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Ayer — Marzo 4th 2026BMJ Open

Comparative effectiveness and safety of digital health delivery models for pulmonary rehabilitation in patients with chronic obstructive pulmonary disease: a protocol for systematic review and network meta-analysis of randomised controlled trials

Por: Xu · L. · Chen · X. · Yang · C. · Feng · M. · Wu · Y.
Introduction

Chronic obstructive pulmonary disease (COPD) affects approximately 480 million individuals globally and is projected to reach 600 million by 2050, representing a substantial burden on healthcare systems and patient quality of life. Pulmonary rehabilitation is a cornerstone intervention for COPD management, delivering clinically meaningful improvements in exercise capacity, health-related quality of life and dyspnoea. Despite strong guideline recommendations and established efficacy, only 2%–4% of eligible patients with COPD access traditional centre-based pulmonary rehabilitation due to geographical barriers, transportation difficulties, scheduling conflicts and limited healthcare resources. Digital health technologies offer promising alternatives to overcome these access barriers while potentially maintaining therapeutic benefits. Various digital delivery models have emerged, including video-based telerehabilitation, virtual reality platforms, mobile health applications and web-based programmes. However, their comparative effectiveness remains unclear, limiting evidence-based clinical decision making. This systematic review and network meta-analysis will aim to compare and rank the effectiveness and safety of different digital health delivery models for pulmonary rehabilitation in patients with COPD, providing evidence to inform optimal intervention selection in clinical practice.

Methods and analysis

We will conduct a systematic review and Bayesian network meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Network Meta-Analyses guidelines. Comprehensive searches will be performed across five electronic databases (PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, CINAHL) from inception to January 2026, without language restrictions. Eligible studies will include randomised controlled trials comparing digital health delivery models for pulmonary rehabilitation in adults with COPD. Digital health interventions will be categorised into four distinct delivery models: video-based telerehabilitation, virtual reality rehabilitation, mobile health rehabilitation and web-based platform rehabilitation. Interventions combining multiple modalities will be categorised according to the predominant component based on intervention frequency, duration and primary therapeutic mechanism. Two independent reviewers will perform study selection, data extraction and risk of bias assessment using the Cochrane Risk of Bias 2 tool. The primary outcome will be change in 6 min walk distance. Key secondary outcomes will include disease-specific quality of life measures, dyspnoea severity, hospitalisation rates, exacerbation frequency, intervention adherence and adverse events. A Bayesian random-effects network meta-analysis will be conducted, calculating mean differences or ORs with 95% credible intervals. Treatment rankings will be estimated using surface under the cumulative ranking curve probabilities. Evidence certainty will be assessed using the Confidence in Network Meta-Analysis framework. Planned subgroup analyses will explore potential effect modifiers including disease severity, intervention duration, supervision mode and technological features.

Ethics and dissemination

As this systematic review will use data from previously published studies, formal ethical approval is not required. Findings will be disseminated through peer-reviewed publication, presentations at relevant scientific conferences and communication to healthcare providers, policymakers and patient advocacy organisations.

PROSPERO registration number

CRD420251268701.

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
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.

Prevalence of potentially inappropriate medication prescribing, inappropriate medication use, prescription omission and drug interactions among older adults in Ethiopia: a systematic review and meta-analysis

Por: Yazie · T. S. · Alemu · M. A. · Zewdu · W. S. · Asmare Emiru · Z. · Tarekegn · G. Y. · Meharie · B. G. · Belete · A. M. · Debasu Addisu · Z.
Objective

To determine the prevalence of potentially inappropriate prescribing (PIP), potentially inappropriate medication (PIM), potential prescription omission (PPO), potentially harmful drug–drug interactions (PDDI) and identify associated factors among older Ethiopians.

Design

Systematic review and meta-analysis

Data source

We searched PubMed, HINARI, Scopus and Web of Science databases to identify eligible studies published up to 31 October 2025.

Study selection

Observational studies reported the prevalence of PIP, PIM, PPO and PDDI among older adults from any healthcare settings were screened.

Data extraction and synthesis

Two independent reviewers selected studies, extracted data and assessed the risk of bias. The quality and risk of bias of the studies were assessed using the Newcastle-Ottawa scale and Hoy risk of bias tool, respectively, while the certainty of evidence of outcomes was assessed using Grading of Recommendations, Assessment, Development and Evaluation based on Cochrane recommendations. We used a random-effects model for analyses to estimate the pooled prevalence and associated factors. All data analyses were done using Stata V.17 software.

Main outcomes and measures

The national prevalence of PIP, PIM, PPO and PDDI was estimated as main outcomes. Variations were estimated based on regions, age groups, outcome evaluation tool, disease type and healthcare setting.

Results

The review included 25 studies (n=5662 participants) for PIP or PIM, 14 studies (n=2706 participants) for PDDI and 6 studies (n=1342 participants) for PPO. The pooled prevalence estimate was 41% (95% CI 33% to 48%), I2=96.87% for PIP, 37% (95% CI 31% to 44%), I2=96.33% for PIM, 55% (95% CI 36% to 73%), I2=99.00% for PDDI and 14% (95% CI 6% to 24%), I2=95.07% for PPO. The majority of the studies have very good quality (very good=13, good=1, satisfactory=11 for PIP and PIM; very good=11, satisfactory=3 for PDDI; very good=6 for PPO) and low risk of bias (low risk=18, moderate risk=7 for PIP and PIM; low risk=12, moderate risk=2 for PDDI and low risk=6 for PPO), while all studies for each outcome have low certainty of evidence. Subgroup analyses revealed significant regional and contextual variations. Polypharmacy was significantly associated with PIP (OR=3.72, 95% CI 2.53 to 5.46, p2=69.56%), PIM (OR=4.20, 95% CI 2.91 to 6.06, p2=57.83%) and PDDI (OR=4.51, 95% CI 3.05 to 6.69, p2=0.00%), while hypertension (OR=2.46, 95% CI 1.38 to 4.36, p2=0.00%) was associated with PIP.

Conclusions and relevance

This review found a high prevalence of PIP, PIM, PDDI and PPO among older adults in Ethiopia, with notable heterogeneity across regions. Polypharmacy was associated with PIP, PIM and PDDI, while hypertension showed association with PIP. Despite generally good study quality, the certainty of evidence was low for the included studies due to the cross-sectional design nature, with high heterogeneity. Therefore, these findings should be interpreted cautiously. This study indicates a high burden of inappropriate medication prescribing and its associated factors, underscoring the importance of further robust studies to clarify prescribing practices and associated factors.

PROSPERO registration number

CRD42024556744.

Transcutaneous auricular vagus nerve stimulation for postoperative pain: a protocol for a systematic review and meta-analysis

Por: Lu · Y. · Lv · H. · Bian · Z. · Shen · Y. · Li · R. · Xia · Y. · Fang · J.-Q. · Wan · Y.
Introduction

Postoperative pain is common after surgery, with a high incidence and risk of becoming chronic. Current multimodal analgesia has drawbacks, including limited efficacy from single agents and opioid side effects and addiction risk. These issues have led to opioid-sparing multimodal analgesia. Transcutaneous auricular vagus nerve stimulation (taVNS) is non-invasive and convenient. Studies have shown it can reduce postoperative pain, improve mood and lower adverse events. However, taVNS lacks a comprehensive evaluation and standardised protocols, so further research is needed to provide reliable evidence.

Methods and analysis

This study strictly adheres to the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. To identify suitable randomised controlled trials (RCTs), eight credible databases will be searched, including four English databases (Web of Science, PubMed, Cochrane Central Register of Controlled Trials, EMBASE) and four Chinese databases (China National Knowledge Infrastructure, VIP Database for Chinese Technical Periodicals, Wanfang Database, Chinese Biomedical Literature Database). RevMan V.5.3 will be employed to integrate the retrieved data and conduct meta-analyses. The methodological quality of included RCTs will be evaluated using the Cochrane Risk of Bias Assessment 2.0 tool. Additionally, the Grading of Recommendations, Assessment, Development and Evaluation system will be applied to assess the strength and certainty of the evidence. We will also conduct publication bias analyses, sensitivity analyses and subgroup analyses.

Ethics and dissemination

No ethical review is required as no private or confidential patient data will be included. Results of this study will be disseminated through a peer-reviewed journal.

PROSPERO registration number

CRD420251207651.

Determinants of barriers to accessing healthcare services among married women in Somalia: a multilevel analysis of nationwide survey data

Por: Ali · A. S. · Hassan · Y. S. A. · Ahmed · M. M. · Omar · M. A.
Objectives

To identify the individual and community-level factors associated with barriers to accessing healthcare services among currently married women in Somalia.

Design

A cross-sectional analysis using data from the 2020 Somalia Demographic and Health Survey.

Setting

Somalia.

Participants

A nationally representative sample of 30 311 currently married women aged 15–49 years with complete data on outcome and explanatory variables.

Primary outcome measures

The primary outcome was ‘reporting at least one barrier to accessing healthcare’, a composite binary variable based on four specific problems: obtaining permission to go for treatment, getting money for treatment, distance to the health facility and not wanting to go alone.

Results

A substantial majority (77.06%) of married women reported experiencing at least one barrier to accessing healthcare. Financial cost was the most common barrier (69.91%), followed by distance to health facilities (65.95%), reluctance to go alone (49.64%) and the requirement for permission (46.03%). Multilevel analysis confirmed that higher household wealth was strongly protective (richest vs poorest: adjusted OR (aOR)=0.27, 95% CI 0.24 to 0.32). Paradoxically, factors typically considered protective were associated with increased barriers: women with secondary education (aOR=1.19, 95% CI 1.00 to 1.41) and those with educated husbands (aOR=1.23, 95% CI 1.14 to 1.33) reported more obstacles. Similarly, urban residents faced higher odds of barriers than their nomadic counterparts (aOR=1.40, 95% CI 1.27 to 1.55). Significant regional disparities were evident, with community-level context explaining 26.30% of the total variance in reporting barriers.

Conclusion

Access to healthcare for married women in Somalia is predominantly hindered by economic, educational and community-level constraints. Targeted interventions addressing socioeconomic disparities, infrastructural deficits and specific community contexts are essential to alleviate these barriers.

Harm reduction and pharmacy practice: a scoping review of services for people who use drugs provided by pharmacy staff

Por: Navarrete · J. · Berg · E. · Hughes · C. · Salokangas · E. · Taylor · M. · Kung · J. Y. · Johnson · J. A. · Hyshka · E.
Objectives

The roles of pharmacy staff have expanded to include public health functions, such as delivering harm reduction services for people who use drugs (PWUD), particularly unregulated substances and non-medical drug use, in response to an ongoing drug overdose crisis. Nonetheless, their involvement across the full spectrum of harm reduction services remains underexplored. This study mapped existing research describing or evaluating the implementation of harm reduction services for PWUD provided by pharmacy staff.

Design

Scoping review.

Data sources

MEDLINE, EMBASE, CINAHL, Web of Science, Scopus and Cochrane Library (inception to July 2025).

Study selection

Studies reporting on the description or evaluation of harm reduction services for PWUD provided by pharmacy staff.

Data extraction

Two team members screened studies for eligibility and extracted the data. The data were analysed primarily to describe harm reduction services and the role of pharmacy staff.

Results

43 articles were included. The most frequently reported harm reduction services were sexually transmitted and blood-borne infection care (33%), needle and syringe programmes (21%), naloxone distribution (19%) and medication treatment for opioid use disorder (19%). Pharmacy staff were integrated into multidisciplinary teams (79%), with their roles varying from education to medication prescribing. Included studies reported harm reduction services for PWUD delivered by pharmacy staff as effective, feasible and safe. However, implementations were not tailored to equity-deserving populations. Services primarily addressed opioid-related harms, while strategies focusing on the use of non-opioid substances were limited.

Conclusion

This scoping review highlights the diverse roles pharmacy staff play in delivering harm reduction services for PWUD. Positioned at the intersection of accessibility and healthcare delivery, pharmacy staff are ideally situated to expand access to equitable care. To fully harness this potential, future research and practice should embed harm reduction as a core philosophy, extending beyond individual interventions to support the creation of person-centred, non-judgmental and low-barrier services.

AnteayerBMJ Open

Relationship between the urinary albumin-to-creatinine ratio and cardiovascular adverse outcomes in the Beijing community population: a prospective cohort study

Por: Liu · S. · Jia · J. · Huo · Y. · Fan · F. · Zhang · Y.
Objectives

To investigate the correlation between the urinary albumin-to-creatinine ratio (UACR) and adverse cardiovascular outcomes in the Beijing community population.

Design

Prospective cohort study.

Setting

Beijing, China, from May 2014 to December 2021.

Participants

Recruited from a survey conducted as part of an ongoing atherosclerosis cohort study in the communities of Gucheng and Pingguoyuan, Shijingshan District in Beijing, China. Excluded participants who already had a history of stroke or myocardial infarction at baseline. Finally, 3627 eligible participants were included in this analysis.

Exposure

The participants were divided into three groups on the basis of baseline UACR: the normal group (UACR

Primary and secondary outcome measures

The primary endpoint was a composite endpoint (major adverse cardiovascular event, MACE) of cardiovascular death, first acute myocardial infarction or first stroke, whereas secondary endpoints included cardiovascular death, first acute myocardial infarction, first stroke or all-cause death.

Results

The study included 3627 participants. According to the multivariable Cox model, compared with those in the normal group, the risks of MACE (HR=1.47; 95% CI 1.06 to 2.06; p=0.023), cardiovascular death (HR=3.03; 95% CI 1.56 to 5.88; p=0.001) and all-cause mortality (HR=1.91; 95% CI 1.23 to 2.97; p=0.004) were significantly greater in the microalbuminuria group. The risk of MACE (HR=3.65; 95% CI 2.14 to 6.23; p

Conclusions

This study indicates that an elevated UACR is a significant risk factor for adverse cardiovascular outcomes within the community population. This association remains consistent in individuals with low-grade albuminuria.

Disparities in adverse event perception between patients and healthcare providers in gynaecologic anticancer therapy: results from an observational web-based study in Japan

Por: Hashimoto · H. · Soejima · A. · Nishimura · Y. · Ike · A. · Sugawara · M. · Shimada · M. · Abe · M.
Objective

To explore patients’ perceptions of managing adverse events (AEs) from anticancer drugs for gynaecological cancer, focusing on AEs they want to avoid, views on dose adjustments and communication with healthcare professionals.

Design

Observational study using a web-based questionnaire.

Participants

Women in Japan who had received chemotherapy for endometrial or ovarian/fallopian tube cancer were enrolled. Healthcare professionals, including obstetrics and gynaecology physicians, nurses and pharmacists, who administered chemotherapy to these patients, were also enrolled.

Outcome measures

AEs that patients wished to avoid or found distressing; varied perceptions of AEs before and after treatment; discrepancies in the communication of AEs between patients and healthcare professionals; administration time and intervals between hospital visits patients found distressing; patient awareness of dose adjustment (reduction, interruption or discontinuation) to suppress AEs.

Results

Participants comprised 153 physicians, 166 nurses, 154 pharmacists and 154 patients. Nausea/vomiting (28.6%), alopecia (18.2%) and peripheral neuropathy (9.1%) were the most distressing AEs overall. Physicians rated nausea/vomiting lower (15.4%) and alopecia higher (38.2%) than patients, while pharmacists emphasised peripheral neuropathy (25.7%). Many patients found AEs, including peripheral neuropathy (53/99), fatigue (52/105) and alopecia (46/120), to be more severe than expected. Communication patterns revealed that 49.4% of patients reported all symptoms, even uncertain ones, but younger patients tended to communicate fewer symptoms. Physicians (54.2%), nurses (92.2%) and pharmacists (85.7%) preferred full disclosure of symptoms. While 28.6% of patients wished to avoid dose reductions because of fears of disease progression, 18.2% preferred dose reduction or discontinuation when AEs became intolerable. Drug administration times and visit intervals influenced patient distress. Treatment administration of over 3 hours (19.5%) and visits occurring more frequently than once every 3 weeks (27.3%) were the most distressing.

Conclusions

This study highlights discrepancies in AE perceptions and communication between patients and healthcare professionals, emphasising the need for tailored communication strategies and shared decision-making to improve cancer treatment experiences and outcomes.

Trial registration number

jRCT1040220088, Japan Registry of Clinical Trials (jRCT).

Efficacy of sequential denosumab after teriparatide for 6 months compared with denosumab monotherapy in reducing risk of osteoporotic fractures in patients with new fractures: a multicentre randomised controlled trial (STAND study) protocol

Por: Chi · Y. · Zhu · Y. · Yuan · J. · Pang · Q. · Cui · L. · Jiang · Y. · Jiajue · R. · Liu · W. · Wang · O. · Li · M. · Xing · X. · Li · H. · Xie · G. · Wu · Y. · Xia · W.
Introduction

Osteoporosis (OP) is a systemic skeletal disorder that increases fragility and susceptibility to fractures. Despite the availability of teriparatide for the treatment of patients with acute fractures with better efficacy, its long-term daily injection and high cost limit its broader use among a wider patient population, especially for those living in low- and middle-income countries. This study aims to evaluate the efficacy of a novel sequential treatment with teriparatide daily for 6 months followed by denosumab every 6 months for another 18 months, in comparison with denosumab monotherapy every 6 months for 24 months, in reducing the risk of fractures in patients with newly diagnosed osteoporotic fractures. The study will also explore the possible difference between two sequential treatments (shifting to denosumab treatment at 6 or 12 months) in their effect on increasing bone mineral density (BMD).

Methods and analysis

This study is designed as a multicentre, open-label, randomised controlled trial among 2478 patients with newly diagnosed osteoporotic fractures from 58 hospitals across China. Participants will be randomly assigned in a 10:10:1 ratio to three treatment groups: 24 months of denosumab monotherapy, early sequential treatment (teriparatide for 6 months followed by denosumab for 18 months) and late sequential treatment (teriparatide for 12 months followed by denosumab for 12 months). The primary outcome is the incidence of vertebral fractures over 24 months of treatment. Secondary outcomes include changes in BMD at the lumbar spine, total hip and femoral neck, changes in bone turnover markers (β-carboxy-terminal telopeptide of type 1 collagen and procollagen type 1 N-terminal propeptide), treatment adherence and cost-effectiveness. Follow-up assessments are scheduled at 3, 6, 9, 12, 18 and 24 months post-randomisation for primary and secondary outcomes, and biannually afterwards for the primary outcome.

Ethics and dissemination

The study protocol has been registered on ClinicalTrials.gov and has received ethical approval from the Peking Union Medical College Hospital Medical Science Research Ethics Committee (1-22PJ939). The findings will be disseminated through peer-reviewed scientific journals.

Trial registration number

NCT05866029.

Symptomatic changes and influencing factors following manipulation under anaesthesia in patients with adhesive capsulitis of shoulder: a protocol for a prospective cohort study

Por: Wang · Y. · Pang · J. · Shi · Y.
Introduction

Adhesive capsulitis of the shoulder is a common shoulder disease. With the ageing population, the incidence of adhesive capsulitis has been rising year by year, posing a significant threat to the quality of life of middle-aged and elderly individuals. As one of the main means of treating adhesive capsulitis, manipulation under anaesthesia (MUA) can achieve good clinical results while maintaining high economic benefits. The purpose of this study is to investigate the prognostic factors and the longitudinal recovery trajectory of patients, so as to provide a basis for the precise treatment of MUA.

Methods and analysis

The study is a longitudinal prospective cohort study with a 12-month follow-up. A trajectory analysis model (latent growth curve modelling) will be used to observe the recovery changes of adhesive capsulitis patients. Linear mixed-effects models will be employed to analyse the prognostic factors of adhesive capsulitis.

Ethics and dissemination

Ethical approval was obtained from the Institutional Review Board of Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine (approval number: 2025-1707-047-02), following ethical guidelines and standard reporting practices. The research findings will be disseminated through presentations at both regional and global medical conferences.

Trial registration number

ChiCTR2500100645.

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.
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.

Effect of bupivacaine combined with morphine intrathecal injection on postoperative recovery quality in patients undergoing pulmonary surgery: a study protocol for a multicentre, randomised, double-blind, controlled trial

Por: Yang · D. · Zhao · M. · Tang · S.-H. · Gong · Y. · Xia · H. · Jiang · M. · Peng · K. · Lai · H. · Han · Q. · Zheng · Z. · Gong · Y. · Zhang · J.
Introduction

Acute pain following pulmonary surgery can affect the recovery process of patients. The use of intrathecal morphine (ITM) injections offers a long-lasting analgesic effect, but its clinical application remains controversial. This study aims to investigate the impact of combining bupivacaine with ITM injections on the quality of postoperative recovery in patients who have undergone pulmonary surgery.

Methods and design

This multicentre, randomised, double-blind, controlled trial will enrol 254 patients undergoing elective lung surgery, who will be randomly assigned in a 1:1 ratio to either group IT (receiving an intrathecal injection of 3 mg bupivacaine and 0.25 mg morphine before general anaesthesia induction) or the control group (C group). The primary outcome includes postoperative recovery quality on day 1 (quality of recovery, QoR-15), with secondary outcomes encompassing postoperative recovery quality on days 2 and 3 (QoR-15), pain scores within 72 hours postoperatively, analgesic rescue, intraoperative haemodynamic parameters, opioid consumption, postoperative adverse reactions, recovery metrics, complications, chronic pain incidence and sleep quality.

Ethics and dissemination

The results will be disseminated through peer-reviewed publications. This study protocol (V.2.0, 30 October 2024) involves human participants and has been approved by the Ethics Committee of Affiliated Hospital of Yangzhou University (number 2024-08-02-2), Taicang Hospital Affiliated to Soochow University (number 2025 SR-041) and Yichang Central People’s Hospital (number 2024-513-02). Each individual who agrees to participate in the research will provide written informed consent after the objectives and procedures of this study are explained to them.

Trial registration number

ChiCTR2400092935. Registered on 26 November 2024.

Applications of artificial intelligence for real-world evidence generation: a protocol for a living scoping review

Por: Oikonomidi · T. · Raad · H. · Diaz-Decaro · J. · Li · H. · Y Smith · M. · Rivera · D. R. · Liu · W. · Soriano Gabarro · M. · Bennett · D. · Mack · C. D. · Teltsch · D. Y. · Gerber · J. E. · Bray · B. · Dickinson · H. · Jani · M. · Naidoo · N.
Introduction

Artificial intelligence (AI) is rapidly evolving, offering an expanding suite of capabilities that go beyond the traditional focus on prediction and classification. Generative AI (GenAI) and agentic AI could create transformative practices to support real-world evidence (RWE) generation for health research by streamlining studies, accelerating insights and improving decision-making. However, there is no published overview available describing the range of applications in RWE generation. This review aims to describe where and how genAI and agentic AI are applied across the domains of healthcare research tasks for RWE generation. Additionally, to map applications by tasks and methods across the product lifecycle continuum, and to identify emerging gaps and opportunities.

Methods and analysis

This Living Scoping Review (LSR) will include studies reporting an application and/or evaluation of genAI or agentic AI applied to one or more RWE generation research tasks. Searches will be conducted in Embase, MEDLINE and additional sources (eg, grey literature). Citations will be independently screened by two human senior reviewers for a substantive training dataset and a commercially available screening algorithm (Robot Screener) will complete screening with a human reviewer. The LSR will include reports of studies (primary or reviews) describing and/or evaluating the application of any genAI model for RWE generation in healthcare, in English, published from 1 January 2025 to the date of search. Data will be extracted from all studies included in the LSR by one independent senior reviewer using a piloted template, with 10% quality check by a second senior reviewer. Descriptive statistics will be used to summarise the applications of genAI per RWE research task, and the results of genAI evaluations. Thematic analysis will be used to describe genAI application patterns, trends, gaps and opportunities. The LSR protocol and reports will be updated annually, and findings will be published on a publicly available website (eg, ISPE—the International Society for Pharmacoepidemiology).

Ethics and dissemination

Ethical approval is not required due to use of previously published data. Planned dissemination includes peer-reviewed publication, presentation and short summaries.

Transmission dynamics and control of tuberculosis in high-altitude regions: a modelling study in Xizang, China

Por: Li · M. · Zheng · R. · Guo · L. · Wu · Y. · Dong · J. · Jiang · H. · Song · D. · Cui · Z. · Li · C.
Objectives

To estimate tuberculosis (TB) incidence trends in the high-altitude Xizang, China, and to explore the key intervention strategies on achieving the WHO 2030 TB control target.

Design

We developed a susceptible–exposed–infectious–recovered transmission model using routinely reported TB surveillance data from 2004 to 2022. Scenario-based simulations were conducted to project future TB incidence under alternative intervention strategies. Model assumptions are as follows: (1) a stable population, (2) lifelong vaccine-induced immunity, (3) infectiousness of active TB cases, (4) relapse risk after recovery and (5) homogeneous mixing within the population.

Setting

Seven prefectures of Xizang Autonomous Region on the Tibetan Plateau, China.

Participants

An estimated population of approximately 3 million individuals residing in Xizang.

Interventions

We assessed the epidemiological impact of four interventions implemented independently: increasing vaccine efficacy rate, reducing transmission rates of susceptible individuals, decreasing progression rate from latent TB infection to active disease and reducing relapse rate among successfully treated patients, compared with continuation of current control measures.

Results

The estimated basic reproduction number (R0 ) for TB in Xizang was 0.39 (95% CI 0.21 to 0.71) in the absence of additional interventions, which was the highest among all regions of China. Model simulations indicated that all four evaluated interventions were each likely to reduce TB incidence, but only reducing the latent-to-active TB progression had a substantial effect. A 50% reduction in the progression rate was predicted to lower TB incidence from 66.56 (62.00–70.11) to 40.54 (37.15–43.77) cases per 100 000 population, meeting the WHO 2030 TB control target.

Conclusion

Targeted management of individuals with latent TB infection should be strengthened to substantially reduce TB transmission in high-altitude areas.

Development and evaluation of a mobile health (mHealth) application for smoking cessation among adolescents in Indonesia: a mixed methods randomised controlled trial study protocol

Por: Ilmaskal · R. · Prabandari · Y. S. · Oktaria · V.
Introduction

Adolescent smoking poses a critical public health challenge in Indonesia, where approximately 7.4% of adolescents are current smokers. This issue is compounded by the tobacco industry’s aggressive marketing strategies, particularly targeting youth. Mobile health (mHealth) interventions offer promising alternatives for smoking cessation because of their accessibility and adaptability. However, while mHealth applications have shown potential in promoting smoking cessation, their efficacy remains inconsistent, particularly among adolescent populations in low- and middle-income countries. This study aims to develop an innovative mHealth intervention model designed explicitly for adolescent users.

Methods and analysis

This study used a mixed-methods, sequential, exploratory approach, including a randomised controlled trial. The research will be conducted in three phases: (1) a qualitative study to inform the app’s design; (2) a development phase using the Rapid Application Development model; and (3) a single-blind, two-arm randomised controlled trial to evaluate the app’s efficacy. Participants will be randomised into either the mHealth intervention group or a paper-based control group using block randomisation to ensure balanced allocation and minimise bias. The protocol is compliant with the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines for transparency and reporting. The study population will consist of adolescent smokers aged 13–15 years who reside in Padang City. A total of 110 participants will be recruited, with 55 adolescents in the intervention group and 55 in the control group. The primary outcome is smoking abstinence at 1-, 3- and 6-month follow-ups, which will be assessed through a self-report questionnaire. Secondary outcomes include changes in self-efficacy, motivation, social support, nicotine dependence and user engagement with the intervention.

Ethics and dissemination

The study complies with protocols, the Helsinki Declaration, the principles of Good Health Research Practice and regulatory requirements. The protocol was approved by the Medical and Health Research Ethics Committee, Faculty of Medicine, Public Health and Nursing, Gadjah Mada University (Ref No: KE-FK-0864-EC-2025). Informed consent will be obtained from both adolescents and their parents/guardians, ensuring confidentiality and voluntary participation. The results of this study will be published in peer-reviewed journals.

Trial registration number

NCT07198828.

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.
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.

ALARUM: Active One Health surveillance in LMICs to monitor and predict Antimicrobial Resistance Using Metagenomics - a cross-sectional study protocol

Por: van der Sande · M. A. B. · Valia · D. · Tigoi · C. · Stoesser · N. · Stamm · L. · Marten · A. · Riems · B. · Musyimi · R. · Sibidou · Y. · Schurch · A. C. · Tiendrebeogo · E. W. · Mwaringa · S. · Kohns Vasconcelos · M. · Ingelbeen · B. · Tinto · H. · Bielicki · J. A. · Cooper · B. S. · B
Background

In rural sub-Saharan Africa (sSA), the burden of antimicrobial resistance (AMR) remains high. As AMR continues to rise, there is a strong need for practical, implementable surveillance to monitor and mitigate risks, as well as inform timely, evidence-based clinical decision-making. Emerging evidence points to possible community-level drivers, such as transmission between human, animal and environmental reservoirs as contributing factors, yet microbiological surveillance or opportunities for wastewater-based surveillance are often limited and insufficient in these settings. Therefore, alternative sustainable and affordable approaches are needed. We intend to build on the demonstrated potential of metagenomic profiling of pooled faecal material, which accurately predicted population-level AMR prevalence in invasive Enterobacterales infections.

Methods and analysis

We aim to validate this metagenomic pooled approach on additional populations, and to evaluate whether AMR patterns could be similarly predicted from surveillance of community One Health reservoirs. We will assemble existing data from hospital-based microbiology diagnostic laboratories in rural Burkina Faso and Kenya, and determine to what extent community-level metagenomic data, and/or faecal material of patients on hospital admission, can predict AMR in clinical isolates. We will perform community-level surveys in eight clusters per country, randomly selecting 15 households per cluster. We will systematically sample suspected environmental AMR exposure sites in and around households (soil, drinking water, latrines, chicken faeces) and collect data on community-level antibiotic use, hygiene practices, contact with domestic animals and sanitary facilities. Samples and data will be collected twice: during the dry and during the rainy season.

In addition to evaluating the accuracy of predicting resistance in clinical isolates, we will quantify community-level exposure risks. We will conduct metagenomic profiling on pooled DNA extracts from human stool samples (hospital and community-level) and from household environments. Bayesian statistical models will quantify relationships between AMR gene abundance in the environment and in human stool, and invasive bacteria identified among clinical patients, accounting for geography and seasonality. A cost-utility analysis will determine under what circumstances the use of pooled metagenomic data to inform empirical antibiotic policies would represent an efficient use of resources.

Ethics and dissemination

The proposed surveillance protocol is developed in partnership with local communities and local and international researchers and has received ethical approval in Kenya and Burkina Faso. It will assess whether intermittent, pooled-sample metagenomics provides a viable, low-cost and practical approach for population-level AMR surveillance in settings that—like many in rural sSA—lack systematic microbiological diagnostics and where sewage systems for wastewater-based surveillance are absent. By providing an alternative to routine microbiological-based surveillance where this proves challenging to implement, this approach may help improve treatment outcomes, contribute to equity and public health. Findings will be disseminated through peer-reviewed publications and academic conferences and will contribute to the recently proposed WHO AMR surveillance strategy, which combines survey-based approaches with routine AMR surveillance.

Association between smoking behaviours during early pregnancy and the severity of gestational diabetes mellitus: a secondary analysis of prospectively collected cohort data in Korea

Por: Lim · J. H. · Joo · E. H. · Han · H.-J. · Ko · J. S. · Chung · B. · Kim · J. W. · Kim · J. Y. · Choi · Y. J. · Yang · S. J. · Han · Y. J. · Kwak · D. W. · Lee · H. J. · Ryu · H. M.
Objective

This study aimed to investigate the association between smoking behaviours during early pregnancy and the risk and severity of gestational diabetes mellitus (GDM), with a particular focus on smoking status, smoking intensity and secondhand smoke exposure.

Design

Secondary analysis of prospectively collected cohort data.

Setting

Multi-centre study conducted in South Korea (Korean Pregnancy Outcome Study) between March 2013 and January 2017.

Participants

From 4537 pregnant women initially enrolled, 3457 singleton pregnancies were included after excluding cases with transfer, loss to follow-up, twin pregnancies, miscarriages and pre-existing diabetes mellitus. All participants were women of Korean ethnicity.

Secondary outcome measures

Primary outcome was GDM and its subtypes (A1GDM: diet-controlled; A2GDM: insulin-requiring). Secondary outcomes were associations with active smoking (before pregnancy and during early pregnancy), smoking intensity dose–response relationships (pack-years) and secondhand smoke exposure among never-smokers.

Results

Among 3457 participants, 231 women (6.7%) were diagnosed with GDM (198 A1GDM, 33 A2GDM). Active smoking before pregnancy (adjusted OR (aOR) 3.98, 95% CI 1.58 to 9.30) and during early pregnancy (aOR 9.90, 95% CI 2.97 to 29.45) were significantly associated with A2GDM, while no significant association was observed with A1GDM. A clear dose-response relationship was observed, with smoking intensity >4 pack-years markedly increasing A2GDM risk (aOR 20.68, 95% CI 6.75 to 59.39). Detailed pack-year analysis showed 4–6 pack-years (aOR 20.57, 95% CI 5.80 to 65.46) and >6 pack-years (aOR 25.98, 95% CI 3.21 to 146.45). Among never-smokers, secondhand smoke exposure showed a borderline association with overall GDM risk (aOR 1.33, 95% CI 0.98 to 1.81).

Conclusions

Maternal active smoking before and during early pregnancy, as well as higher smoking intensity, was associated with an increased risk of pharmacologically treated GDM (A2GDM). Although secondhand smoke exposure did not reach statistical significance, the trend suggested a potential association with GDM risk among never-smokers. These findings provide important evidence for public health strategies for prenatal care, as smoking cessation and environmental smoke avoidance during prenatal and early antenatal care in women reduce the risk of gestational diabetes.

Patiromer utility as an adjunct treatment in patients needing urgent hyperkalaemia management (PLATINUM): a randomised controlled trial in the emergency department

Por: Rafique · Z. · Safdar · B. · Duanmu · Y. · Boone · S. · Meltzer · A. · Bischof · J. J. · Robinson · D. · Budden · J. · Budd · J. · Quinn · C. M. · Milliet · C. · Singer · A. J. · Soto · K. · Peacock · F.
Objectives

Hyperkalaemia (HK) is common in the emergency department (ED) and can cause life-threatening arrhythmias. Patiromer is a potassium binder whose role in acute HK management is uncertain; therefore, we investigated the efficacy and safety of patiromer as an adjunct to the standard of care treatment of HK in the ED.

Design

A prospective, randomised, double-blind, placebo-controlled study.

Setting

16 ED sites across the USA.

Participants

Patients aged ≥18 years treated at a participating ED who were found to have serum potassium ≥5.8 mEq/L.

Interventions

Participants were randomised 1:1 to standard combination therapy (25 g intravenous dextrose, 5 units intravenous insulin and 10 mg albuterol) with either patiromer or placebo. The initial dose was given within 1 hour of the potassium result, and the second dose 24 hours later.

Primary and secondary outcome measures

The primary endpoint was net clinical benefit (NCB) at 6 hours, defined as the change in number of potassium-lowering interventions minus change in serum potassium. Adverse events (AEs) were also recorded.

Results

The study was terminated early and did not reach the prespecified sample size. Overall, 111 patients (53 patiromer and 58 placebo) were analysed. Mean (SD) age was 61.34 (15.21) years, 34% were female, 48% white and 22.5% received chronic haemodialysis. Mean baseline potassium was 6.5 mmol/L. NCB at 6 hours was similar between patiromer and placebo (–0.6 vs –0.4; p=0.44). Potassium levels at 2, 4 and 6 hours were similar between the groups (5.50 vs 5.70, 5.45 vs 5.65, 5.50 vs 5.60; patiromer and placebo (all p>0.05)). The number of interventions per patient was similar (p>0.05) between groups at each time point. The proportion of patients experiencing AEs was not significant between the patiromer and placebo groups (16.98% vs 32.76%; p=0.08).

Conclusions

No differences in efficacy were reported in this study, which was underpowered to detect statistical efficacy of patiromer over placebo.

Trial registration number

NCT04443608.

Neoadjuvant hepatic arterial infusion chemotherapy (HAIC) with GEMOX and lenvatinib in combination with adebrelimab for resectable high-risk recurrent intrahepatic cholangiocarcinoma (ICC): study protocol of the NEO-ERA-01 feasibility trial

Introduction

Intrahepatic cholangiocarcinoma (ICC) has a high recurrence rate after curative surgery, with no standard neoadjuvant therapy. Hepatic arterial infusion chemotherapy (HAIC) has shown efficacy in locally advanced ICC, while immune checkpoint inhibitors and anti-angiogenic agents have demonstrated promising response rates. The NEO-ERA-01 study evaluates the feasibility of neoadjuvant HAIC-GEMOX plus lenvatinib and Adebrelimab in high-risk resectable ICC.

Methods and analysis

NEO-ERA-01 is a prospective, multicentre, phase II trial using Simon’s two-stage design. Thirty patients with histologically confirmed resectable ICC and high-risk recurrence factors will be enrolled in China. Neoadjuvant therapy consists of HAIC-GEMOX (gemcitabine 800 mg/m², oxaliplatin 85 mg/m² every 3 weeks), lenvatinib (8 mg/day from Day 5) and Adebrelimab (1200 mg on Day 3, every 3 weeks) for 2–4 cycles. Surgery eligibility will be assessed post-treatment. Resected patients will receive adjuvant capecitabine (1250 mg/m² two times per day on Days 1–14, every 3 weeks) and Adebrelimab (1200 mg on Day 1, every 3 weeks) for 6 months.

The primary endpoint is the completion rate of study treatment. Secondary endpoints include safety, R0 resection rate, response rate, event-free survival, disease-free survival and overall survival. Exploratory endpoints include immune microenvironment and biomarker analysis.

Ethics and dissemination

The study is approved by the ethics committee of all sites and follows the Declaration of Helsinki and good clinical practice guidelines. Results will be disseminated via peer-reviewed publications and conferences.

Trial registration number

NCT06208462.

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