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Health worker capacity-building interventions and quality of primary healthcare delivery in sub-Saharan Africa: a systematic review protocol

Por: Amu · H. · Dzadza · A. E. L. A. · Glover · R. M. · Akpene · D. A. · Tiah · J. A. Y. · Agula · C. · Bawah · A. A.
Background

Achieving high-quality primary healthcare (PHC) remains essential to improving health systems performance and advancing progress towards attainment of universal health coverage, particularly in sub-Saharan Africa (SSA), where gaps in service delivery persist. Capacity-building interventions, such as mentorship, in-service training and supportive supervision, have been widely employed to improve the quality of PHC delivery. The evidence base is, however, fragmented across diverse settings, intervention types and outcome measures. This systematic review will examine the evidence on how capacity-building interventions improve the quality of PHC services in SSA, with a focus on the domains of effectiveness, safety, people-centredness, timeliness, equity, integration and efficiency as propounded by the WHO.

Methods

We will conduct a systematic review using established evidence synthesis methods and report the findings in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Eligible studies will include peer-reviewed and grey literature published in English between 2000 and 2025, focusing on capacity-building interventions aimed at improving PHC quality in SSA. We will search databases including PubMed, Embase, Web of Science, Scopus, Google Scholar and the African Journals Online. Study selection will follow the Population (PHC providers), Exposure (capacity-building interventions) and Outcome (quality of PHC delivery across WHO domains) framework. Quality assessment will use the Mixed Methods Appraisal Tool (MMAT). Data will be narratively synthesised using Atlas.ti software.

Ethics and dissemination

Ethical approval is not required because there will be no collection of primary data. Only published studies/records available on peer-reviewed literature and grey sources will be included. Findings will be disseminated through a peer-reviewed journal, academic conferences and stakeholder platforms in SSA.

Registration

The protocol has been registered in PROSPERO (CRD420251131534) and reported according to PRISMA-P guidelines.

Autism outcomes and neurobehavioural markers in young children born to mothers with HIV in Kenya: a protocol for the Alama project

Por: Oyungu · E. · Keehn · B. · McHenry · M. S. · Monahan · P. O. · Joseph · R. M. · Yoon · S.-Y. · Carlucci · J. G. · Saina · C. · Khaitan · A. · Baliddawa · J. · McNally Keehn · R.
Introduction

The over 14 million African children who are HIV-exposed but uninfected (CHEU) are at risk for poor health outcomes, including neurodevelopmental conditions such as autism; however, no study to date has examined autism in CHEU in Africa, where the vast majority of these children live. Scalable diagnostic and neurobehavioural tools, including powerful, low-cost approaches such as eye-tracking, for detection and study of mechanistic neural processes are necessary to advance autism research in these settings. The objective of this study is to examine autism diagnostic outcomes and eye-tracking biomarkers in relation to CHEU while at the same time building capacity for neuro-health research in Kenya.

Methods and analysis

This study will leverage a longitudinally assessed cohort of CHEU and children who are HIV-unexposed and uninfected (CHUU) with well characterised HIV-related and contextual exposures. We will first determine and compare autism diagnostic outcomes between young CHEU and CHUU across a large cohort (n=850) of Kenyan children using research-grade autism assessment tools, and, second, determine whether neurobehavioural eye-tracking markers predict autism outcomes across this cohort.

Ethics and dissemination

Human subjects approvals have been obtained from Moi University Institutional Review and Ethics Committee (IREC; IREC/909/2024; Approval #0004835), Kenya’s National Commission for Science, Technology and Innovation (NACOSTI; Reference #NACOSTI/P/25/415028), the Institutional Review Board of the Indiana University School of Medicine (Protocol #23171), with reliance agreements executed with Purdue University and Boston University. Dissemination of findings will occur through multiple channels within the research and clinical community, including peer-reviewed journal publications and conference abstracts and presentations. As part of capacity building efforts, the research team will also communicate study results to policy makers, the lay public and other health systems involved in the care of young children with disabilities via study-hosted workshops and conferences.

Association of eating disorders and/or insulin omission with impaired glycaemic control in persons living with type 1 diabetes: cross-sectional analysis of the French SFDT1 study

Por: Ritz · P.-J. · Aguayo · G. A. · Cosson · E. · Canha · D. · Renard · E. · Merwin · R. M. · Amouyal · C. · Arnault · G. · Bilariki · K. · Borot · S. · Chevalier · N. · Lemoine · A. · Franc · S. · Fremy · B. · Gouet · D. · Julla · J.-B. · Marchand · L. · Pinto · S. · Rigalleau · V. · Sonnet · E.
Objective

To address whether eating disorders (ED) or insulin omission (IOM) in adult persons living with type 1 diabetes (pwT1D) are associated with impaired glycaemic control.

Design

Cross-sectional analysis.

Settings

The French-Speaking Diabetes Society—Type 1 Diabetes Cohort (SFDT1) is an ongoing epidemiological cohort study that includes pwT1D in France who attend hospitals or private ambulatory diabetes centres.

Participants

Adult participants from the SFDT1 study, with data on ED and IOM. The current analysis was performed on data collected during the baseline visit in participants enrolled between December 2020 and March 2024.

Main outcome measures

Using the SCOFF, a self-reported questionnaire to screen for ED, and a single question on IOM to screen for IOM, we described four categories of pwT1D: no ED & no IOM, ED & no IOM, no ED & IOM and ED & IOM. We performed unadjusted and adjusted (for age, sex, diabetes duration, social vulnerability, smoking, alcohol status and insulin treatment) multinomial logistic regression models with the four categories as the outcome and glycaemic variables as explanatory variables, including continuous glucose monitoring (CGM) variables and HbA1c. No ED & no IOM was the reference outcome for all comparisons. We stratified each model by sex and fear of hypoglycaemia.

Results

We included 1113 participants, 51% males, median (IQR) age 38 (29–50) years, diabetes duration 21 (12–32) years. Prevalences were as follows: no ED & no IOM: 68% (n=758), ED & no IOM: 11% (n=124), no ED & IOM: 16% (n=177) and ED & IOM: 5% (n=54). With the fully adjusted model, and compared with the group no ED & no IOM, time in range (OR (95% CI) 0.5 (0.4 to 0.7)) and time below range (0.5 (0.3 to 0.8)) were inversely associated with ED & IOM. Moreover, time in range (0.4 (0.4 to 0.5)) was associated with IOM & no ED. Time above range (2.2 (1.6 to 2.9)), Glycaemic Risk Index (1.8 (1.3 to 2.5)), glucose monitoring indicator (2.2 (1.7 to 2.9)) and HbA1c (2.0 (1.5 to 2.5)) were directly associated with ED & IOM. We did not observe associations between CGM variables and ED & no IOM. Most associations were valid in both men and women. The associations were stronger in participants with a fear of hypoglycaemia. However, the associations remained even in people with a fear of hypoglycaemia.

Conclusions

Both ED and IOM are frequent in pwT1D, and IOM seems to be associated with impaired glycaemic control. As our analysis was cross-sectional, we cannot infer causality and cannot know whether IOM was a result of glycaemic control or the inverse (reverse causality). Our results suggest that IOM should be systematically screened in clinical practice. Further research is needed to better identify and care for EDs, with or without IOM, in T1D.

Trial registration number

NCT04657783.

Perspectives of female and under-represented physicians on well-being in medicine: a qualitative study from an academic medical centre in the USA

Por: Agarwal · A. K. · Gonzales · R. E. · Sharma · M. · Schroeder · D. · Asch · D. A. · Mitra · N. · Southwick · L. · Bellini · L. M. · Merchant · R. M.
Background

Stress and burnout are pervasive among physicians. Academic physicians who are female and physicians who are under-represented in medicine (URM) face inequities in the workplace and beyond. Understanding their experiences is crucial for workforce sustainability and diversity, especially given the disproportionate effects on these individuals and overall workforce capacity.

Objective

To qualitatively explore the perspectives of academic female and URM physicians and identify key themes affecting their careers and well-being.

Design

Semi-structured interviews were conducted with 30 physicians at an urban academic health system. Interviews were audio-recorded, transcribed and thematically analysed using a general inductive approach. Interview guides were informed by prior literature and constructs.

Intervention

None.

Setting and participants

Female and URM physicians from a large, academic medical centre were recruited via email. Participants self-reported demographic information, including sex, race, ethnicity and tenure.

Outcomes and measures

The primary outcomes encompassed the main themes identified through the analysis of interviews with female and URM physicians regarding their perspectives on well-being, mental health and academic medicine.

Results

30 female or URM physicians were interviewed (27 (90%) female; 14 (47%) black, Asian or multi-racial). Thematic analysis revealed four key themes: physician identity (URM, female, family), well-being in the workplace (emotional health, staffing burden, non-clinical responsibilities), barriers to accessing well-being resources (workplace environment, culture, overgeneralisation) and facilitators to well-being (physician camaraderie, leadership support). Physicians discussed how their identities influenced their experiences of well-being. They highlighted emotional health challenges, staffing burdens and administrative tasks contributing to stress. Barriers to accessing resources included workplace culture and broad-based interventions, while supportive leadership and camaraderie were identified as facilitators of access.

Conclusion

Female and URM physicians face systemic challenges impacting their well-being and careers. These findings underscore the need to address systemic changes and specifically design programmes focused on promoting the well-being and inclusivity of female and URM physicians. Tailored interventions to these individuals, supportive leadership structures and collaborative working cultures are crucial for addressing these issues and sustaining a diverse physician workforce.

Delivering hospital care at home in a Dutch Tertiary University Hospital: protocol for a prospective feasibility cohort study evaluating a Virtual Ward for early discharge of inpatients

Por: van Herwerden · M. C. · Scholte · N. T. B. · Mkrtchjan · A. · Feyz · L. · Mol · A. P. · Aitken · J. · de Boer · R. A. · Chandoesing · P. P. · Gommers · D. A. M. P. J. · De Haan · B. · Den Hoed · C. M. · van den Hoogen · M. W. F. · Peeters · R. P. · Wlazlo · N. · Van Der Boon · R. M.
Introduction

Virtual Wards (VWs) facilitate hospital-level monitoring, diagnostics and treatment within patients’ homes, while the hospital team retains responsibility for care. International research indicates that VWs decrease hospital length of stay without increasing readmissions; however, the feasibility and key operational determinants within Dutch care remain uncertain. This protocol outlines the VW for Early Discharge in Patients Receiving Inpatient Care (VIP Care) study.

Methods and analysis

The VIP Care study is a single-centre prospective feasibility cohort study conducted at Erasmus University Medical Center (Erasmus MC), Rotterdam, the Netherlands. The study encompasses seven predefined subcohorts with n=51 eligible patients per subcohort: (1) bacterial, fungal or parasitic infections; (2) viral respiratory infections; (3) dehydration; (4) decompensated heart failure; (5) high-dose corticosteroid treatment; (6) post-transsphenoidal pituitary surgery follow-up and (7) severe inflammatory skin disease with or without bacterial or viral superinfection. Adults who require hospital-level monitoring and/or therapy may qualify for early discharge to the VW.

The VW integrates scheduled, patient-performed measurements using (European Conformity) CE-marked devices with structured symptom assessment submitted via a patient application, and data review in an electronic health record-integrated clinician cockpit. Submissions are evaluated by VW tele-nurses using prespecified Early Warning Score based thresholds and an escalation protocol. Patients receive a daily physician telephone review. Diagnostics and treatments are administered at home to hospital standards through established home-care services.

The primary outcome (feasibility) is adherence to transfer, defined as the proportion of eligible inpatients who provide written informed consent and are subsequently successfully transferred to the VW. The prespecified feasibility threshold is 30%. Secondary outcomes include reach (eligibility, invitation and consent rates among admitted patients), operational performance during the VW episode (alert frequency and handling, contact volumes and actions), length of stay on the ward and in the VW, emergency department reassessments and 30-day readmissions. Qualitative interviews will be conducted to identify implementation determinants.

Ethics and dissemination

The study received approval from the Erasmus MC Medical Ethics Committee (MEC-2024–0060; amendment MEC-2024–0060 A0001). Incremental risk is considered minimal. Written informed consent is obtained. Findings will be disseminated through peer-reviewed publications, conference presentations and an accessible lay summary.

Trial registration number

ClinicalTrials.gov NCT06936891; CCMO NL85516.078.24. Recruitment began in May 2025 and is ongoing.

Feasibility of a phase 3 partially randomised clinical trial to assess the safety and efficacy of paediatric praziquantel for schistosomiasis treatment in children aged 3 months to 6 years in endemic regions of Brazil: a pilot study

Objective

This study assessed the feasibility of implementing a phase 3 field-based clinical trial protocol to evaluate paediatric praziquantel (PED-PZQ) for the treatment of Schistosoma mansoni infection in children aged 3 months to 6 years in endemic areas of Brazil, focusing on operational aspects such as recruitment logistics, documentation management, investigational product handling and protocol adherence.

Design

Pilot and feasibility study for a phase 3 clinical trial, comprising two components: a randomised, open-label, parallel-group, two-arm trial and a single-arm trial.

Setting

Conde, Bahia, Brazil, from December 2024 to January 2025.

Participants

Two trials aim to screen 5774 participants from three rural areas in Bahia and three in Sergipe, states in northeastern Brazil, and enrol 403 children eligible for either randomisation or allocation. Trial 1 will randomise (1:1 ratio) 240 children aged 4–6 years into the PED-PZQ treatment arm or the standard praziquantel (PZQ) 1. Trial 2 will enrol 163 children aged 3 months to 3 years, all receiving PED-PZQ. Both trials are open label. Eligible participants shall meet age criteria, test positive for S. mansoni and fulfil other inclusion criteria. In the first recruiting centre, Conde (Bahia), it was estimated that 650 participants would need to be screened for trial 1 and 552 for trial 2, assuming schistosomiasis prevalence of 5% and 4%, respectively. This pilot study reports on the first 60 participants enrolled.

Primary and secondary outcome measures

The primary outcome of this pilot study is the feasibility of implementing the research protocol in a real-world field setting, focusing on key aspects such as study documentation challenges, participant safety, investigational medicinal product custody chain and protocol adherence. In addition to providing preliminary data on the parasitological cure rate, secondary outcomes include the prevalence of S. mansoni infection and the reduction in S. mansoni egg count (Kato-Katz method). Furthermore, the occurrence and severity of drug-related adverse events are monitored from drug administration to day 21 post-treatment, alongside changes in renal, hepatic and cardiac functions assessed through biochemical markers.

Results

A total of 60 participants were recruited, and 55 provided stool samples for screening. The pilot phase demonstrated the feasibility of implementing the clinical protocol under field conditions, with successful completion of all planned procedures and minimal protocol deviations. Operational challenges were identified mainly in documentation processes, participant recruitment and investigational product management and were addressed through preventive and corrective quality assurance actions. The experience also highlighted logistical and infrastructural barriers typical of field-based trials in remote endemic areas, which informed adjustments for the subsequent phase 3 study. Preliminary parasitological results indicated an overall S. mansoni prevalence of 9.1% (5/55), with 21% in trial 1 and 2.8% in trial 2. All infected participants met the eligibility criteria, received treatment and completed follow-up. Four achieved a parasitological cure, and one case of treatment failure was observed (trial 1, PZQ group). Two mild adverse events (diarrhoea) were reported, with no serious complications or clinically significant changes in biochemical parameters.

Conclusions

This pilot study demonstrated the feasibility of implementing a field-based phase 3 clinical trial protocol for PED-PZQ in endemic areas of Brazil. The findings confirm that the protocol can be successfully applied in primary care settings, despite operational challenges related to recruitment, logistics and documentation. The study also provided preliminary evidence supporting the safety and effectiveness of the paediatric formulation and highlighted the need to revise prevalence assumptions to improve future screening strategies. Overall, the experience offers valuable insights to guide the large-scale phase 3 trial and supports the incorporation of PED-PZQ into national schistosomiasis control policies.

Trial registration number

Brazilian Clinical Trials Registry; RBR-86kcy37.

Randomised controlled trial of laparoscopic primary crural repair versus additional circular bioabsorbable mesh reinforcement in hiatal hernia (PRIME-II trial): an RCT protocol

Por: de Haas · J. W. A. · Geerts · J. H. · de Boer · E. · Brohet · R. M. · Hazebroek · E. J. · Wassenaar · E. B. · Nieuwenhuijs · V. B.
Introduction

Laparoscopic hiatal hernia (HH) repair is associated with a high recurrence rate. Repair reinforced with mesh lowers short-term recurrence but can cause dysphagia and visceral erosion. Results of the PRIME trial, in which non-absorbable mesh reinforcement of the posterior crural repair was investigated, showed equal recurrence compared with primary suture repair after 6 months. This study investigates the use of circular absorbable mesh reinforcement in primary HH repair.

Methods and analysis

Prospective double-blinded randomised controlled superiority trial comparing two laparoscopic procedures for HH repair (110 vs 110). Adult patients with proven HH Skinner types II–IV (defined by preoperative CT scan) are included. Patients are randomised to undergo a laparoscopic primary crural repair with sutures alone or suture repair augmented with biosynthetic absorbable, circular mesh at the hiatus. Radiologic integrity of the hiatal repair 1 year after surgery is the main endpoint. Secondary objectives are clinical recurrence of the hernia, development of postoperative reflux disease, postoperative side effects and satisfaction with surgical outcome. Outcome assessors are blinded to allocation. Data are collected at baseline, and follow-up includes interviews and digital questionnaires at 3, 12, 24, 36, 48 and 60 months, as well as CT scan at 12 and 60 months. All patients randomised will be analysed according to the intention-to-treat principle.

Ethics and dissemination

Ethics approval has been obtained by the local ethics committee at Isala, Zwolle, the Netherlands (Medical Ethics Review Committee (METc) Isala, study number: 190516). METc Isala is no longer active; all duties have been taken over by METc of the University Medical Center Groningen. The trial’s results will be submitted to a peer-reviewed international journal as well as (inter)national conferences.

Trial registration number

Registered in the Dutch national trial registry: OMON (NL-OMON48062).

Efficacy of YOga in people with chronic non-specific low BACK pain and poor PROgnosis (YOBACK-PRO): protocol for a randomised clinical trial

Por: Nunes · S. M. · Rizzo · R. R. · Franco · M. R. · Ferreira · F. R. · Barros · L. J. G. · Maciel · I. T. · Santos · R. L. · Nascimento · R. R. · Couto · A. J. · Quaresma · L. S. · Fontes · R. M. · Ferreira · E. M. R. · Maher · C. G. · McAuley · J. H. · Pinto · R. Z.
Introduction

Yoga has been shown to improve pain and function compared with no exercise in people with chronic low back pain (LBP), but treatment effects are small. Given that yoga is a mind–body intervention that addresses physical as well as psychological factors, it may be more effective for patients with chronic LBP who are at high risk of poor prognosis. The study aims to investigate the efficacy of a 12-week yoga programme combined with education in reducing pain and disability for individuals with chronic LBP at high risk of poor prognosis at short (12 weeks) and intermediate (24 weeks) terms, compared with a control group receiving education only.

Methods and analysis

A randomised controlled trial will include 110 adults with chronic non-specific LBP reporting an average pain intensity of 3 points or more on a 0–10 scale over the past week and classified as high risk of poor prognosis (ie, scoring 50 points or above) on the Orebro Musculoskeletal Pain Questionnaire short-form. Participants in the control group will receive an educational booklet and attend three face-to-face lectures over a 3-month period. In the intervention group, in addition to the booklet and lectures, participants will attend group yoga sessions twice a week for 12 weeks, totalling 24 yoga sessions. The primary outcome is disability assessed at 12 weeks, measured using the Roland-Morris Disability Questionnaire.

Ethics and dissemination

The study was approved by the Human Research Ethics Committee of Universidade Federal de Minas Gerais (Protocol number CAAE: 57028022.0.0000.5149). Findings will be disseminated to trial participants, clinicians and the broader public and scientific community.

Trial registration number

NCT05953155.

Can a digital intervention 'Momentum improve social functioning and transdiagnostic symptoms for Australian youth at ultrahigh risk for psychosis? Protocol for a superiority randomised controlled trial comparing treatment as usual with and without Momentu

Por: Mangelsdorf · S. N. · Cagliarini · D. · Nelson · B. · McEnery · C. · Whiting · J. · Chinnery · G. · Valentine · L. · Lee · Y. Y. · Mihalopoulos · C. · Liu · V. · Bendall · S. · Koval · P. · DAlfonso · S. · Gonzalez-Blanch · C. · Ryan · R. M. · Lederman · R. · H Lim · M. · McGorry · P. · Po
Introduction

Existing psychological and pharmacological interventions for young people at ultra-high risk (UHR) for psychosis have shown benefit in at least delaying the transition to psychosis, but they have limited benefit for comorbid disorders or social dysfunction, which are prominent for those at UHR. We developed a moderated online social therapy platform (named Momentum) including: (1) transdiagnostic therapeutic interventions targeting social functioning, depression, generalised anxiety and social anxiety; (2) a moderated, peer-led online community and (3) specialised human support from clinicians, career consultants and peer workers. The aim of this trial is to determine whether, in addition to treatment as usual (TAU), Momentum, a 12-month digital intervention, informed by the complex intervention framework, is superior to 12 months of TAU in improving social functioning in UHR young people.

Methods and analysis

The study design is a prospective, parallel group, rater-masked randomised controlled trial. We will recruit young people aged 14–27 years, meeting one or more UHR for psychosis criteria. Participants are randomly assigned to the condition using randomly permutated blocks with a 1:1 allocation ratio. Participants are stratified by age (

Ethics and dissemination

Melbourne Health Human Research Ethics Committee (HREC/42964/MH-2018) provided ethics approval for this study. Findings will be made available through scientific journals and forums and to the public via social media and the Orygen website. De-identified individual participant data will be available after publication for 3 years via the Health Data Australia catalogue (https://www.researchdata.edu.au/health). Requests must include a methodologically sound proposal. Specific conditions of use may apply and will be specified in a data sharing agreement (or similar) that the requester must agree to before access is granted. Supplementary material including study protocol, informed consent material and statistical analysis plan will also be available.

Trial registration number

Australian New Zealand Clinical Trial Registry (ANZCTR), ACTRN12619001411134.

Sleep improvement strategies for people with vision impairment: a scoping review

Por: Leonard-Hawkhead · B. · Piyasena · M. P. · Peto · T. · Virgili · G. · van Nispen · R. M. A. · Curran · K.
Objectives

To explore existing strategies for managing sleep disorders in individuals with vision impairment (VI), identifying interventions, geographical trends and research gaps.

Design

Scoping review.

Data sources

Medline ALL (Ovid), Embase and Web of Science Core Collection, with supplementary searches in Google Scholar. The final search was completed on 28 November 2025.

Eligibility criteria for selecting studies

Original research studies examining strategies to manage sleep disorders in adults (≥18 years) with VI, published in English. Studies focusing on animal models or unrelated to sleep management were excluded.

Data extraction and synthesis

Two reviewers independently screened titles, abstracts and full texts using Covidence, extracted data using a predefined form and resolved discrepancies by consensus. A narrative synthesis approach was used to summarise findings by intervention type, study design and outcomes.

Results

Of 4368 records screened, 16 studies met inclusion criteria. Participants ranged from 18 years to 85 years (median 40.5). Most studies included individuals with no light perception, though VI definitions were often inconsistent. Pharmacological interventions dominated (13/16, 81.3%), mainly melatonin or melatonin receptor agonists, with some use of zopiclone, low-dose benzodiazepines and tricyclic antidepressants. Non-pharmacological approaches were under-represented, including bright light exposure (n=1), virtual Hatha yoga (n=1) and caffeine modulation (n=1). Substantial variation existed in sleep assessment methods.

Conclusions

This scoping review highlights the predominant focus on pharmacological treatments, especially melatonin, while non-pharmacological strategies remain underexplored. Future research should explore accessible, non-pharmacological interventions and address sleep health inequities faced by individuals with VI.

Registration

10.17605/OSF.IO/7E83R.

The MenoStim Trial: Study Protocol for a Randomised, Sham-Controlled, Double-Blinded, Pilot Clinical Trial Exploring the Neurophysiological, Cognitive, Mood and Biochemical Effects Associated with Non-Invasive Brain Stimulation During the Menopause Transi

Por: Metri · N.-J. · Cavaleri · R. · Alhassani · G. · Ee · C. · Lim · C. K. · Francis · H. M. · Hochstrasser · D. · Bou Merhy · R. M. · Steiner-Lim · G. Z.
Introduction

Intermittent theta-burst stimulation (iTBS) is a non-invasive brain stimulation technique that has been shown to improve cognition and mood when applied to certain brain structures and regions. Despite research demonstrating that iTBS may have clinical utility in treating cognitive and mood changes, no study has yet been conducted to explore the potential to modulate the neurophysiological changes that can underpin cognitive and mood changes during the menopause transition. Cognitive and psychological symptoms are commonly reported by females experiencing the menopause transition, and it is thought that these symptoms arise due to various neurophysiological, metabolic and endocrinological changes. Despite being common, there is a lack of treatments available for managing these symptoms and a scarcity of data regarding the mechanisms by which they occur.

Methods and analysis

The aim of this 5-week randomised, sham-controlled, double-blinded pilot clinical trial (n=72) is to assess the underlying mechanisms of action of iTBS in females in the late menopause transition and the relationship with cognition and mood. Data will be analysed using StataTM. Normality checks will guide the choice between parametric and non-parametric tests. Generalised linear models will assess within-subject and between-subject effects across timepoints, with additional regression analyses exploring associations between biomarkers, cognition and mood. Effect sizes, CIs and relevant test statistics will be reported, with significance set at p

Ethics and dissemination

The study protocol has been reviewed and ethically approved by the Western Sydney University Human Research Ethics Committee (H16200; 8 November 2024). All participants will provide written informed consent prior to enrolment. Results from this trial will be disseminated via peer-reviewed publications and conference presentations, with findings shared in accordance with open science and data transparency principles.

ANZCTR registration number

ACTRN12625000030471, Australian New Zealand Clinical Trials Registry

Investigating dysfunctional cognition change as a putative mechanism of CBT for youth anxiety, OCD and PTSD: protocol for an individual participant data meta-analysis

Por: Buric · I. · Klein · A. · Rapee · R. M. · Levis · B. · Kendall · P. C. · Storch · E. A. · Mobach · L.
Introduction

Anxiety disorders, obsessive–compulsive disorder (OCD) and post-traumatic stress disorder (PTSD) are common in children and adolescents and can lead to significant impairment. Cognitive behavioural therapy (CBT) with exposure is the first-line treatment, yet approximately half of treated youth do not achieve full remission. Dysfunctional cognitions—negative automatic thoughts, maladaptive beliefs and distorted interpretations—are considered key targets of CBT, but evidence in youth is mixed and underpowered. This study will examine whether change in dysfunctional cognitions mediates treatment outcome in anxiety, OCD and PTSD symptoms and whether this association varies across individual characteristics.

Methods and analysis

An individual participant data meta-analysis (IPDMA) of randomised controlled trials of CBT for youth aged 5–18 years with anxiety disorders, OCD or PTSD will be conducted. The search strategy includes the databases APA PsycINFO, MEDLINE and Web of Science Core Collection from inception to 8 September 2025. It is supplemented by screening reference lists, trial registries, grey literature and outreach to relevant research groups. Eligible trials must include at least one validated measure of dysfunctional cognitions administered at minimum pre- and post-treatment, and clinical outcomes assessed at post-treatment and follow-up. The two primary outcomes are (1) child-reported symptom severity and (2) clinician-rated clinical severity. Data will be harmonised for dysfunctional cognition scores, moderators (age, gender, socioeconomic status, comorbidity), and primary outcomes. One-stage Bayesian mixed-effects models will examine whether changes in dysfunctional cognitions predict improvements in primary outcomes and whether these effects are moderated by individual characteristics. Missing data will be addressed using multiple imputation within the Bayesian framework, and study-level heterogeneity will be modelled using random intercepts and slopes.

Ethics and dissemination

All datasets will be de-identified and managed under General Data Protection Regulation standards. Each included trial will have ethical approval permitting data sharing and reuse, and the secondary analysis of the shared datasets has been approved by the University of Amsterdam. Findings will be disseminated via a peer-reviewed publication, scientific conferences and open sharing of analysis scripts and harmonisation procedures.

PROSPERO registration number

CRD420251139130.

The cost-effectiveness of penicillin allergy assessment pathway (PAAP): a decision analysis

Por: Yang · M. · Bestwick · R. · Howdon · D. · Ahmed · S. · Powell · N. · Armitage · K. F. · Fielding · J. · Porter · C. E. · Savic · S. · West · R. M. · Howard · P. · Galal · U. · Pavitt · S. · Sandoe · J. A. · Mujica-Mota · R. E.
Objective

To evaluate the cost-effectiveness of implementing a penicillin allergy assessment pathway (PAAP) versus usual care within the NHS.

Design

A decision tree analysis over a 5-year time-period, informed by a randomised controlled trial (RCT) of PAAP and systematic review. Value of information analysis was also conducted to estimate the value of conducting a new trial.

Data sources

Model inputs were informed by the ALABAMA RCT participants included in the primary analysis, 811 adults with penicillin allergy labels and recent antibiotic prescriptions, and data from published literature.

Interventions

Participants in the ALABAMA trial included in the primary analysis: PAAP (n=401) and usual care (n=410).

Primary and secondary outcome measures

Costs are presented in GBP (£) at 2022–2023 prices, quality-adjusted life years (QALYs), incremental cost-effectiveness ratio, incremental net monetary benefit (INMB), the probability of cost-effectiveness at the £20,000 and £30,000 per QALY threshold, and the cost effectiveness of a new follow-on trial.

Results

PAAP had incremental costs of £–83 (probability of cost saving 47.5%) and incremental QALYs of 0.036 (probability of positive benefits 47.5%). The INMBs (probability of cost-effectiveness) were £806 (48%) and £1167 (48%) under the decision thresholds of £20,000 and £30,000 per QALY, respectively. PAAP was more cost-effective among females, people aged >65 years, and more frequent antibiotic users. A new follow-on trial involving 1267 participants was estimated to cost £2.4 million and, by reducing uncertainty in the evidence, would avoid £19.6 million in costs of incorrect management decisions for eligible patients over the next 10 years.

Conclusion

The PAAP was considered cost-effective, but significant uncertainty remained. Future trials with adequate power and longer follow-up are needed to determine the most cost-effective models for penicillin allergy testing.

Trial registration number

ISRCTN20579216.

Public health assistance for people with haemophilia in Brazil (PATCH study): a cross-sectional study protocol

Por: Roberti · M. d. R. F. · Gea · Y. R. e. A. · Marinho · I. A. · Inacio · P. P. · Camelo · R. M. · de Castro · T. F. · Batista · S. R. R.
Introduction

Haemophilia is a rare inherited bleeding disorder with complex support and costly treatment. Comprehensive care for people with haemophilia (PwH) must take place in structured and continuously evaluated treatment centres. The aim of the Public Assistance for People with Haemophilia in Brazil Project (PATCH Project) is to assess the infrastructure, human resources and healthcare delivery processes of Brazilian Blood Centres (BC) involved in the provision of haemophilia care.

Methods and analysis

This is a nationwide cross-sectional study involving 98 BC across Brazil’s 26 states and the Federal District, focusing on the care provided to PwH. A self-administered structured questionnaire was prepared, based on national and international recommendations for management, treatment and outcomes assessment in PwH. The criteria of the World Federation of Haemophilia and the European Association for Haemophilia and Allied Disorders will be used to define standards of quality.

Ethics and dissemination

Ethical approval for this study was granted by the Human Research Ethics Committee of the Federal University of Goiás, the coordinating centre (protocol CAAE 53863221.8.0000.5078), and subsequently by all participating institutions. Written informed consent is obtained from all participants prior to enrolment. Study findings will be disseminated through publication in peer-reviewed journals and presentation at international scientific conferences. Research data will be managed in accordance with ethical and legal standards and will be made available on reasonable request to support future investigations.

Protocol registration

Not applicable

Perception of primary-secondary care collaboration among general practitioners and specialists and the perceived potential for innovation: an exploratory qualitative study

Objectives

Our objective was to examine the barriers and facilitators encountered by primary and secondary healthcare professionals when collaborating at the care continuum between primary and secondary care. We aimed to identify specific challenges, observed benefits and proposed changes. By analysing these experiences and identifying opportunities for redesign, we aimed to define specific domains that could improve collaboration, thereby supporting sustainable access to and quality of care in the face of rising demand and constrained resources.

Design

A qualitative exploratory study using semi-structured interview data guided by two domains of the Consolidated Framework for Implementation Research (CFIR), including Inner Setting—Tension for Change and Individual Characteristics, as well as selected implementation outcomes defined by Proctor et al, all viewed through a service (re)design lens.

Setting

Consultation and communication between primary and secondary healthcare professionals in a Dutch urbanised area.

Participants

37 users of collaboration services (eg, telephone, correspondence) were interviewed between August 2021 and October 2022, including 14 general practitioners (GPs) (10 females, 4 males) and 23 specialists (10 females, 13 males).

Results

Four key domains with subthemes, subdivided per operation and CFIR domain, were identified as central to optimising the collaboration of professionals within the primary-secondary care continuum: (1) software and record integration; (2) seamless personal interaction; (3) eliminating a sense of ‘us vs them’ and (4) gaps in continuity of care.

Conclusions

This study reveals that healthcare professionals in both primary and secondary care face similar collaboration challenges due to system-level issues and inadequate collaboration tools, leading to increased workload, miscommunication and reduced quality of care. Improving collaboration between GPs and specialists requires not only adjustments to individual services, but a comprehensive overhaul of the referral and back-referral process. A more integrated approach, addressing key domains, is crucial for enhancing care quality, streamlining workflows and improving health outcomes.

Testing psychosocial work adversities as a necessary condition for work-related emotional exhaustion in young workers: a cross-sectional necessary condition analysis on a national general working population-based survey

Por: Schelvis · R. M. C. · van Veen · M. · Tamminga · S. J. · Oude Hengel · K. M. · Nieuwenhuijsen · K. · Boot · C. R. L. · Dul · J.
Objectives

Being exposed to adverse psychosocial working conditions contributes to poor mental health in young workers. This study explores whether psychosocial work adversities are a necessary condition for work-related emotional exhaustion in young workers.

Design

Data from the ‘Netherlands Working Condition Survey 2021’ was used. By applying a novel method called Necessary Condition Analysis, we tested two psychosocial work adversities as necessary conditions for high work-related emotional exhaustion in young workers: (1) a composite score of high job demands and low job resources and (2) a composite score of high job demands. Additionally, we tested whether the threshold for job demands as a necessary condition for high work-related emotional exhaustion differed for young workers with low versus high resources.

Setting

Secondary data analysis on a national working population-based survey.

Participants

The sample included 5791 young workers in the Netherlands (aged

Primary outcome measure

Work-related emotional exhaustion.

Results

A high level of the composite on job demands and job resources is necessary for a high level of work-related emotional exhaustion in young workers (effect size=0.11, p

Conclusions

Both psychosocial work adversities were necessary conditions for high work-related emotional exhaustion in young workers. The necessity threshold for job demands was higher for young workers with high job resources, compared with the group with low resources. This indicates that removing psychosocial work adversities and ensuring the presence of job resources might contribute to the prevention of high work-related emotional exhaustion in young workers.

Readiness Brain Operation Optimization Training (ReBOOT) protocol: a feasibility randomised controlled trial for a cognitive prehabilitation programme for epilepsy surgery conducted at Cleveland Clinic, USA

Por: Arrotta · K. · Babiker · S. · Lake · J. · Thompson · N. · Lioi · A. · Najm · I. · Busch · R. M.
Introduction

Risk of cognitive decline following epilepsy surgery can be a significant barrier for patients pursuing surgery, and post-surgical cognitive changes can impact quality of life (QOL), surgical satisfaction and functional independence. Readiness Brain Operation Optimization Training (ReBOOT) is a virtual cognitive prehabilitation intervention that provides patients with psychoeducation and cognitive strategies prior to surgery to increase pre-surgical preparedness and post-surgical functional independence in the circumstance that a patient experiences cognitive decline after surgery. The primary aim of this feasibility trial is to evaluate the acceptability, adherence and procedural feasibility of implementing ReBOOT in patients being evaluated for epilepsy surgery. Secondary, explorative objectives include examining preliminary trends in QOL, compensatory strategy use, cognitive function and psychosocial outcomes to inform a future definitive trial.

Methods and analysis

This is a single-centre, parallel-group, feasibility randomised controlled trial of a standardised cognitive prehabilitation programme for patients who are considering epilepsy surgery. Participants are randomly assigned to intervention (n=32) or control groups (n=32). The intervention group is enrolled in ReBOOT, a virtual programme that includes two 1-hour individual sessions and four 1-hour group sessions. Feasibility outcomes include attendance, homework adherence, attrition and participant satisfaction for participants randomised to the intervention group. Exploratory analyses will use longitudinal linear mixed-effects models to describe trends in exploratory outcomes over time. Data will be used to refine procedures and estimate parameters (eg, effect sizes and variance) for a future fully powered trial.

Ethics and dissemination

Cleveland Clinic Institutional Review Board approved the study protocol, which is publicly available and registered on the National Institutes of Health ClinicalTrials.gov (NCT05992402) site. Results will be disseminated through conference presentations and academic publications, as well as shared with outside study sponsors (Society for Clinical Neuropsychology—Division 40 of the American Psychological Association; American Epilepsy Society).

Trial registration number

NCT05992402.

Clusters of adolescent pregnancies and neonatal deaths in Sao Paulo state, Brazil: a population-based spatial analysis with a socioeconomic approach

Objective

Adolescent pregnancy is a global issue. Early childbearing is strongly linked to poverty and negative health outcomes, including increased neonatal death risk. This study explores spatial patterns of adolescent pregnancies and neonatal deaths and their association with socioeconomic characteristics.

Design

This population-based study used spatial analysis techniques to investigate the geographical distribution of adolescent pregnancies, socioeconomic characteristics and neonatal mortality rate (NMR).

Setting

The 645 municipalities of State of Sao Paulo, Brazil.

Participants

All live births to mothers residing in the State of Sao Paulo, Brazil, between 2004 and 2020.

Primary and secondary outcome measures

The socioeconomic indicators used were: municipal human development index and per capita income (PCI). Spatial patterns were assessed for spatial autocorrelation (Moran’s I, LISA), and smoothed using local Bayesian estimation. Spearman’s correlation was used to ascertain the relationship between the percentage of live births to adolescent mothers and socioeconomic indexes. This calculation was also undertaken between different maternal age groups of NMR.

Results

The study analysed over 10 million live births, with 14.3% attributed to adolescent mothers. Spatial analysis revealed significant clustering of adolescent pregnancies, strongly associated with lower socioeconomic indicators. NMR also exhibited spatial clustering, particularly after smoothing. Statistically significant differences were observed in PCI medians between high–high and low–low clusters for adolescent births. High and low incidence areas of NMR, both in all maternal ages and stratified by adolescent and non-adolescent mothers, demonstrated considerable overlap.

Conclusion

The results indicated the existence of clustering areas of adolescent pregnancy and neonatal deaths and suggested that the prevalence of births to adolescent mothers is not distributed equally and is higher in lower socioeconomic developed areas.

Cohort profile: a prenatal birth cohort study of intergenerational risk and resilience after conflict and forced displacement

Por: Wuermli · A. · Hiott · M. C. · Ugarte · E. · Rahman · M. S. · Elahi · M. · Rahim · A. · Dutta · G. K. · Ahamed · M. S. · Roy · B. R. · Akhter · R. M. · Hossain · E. · Michael · D. · Ayrin · T. K. · Haseen · S. H. · Alam · R. B. · Ratul · T. I. · Horaira · M. A. · Gladstone · M. · Sanin · K.
Purpose

As of 2024, 123.2 million people had been forcibly displaced as a result of persecution, armed conflict or climate-related catastrophes, and these numbers are predicted to rise. There is a growing awareness of possible intergenerational effects of trauma on life-course health and well-being, however few studies have followed individuals longitudinally starting prenatally. This paper describes the first large prenatal birth cohort study in a refugee context in a lower middle-income country. This study aims to investigate the potential lifespan health and developmental implications of being born into a protracted humanitarian context, and what factors can buffer from the adversity posed by conflict and displacement.

Participants

We outline our approach of recruiting, consenting and gathering data from pregnant Rohingya refugee and host community women (N=2888; 80% Rohingya) over the course of 12 months in Cox’s Bazar, Bangladesh.

Findings to date

A fifth wave of data collection, when children were 6 months old, was completed in April 2025. Rohingya women were substantially less literate; were marrying and having children at slightly younger ages, were more likely to live in crowded, resource-limited households and exhibited higher rates of clinically significant post-traumatic stress disorder and anxiety than host community women.

Future plans

There is a critical need for research in displaced populations in order to elucidate potentially lasting transgenerational impacts of experiencing conflict and displacement trauma, and the prenatal and postnatal factors that support health and development across the life span. The next follow-up is planned when the children turn 36 months of age (starting March 2026).

Diagnosing deep vein thrombosis early in critically ill patients (DETECT) trial: a protocol for a randomised controlled trial

Por: Arabi · Y. M. · Alenezi · F. · Al-Hameed · F. · al Humedi · H. I. · Kharaba · A. · Alhazzani · W. · Alshahrani · M. S. S. · Algethamy · H. · Maghrabi · K. · Chalabi · J. · Ardah · H. I. · Alahmari · A. M. · AlQahtani · R. M. · Ababtain · A. A. · Al-Filfil · W. A. M. · Al-Fares · A. A.
Introduction

Deep vein thrombosis (DVT) in critically ill patients is often undetected. However, it is unclear whether ultrasound surveillance for early detection of DVT in high-risk medical-surgical intensive care unit (ICU) patients improves patients’ outcomes. The DETECT trial (Diagnosing deep-vein thrombosis early in critically ill patients) evaluates the effect of twice-weekly bilateral lower limb ultrasound compared to usual care on 90-day mortality of critically ill adult patients admitted to medical, surgical and trauma ICUs.

Methods and analysis

The DETECT trial is an international, parallel-group, open-label, randomised trial, which will recruit 1800 critically ill adults from over 14 hospitals in Saudi Arabia and Kuwait. Eligible patients will be allocated to twice-weekly bilateral lower limb ultrasound or usual care. The primary outcome is 90-day mortality. Secondary outcomes include lower limb proximal DVT, pulmonary embolism and clinically important bleeding. The first patient was enrolled on 21 March 2023. As of 8 April 2025, 711 patients have been enrolled from 14 centres in Saudi Arabia and Kuwait. The first interim analysis was conducted on 14 May 2025. We expect to complete recruitment by December 2026.

Ethics and dissemination

Institutional review boards (IRBs) of each participating institution approved the study. We plan to publish the results in peer-reviewed journals and present the findings at international critical care conferences.

Trial registration number

Clinicaltrials.gov: NCT05112705, registered on 9-11-2021.

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