More than half of older adults living with Alzheimer’s disease and related dementias (ADRD) never receive a formal diagnosis, and when a diagnosis occurs, it is often years after symptom onset. Primary care clinicians are ideally positioned to detect ADRD early; however, current workflows lack scalable tools that support systematic identification and follow-up. The Passive Digital Marker (PDM), a machine learning model that uses structured electronic health record (EHR) data, can identify patients at elevated risk for ADRD without adding burden to clinicians. This protocol outlines a feasibility study to develop and evaluate a patient-informed secure messaging intervention paired with PDM-based risk stratification to enhance patient engagement in cognitive assessment in primary care settings.

This will be a non-randomised pilot study conducted across 12 single health system primary care clinics. The PDM will be applied to EHR data to identify patients aged ≥65 years who are at high risk for ADRD. High-risk patients will receive a co-designed secure message prior to and after upcoming primary care visits encouraging follow-up evaluation with a trained nurse, the Brain Health Navigator (BHN). The primary objectives are to: (1) determine the feasibility of applying the PDM to EHR data across 12 primary care clinics; (2) assess the feasibility of engaging patients identified as positive on the PDM through secure text messaging prior to a primary care encounter and (3) evaluate engagement with the BHN following secure text messaging. Study outcomes will assess the feasibility of implementing the PDM and secure messaging workflow, including identification of high-risk patients using the PDM, message delivery and patient engagement measured through message open rates, completion of cognitive concern questions and appointments scheduled with the BHN. Quantitative data will be analysed using descriptive statistics.

This study was deemed exempt as part of enhanced patient care. The findings will be disseminated through peer-reviewed publications, professional conferences, health system reports and public-facing communications.

NCT07016178.

Oligoprogressive disease (OPD) is a clinically significant pattern of progression observed in patients with oestrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer treated with endocrine therapy (ET) and cyclin-dependent kinase (CDK) 4/6 inhibitors. Stereotactic ablative body radiotherapy (SABR) is an emerging strategy that may ablate resistant subclones and prolong the benefit of systemic therapy. The AVATAR-II trial investigates whether the addition of SABR to continued systemic therapy can delay the need to change treatment strategy.

AVATAR-II is a multicentre, randomised, open-label, phase II randomised controlled trial enrolling 74 patients with histologically confirmed ER-positive, HER2-negative advanced breast cancer and 1–5 sites of extracranial OPD. Eligible patients must have demonstrated clinical benefit (stable disease or partial response) from ET and CDK4/6 inhibitors for at least 6 months prior to randomisation. Participants will be randomised 1:1 to either SABR to all OPD sites with continuation of current systemic therapy (Arm A) or physician’s choice of systemic therapy (Arm B). The primary endpoint is time to treatment failure, defined as progression not amenable to SABR, cessation of systemic therapy or death. The secondary endpoints include progression-free survival (PFS), PFS2, overall survival, treatment-related adverse events and patient-reported quality of life using the Functional Assessment of Cancer Therapy–Breast score.

This study received ethical approval from the Peter MacCallum Cancer Centre Human Research Ethics Committee (HREC), under approval number 25/45 and HREC reference HREC/105165/PMCC. Results of the study will be disseminated via peer-reviewed presentation at scientific conferences and open-access publication.

NCT06882499.

We examined the utility of quality indicators (QIs) for transcatheter aortic valve implantation (TAVI) in the assessment of TAVI care quality and variation in practice.

We performed a retrospective population-level cohort study in Ontario, Canada, where all residents receive publicly funded universal medical care. We examined the association between QI attainment and outcomes using multivariable hierarchical logistic models. We used median ORs to understand if variation in clinical outcomes between hospitals was attributable to variation in QI attainment.

We used all-comer registry data from the provincial CorHealth registry in Ontario, with linkage to administrative datasets using unique patient encoded identifiers.

TAVI recipients between 2018 and 2023 in Ontario, Canada.

We derived a unique set of QIs from internationally agreed ones.

The primary endpoint was a composite of all-cause mortality or rehospitalisation at 1 year from the date of TAVI.

Data from 9748 TAVI procedures were included between 2018 and 2023. We identified five feasible QIs, the majority of which had high compliance and minimal variation; the lone exception was the performance of transfemoral TAVI without general anaesthesia (median 0.87; IQR 0.78–0.93). Adherence to QIs was associated with a reduction in the composite endpoint. The strongest association was observed with multidisciplinary heart team involvement (defined as the presence of an interventional cardiologist and a cardiac surgeon) in the TAVI procedure (OR 0.67, 95% CI 0.50 to 0.90, p=0.007), the performance of transfemoral TAVI without general anaesthesia (OR 0.80, 95% CI 0.71 to 0.91, p<0.0004) and the utilisation of the transfemoral access (OR 0.84, 95% CI 0.69 to 1.04, p=0.10). However, variation in clinical outcomes following TAVI between hospitals was not attributable to variation in QI attainment. Falsification analysis suggests substantial residual confounding.

We developed a feasible set of QIs for TAVI and validated these QIs using routinely collected data from a large all-comer registry in Ontario. We have identified overall high quality of care for TAVI, but with some variation in practice, which in part is attributable to differences in patient factors. Our work suggests that QIs can inform quality improvement efforts by prompting future work into discretionary versus non-discretionary variation.

The Entebbe Mother and Baby Study (EMaBS) was established in 2001 to test the hypothesis that treating helminth infections during pregnancy and early childhood could improve children’s responses to Bacillus Calmette-Guérin (BCG) and other vaccines given in infancy and influence immune responses to other infectious pathogens. Follow-up was subsequently extended to address further research questions and continue to the present day.

Two thousand five hundred and seven pregnant women were recruited when attending antenatal services at Entebbe General Hospital, Uganda; 2345 resulting live-born children were enrolled into the EMaBS birth cohort.

Initial results from EMaBS showed that treating helminths in pregnancy and early childhood was safe and that treatment with albendazole reduced anaemia in mothers with heavy hookworm infections. Maternal anthelminthic treatment had small effects on infant response to tetanus immunisation, but no effect, either beneficial or detrimental on the occurrence of infectious diseases in childhood. However, treatment of helminths during pregnancy resulted in increased rates of eczema in early childhood, although this was not sustained to nine years. Subsequent work in early adolescence found that postnatal weight gain was important in the developmental programming of blood pressure in this population and current and early-life malaria modified blood pressure and lipid levels. We also showed that variation in host genes significantly shapes antibody responses to multiple childhood vaccines, highlighting genetics as a key determinant of vaccine performance.

Cohort ‘children’ are currently aged 19–22 years, and future plans focus on investigating longer term effects of early-life and childhood exposures. A new round of data collection is ongoing with the aim of determining the impact of early-life exposures on adult non-communicable disease risk. Work determining whether frequent childhood infections lead to specific epigenetic changes implicated in later disease development is also underway.

The EMaBS began as a randomised controlled trial (ISRCTN32849447). Two further randomised controlled trials have been nested within the cohort: TB042 (NCT03681860) and POPVAC C (ISRCTN10482904).

Anxiety disorders are the most common youth mental health problems in the USA. Most children do not receive treatment and among the few who do, many do not experience significant improvement. Thus, there is an urgent need to identify novel intervention targets to improve treatments for childhood anxiety. Past research demonstrates that parent anxiety plays a role in the development and maintenance of child anxiety, but empirical evidence for the mechanisms that drive this transmission is lacking. Interpretation bias, or the tendency to perceive threat in ambiguous situations, may lead parents to engage in anxiety-promoting parenting behaviours, which may transfer this cognitive bias to their children, resulting in youth anxiety. Given the current lack of empirical evidence supporting this theorised mechanism, the present study will test effects of parent interpretation bias on parent behaviour and child interpretation bias. Our central hypothesis is that parent interpretation bias influences child interpretation bias through its effects on anxiety-promoting parenting behaviours. The study will also evaluate potential moderators of these theorised relationships, such as parent sex, race and ethnicity, parent anxiety, child age and child sex.

We will randomise 300 parents of children aged 7–12 to a smartphone app-delivered interpretation bias manipulation condition or a self-assessment control condition. Through a series of study assessments over the course of 3 months, parents and children will complete self-report, interview, behavioural and daily diary measures to assess the primary proximal outcome (anxiety-promoting parenting behaviours), the secondary distal outcome (child interpretation bias) and moderators. To test our central hypothesis, we will first use hierarchical linear modelling to assess whether parents in the interpretation bias manipulation condition show fewer anxiety-promoting parenting behaviours compared with control, and whether children of those parents show improved interpretation bias compared with control. We will then implement mediation models to evaluate whether a reduction in anxiety-promoting parenting behaviours mediates the association between parent and child interpretation bias.

Ethical approval for this study was granted by the Mass General Brigham Institutional Review Board (2022P003245). We will disseminate the results of this study to the scientific community, clinical community and the public through several channels such as peer-reviewed publications in scientific journals, national conferences, hospital lectures, press releases and Psychology Today blog posts.

NCT05665491.

To evaluate the association between use of newer glucagon-like peptide-1 receptor agonists (GLP-1 RAs; semaglutide, tirzepatide) and alcohol-related hospitalisations among adults with alcohol use disorder (AUD) and type 2 diabetes (T2D) or obesity.

Retrospective cohort study using target trial emulation.

Electronic health record data from a collective of US healthcare systems.

Adults with AUD and T2D or obesity who started a newer GLP-1 RA (semaglutide or tirzepatide) or a relevant active comparator between 1 January 2018 and 31 December 2024.

Initiation of a newer GLP-1 RA compared with an active comparator across four target trials: (1) anti-diabetic medication (ADM) trial, (2) anti-obesity medication (AOM) trial, (3) medications for alcohol use disorder with T2D (MAUD-T2D) trial, and (4) medications for alcohol use disorder with obesity (MAUD-obesity) trial.

Time to first alcohol-related emergency department visits or hospitalisation within 1 year of treatment initiation. Non-alcohol-related hospitalisation was assessed as a negative control outcome. Propensity score based methods (weighting and matching) were used to control confounding and Cox proportional hazards models were used to estimate treatment effects.

A total of 40 703 adults met study criteria, including 18 676 in the ADM trial, 9391 in the AOM trial, 8942 in the MAUD-T2D trial and 11 198 in the MAUD-obesity trial. Initiation of a newer GLP-1 RA was associated with a lower hazard of alcohol-related hospitalisation in the ADM trial (HR 0.74, 95% CI 0.62 to 0.89 vs sulfonylureas; HR 0.78, 95% CI 0.65 to 0.92 vs other ADMs), the AOM trial (HR 0.68, 95% CI 0.54 to 0.85 vs other AOMs), the MAUD-T2D trial (HR 0.37, 95% CI 0.29 to 0.46) and the MAUD-obesity trial (HR 0.35, 95% CI 0.26 to 0.47).

Among adults with AUD and T2D or obesity, initiation of newer GLP-1 RAs was associated with a lower observed risk of alcohol-related hospitalisation.

Drowning remains a substantial global health challenge, and research in this area predominantly relies on observational study designs due to ethical, practical and administrative limitations. Although the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement is available, adherence within the drowning research community has been inconsistent and frequently incomplete. Consequently, essential methodological components and drowning-specific factors are often under-reported or inconsistently described, impeding quality, reproducibility, critical appraisal and evidence synthesis.

This protocol outlines the development of an extension to the STROBE statement, specifically for reporting observational studies in drowning epidemiology (STROBE-D). The proposed extension aims to provide structured guidance for authors, reviewers and editors, thereby enhancing the clarity, transparency and comparability of reporting practices.

The development of the STROBE-D statement will follow established recommendations and methodological frameworks for guideline creation. The process will include a scoping review and initial draft preparation, a two-round modified Delphi process using surveys with multidisciplinary and international expert participation, an expert consensus meeting to finalise the content and manuscript, public comment with interest-holder involvement and a final revision before submission for peer review.

The Committee on Health Research Ethics in the Region Zealand of Denmark waived the need for ethical approval as this is a consensus study (EMN-2025-09099). Findings will be disseminated through open access peer-reviewed publications, targeted communication through professional networks, conferences and social media platforms. The STROBE-D statement will serve as an extension to the STROBE statement, specifically tailored to observational studies in drowning epidemiology to improve consistency and transparency. Simultaneous publications of the original STROBE-D statement and the accompanying explanation and elaboration paper will be pursued in line with existing best practices.

Avoidable and unfair variation in access to palliative care exists for different groups of people and communities. Primary and community care teams deliver most palliative care and care to people at the end of life at home but the quality of care provided is variable. This is an under-researched area and receives little attention in service design and policy. This study will investigate the key contexts, resources and components required for an integrated approach to palliative care to deliver improved and more equitable outcomes for patients and carers.

This mixed-methods study adopts a realist methodological approach, and comprises four work packages:

A multi-perspective mixed-methods study to understand patient preferences and priorities in palliative care, prioritising recruitment of patients and family members/carers from areas of socioeconomic deprivation. Data collection will comprise: (1) qualitative interviews, (2) review of patient case notes and (3) a discrete choice experiment. Realist analysis will result in the development of theory based on the identification of the key contexts and underlying mechanisms required to achieve beneficial outcomes through an integrated approach to palliative care.

A realist evaluation of existing integrated models of palliative care will involve theory-refining interviews and theory-consolidating focus groups with professionals working in three different service areas.

Dynamic simulation modelling of the healthcare resources needed to deliver the proposed integrated approach, ensuring quality and equity.

The theoretical and economic modelling will be tested out at two expert stakeholder workshops to determine the key enablers to implementation in practice.

The study design was informed by patient and public involvement (PPI) with 16 patients and members of the public from diverse and socioeconomically deprived communities for 12 months in a National Institute for Health and Care Research-funded palliative care partnership. PPI will be continuous throughout the study, prioritising inclusivity.

Ethical approval was obtained from the East of Scotland Research Ethics Service Research Ethics Committee 2, on 20 August 2025 (IRAS ID: 354755) and Health Research Authority approval on 1 October 2025. The targeted dissemination strategy will include outputs and resources for key audiences including patients and families, professionals in primary care and specialist palliative care and service commissioners. The results will inform service delivery to reduce inequities and optimise the use of finite resources to maximise impact.

The study is registered with the ISRCTN UK Clinical Study Registry: https://www.isrctn.com/ISRCTN61092011.

School-aged children frequently experience psychological distress due to academic pressures, a challenge that is often more severe for those from underserved and minority communities. This study aims to evaluate the effectiveness of mental health interventions implemented in school and community settings for children aged 5 to 19. It also seeks to compare the outcomes between children from minority and underserved populations and their peers.

This systematic review will follow Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to identify relevant studies. Major databases will be searched using a structured search strategy developed by the research team. The review will include randomised controlled trials (RCTs) that assess the impact of interventions conducted in school or community settings to prevent psychological distress—specifically depression, anxiety and stress. To minimise bias, two reviewers will independently select studies and extract data at various stages. The quality of included studies will be assessed. A meta-analysis will be conducted to compare intervention outcomes between children from underserved/minority communities and other children. Pooled prevalence rates and subgroup analyses will be used to explore differences in effectiveness. Heterogeneity among studies and publication bias will also be assessed. Meta-analyses of proportions, ORs and relative risks will be conducted using a random-effects model to estimate effect sizes from multivariate analyses.

Ethical approval was not required, as this study involved secondary analysis of published literature and did not involve human participants. To date, no systematic review has comprehensively compared school-based and community-based interventions in terms of their effectiveness in addressing anxiety, depression and stress among school-aged children. This review aims to fill that gap by providing clinical insights into the comparative effectiveness of various intervention types and settings.

CRD42023479389.

Cocaine use disorder (CUD) is a significant public health concern in the USA, with considerable prevalence and mortality and no Food and Drug Administration (FDA)-approved pharmacotherapies. Recent advances in addiction science emphasise the need for novel, mechanism-based treatments. Glucagon-like peptide-1 receptor agonists, such as semaglutide, have shown promise in modulating reward-related behaviours and may offer therapeutic benefits for CUD. We present a study protocol evaluating semaglutide, as an adjunct to cognitive behavioural therapy (CBT), as a novel approach for treating CUD.

This is a randomised, double-blind, placebo-controlled trial enrolling 75 treatment-seeking adults with CUD. Participants will be randomised 1:1 to receive either once-weekly semaglutide (0.25–1.0 mg) or placebo injections over 14 weeks, alongside weekly individual CBT. Primary outcomes include changes in neurophysiological reactivity to drug-related and non-drug-related motivationally relevant cues (late positive potential), behavioural economics (cocaine demand), craving (Cocaine Craving Questionnaire) and cocaine use (self-report, urine drug screens). Exploratory aims assess associations between mechanistic changes and cocaine use, consumption of other substances (ie, tobacco, alcohol and cannabis) and dose–response relationships. Data will be analysed using Bayesian statistical methods using an intention-to-treat approach.

The study has been approved by the UTHealth Committee for the Protection of Human Subjects (HSC-MS-25-0412) and is registered on ClinicalTrials.gov. All participants will provide written informed consent. Findings will be disseminated through peer-reviewed publications and scientific conferences.

NCT07227948.