Women who use drugs in Tanzania face a disproportionately high burden of HIV and mental health disorders. Despite the availability of pre-exposure prophylaxis (PrEP), uptake remains low, highlighting the need for integrated, scalable interventions that address co-occurring substance use and mental health challenges. Motivational interviewing (MI) and cognitive-behavioural approaches, such as the Common Elements Treatment Approach (CETA), show promise for enhancing HIV prevention outcomes in this population. This study presents the protocol for a pilot feasibility trial assessing the acceptability, feasibility and preliminary efficacy of MI for PrEP (MI-PrEP) and a combined CETA and MI-PrEP intervention (CETA + MI-PrEP) to improve PrEP engagement among women who use drugs in Tanzania.

This individually randomised, parallel-group pilot trial will be conducted in Dar es Salaam, Tanzania, guided by the situated Information, Motivation and Behavioral Skills model. Eligible participants are adult women who use heroin, report recent drug-related or sex-related HIV risk behaviours, are HIV-negative and exhibit symptoms of depression, anxiety or post-traumatic stress disorder. Participants are randomised to one of three arms: MI-PrEP, CETA + MI-PrEP or enhanced treatment as usual. Interventions are delivered face-to-face by trained counsellors. Feasibility and acceptability will be assessed using recruitment and retention data, surveys and qualitative interviews. Preliminary effects will be measured for PrEP initiation, symptoms of common mental disorders and substance use.

Ethical approval has been obtained from the Johns Hopkins Bloomberg School of Public Health Institutional Review Board (25580), the Muhimbili University of Health and Allied Sciences Ethics Review Committee (MUHAS-REC-12-2023-1994) and the National Health Research Ethics Committee at the National Institute for Medical Research in Tanzania (NIMR/HQ/R.8a/Vol.IX/4830). Results will be disseminated through ClinicalTrials.gov, peer-reviewed publications, conferences, presentations and research briefings to community stakeholders.

ClinicalTrials.gov ID: NCT06835751. Initially registered 14 February 2025, https://clinicaltrials.gov/study/NCT06835751, last updated 5 December 2025.

Chronic dyspnoea is a prevalent symptom, and primary care is ideally placed to identify and manage it. However, chronic dyspnoea is under-reported by patients and can be a diagnostic dilemma for practitioners. A fully automated system of patient screening, coupled with a clinical decision support system (CDSS) that uses a validated and evidence-based dyspnoea algorithm, may improve detection, diagnosis and management of the condition. There is currently no CDSS validated for chronic dyspnoea diagnosis and management in primary care in Australia. The objectives of this study are to assess the clinical impact of a CDSS for chronic dyspnoea in primary care. We hypothesise that the use of the CDSS will lead to a clinically significant improvement in patient-reported dyspnoea scores, reduced time to diagnosis and healthcare costs at 12 months compared with standard care.

The BREATHE study is an open-label, cluster-randomised controlled trial of standard of care compared with a CDSS. General practices (n=40) in metropolitan, regional/rural and rural/remote settings will be recruited and randomised equally to pre-screening for chronic dyspnoea and usual standard-of-care management or pre-screening and CDSS-guided management. The CDSS includes an algorithm derived from a robust data and clinical knowledge model and incorporates evidence-based recommendations for the assessment and management of chronic dyspnoea. It is integrated into general practice medical software systems, fitting in the workflow of general practitioners (GPs). Eligible patients will be ≥18 years old and will have previously consented to receive SMS communication from their practice. In-scope patients will receive an automated text message prior to their GP appointment and will be screened for chronic dyspnoea (≥4 weeks). Patients identified with chronic dyspnoea will be invited to participate in the BREATHE study and followed up for 12 months. The primary outcome is improvement in the Dyspnoea-12 (D-12) score from baseline to 12 months, measured by the Dyspnoea-12 (D-12) questionnaire. Secondary outcomes include disease-specific questionnaires to assess changes in clinical outcomes, time to final diagnosis, quality of life, healthcare utilisation and costs incurred to patients.

The trial is registered at ANZCTR (ACTRN12624001451594). ANZCTR is a primary registry that meets the requirements of the ICMJE and is listed on the ICTRP Registry Network.

The study protocol has been approved by the University of New South Wales Human Research Ethics Committee (HREC) (iRECS6645) and complies with the National Health and Medical Research Council ethical guidelines. Participating practices and each GP will provide written, informed consent. All patients being screened will provide electronic informed consent. Results of the study will be disseminated through various forums, including peer-reviewed publications and presentation at national and international conferences. Following the study, participating practices will be provided with a summary of the findings of the study, together with a full copy of any publications and a plain language statement for participants, which will be made available in the practice reception area.

For people whose stroke risk would be reduced by taking a long-term oral anticoagulant (OAC), it is important to implement effective strategies to support medication initiation, adherence and persistence. To do this, a better understanding of the factors associated with implementation of interventions to optimise OAC management is needed.

This scoping review aimed to summarise the evidence-based characteristics associated with implementing interventions designed to optimise long-term OAC adherence.

Primary research (published post-2000) evaluating any intervention designed to optimise implementation of long-term OAC for stroke prevention by way of change in OAC services, staff or patient behaviour.

Five databases (MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycInfo, Cochrane Library) were searched from 1 January 2000 to 4 August 2023 using a combination of terms relating to population, intervention and study design.

Titles/abstracts were screened by at least one reviewer. Data from each full text were abstracted (with 20% double-checked for accuracy) and its implementation content reviewed, guided by the Expert Recommendations for Implementing Change strategies.

216 studies were included, with varying descriptive reporting of implementation strategies, and only 61 (28%) self-identifying as an implementation study. The median number of implementation strategies used was three, with recently published studies (2015 onwards), those including patients receiving either direct OACs (DOACs) or vitamin K antagonists (VKAs) and those including multiple intervention targets (service, staff or patients) associated with using more implementation strategies. ‘Train and educate stakeholders’ strategies were the most commonly used, and ‘Adapt and tailor to the context’ strategies were the least used by included studies. Conversely, self-defined implementation studies were less likely to use ‘Train and educate stakeholders’ strategies, although they were positively associated with use of ‘Adapt and tailor to the context’. ‘Use evaluative & iterative’ strategies were used more frequently in studies where patients used either VKAs or DOACs, or were published more recently.

Studies need to self-define as implementation studies, improve implementation strategy reporting and be transparently registered, alongside conducting process evaluations or more richly describing implementation processes. Future research could explore why some implementation strategies are used more than others and whether aligning strategy clusters with intervention targets results in clinically significant differences in patient care.

The primary objective of this clinical trial is to determine the clinical and cost-effectiveness of psychoeducation and emotional stabilisation (PES), together with eye movement desensitisation and reprocessing (EMDR) plus treatment-as-usual (TAU) in reducing symptoms of post-traumatic stress disorder (PTSD) among adults with intellectual disabilities compared with TAU. Secondary objectives include: (1) determining whether PES/EMDR plus TAU is superior to TAU in improving mental health problems and quality of life (QoL) among adults with intellectual disabilities who had a diagnosis of PTSD and (2) completing a process evaluation to examine intervention implementation and acceptability.

This is a two-arm parallel single-blind randomised controlled trial comparing PES-EMDR+TAU to TAU including an internal pilot phase. Outcome data will be captured prior to randomisation, and at 4 (after PES), 8 (after EMDR) and 14 months postrandomisation by masked assessors. 144 adults with intellectual disabilities with a diagnosis of PTSD will be allocated (1:1) randomly using minimisation from National Health Service (NHS) community and inpatients services for adults with intellectual disabilities in England. Participants are eligible to take part in this trial if: (1) they are aged 18 or older, but younger than 66, (2) have a Full Scale IQ

The primary outcome will be assessed using an intention-to-treat analysis. Baseline characteristics will be compared between arms to determine whether any potentially influential imbalance occurred. The primary outcome will be analysed by analysis of covariance, adjusting for baseline values of the outcome and any variables used in the randomisation process. Secondary outcomes will be analysed using linear or logistic regression models as appropriate reflecting the distribution of the outcome variable. The treatment effect will be estimated as an adjusted difference between sample means, presented with 95% CIs and p values. A complier average causal effect analysis will be considered should the data availability be sufficient to estimate the impact of non-compliance. A series of subgroup analyses on the primary outcomes will be considered considering differences in the Impact of Event Scale–Intellectual Disabilities scores at 14 months for (1) differing levels of general intellectual functioning and (2) PTSD versus complex PTSD.

This clinical trial was designed to allow for conclusions about whether PES/EMDR+TAU is efficacious in reducing symptoms of PTSD, relative to TAU, for adults with intellectual disabilities. A favourable ethical opinion has been received from an NHS ethics committee in the UK. The findings from this trial will be published within peer-reviewed journals and shared at national and international conferences. We will also aim to record and distribute podcasts detailing our findings together with our partners.

ISRCTN35167485.

This project explores the feasibility of setting up a neuropsychiatric de-identified database (DiD) and a Research Register (RR) to collect, analyse, monitor and systematically report clinical data for people with intellectual disabilities (PwIDs) and epilepsy.

A multicentre project designed to collect de-identified data from clinical records at three adult ID specialist services in England and Wales and to develop an RR of PwID and epilepsy. Patients added to the DiD will be identified from patient clinic lists, clinic letters, in-house databases and electronic systems. Patients to be added to the RR will also be identified through attendance for regular review at clinic appointments. The collected data will be entered into the Research Electronic Data Capture (REDCap) database. Personal details of PwID and their consultees will also be collected from participants who consent to be on the RR. Around 600 PwID and epilepsy (200 per site) will be added to the DiD at the three sites, while around 45–60 participants (15–20 per site) are anticipated to be added to the RR. Data analysis will involve using descriptive statistics to summarise feasibility outcomes, such as screening and recruitment rates, as well as the completeness of the collected data. The characteristics of the participants (demographic, ID classification, clinical, epilepsy history and antiseizure medication) will be summarised descriptively. Progression will be assessed using the Red/Amber/Green stop-go criteria to determine if a national register should be created.

Ethical approval (24/NW/0210) has been obtained from the Northwest-Haydock Research Ethics Committee and the University of Plymouth Faculty Research Ethics and Integrity Committee (reference no. 5284). The project is funded by Jazz Pharmaceuticals as an independent investigator-initiated support grant and, as such, has received independent peer review.

NCT06780501.

Inequities in health status exist in New Zealand across the rural–urban spectrum. In parallel, rural–urban differences in health service utilisation vary by service type. Despite the New Zealand public health system being based on principles of universal access, equity and fairness, levels of health expenditure on rural and urban populations are not well understood. The purpose of the study is to undertake a rural–urban analysis of public health system expenditure, based on individual-level service utilisation and national pricing of health service events.

Individual-level service utilisation and pricing will be collated from national collection databases for all eligible users of publicly funded services. The analysis will include calendar years 2017–2024. Descriptive analysis and a two-part generalised linear regression model will be used to identify if rural–urban differences in expenditure exist, and what the association of rurality is with expenditure (if any). The model will also be used to identify geographic regions with expenditure levels that vary from those predicted using regression model weights. As the specific statistical approach will be determined by data attributes, this protocol outlines the intended approach to construct the analytical model.

Ethics approval was obtained from the University of Otago Human Research Ethics Committee (HD23/052). Māori consultation has been undertaken with the Ngāi Tahu Research Consultation Committee and will continue throughout the research process.

The aim of this work was to understand carer involvement in transitions of care from hospital to home in relation to medicines management. Specifically, via a realist review, to describe how carers provide support, to what extent do they support patients and under what circumstances are carers able to provide support towards patient care in relation to medicines management.

A realist review was conducted in line with a published protocol and as registered via PROSPERO (CRD42021262827). An initial programme theory (PT) was developed before searches of three databases, PubMed, CINHAL and EMBASE, were conducted in accordance with eligibility criteria. Data were extracted from eligible studies and synthesised into realist causal explanations in the form of Context-Mechanism-Outcome-Configurations (CMOCs) and the PT was refined. Throughout the review, a patient and PPIE group (n≥5) was involved, meeting five times, to inform the research focus and develop CMOCs and the PT by providing feedback and ensuring they capture the carer experience.

Following title and abstract screening of 4835 papers, the final number of included articles was 208. The evidence synthesis identified 31 CMOCs which were categorised into three themes: (1) continuum of support; (2) understanding the carers’ priorities, role and responsibilities through shared decision-making (SDM) and (3) access to appropriate materials, resources and support information. These themes were formed into an updated PT with accompanying narrative that explained the transition from hospital to home involving carers in medicines management and identified possible areas for future intervention development.

This review provides insights and recommendations on how carers can be better supported when managing medicines when patients are discharged from hospital. Carers need a continuum of support throughout and following the transition. Healthcare professionals can support this by understanding the carer’s priorities, role and responsibilities through SDM during the hospital stay. Consequently, carers can then be offered access to appropriate materials, resources and support information which allows them to provide better care relating to medicines in the long term.

Digital inclusion (which includes skills, accessibility and connectivity to the internet and digital devices) is a ‘super social determinant of health’ because it affects many aspects of life that influence health. Older people are especially vulnerable to digital exclusion. Existing digital inclusion interventions are commonly offered opportunistically to people who come into contact with services, or in specific locations. The lack of systematic identification of need unintentionally excludes older people who may be most in need of support, and that support is not addressing their needs.

This multi-method project includes six workstreams: (1) A survey of people aged 65+ to ask about digital use and engagement. Survey data will be used to develop a model that predicts digital exclusion from data available in primary care records. (2) Testing, via a further survey, the external validity of the model to identify those who are digitally excluded. (3) Interviews with community service providers to identify, understand and define the components of existing digital inclusion services for older people. Concurrently, a rapid review of the literature will identify evidence for interventions aimed at supporting digitally excluded adults aged 65+. (4) Interviews with people aged 65+ representing a range of digital use will explore factors from the COM-B model that influence digital behaviours—their capability (C), opportunity (O) and motivation (M) relating to digital engagement. Analysis outputs will identify the intersectional nature of barriers or facilitators to digital inclusion. (5) Co-production workshops with older people and community service providers will identify key components of interventions that are required to address digital exclusion. Components will be mapped against existing interventions, and the ‘best fit’ intervention(s) refined. An implementation plan will be developed in parallel. (6) Feasibility testing of the refined intervention(s) to assess acceptability and obtain feedback on content and delivery mechanisms.

This study was approved by the Yorkshire & The Humber - Bradford Leeds Research Ethics Committee on 23 October 2023 (ref. 23/YH/0234). Findings will be disseminated in academic journals and shared at webinars, seminars, conferences and events arranged by organisations operating across the digital inclusion and older people fields.

https://www.isrctn.com/ISRCTN18306736

Gestational diabetes mellitus (GDM) is common in pregnancy and is increasing in prevalence. It is associated with an increased risk of maternal and perinatal complications if not diagnosed and managed early. Most guidelines suggest making a diagnosis of GDM using an oral glucose tolerance test (OGTT) between 24 and 28 weeks of pregnancy at which stage there still is an increased risk of complications. Increased beta-cell secretory product concentrations have been observed prior to changes in glycaemia and can potentially be used as an early marker to diagnose and assess risk of developing GDM.

The study was a prospective, longitudinal cohort study. OGTTs were carried out at visit one: 16–18 weeks and visit two: 24–28 weeks gestation in pregnant women with at least one risk factor for GDM [Body Mass Index >30 kg/m², previous macrosomic baby (>4.5 kg), previous GDM, first degree relative with type 2 diabetes mellitus (T2DM)]. Blood sampling was performed at fasting, 30 min, 1 and 2 hours following a 75-g oral glucose load. Samples were analysed for glucose, total and intact proinsulin, insulin and C-peptide. Hormonal concentrations at visit 1 were compared between those that remained normal glucose tolerant (NGT) and those that progressed to GDM at visit 2 using receiver operator characteristic (ROC) area under the curve (AUC) to assess for discrimination between the two groups.

Unfortunately, a smaller than planned sample size was recruited due to the start of COVID-19 pandemic midway through the study. 83 pregnant women had OGTT at visit 1. Of these, 12 reached the threshold for GDM at visit 1 and were excluded. In total, data from 66 patients were included for analysis (5 Did Not Attend). Visit 1 hormone comparisons were carried out between 51 who remained NGT and 15 who progressed to GDM at visit 2. There were no significant differences at each time point in ROC AUC between the two groups for total and intact proinsulin and insulin. However, there were significant differences observed in C-peptide ROC AUC at 30 (p=0.041) and 60 min (p=0.003) between the two groups.

This study did not demonstrate significant increase in early proinsulin concentrations in patients that developed GDM. However, there were differences in C-peptide concentrations. The COVID-19 pandemic restricted the recruitment of patient numbers and further studies in a larger cohort will be needed to validate these findings.

ISRCTN16416602.

Cystic fibrosis (CF) is a genetic condition of impaired membrane electrolyte transport and is characterised by defects in the production and function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Ground-breaking CFTR modulator therapy has resulted in a notable shift in the clinical presentation and progressive nature of CF, across both pulmonary and extrapulmonary systems. Access to CFTR modulator therapies in people with CF is occurring in a staged, descending age process, with clinical trials focusing primarily on safety and efficacy. There is a lack of robust, real-world longitudinal data on CFTR modulator therapy in infants and young children where extrapulmonary outcomes such as growth, micronutrient status and pancreatic function are the key focus.

Pancreatic, nutritional and clinical outcomes in children 0–5 years with CF during the first 2 years of CFTR modulator therapy (PaNC) is a prospective cohort study involving all eight tertiary paediatric CF centres in Australia. Infants and children 4 months to 5 years of age who are eligible for elexacaftor/tezacaftor/ivacaftor (ETI) or ivacaftor (IVA) meet the inclusion criteria for PaNC, with a total eligible cohort of 303 children at the commencement of recruitment. The primary outcomes are change in weight-for-length/body mass index z score and change in serum micronutrient status, at 6–12 monthly intervals, during the first 2 years of treatment with ETI or IVA. Secondary outcomes include change in exocrine pancreatic function, measured by faecal elastase-1, change in the use and dose of pancreatic enzyme replacement therapy, nutritional and gastrointestinal therapies and change in sweat chloride levels. Linear mixed modelling will be used to analyse primary and secondary endpoints. This protocol is reported in accordance with ‘The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement’ reporting guidelines.

Overarching governance and ethics approval has been granted by Monash Health Human Research Ethics Committee, in addition to all eight sites receiving site-specific authorisation approvals prior to the commencement of recruitment. Opportunities for CF consumers to be involved in targeted dissemination plans will be initiated via CF Australia at the completion of the study period. Additionally, a summary of non-identifiable results will be provided to CF consumers and CF healthcare providers via scientific and lay conferences and via peer-reviewed journals.

ACTRN12624001185550; Pre-results.

We examined studies that analysed the spatial association of cancers with demographic, environmental, behavioural and/or socioeconomic factors and the statistical methods applied.

Systematic mapping review.

Web of Science (SSCI) (search on 28 July 2022), MEDLINE, SocINDEX and CINAHL (search on 4 August 2022), additional searches included grey literature.

(1) Focused on the constituent countries of the UK (England, Wales, Scotland and Northern Ireland) and its major regions (eg, the North West); (2) compared cancer(s) outcomes with demographic, environmental, behavioural and socioeconomic characteristics by applying methods to identify their spatial association; (3) reported cancer prevalence, incidence rates, relative risk or ORs for a risk factor or to an average level of cancer.

A standardised data extraction form was developed and for all studies, core data were extracted including bibliographic information, study design, geographical factors analysed, data aggregation level, methods applied and main findings. We described and synthesised the characteristics of the studies using summary tables, charts and graphs.

52 studies were included covering a variety of objectives and geographical scales. These studies considered different types of cancer, with the most common cancer types analysed being blood and lymphoid cell cancers. The most common methods used to assess the association between cancers and geographical level factors were regression analyses, with the majority being Poisson regression, then logistic and linear regression. Studies were usually conducted at ward and local authority level, or by exact point location when distances from putative risk sources were considered. The results were usually presented in plots or as tables, instead of maps.

Our results highlight the lack of consideration of spatially explicit models in the analysed studies, with the risk of having failed the assumption of independence in the data.

CRD42022349165.

There is a need for early, non-invasive and inexpensive biomarkers for Alzheimer’s disease (AD), which could serve as a proxy measure in prevention and intervention trials that might eventually be suitable for mass screening. People with Down syndrome (DS) are the largest patient group whose condition is associated with a genetically determined increased risk of AD. The REVEAL study aims to examine changes in the structure and function of the eye in individuals with DS compared with those with mild cognitive impairment (MCI) and cognitively healthy control (HC) individuals. REVEAL will also explore whether these changes are connected to inflammatory markers previously associated with AD.

The protocol describes a cross-sectional, non-interventional, single-centre study recruiting three cohorts, including (1) participants with DS (target n=50; age range, 6–60 years), (2) participants with MCI (target n=50; age range, 50–80 years) and (3) HC participants (target n=50; age range, 50–80 years). The primary research objective is to profile retinal, choroidal and lenticular status using a variety of eye imaging modalities and retinal functional testing to determine potential associations with cognitive status. The REVEAL study will also measure and compare established blood markers for AD and proteomic and transcriptomic marker profiles between DS, MCI and HC groups. Between-group differences will be assessed with an independent sample t-test and ² tests for normally distributed or binary measures, respectively. Multivariate regression analysis will be used to analyse parameters across all three cohorts. Data collection began in October 2023 and is expected to end in October 2025.

The study gained a favourable opinion from Health and Social Care Research Ethics Committee A (REC reference 22/NI/0158; approved on 2 December 2022; Amendment 22/0064 Amend 1, 5 April 2023; Amendment 22/0064 Amend 2; 23 May 2024; Amendment 22/0064 Amend 3; 25 June 2024; Amendment 22/0064 Amend 4; 16 January 2025; Amendment 22.0064 Amend 5; 9 May 2025; Amendment 22.0064 Amend 6; 9 June 2025). The study has also been reviewed and approved by the School of Biomedical Sciences Research Ethics Filter Committee within Ulster University. Findings from the REVEAL study will be presented to academic audiences at international conferences and peer-reviewed publications in targeted high-impact journals after data collection and analysis are complete. Dissemination activities will also include presentations at public events.