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Ayer — Marzo 4th 2026BMJ Open

Utility of Xpert MTB/RIF using bronchoalveolar lavage samples for the diagnosis of pulmonary tuberculosis in negative or sputum-scarce adults: a systematic review and meta-analysis protocol

Introduction

Tuberculosis is the leading cause of death globally from a single infectious agent. Early diagnosis is critical to reducing morbimortality. In cases of negative smear microscopy or limited sputum production, bronchoalveolar lavage (BAL) samples offer an alternative for diagnosis. Culture, the gold standard, requires a high bacterial load, extensive infrastructure and is time-consuming. Xpert MTB/RIF provides faster results with a higher cost. Previous systematic reviews present substantial limitations, including significant heterogeneity. Therefore, the diagnostic utility of Xpert MTB/RIF using BAL samples in adults with negative or scant sputum for pulmonary tuberculosis (PTB) needs to be reassessed.

Methods and analysis

A systematic search of MEDLINE, Embase, LILACS and Web of Science will be conducted without language or publication date restriction. Cross-sectional diagnostic studies of negative or sputum-scarce adults with presumptive PTB who underwent bronchoscopy to obtain samples for Xpert MTB/RIF and culture will be included. Screening and data extraction will be performed independently. Methodological quality will be assessed using the QUADAS-2 tool. A bivariate hierarchical random-effects model will synthesise sensitivity and specificity. Meta-analysis will be performed using Meta-DiSc 2.0. Heterogeneity will be assessed using I2 and Cochrane thresholds. Subgroup analyses will be performed based on study design, population differences, country, culture method and risk of bias. Publication bias will be investigated using a funnel plot. The certainty of evidence will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation approach. There was no patient or public involvement in the development of the systematic review protocol.

Ethics and dissemination

Ethical approval is not required as this study will use publicly available data. Findings will be disseminated through peer-reviewed publication.

PROSPERO registration number

CRD42025639440.

Efficacy of perioperative intravenous lidocaine infusion on postoperative recovery and analgesia in patients undergoing video-assisted thoracoscopic surgery: study protocol for a randomised, double-blind, placebo-controlled trial

Por: Omindo · W. W. · Xiao · Z. · Wang · X. · Fu · L. · Wang · J. · Zhang · R. · Ping · W. · Zhou · B. · Zhang · N.
Introduction

Despite the minimally invasive nature of video-assisted thoracoscopic surgery (VATS), moderate-to-severe postoperative pain remains frequent and impairs recovery. Intravenous lidocaine possesses multimodal analgesic, antihyperalgesic and anti-inflammatory properties that may improve pain control and functional outcomes, but robust evidence in thoracic surgery is lacking. Moreover, its potential to attenuate neuropathic pain, a key component of chronic post-thoracic pain syndromes, has not been adequately investigated. This trial will determine whether continuous perioperative intravenous lidocaine infusion improves recovery, reduces acute pain intensity and prevents the development of neuropathic pain after VATS.

Methods and analysis

This single-centre, randomised, double-blind, placebo-controlled trial will enrol 84 adult patients undergoing elective VATS. Participants will be randomised (1:1) to receive either intravenous lidocaine (bolus 1 mg/kg at induction followed by continuous infusion at 1.5 mg/kg/hour intraoperatively and postoperatively for 24 hours) or matched normal saline postoperatively, with identical intraoperative management in both groups. The primary outcome is the incidence of moderate-to-severe movement-evoked pain at 24 hours postoperatively. Secondary outcomes include pain at 48 and 72 hours, opioid consumption, pulmonary complications, sleep quality, quality of recovery, neurocognitive outcomes and chronic neuropathic pain at 3 months. Analyses will follow the intention-to-treat principle.

Ethics and dissemination

The study protocol was approved by the Institutional Review Board of Tongji Hospital (Reference No. TJ-IRB202509102) and registered in the Chinese Clinical Trial Registry (ChiCTR2500111163). Written informed consent will be obtained from all participants. Results will be submitted to peer-reviewed journals and academic conferences.

Trial registration number

ChiCTR2500111163.

From mother to child: a protocol paper on the longitudinal effects of a perinatal intervention on maternal self-efficacy and emotion regulation and child outcomes

Por: Montreuil · T. · Skinner · J. · Humez · L. · Gratton · C. · Herba · C. M. · Cote · S. M.
Introduction

Parental psychological challenges and poor well-being are key factors in shaping both the quality of parent-child interactions and child development. Specifically, maternal psychological distress is a central determinant of child development. Elevated levels of distress in mothers are associated with poorer child cognitive, behavioural and social-emotional outcomes, with effects persisting into adolescence and adulthood. While this highlights the critical importance of early prevention and intervention efforts to support parents, postpartum mental healthcare remains limited, despite ongoing and evident needs.

Methods and analysis

This protocol outlines a 2-year longitudinal follow-up study investigating the impact of a secondary perinatal programme (ie, Toi, Moi, Bébé), completed by mothers during pregnancy, and its impact on children’s cognitive and social-emotional functioning at 24 and 48 months. Further, the study aims to explore whether maternal self-efficacy and emotion regulation may serve as potential mediators or moderators of the relationship between programme participation and child development outcomes. The research aims to leverage the Toi, Moi, Bébé programme, by recruiting mother-child dyads (n=250) in which the mothers participated in the programme during pregnancy. Mothers were randomly assigned to complete the parenting well-being intervention either independently or with added telephone support. Participants who consent will be invited to take part in a two-wave follow-up at 24 months (T1) and 48 months postpartum (T2). At both time points, mothers will complete demographic questionnaires and standardised measures assessing maternal well-being (Generalised Anxiety Disorder-7, Edinburgh Postnatal Depression Scale and Perceived Stress Scale), child cognitive functioning (Ages and Stages Questionnaire-3 and MacArthur-Bates Communicative Development Inventory), child social-emotional functioning (Ages and Stages Questionnaire, Social Emotional—second Edition-2 and Child Behaviour Checklist for Ages 1.5–5), maternal emotion regulation (Cognitive Emotion Regulation Questionnaire) and maternal self-efficacy (Parental Cognitions and Conduct Towards the Infant Scale & Me as a Parent Scale). Parents’ perceptions of their parenting experience will be measured using the Parental Reflective Functioning Questionnaire. Mother-child interaction, parenting quality and cognitive stimulation in the home environment will be measured using a brief virtual interview (StimQ2-Toddler) and a naturalistic observation assessment (Parenting Interactions with Children: Checklist of Observations Linked to Outcomes). Using RStudio, linear mixed models will be used to assess the impact of the intervention (online intervention only vs only with telephone support) on child cognitive and social-emotional development at T1 and T2. In parallel, separate models will be conducted to examine associations between maternal emotion regulation and self-efficacy on the child development outcomes at the same timepoints. Exploratory analyses will be conducted to examine potential moderating effects of child sex and group assignment on the associations between maternal emotion regulation and self-efficacy and child developmental (cognitive and socioemotional) outcomes, using causal inference models.

Ethics and dissemination

The current study has been registered, reviewed and approved (MP-37-2025-10894) by the Research Institute of the McGill University Health Centre Research Ethics Board. Findings from this research will be disseminated through peer-reviewed open access publications, and presentations at national and international conferences.

Trial registration number

NCT05110456.

Fighting for care: how can we better support people with multiple long-term conditions who are accessing community mental health groups? A qualitative interview study within a UK arts therapies trial

Por: Hounsell · L. · Millard · E. · Medlicott · E. · Fry · E. · Fernandes · J. · Carr · C.
Objective

To explore the impact of multiple long-term conditions (MTLCs) and a comorbid mental health condition on decision-making processes, attendance and engagement in NHS community-based therapy groups.

Design

Qualitative in-depth interviews analysed using reflexive codebook analysis as part of a study within a trial.

Setting

Secondary community mental health teams from two UK sites.

Participants

Purposive sample of 20 participants recruited to a randomised controlled trial of group therapies (arts therapies and counselling) holding a mental health diagnosis and self-reported as having at least one additional physical health condition.

Results

Six themes were constructed: (1) MLTCs influenced arts modality choices and goals; (2) importance of planning ahead to be organised; (3) the journey loomed over participants; (4) the impact of MLTCs on group attendance and participation; (5) the group was valued and important; (6) determination and fighting to get what I need.

Decisions about arts modalities and group attendance were based on a self-perceived level of felt capability. It was important for participants to plan in advance and feel informed ahead of making commitments, enabling them to prepare and manage symptoms. Travelling to the groups was dreaded, and many participants required support with travel in order to attend. Managing symptoms during the journey and groups was challenging; however, participants had a strong determination to uphold the commitment to attend despite their difficulties, as the group was highly valued.

Conclusions

MLTCs have a large impact on people’s capacity to engage in community groups, requiring additional planning and effort. The scale of this impact is often not recognised. Despite this, the benefits of groups for people with MLTCs are especially important, including motivation to leave the house, opportunities for socialisation and a means of reaching one’s own goals. Clinicians are recommended to accommodate the needs of MLTCs when designing community group interventions and consider multiple attendees with MLTCs in the group composition to improve attendance and group engagement.

Trial registration number

ISRCTN88805048.

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.
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.

Effectiveness and cost-effectiveness of a 9 week multi-component cycling programme versus an existing single cycling training session: protocol for the Cycle Nation Communities randomised controlled trial

Por: Lawlor · E. R. · Gabler Trisotti · M. F. · McIntosh · E. · McConnachie · A. · Gill · J. M. R. · Gray · C. M.
Introduction

Cycling can be beneficial for health, well-being and the environment; however, cycling participation in the UK remains low. Effective and cost-effective strategies are needed to support people in the community to increase cycling. The Cycle Nation Communities randomised controlled trial (RCT) will evaluate whether a 9 week multi-component cycling programme (Cycle Nation) is more effective and cost-effective than an existing national cycle training session on cycling participation, transport use and health and well-being.

Methods and analysis

This pragmatic, single-blinded, two-arm RCT will recruit ≥268 adults who cycle infrequently. Participants will be randomised to the 9 week multi-component individual/social-level group-based Cycle Nation programme or an existing national standard single group-based cycle training session. Both arms will be delivered by community-based cycling organisations in Glasgow. Participants will complete self-reported measurements at baseline, 12 weeks and 12 months. The primary outcome is the proportion of participants cycling at least weekly at 12 months. Secondary outcomes include proportion of participants cycling at least weekly at 12 weeks; change in weekly number of rides and minutes of cycling and use of private car, taxi, public transport and walking at 12 weeks and 12 months; change in motivation, perceptions of cycling safety, confidence to cycle, self-esteem, vitality, health-related quality of life and perceived general physical health at 12 weeks and 12 months. A within-trial economic evaluation from a National Health Service/personal social service and a broader societal perspective will be undertaken. Pending within-trial results, a long-term model may be developed. An embedded process evaluation will use participant and facilitator interviews, participant acceptability questionnaires, facilitator delivery proforma and session observations.

Ethics and dissemination

Ethical approval has been obtained from the University of Glasgow Medical, Veterinary and Life Sciences Ethics Committee (11 April 25). Findings will be published in peer-reviewed journals and communicated to stakeholders and the public.

Trial registration number

NCT07005674.

Cross-sectional observational study evaluating social brain health in HIV using a research domain criteria-based approach: a protocol

Por: Vance · D. E. · Brennan-Ing · M. · Lambert · C. C. · Hellemann · G. · Zeng · X. · Lee · J.
Introduction

Some people with HIV (PWH) experience brain changes that affect neurocognition, but little is known about how HIV impacts social cognition or related brain regions. Social cognition, the ability to perceive, understand and respond to social information, is important for maintaining relationships and quality of life. This article provides the protocol for the first comprehensive study examining social brain function in PWH and people without HIV (PWoH). With three aims, this study will: (1) examine neural circuits related to social cognition; (2) examine social cognitive performance across two social cognitive domains and (3) examine the role of social cognition in everyday social functioning.

Methods and analysis

Referred to as Social Brain Health Study in HIV Study, this cross-sectional study will enrol 105 PWH and 105 demographically matched PWoH aged 18–65 years. The study administers a comprehensive assessment battery across two visits within a 2-week period. Visit 1 includes behavioural measures of social cognition (Perceiving Social Cues and Understanding Others), neurocognition and social functioning (social network size and loneliness). Visit 2 involves functional MRI procedures with three social cognitive tasks designed to activate key brain regions (ie, fusiform face area, superior temporal gyrus, temporo-parietal junction, dorsal medial prefrontal cortex).

Ethics and dissemination

This study was funded by the National Institute of Mental Health (MH139613) and approved by the Institutional Review Board of the University of Alabama at Birmingham (IRB-300013394). Data collection is ongoing. The first results are expected to be submitted for publication in 2030. Findings of this study will be published in peer-reviewed journals and presented at local, national and international conferences as well as patient organisations such as AIDS service organisations and community talks.

Effect of prehabilitation before total knee replacement on postoperative patient-reported joint awareness, enablement and knee function: protocol for the PROTEKT randomised controlled trial

Por: Ljung · M. · Gustafsson · K. · Kvist · J.
Introduction

Knee osteoarthritis (OA) causes pain, reduced function and disability and may require total knee replacement (TKR). Although TKR is effective, up to 20% of patients remain dissatisfied, partly due to poor preoperative function and unrealistic expectations. Long waiting times for surgery may worsen patients’ function, yet preoperative physiotherapy is rarely offered. Prehabilitation—exercise and education before surgery—could improve postoperative recovery, but current evidence is limited. This trial investigates whether adding prehabilitation to standard care before TKR improves postoperative patient-reported joint awareness, enablement and knee function.

Methods and analysis

This multicentre, randomised controlled parallel-group trial is planned to be conducted within two specialised orthopaedic outpatient rehabilitation units in the southeast healthcare region of Sweden. Eligible patients (40–85 years, awaiting unilateral TKR) are randomised 1:1, stratified by age (≤67, >67 years), to either 8 weeks of prehabilitation—comprising two times per week supervised exercise therapy (strength, range of motion and balance) and education—in addition to standard care, or to standard care alone. Standard care consists of self-care, a single standardised preoperative education session and standardised postoperative rehabilitation. Assessments are conducted at baseline, post-intervention, 1 week pre-surgery and 6, 12 and 52 weeks post-surgery. A total of 110 patients will be recruited to the trial. Primary outcomes are joint awareness (Forgotten Joint Score-12) and patient enablement (modified Patient Enablement Instrument-2). Secondary outcomes are patient satisfaction (5-category Likert scale), the Knee injury and Osteoarthritis Outcome Score, the EuroQol 5 Dimension 3 Level questionnaire, the International Physical Activity Questionnaire—short form, objective function and accelerometer-based physical activity. Analyses will follow intention-to-treat and per-protocol principles. Between-group and within-group differences will be tested using t-tests or non-parametric equivalents, and linear mixed models or generalised linear models. Multiple linear regression and logistic regression will be used to analyse predictor variables for the primary outcomes. Sensitivity analyses will be performed to quantify the magnitude of missing data from patients lost to follow-up.

Ethics and dissemination

The trial has received ethical approval from the Swedish Ethical Review Authority (reg. no.2023-05120-01) and complies with the Declaration of Helsinki. Signed informed consent is collected for all patients before entering the trial. Results will be submitted for publication in a peer-reviewed journal and presented at international/national conferences. The findings may improve future clinical guidelines and care pathways for patients undergoing TKR.

Trial registration number

NCT06290336.

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.

Household determinants of healthcare utilisation in three informal settlements in Freetown, Sierra Leone: a cross-sectional survey

Por: Sesay · S. · Sesay · I. J. · Tengbe · S. M. · Wurie · H. · Fullah · S. · Vangahun · D. · Gandi · I. · Teixeira de Siqueira Filha · N. · Lakshman · R. W. D. · Conteh · A. · Saidu · S. · Koroma · B. · Mansaray · B. · Elsey · H. · Whittaker · L. · Dean · L. · Wiltgen Georgi · N. · Nganda · M
Objective

Healthcare utilisation (HU) is key to improving the health of residents in urban informal settlements. This study aimed to explore household-level factors influencing HU among informal settlement households in Freetown, Sierra Leone.

Design

Cross-sectional survey.

Setting

Three informal settlements (Cockle Bay, Dwarzark and Moyiba) in Freetown, Sierra Leone.

Participants

Primary data from 4871 households were collected during the Health and Wellbeing survey conducted between April and May 2023, targeting households with adults aged 18 years and older.

Primary outcome measures

The primary outcomes were households HU both within and outside informal settlements. Household-level predisposing and enabling explanatory variables were derived from Andersen’s Behavioural Model of HU.

Results

Disability in households increases HU within settlements (especially in Dwarzark, 13% and Moyiba, 10%) but is less likely outside. Households engaged in income-generating activities are more likely to seek healthcare within settlements, but 12% less likely outside in Cockle Bay and Dwarzark. Food insecurity decreases HU within Dwarzark (9%) and increases HU outside by 174% in Moyiba. Longer water fetching times and water shortages were associated with higher HU (between 6% and 16%) within settlements, especially in Cockle Bay and Dwarzark. Clean water sources (eg, piped dwelling, bowser, surface, bottled) were consistently associated with higher HU both within and outside settlements. Shared sanitation facilities (such as shared toilets) were positively associated with HU both within and outside settlements, particularly in Dwarzark and Moyiba. Households with income from fishing, informal salaried work and bike riding showed higher HU both within and outside settlements, especially in Dwarzark and Moyiba.

Conclusions

We identified strong settlement-specific patterns of household-level factors that influence HU both within and outside Freetown’s informal settlements. These findings provide a foundation for developing targeted policies such as strengthening local services, addressing affordability and accessibility barriers and supporting vulnerable occupation groups.

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.
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.

Common mental health outcomes among children in conflict with the law in Africa: a systematic review protocol

Por: Maotoana · M. · Phalane · K. · Ndlovu · S. M. · Rapau · M. · Quarshie · E. N.-B. · Ntho · T. A. · Sepadi · M. D. · Oppong Asante · K. · Sodi · T. · Themane · M. J.
Introduction

Common mental health outcomes among children in conflict with the law in correctional facilities in Africa are an under-researched area with significant public health implications. This review will synthesise available and accessible evidence on the prevalence and associated factors of common mental health outcomes among children in conflict with the law in Africa.

Methods and analysis

Comprehensive electronic searches will date from 01 January 2015 to 31 December 2025 and will be conducted in PubMed, Sabinet, Scopus, EBSCOhost, Web of Science and PsycINFO. Articles will be screened using defined inclusion and exclusion criteria and assessed for eligibility by three independent reviewers. Discrepancies will be reviewed by a ninth reviewer. The selection process of included articles will be reported by using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses will be used. The Mixed Methods Appraisal Tool will assess study quality, and data will be synthesised using meta-analysis or a narrative synthesis approach, depending on heterogeneity levels.

Ethics and dissemination

This study will not require ethical approval from an institutional review board, as it does not entail the direct collection of data from children in conflict with the law, nor does it pose any risk to their privacy. Once finalised, the full review report will be submitted for publication in a peer-reviewed journal. The key findings will also be shared at both local and international conferences, highlighting common mental health outcomes among children in conflict with the law.

PROSPERO registration number

CRD420251011484.

ReFIT study (reversing frailty in transplantation): protocol for a longitudinal study to assess clinical and biomedical changes in frailty through kidney transplantation

Por: Payne · T. · Shaw · A. · Hanjani · L. S. · Homes · R. · Giddens · F. · Ravuri · H. G. · Yap · C. X. · Walsh · J. · Kumar · V. · Garton · F. C. · Rhee · H. · Huang · A. · Francis · R. S. · Reid · N. · McAdams-DeMarco · M. · Gordon · E. · Midwinter · M. · Hubbard · R.
Introduction

Losses of functional reserve across multiple physiological systems have been identified in frail patients, yet the exact aetiology of frailty remains unclear. Although strongly associated with chronological age, frailty often develops at a younger age in patients with organ failure. Frailty is prevalent in patients with kidney failure; however, individuals experience improvements in physical frailty measures following kidney transplantation. This makes younger patients with kidney failure a unique population for studying both the accelerated onset of frailty and its reversal. This research project aims to test the hypothesis that frailty secondary to organ failure and age-related frailty are associated with similar molecular and physiological measures.

Methods and analysis

This longitudinal study will recruit 150 patients in three groups. Group A (kidney transplant recipients aged ≥40 years; n=50) and Group B (patients aged ≥40 years active on the kidney transplant waitlist; n=50) will comprise younger adults with frailty from organ failure. Group C (adults aged ≥65 years (or ≥55 years for Aboriginal and Torres Strait Islander patients); n=50) will comprise older community dwellers. The primary outcome is the Frailty Index (FI). Secondary outcomes include the change in FI over time, and at baseline when considering various clinical metadata, immune parameters, kidney function and nutrition intake which will be measured at baseline and 12-month time points. Longitudinal changes in frailty will be analysed using linear mixed models with multiple testing corrections for false discovery rates.

Endocrine profiles and metabolomics, measures of immune function and microcirculatory dysfunction, will be measured by liquid chromatography-mass spectrometry and/or gas chromatography-mass spectrometry. The gut microbiome will be sequenced via shotgun metagenomics (Illumina NextSeq500, 150 bp paired-end, 3Gbp/sample). Circulating cell-free DNA/mitochondrial DNA will be quantified through droplet digital PCR. Microcirculation will be assessed via sublingual dark field videomicroscopy with glycocalyx markers measured by ELISA.

Ethics and dissemination

This study will be conducted with all stipulations of this protocol, and the conditions of the ethics committee approval. Ethical principles have their origin in the Declaration of Helsinki, all Australian and local regulations and in the spirit of the standard of Good Clinical Practice (as defined by the International Conference on Harmonisation). Organs/tissues will be sourced ethically and will not be sourced from executed prisoners or prisoners of conscience or other vulnerable groups.

Ethics approval was received by the Metro South Health Research Ethics Committee (HREC/2023/QMS/95392) and ratified by the University of Queensland.

Results will be disseminated through peer-reviewed publications, academic conferences, participant newsletters and health organisation collaboration.

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.
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.

Predictors of rural medical practice in Aotearoa New Zealand: a national outcomes prospective cohort study

Por: Costello · K. · Nixon · G. · Stokes · T. · Frampton · C. · Lander · J. · Wilkinson · T.
Objectives

Identifying the factors that increase the likelihood of medical graduates choosing rural medical careers is key to addressing the global shortage of rural doctors. Using linked graduate-workforce outcomes data, this study aimed to identify predictors of rural medical practice in Aotearoa New Zealand (NZ).

Design

A national prospective cohort study linking data from the longitudinal Medical School Outcomes Database to workforce location data. Univariate and multivariate analyses were conducted to generate ORs for putative predictors of rural medical career.

Setting and participants

All NZ medical graduates from 2011 to 2019 were followed for a minimum of 3 years.

Results

During the study period, there were a total of 4152 medical graduates nationally. Included in the analysis were 3291 graduates who had linked longitudinal medical school and workforce data, of whom 133 (4%) doctors were classified as having decided on a career in rural medicine. Independent predictors of rural practice included being of rural origin (OR 2.13, 95% CI 1.19 to 3.81, p=0.011), age older than 25 years at entry to medical school (OR 2.88, 95% CI 1.54 to 5.36, p

Conclusions

This is the first national study linking medical school data to rural medical workforce outcomes. It demonstrates that previously known predictors of rural practice intention are borne out with actual career outcomes, and these also hold true at a national level. However, this research highlights that diverse pathways into rural practice are vital, given that urban-origin students and those with no early rural career intention make up a substantial number of the early-career rural medical workforce.

Adapting substance use treatment for black adolescents in the US legal system: protocol for a mixed-method, exploratory, feasibility and acceptability study using the eight-step ADAPT-ITT framework

Por: Bryant · B. E. · Tolou-Shams · M. · Ezimora · I. · Zapolski · T. C. · DiClemente · R. · Jordan · A. · Becker · S. J. · Squeglia · L. M.
Introduction

This community-led research study protocol emphasises placing black youth impacted by the legal system, their families and their communities at the forefront of substance use treatment development research and decision-making. The study, the Cultural Adaptation of a Substance Use Treatment (CAST) Project, challenges traditional top-down approaches to treatment creation, advocating for a grassroots model that centres community knowledge, values and active participation.

Methods and analysis

The CAST project is a US-based mixed-methods study with an exploratory design that examines the impact of racial discrimination on substance use in black youth impacted by the legal system. The study participants are black youth impacted by the legal system (N=15), parents of black youth impacted by the legal system (N=10) and community members who serve black youth (N=10) (total N=35 study participants). Study participants from each group (youth, parents and community members) will participate in three separate focus groups, respectively, to provide feedback on the culturally responsive content needed to best support black youth impacted by the legal system around substance use and mental health. The eight-step Assess, Decision, Adaptation, Production, Topical Expert, Integration, Training, Testing framework will be used as a guide to inform adaptations to the Motivational Enhancement Therapy and Cognitive Behavioural Therapy (MET/CBT12) for black youth impacted by the legal system. Once the cultural adaptation process has been completed, the study will conclude with an open feasibility and accessibility trial of the culturally adapted MET/CBT12 manual. The primary outcomes of this study are the feasibility and acceptability of the culturally adapted manual, measured by treatment attendance and participant feedback. Secondary outcomes include reductions in substance use and discrimination distress, and improvements in mental health symptoms.

Ethics and dissemination

This study was approved by the Institutional Review Board (IRB) at the University of California, San Francisco (IRB Protocol Number: 23-40126). All study procedures will be conducted in accordance with the ethical standards outlined by the institutional review board. The results from this study will be shared through peer-reviewed publications, academic conferences, community forums and policy briefs to support broader implementation of culturally adapted adolescent substance use interventions that address discrimination-related stress and substance use among black individuals impacted by the legal system.

Trial registration number

NCT06003725.

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.

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.
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.

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.

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