits in selected high-risk populations, its implementation remains limited in many healthcare settings. Artificial intelligence (AI)-assisted CXR interpretation has the potential to enhance pulmonary nodule detection. However, evidence from Malaysian clinical practice is scarce. This study aims to evaluate the diagnostic performance of AI-assisted CXR interpretation for detecting IPNs across healthcare facilities in the Klang Valley, Malaysia.

Methods and analysis

This prospective, multicentre study will include 2452 CXRs from patients aged ≥35 years over a 6-month period across four Klang Valley healthcare facilities. Each CXR will be independently interpreted by an experienced radiologist (>5 years of experience) and analysed separately using an AI system (qXR-LNMS). An independent thoracic radiologist will determine the final classification for analysis if there is IPN detection discordance. Diagnostic performance metrics (sensitivity, specificity, positive and negative predictive values, and overall accuracy) will be calculated using a 2x2 classification matrix. Agreement between AI-assisted interpretation and radiologist reports will be assessed using Cohen’s kappa statistic. The prevalence of IPNs detected by AI-assisted interpretation and radiologist reporting will be compared using a two-proportion z-test. AI discriminative performance will be evaluated using receiver operating characteristic curve analysis and area under the curve estimation. Statistical analyses will be conducted using Statistical Package for the Social Sciences V.29, with p

Ethics and dissemination

Ethical approval has been obtained from the Universiti Kebangsaan Malaysia Research Ethics Committee and the Ministry of Health Malaysia Medical Research and Ethics Committee. Written informed consent will be obtained from all participants. The findings will be disseminated through peer-reviewed publications, scientific conferences and engagement with relevant stakeholders.

☐ ☆ ✇ BMJ Open

Population-based study of pharmacogenetics and pharmacokinetics in Southern African patients with multidrug-resistant tuberculosis (PoPG): a protocol for the Namibian cohort

Por: Boois · L. · Ekandjo · H. · Shavuka · O. · Nepolo · E. · Ndong Sima · C. A. · Oelofse · C. · Uren · C. · Petersen · D. C. · Möller · M. · Wijk · M. · Kellermann · T. · Decloedt · E. · McIlleron · H. · Denti · P. · Claassens · M. M. — Marzo 3rd 2026 at 13:40
Background

Multidrug-resistant tuberculosis (MDR-TB) is an urgent public health challenge in Namibia, with profound socioeconomic consequences. The high burden of both tuberculosis and HIV complicates treatment and underscores the need for optimised drug therapies. Precision medicine, which leverages patient-specific genetic and molecular information, offers promise for improving MDR-TB outcomes. However, its effective application relies on population-specific data, particularly understanding how individuals metabolise tuberculosis drugs and how genetic diversity drives variability in treatment response. Currently, no pharmacokinetic (PK) or pharmacogenetic (PG) data on TB treatment exist for Namibian populations. This gap is particularly concerning, given the country’s genetic diversity, environmental factors and comorbidities that may uniquely influence drug metabolism. This study aims to generate PK and PG data to inform dose optimisation and support personalised treatment strategies for MDR-TB in Namibia. The findings will contribute to improved patient care and inform health system strengthening based on locally relevant evidence.

Methods

This cross-sectional study will consist of 100 Namibian participants with matched human DNA and PK data of MDR-TB cases receiving isoniazid, clofazimine, bedaquiline and the fluoroquinolones (levofloxacin or moxifloxacin). PK sampling will be divided as follows: 30 individuals will undergo intensive PK sampling, while the remaining (n=70) will undergo sparse PK sampling. DNA will be extracted at Stellenbosch University (SU), and samples will be genotyped using the H3Africa microarray. Sequences will be aligned to the human reference genome, hg38 (GRCh38p13), using the freely available Burrows-Wheeler Aligner. A subset of the samples (n=20–30) will undergo whole genome sequencing (WGS) to verify imputation results and identify novel genetic variants potentially affecting PK in this population.

Data analysis

Quality control and variant call format file generation will be performed using the Genome Analysis Toolkit best practices (V.3.5). Intensive and sparse PK data will be pooled for the development of a population PK (popPK) model using a non-linear mixed-effects modelling approach. The popPK model will characterise the relationship between TB drug dose and exposure, including quantifying covariates, including genetic variation, explaining PK variability, providing a foundation for dose optimisation and personalised treatment strategies.

Ethics and dissemination

Ethics approval was obtained from the University of Namibia Human Research Ethics Committee for Health (Ref. SOM18/2024), the Ministry of Health and Social Services (Ref. 22/4/2/3), the SU Health Research Ethics Committee (Ref. N21/11/136) and the University of Cape Town Human Research Ethics Committee (Ref. 500/2022).

☐ ☆ ✇ BMJ Open

Assessment of health-related quality of life, cognitive, physical and psychological impairments in critically ill adults after status epilepticus (POSEIDON 2): protocol for a multicentre longitudinal study

Por: Legriel · S. · Bernard · C. · Sboui · G. · Sigaud · F. · Lascarrou · J.-B. · Mayenco-Cardenal · N. · Chelly · J. · Bruel · C. · Mongardon · N. · Marzouk · M. · Quenot · J.-P. · Hugues · R. · Schnell · D. · Beuret · P. · Bailly · P. · Lesieur · O. · Argaud · L. · Chambon · R. · Jacq · G. — Marzo 3rd 2026 at 13:40
Introduction

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.

Methods and analysis

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.

Ethics and dissemination

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.

Trial registration number

NCT06100978.

☐ ☆ ✇ BMJ Open

Beyond the doctors office: a longitudinal study mapping womens experiences of the maternal healthcare journey as a pathway to reducing maternal mortality in Nigeria

Por: Ope · B. W. · Attwood · P. · Mullins · E. · Hirst · J. E. · Norton · R. · Peden · M. — Marzo 2nd 2026 at 13:30
Objectives

Nigeria has one of the highest maternal mortality burdens globally. Improving maternal outcomes requires a better understanding of how women experience care across pregnancy, childbirth and the postnatal period. This study explored women’s maternal healthcare experiences across the perinatal continuum in Nigeria, with a focus on how challenges emerge and interact over time.

Design

Longitudinal qualitative study using patient journey mapping.

Setting

Public primary, secondary and tertiary healthcare facilities in Abuja, Nigeria.

Participants

12 pregnant women were purposively sampled. Each woman participated in two rounds of in-depth interviews: once in late pregnancy and again 2–6 weeks postpartum. All participants completed both interview rounds.

Methods

Data were collected through 24 semistructured in-depth interviews conducted longitudinally to capture changes in women’s experiences before and after childbirth. Interview guides were informed by existing maternal health frameworks. Transcripts were analysed using reflexive thematic analysis and organised across five stages of the maternal healthcare journey: Awareness, Consideration, Access, Treatment and Recovery.

Findings

This study introduces a five-stage framework: Awareness, Consideration, Access, Treatment and Recovery, to comprehensively explore maternal healthcare experiences. The findings reveal systemic inefficiencies at every stage of the pregnancy journey, from limited awareness of pregnancy test kits to unreliable booking systems and inadequate postpartum mental health support. This study highlights how early-stage barriers cascade into later phases, unlike traditional research that focuses only on clinical interactions. This study emphasises the importance of maternal care accessibility and recovery support, moving beyond a treatment-centric lens. 

Conclusion

This study presents a transformative framework for understanding maternal healthcare as a continuum of interconnected experiences. The research offers actionable insights to enhance maternal health outcomes through stage-specific strategies. The globally adaptable framework provides policymakers and healthcare practitioners with a roadmap to improve maternal healthcare systems in Nigeria and beyond. This holistic approach lays the foundation for reducing maternal mortality while ensuring equitable care for all.

☐ ☆ ✇ International Wound Journal

Advice From Patients to Improve Diabetic Foot Ulcer Management and Amputation Prevention

ABSTRACT

Understanding the patient perspective is crucial for enhancing healthcare delivery and outcomes for chronic conditions like diabetic foot ulcers. This qualitative study examined the perspectives of patients with diabetic foot ulcers to inform clinical strategies for both physicians and current patients to enhance care and prevent lower extremity amputations. Fifteen patients with a history of diabetes and diabetic foot ulcers and/or amputations participated in semi-structured interviews which explored their lived experiences and advice for both physicians and fellow patients to improve diabetic foot ulcer related care. Interview transcriptions were analysed to identify recurring themes. Advice for physicians emphasised increasing patient education, initiating preventive foot care at the time of diabetes diagnosis, providing instructions for managing diabetic ulcers early and demonstrating empathetic bedside manner. Advice for fellow patients focused on adopting healthy lifestyle practices, regular foot self-examinations, consistent blood glucose monitoring, medication adherence and seeking prompt medical attention for new or worsening foot lesions. Participants also stressed the importance of routine check-ups with providers to support prevention and management efforts. This qualitative study highlights the value of incorporating patient perspectives to improve our understanding of diabetic foot ulcer onset, care and outcomes and thereby reduce the risk of lower extremity complications.

☐ ☆ ✇ BMJ Open

Dairy intake in relation to metabolic health status, serum levels of brain-derived neurotrophic factor and adropin: a cross-sectional study on Iranian adults

Por: Moradmand · Z. · Amani Tirani · S. · Shahdadian · F. · Hajhashemy · Z. · Rouhani · P. · Saneei · P. — Febrero 26th 2026 at 13:47
Objective

Findings of previous studies on associations between dairy consumption and metabolic health status were inconsistent. This study aimed to assess the link between consumption of dairy foods and metabolic health status, brain-derived neurotrophic factor (BDNF) and adropin levels in adults.

Design

Cross-sectional.

Setting

An observational study in Isfahan, Iran.

Participants

Adults (n=527) selected by multistage cluster random sampling. Dietary intakes were assessed via a validated 168-item food frequency questionnaire.

Primary outcome and secondary outcome measures

Anthropometric indices, blood pressure and biochemical parameters were assessed. The criteria proposed by Wildman et al were used to categorise participants into metabolically healthy and metabolically unhealthy (MU).

Results

Participants had a mean age of 42.66 years (45.7% women). Moderate consumption of total dairy was, respectively, linked to 58% lower odds of MU (OR T2 vs T1=0.42; 95% CI 0.18 to 0.96), after taking all confounders into account. Participants in the middle versus low tertile of low-fat dairy intake showed 51% marginally lower odds of MU (OR T2 vs T1=0.49; 95% CI 0.22 to 1.08; p=0.08). No significant association was discovered between high-fat dairy intake and MU chance. However, higher total dairy intake was associated with lower odds of hypertension (OR T3 vs T1=0.36; 95% CI: 0.14 to 0.93). No significant associations were observed between dairy intake and BDNF or adropin levels.

Conclusion

Moderate consumption of total and low-fat dairy was associated with lower odds of being metabolically unhealthy in Iranian adults, but high-fat dairy intake was not. Hypertension was less common among individuals with higher dairy intake. No association was found between dairy intake and serum levels of BDNF or adropin.

☐ ☆ ✇ BMJ Open

Interventions to improve functionality among paediatric patients with oncological diagnosis: a systematic review and meta-analysis protocol

Por: Holanda · K. M. · Vivas Costa · J. · Pereira · W. M. G. · Barbosa · A. S. · Martinez-Silveira · M. · Garcia-Hermoso · A. · Guerra · P. H. · Bezerra · I. N. · Barbosa Filho · V. — Febrero 26th 2026 at 13:47
Introduction

Cancer is the leading cause of death and morbidity among children and adolescents worldwide. Functionality-based interventions are relevant among children and adolescents with an oncological diagnosis, whence studies summarising evidence on this topic are needed. This systematic review will summarise evidence on the effect of interventions to improve functionality indicators among paediatric patients diagnosed with cancer.

Methods and analysis

This protocol will follow Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA)-Protocols reporting guidelines. The systematic review will be conducted according to the Cochrane Handbook and PRISMA 2020. Studies will be searched in MEDLINE (PubMed), Embase, Web of Science, CENTRAL, LILACS and PEDro. Additional searches will include Google Scholar, reference lists of included studies, relevant reviews and trial registries. Studies will be included if they implement a functionality-based intervention. They must evaluate effects among paediatric patients with an oncological diagnosis. Secondary outcomes will include health-related quality of life. There will be no limits to language or year of publication, and articles published in peer-reviewed journals will be accepted. Only randomised controlled trials will be included. Risk of bias will be assessed using the Cochrane Risk of Bias Tool 2. Two independent reviewers will select studies, extract data and assess risk of bias. A narrative synthesis and meta-analysis will be conducted if studies are clinically and methodologically homogeneous. Statistical heterogeneity will be assessed using Higgins’ inconsistency test (I²). Meta-analysis may estimate combined effects using random-effects and the inverse variance method. The R statistical software will be used. The certainty of evidence will be evaluated for each outcome using the Grading of Recommendations Assessment, Development and Evaluation system.

Ethics and dissemination

This study used data from previously published studies, thus waiving submission to an Ethics Committee. Scientific dissemination strategies will include publication in peer-reviewed journals, conference presentations and workshops for the public.

PROSPERO registration number

CRD42024462833.

☐ ☆ ✇ BMJ Open

Lack of association between the brain penetrance of calcium channel blockers and the incidence of neuropsychiatric outcomes: a retrospective, multidatabase cohort study

Por: Kern · D. M. · Bohn · J. · Maher · M. P. · Dymshyts · D. · Shoaibi · A. — Febrero 26th 2026 at 13:47
Objective

To use best practices in pharmacoepidemiology to assess the association between new use of brain-penetrant calcium channel blockers (BP-CCBs) compared with use of non-brain-penetrant CCBs (NP-CCBs) and the incidence of neuropsychiatric outcomes.

Design

Retrospective comparative cohort study.

Setting

Secondary data from nine claims and electronic health record databases from across the globe were used.

Participants

First use of a CCB was the index date. There were 1.2 million BP-CCB patients and 9.3 million NP-CCB patients identified across all databases, with 881 758 matched in each group.

Interventions

Patients were categorised as either initiating BP-CCBs or NP-CCBs. On-treatment and intention-to-treat analyses were conducted. Large-scale propensity models were used to match cohorts and control for observed confounding. Cox models were used to analyse the time to incident neuropsychiatric disorders. Negative control outcomes were used to calibrate estimates, CIs and p values to account for residual confounding. Diagnostics were used to assess the validity of the analysis.

Primary and secondary outcome measures

The time to first diagnosis of schizophrenia, schizoaffective disorder, major depressive disorder (MDD) and bipolar disorder was assessed independently. HRs compared the BP-CCB group to the NP-CCB group.

Results

For the outcome of incident MDD in the intention-to-treat design, the meta-analytic HR (95% CI) was 1.02 (0.97, 1.08). Meta-analytic HRs for bipolar disorder (1.04 (0.96, 1.13)), schizophrenia (1.05 (0.94, 1.18)) and schizoaffective disorder (1.04 (0.87, 1.23)) showed similar null effects. The on-treatment analysis was largely consistent: MDD (1.01 (0.96, 1.06)), bipolar (1.05 (0.86, 1.27)), schizophrenia (1.09 (0.87, 1.38)) and schizoaffective (1.00 (0.71, 1.40)).

Conclusions

There was no evidence of an association with any of the neuropsychiatric conditions of interest between use of BP-CCB and NP-CCB. This does not rule out the potential beneficial effect of CCB formulations and doses targeted specifically for the brain rather than the cardiovascular system.

☐ ☆ ✇ BMJ Open

Effectiveness of exoskeleton training on turning-while-walking and balance control in subjects with incomplete spinal cord injury: protocol for a randomised clinical trial

Por: Chen · M. · Chan · C. W.-n. · Wang · P. Y. · Tsang · W. W.-n. — Febrero 26th 2026 at 13:47
Introduction

Individuals with incomplete spinal cord injury (iSCI) often experience impaired balance control and turning-while-walking ability, which increase the risk of falls and limit their community mobility. While overground exoskeleton training has shown promise in improving gait and balance, evidence from randomised controlled trials (RCTs) on ambulation of individuals with iSCI remains limited. This protocol outlines a cluster RCT investigating the effectiveness of overground exoskeleton-assisted gait training compared with conventional training and usual care in improving turning-while-walking performence, balance control, and functional mobility in individuals with iSCI.

Methods and analysis

This multicentre, cluster RCT will compare 12-week interventions across three groups: (1) overground exoskeleton training group, (2) conventional training group and (3) usual care group. Participants with ambulatory iSCI will be recruited from three centres in Hong Kong SAR and mainland China. Primary outcomes include turning duration and number of steps during a 2-m turning-while-walking test. Secondary outcomes include static and dynamic balance, sensorimotor integration, gait performance, muscle strength, spasticity, quality of life, self-efficacy and fall incidence. Assessments will be conducted at baseline, mid-intervention, postintervention and at the 1-month follow-up.

Ethics and dissemination

This study has received approval from the Research Ethics Committees of Hong Kong Metropolitan University, the Affiliated BenQ Hospital of Nanjing Medical University, and Changzhou Sunshine Rehabilitation Hospital. Written informed consent will be obtained from all participants before enrolment. Study findings will be shared through peer-reviewed publications, conference presentations and summaries available to participants upon request.

Trial registration number

NCT06971510.

☐ ☆ ✇ BMJ Open

Protocol of the RADIO-STAR trial: a phase 1 safety and dose finding study of hypofractionated radiotherapy to the stellate ganglia for the treatment of ventricular arrhythmia

Por: Bussmann · B. M. · George · B. · Robinson · M. · Grist · J. · Sukumar · P. · Chinherende · E. · Sheerin · F. · Enzhil · V. · Rider · O. · Jones · B. · Sabharwal · A. · Herring · N. — Febrero 26th 2026 at 04:41
Introduction

Sympathetic activation is the hallmark of cardiac disease, driving disease progression and triggering ventricular arrhythmia (VA). Despite optimal medical therapy, many patients experience recurrent VAs refractory to medical therapy, leading to repetitive implantable cardioverter defibrillator (ICD) therapy, worse quality of life and adverse outcomes. Cardiac sympathetic denervation (CSD) through surgical removal of the stellate ganglia is an effective treatment for refractory VAs but carries a high complication rate. We hypothesise that high precision image guided radiotherapy can be used to target the stellate ganglia to achieve CSD non-invasively.

Methods and analysis

RADIO-STAR (hypofractionated radiotherapy to the stellate ganglia for ventricular arrhythmia) is a first-in-human, phase 1 safety and dose finding study of radiotherapy to the stellate ganglia in patients with recurrent VAs. Patients with structural heart disease requiring recurrent ICD therapy for VAs are invited to undergo radiotherapy bilaterally to their stellate ganglia with a predetermined sample size of n=13. Radiotherapy dose will be determined by a prespecified dose escalation protocol. The primary outcome is safety defined as any treatment-related grade 3–5 toxicity occurring within 6 months of radiotherapy treatment, as defined by the Common Terminology Criteria for Adverse Events or any treatment-related side effects detected on patient symptom questionnaires and clinical examination during study visits. Secondary outcome measures to evaluate feasibility and efficacy include ability to safely deliver radiotherapy and consequent changes in circulating catecholamines and neuropeptide-Y, heart rate variability, structural changes in the stellate ganglia on MRI imaging and ICD therapy burden.

Ethics and dissemination

This study has received ethical approval by the South Central—Oxford B Research Ethics Committee (REC/SC/0005). Study findings will be submitted for publication in peer-reviewed scientific journals and presented at national and/or international scientific conferences.

Trial registration number

ISRCTN49861434.

☐ ☆ ✇ BMJ Open

Mechanisms of SGLT inhibitor action and physiological mediators: systematic review and protocol for the MOSAIC collaborative meta-analysis

Por: Kugathasan · L. · Nardone · M. · Muskiet · M. · Diaz Martinez · J. P. · Lovblom · L. E. · Orchanian-Cheff · A. · Nielsen · S. · Rotbain · V. · Kazup · A. · Cersosimo · E. · Gullaksen · S. · Vernstrom · L. · van Baar · M. J. B. · van Bommel · E. · Kannenkeril · D. · Scholtes · R. · Hesp — Febrero 26th 2026 at 04:41
Introduction

Sodium-glucose cotransporter (SGLT) inhibitors have shown substantial benefit in reducing cardiovascular and kidney events across diverse clinical populations, but the underlying physiological mechanisms remain unclear. However, existing mechanistic studies on renal and cardiovascular haemodynamics show variability in design, have limited statistical power and yield inconsistent outcomes, thus limiting the ability to draw generalisable conclusions. To address this gap, we conducted a systematic review and proposed the first meta-analysis to aggregate individual participant-level data from mechanistic studies to identify consistent physiological patterns and enhance understanding of the therapeutic effects of SGLT inhibition.

Methods and analysis

Gold-standard measured glomerular filtration rate (mGFR) was selected as the primary outcome for this systematic review, which aimed to identify all completed mechanistic studies investigating the effects of SGLT inhibition. Electronic databases including Ovid MEDLINE; Ovid Embase; Cochrane Database of Systematic Reviews; and Cochrane Central Register of Controlled Trials were searched using a detailed search strategy. In total, 24 studies (n=1296) were identified. This systematic review was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Key variables including demographics, medical history, concomitant medications, vital signs, mGFR, renal haemodynamics, urine and plasma biochemistry, tubular sodium handling, echocardiography, cardiac output monitoring, arterial stiffness and fluid volume will be extracted. A one-stage individual participant data meta-analysis under a Bayesian framework will be conducted, using hierarchical models to simultaneously analyse data from all eligible studies. The risk of bias due to missing results will be assessed. Sensitivity analyses and subgroup evaluations will be incorporated to explore sources of heterogeneity and assess robustness of findings.

Ethics and dissemination

Ethics approval was obtained from University Health Network, Toronto, Canada. Findings from the Mechanisms of SGLT Inhibitor Action and Physiological Mediators (MOSAIC) meta-analysis will be published in peer-reviewed journals and results will be disseminated at scientific conferences.

PROSPERO registration number

CRD420251001413.

☐ ☆ ✇ BMJ Open

Cause-specific excess mortality in rural India during the COVID-19 pandemic 2020-2023: longitudinal analyses of deaths in 0.2 million rural health facilities

Por: Kumar · P. · Suraweera · W. · Karlinsky · A. · Jha · P. — Febrero 26th 2026 at 04:41
Objective

India had an estimated three to five million excess deaths from causes attributable to SARS-CoV-2 during 2020–2021, far exceeding official government statistics. Most deaths in India occur in rural areas, where medical certification of deaths is limited. Yet, the effects of the pandemic in rural settings remain largely undocumented. We estimated the cause-specific excess mortality in rural areas of selected states of India.

Design

Longitudinal analyses of hospital mortality data.

Settings

India’s Health Management Information System (HMIS) reports the number of deaths by cause for adolescents or adults aged 10 years or more. We examined eight states with high coverage of the expected number of deaths in rural areas.

Participants

We analysed monthly death reports from the HMIS, which covered approximately 0.2 million health facilities during 2018–2023. We compared excess deaths during the peak COVID-19 months in rural health facilities to pre-COVID-19 and non-peak periods of 2021, and categorised reported causes by their probable association with COVID-19.

Primary outcome measure

Excesses of cause-specific and total mortality.

Results

During the April–June 2021 SARS-CoV-2 wave, predominantly driven by the Delta variant, monthly deaths in rural health facilities across India surged from approximately 200 000 to 500 000. In eight states with high-quality reporting, rural facility deaths increased by 270% (95% CI 267% to 272%) compared with the same months in 2018–2019, prior to the COVID-19 pandemic. Notably, this surge occurred despite a sharp decline in hospital admissions following the national lockdown in March 2020. The largest relative increase was for fever-related and respiratory diseases, and these deaths were markedly elevated even when compared to non-peak months of 2021. Generalising these findings from eight states to all of rural India yields an estimate of approximately 2.6 million excess rural deaths in April–June 2021. In contrast, there were few excess deaths during the Omicron viral waves in 2022–2023.

Conclusion

COVID-19 substantially increased deaths in rural India during April–June 2021, but reassuringly, no significant excess mortality was observed in subsequent years. The HMIS provides an important opportunity to strengthen routine mortality surveillance in rural India.

☐ ☆ ✇ BMJ Open

Predictors of unplanned 30-day hospital readmission: a retrospective cohort study in north-east Italy

Por: Sartor · G. · Fusco · M. · Milana · M. · Marcon · E. · Battagello · J. · Zardetto · A. · Ruggieri · M. G. · Grotto · G. · Rigon · L. · Arcara · G. · Conte · P. · Buja · A. — Febrero 26th 2026 at 04:41
Objective

Unplanned hospital readmissions within 30 days of discharge measure the quality of healthcare. This study aims to identify the characteristics of patients at higher risk of readmission.

Design

Retrospective cohort study.

Setting

North-east Italy (Marca Trevigiana Local Health Authority).

Data source

The study examined a total of 39 467 index admissions from hospital discharges (SDO) in the 890 000-inhabitant area during 2022.

Outcome measure

Readmission rates and 95% CIs were computed by risk factor, age and type of admission (surgical or medical). A logistic mixed-effects model was used to estimate readmission OR, adjusting for potential confounders.

Results

A total of 2197 readmissions occurred within 30 days of the index admission, resulting in an overall rate of 30-day readmissions of 6.7% (CI 6.4% to 7.0%). The median time to readmission was 11 days (IQR 5 to 20). In the multivariate analysis, after adjusting for age and sex, the following clinical conditions were associated with a higher risk of readmission: alcohol-related disease (OR=2.06, CI 1.36 to 3.13), metastatic cancer (OR=1.98, CI 1.57 to 2.50), epilepsy (OR=1.93, CI 1.36 to 2.75), dialysis or end-stage kidney disease (OR=1.92, CI 1.39 to 2.66), chronic obstructive pulmonary disease (OR=1.88, CI 1.49 to 2.36), stoma (OR=1.72, CI 1.22 to 2.44), transplant (OR=1.62, CI 1.03 to 2.55), being bedridden (OR=1.57, CI 1.28 to 1.93), anaemia (OR=1.57, CI 1.35 to 1.83), urinary tract infection (OR=1.54, CI 1.30 to 1.83), pneumonia (OR=1.52, CI 1.31 to 1.75), dementia (OR=1.49, CI 1.24 to 1.79), diabetes (OR=1.37, CI 1.17 to 1.61) and transfusion (OR=1.34, CI 1.03 to 1.73).

Conclusion

Several chronic and acute conditions at index admission significantly increased the risk of readmission. Strengthening transitional care, outpatient services and palliative care could mitigate readmissions.

☐ ☆ ✇ BMJ Open

Markov-model cost-effectiveness evaluation of a cessation programme when tobacco policies are comprehensive

Por: Mussio · I. · Triunfo · P. · Gerstenblüth · M. — Febrero 24th 2026 at 16:52
Objectives

This study conducts a cost-effectiveness analysis of the Tobacco Treatment Programme (TTP) of Uruguay’s National Resource Fund (NRF), within the context of the country’s advanced implementation of tobacco control policies.

Design

We run a 10 000 Markov model simulation with three states (people who smoke, people who have quit smoking and death) to simulate the trajectories of a cohort. The model has been widely used in previous studies evaluating smoking cessation interventions.

Participants

For the simulations, we use information from the 2016 to 2017 NRF TTP cohort. Nearly half of the participants lived in the capital, one-fifth had tertiary education, and about one-third had public health coverage. Participants began smoking at an average age of 16 years and smoked about 20 cigarettes per day when entering the TTP.

Interventions

The process of tobacco cessation is simulated under different alternatives: no intervention, the current TTP (bupropion, nicotine gum and counselling), an expanded TTP that incorporates nicotine patches as a replacement therapy, and a potential future programme with cytisine and counselling (with and without mortality adjustments).

Setting

We focus on Uruguay, which has been recognised as a global leader in tobacco control, including 100% smoke-free environments, a full advertising ban, plain packaging and steady tax increases.

Measurements

We compare cost-effectiveness of policy alternatives using years of life lost (YLL) and incremental cost-effectiveness ratios, comparing policy alternatives with no intervention and the current tobacco cessation programme in the country. The analysis considers the direct costs of treatments for smoking-related diseases (healthcare perspective) as well as social costs resulting from loss of productivity (societal perspective).

Results

The results indicate that all policy interventions lead to a reduction in the YLL compared with no intervention. Among these options, the inclusion of cytisine emerges as the most cost-effective choice. In a scenario including the transition probabilities from the TTP cohort, this alternative would result in a 10.9% reduction in YLL, with a particularly positive impact among women (–16.5% vs –4.0% in men). In terms of cost-effectiveness, the costs per YLL averted would be on average US$3991 per YLL from a healthcare perspective, and US$3773 per YLL from a societal perspective.

Conclusions

Tobacco cessation programmes in Uruguay are highly cost-effective, and our results justify their expansion and optimisation. The incorporation of cytisine into the TTP and a focus on groups with more severe tobacco consumption are recommended.

☐ ☆ ✇ BMJ Open

Non-infectious skeletal complications in the lower extremity after treatment with a transfemoral bone-anchored prosthesis: a retrospective observational study

Por: Svensson Malchau · K. · Malchau · H. · Thomsen · P. · Hagberg · K. — Febrero 24th 2026 at 16:52
Background

The use of bone-anchored prostheses (BAPs) has greatly increased quality of life for lower limb amputees. However, the long-term frequency of skeletal fractures and the need for arthroplasty surgery in the lower extremities following BAP use is scarce.

Objectives

The current study aimed to investigate the frequency of fractures and arthroplasties in the lower limb after BAP surgery with the Osseointegrated Prosthesis for the Rehabilitation of Amputees (OPRA) system.

Design

Retrospective cohort study using the OPRA database and medical record review for data collection.

Setting

A single-centre study at a tertiary hospital.

Participants

All patients with a transfemoral BAP (OPRA system) who underwent surgery between 1999 and 2019, and had completed at least 2 years of follow-up were included in the study. Patients with bilateral transfemoral amputations were excluded. A total of 100 patients were included.

Primary outcome measure

The primary outcome measure was to identify patients who had a fracture or had undergone arthroplasty surgery in the lower extremities after BAP surgery.

Results

Of the 100 patients included, 16 patients (16%) had an event in their lower limb. 11 patients (11%) had a fracture, all of the femur, and six patients (6%) underwent arthroplasty surgery due to osteoarthritis. Long-term prosthetic use was not affected by the occurrence of an event.

Conclusions

Patients with BAP may be at a higher risk for femur fractures and arthroplasty surgery than the general population. Although encouraging that prosthetic usage is not affected after a fracture or arthroplasty surgery, prospective studies on larger cohorts and control groups need to be conducted.

☐ ☆ ✇ BMJ Open

Generative artificial intelligence in dementia care: a scoping review protocol on nursing roles, experiences and ethical perspectives

Por: Chen · Y.-C. · Nieh · H.-C. · Chen · H.-C. · Chen · J.-C. · Chang · M.-Y. · Wu · P.-O. — Febrero 24th 2026 at 16:52
Introduction

Generative artificial intelligence (GAI), including large language models and multimodal generative systems, is rapidly emerging in healthcare with growing interest in its potential applications for dementia care. These technologies offer new possibilities for communication support, cognitive engagement and personalised interaction, yet they also introduce complex ethical, relational and practical challenges. Nurses—who hold central, sustained roles across dementia care settings—are key mediators of technology adoption and are positioned to assess the appropriateness, safety and ethical implications of GAI use. However, existing literature remains fragmented and largely focused on technological development or patient-facing outcomes, with limited synthesis of nurses’ roles, experiences and ethical perspectives. This scoping review aims to map the current evidence regarding how nurses engage with GAI in dementia care and to identify gaps that may inform practice, policy and future research.

Methods and analysis

This review will follow the methodological framework of Arksey and O’Malley, refined by Levac et al and guided by the Joanna Briggs Institute Manual for Evidence Synthesis. Reporting will adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist. The review will be conducted between March 2026 and October 2026, encompassing database searching, screening, data charting, synthesis and reporting. A comprehensive search will be conducted across MEDLINE (Ovid), CINAHL, PsycINFO, Scopus and Web of Science using controlled vocabulary and keywords related to nursing, generative artificial intelligence and dementia. Eligible sources will include empirical studies, reviews, conceptual papers and policy analyses that report nursing roles, experiences or ethical considerations related to GAI in dementia care. Two reviewers will independently screen titles/abstracts and full texts and extract data using a structured charting form. Findings will be synthesised through descriptive statistics and inductive thematic analysis, supported by conceptual mapping to illustrate relationships among GAI types, nursing roles, ethical concerns and care settings. Critical appraisal will not be undertaken, as it is optional in scoping reviews and is not aligned with the primary mapping objectives of this review.

Ethics and dissemination

Ethical approval is not required as the review synthesises publicly available literature. Should the optional interest-holders consultation be undertaken, ethical clearance will be obtained from an appropriate institutional review board prior to participant engagement. Findings will be disseminated through peer-reviewed publication, conference presentations and knowledge-translation outputs targeted at clinicians, educators, policymakers and AI developers. The review will support informed, ethically grounded integration of GAI in dementia care.

☐ ☆ ✇ BMJ Open

Identifying innovative models of urgent care in rural coastal areas in England: the Elevate study - a mixed-methods protocol

Por: Lampard · P. · Adamson · J. · Anderson · H. · Ballantine · L. · Bell · F. · Benger · J. R. · Blakey · R. L. · Dickinson · P. · Dykes · S. · Gaughan · J. · Maitland-Knibb · S. · Mensah · D. · Ransome · Z. A. · Richardson · G. · Santos · R. · Sheridan · R. · Sivey · P. · Smith · E. · Song · W — Febrero 24th 2026 at 16:52
Introduction

Urgent and emergency care (UEC) systems in England face unprecedented pressures, with record accident and emergency attendances, persistent breaches of ambulance response targets and poorer outcomes for time-sensitive conditions. National UEC recovery plans have introduced multiple innovations—such as same-day emergency care, virtual wards and specialty hubs—to manage these pressures and improve patient flow. Rural coastal areas are particularly vulnerable to excessive demand due to higher levels of deprivation, older populations with complex health needs, seasonal surges that generate unpredictable demand and challenges in attracting and retaining staff. Following the Chief Medical Officer’s 2021 Annual Report, funding research and developing bespoke solutions to manage UEC demand and address geographical disparities has been recognised as a national priority. The Elevate study responds to this priority by identifying and evaluating innovative models of UEC in rural coastal communities in England.

Methods and analysis

The Elevate study is a 30-month, mixed-methods evaluation that comprises three interlinked work packages: (1) National service mapping—outlining provision of innovative models of UEC in rural coastal areas of England. This will be developed through document review and interviews with regional and national service leaders. (2) Quantitative analysis—quasiexperimental and longitudinal approaches will use National Health Service (NHS) England’s Emergency Care Data Set and linked routine NHS datasets to evaluate the impact of UEC models on health and process outcomes. Standard and bespoke metrics will be developed and used to assess performance. (3) Qualitative case studies—up to 12 case studies of UEC models in rural coastal communities. Interviews with patients and staff and non-participant observation will explore how and why different UEC models influence patient experience, clinical outcomes, resource use and the workforce. Findings will be integrated using the Consolidated Framework for Implementation Research to identify components of UEC models that are effective, scalable and sensitive to local context,

Ethics and dissemination

Ethical approval for qualitative components was granted by the North of Scotland Research Ethics Committee (25/NS/0099). Dissemination will include peer-reviewed publications, policy briefs, creative media and community engagement activities to ensure findings are communicated inclusively and effectively to policymakers, health and social care practitioners and the public.

Trial registration number

Research Registry (researchregistry11126).

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