Cost-consequence analysis of an e-health intervention to reduce distress in dementia carers: results from the iSupport randomised controlled trial

Objective
The use of e-health interventions has grown in demand due to their accessibility, low implementation costs and their potential to improve the health and well-being of people across a large geographical area. Despite these potential benefits, little is known about the cost-effectiveness of self-guided e-health interventions. The aim of the study was to compare the cost and consequences of ‘iSupport’, an e-health intervention to reduce mental health issues in dementia carers.

Design
A cost-consequence analysis (CCA) of a multi-centre, single-blind randomised controlled trial of iSupport. The CCA was conducted from a public sector (National Health Service, social care and local authority) perspective plus a wider societal perspective. Delivery costs of iSupport were collected using a bottom-up micro-costing approach.

Setting
352 participants were recruited from three centres in England, Wales and Scotland.

Participants
Participants eligible for inclusion were adults over the age of 18 years who self-identified as an unpaid carer with at least 6 months of experience caring for an individual with a diagnosis of dementia. Between 12 November 2021 and 31 March 2023, 2332 carers were invited to take part in the study. 352 participants were randomised: 175 randomised to the iSupport intervention group and 177 to the usual care control group. The mean age of participants in the intervention and control groups was 63 and 62, respectively.

Main outcome measures
The CCA presented the disaggregated costs and health-related quality of life measured using the EuroQol five-dimension.

Results
There was no significant difference in generic health-related quality of life measured using the EQ-5D-5L (p=0.67). Both groups reported higher mean costs between baseline and 6 months, but the change in costs was significantly lower in the intervention group. Between baseline and 6 months, the mean change in total resource use costs from the public sector perspective was significantly different between groups (p=0.003, r=–0.161) reporting a mean change per participant of £146 (95% CI: –33 to 342) between the intervention and control groups. From the wider societal perspective, there was no significant difference (p=0.23) in the mean change in total resource use and informal care costs between the two groups from baseline to 6 months.

Conclusion
Use of iSupport was associated with reduced health and social care resource use costs for carers compared with care-as-usual. Self-guided e-health interventions for dementia carers may have the potential to reduce health and social care resource use and wider societal costs, but evidence relating to their effectiveness and cost-effectiveness is lacking.

Trial registration number
ISRCTN17420703.

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Analysis of the most influential factors affecting outcomes of lung transplant recipients: a multivariate prediction model based on UNOS Data

Objectives
In lung transplantation (LTx), a priority is assigned to each candidate on the waiting list. Our primary objective was to identify the key factors that influence the allocation of priorities in LTx using machine learning (ML) techniques to enhance the process of prioritising patients.

Design
Developing a prediction model.

Setting and participants
Our data were retrieved from the United Network for Organ Sharing (UNOS) open-source database of transplant patients between 2005 and 2023.

Interventions
After the preprocessing process, a feature engineering technique was employed to select the most relevant features. Then, six ML models with optimised hyperparameters including multiple linear regression, random forest regressor (RF), support vector machine regressor, XGBoost regressor, a multilayer perceptron model and a deep learning model were developed based on the UNOS dataset.

Primary and secondary outcome measures
The performance of each model was evaluated using R-squared (R2) and other error rate metrics. Next, the Shapley Additive Explanations (SHAP) technique was used to identify the most important features in the prediction.

Results
The raw dataset contains 196 270 records with 545 features in all organs. After preprocessing, 32 966 records with 15 features remain. Among various models, the RF model achieved a high R2 score. Additionally, the RF model exhibited the lowest error values, indicating its superior precision compared with other regression models. The SHAP technique in conjunction with the RF model revealed the 11 most important features for priority allocation. Subsequently, we developed a web-based decision support tool using Python and the Streamlit framework based on the best-fine-tuned model.

Conclusion
The deployment of the ML model has the potential to act as an automated tool to aid physicians in assessing the priority of lung transplants and identifying significant factors that play a role in patient survival.

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Genomic Editing of a Pathogenic Mutation in ACTA2 Rescues Multisystemic Smooth Muscle Dysfunction Syndrome in Mice

Circulation, Ahead of Print. Background:Vascular smooth muscle cells (vSMCs), the predominant cell type in the aortic wall, play a crucial role in maintaining aortic integrity, blood pressure, and cardiovascular function. vSMC contractility and function depend on smooth muscle alpha-actin 2 (ACTA2). The pathogenic variantACTA2 c.536G >A(p. R179H) causes multisystemic smooth muscle dysfunction syndrome (MSMDS), a severe disorder marked by widespread smooth muscle abnormalities, resulting in life-threatening aortic disease and high-risk early mortality from aneurysms or stroke. No effective treatments exist for MSMDS.Methods:To develop a comprehensive therapy for MSMDS, we utilized CRISPR-Cas9 adenine base editing to correct theACTA2R179H mutation. We generated isogenic human induced pluripotent stem cell (iPSC) lines and humanized mice carrying this pathogenic missense mutation. iPSC-SMCs were evaluated for key functional characteristics, including proliferation, migration, and contractility. The adenine base editor (ABE) ABE8e-SpCas9-VRQR under control of either a SMC-specific promoter or a CMV promoter, and an optimized single guide RNA (sgRNA) under control of U6 promoter were delivered intravenously to humanized R179H mice using adeno-associated virus serotype 9 (AAV9) and phenotypic outcomes were evaluated.Results:The R179H mutation causes a dramatic phenotypic switch in human iPSC-SMCs from a contractile to a synthetic state, a transition associated with aneurysm formation. Base editing prevented this pathogenic phenotypic switch and restored normal SMC function. In humanized mice, the ACTA2R179H/+mutation caused widespread smooth muscle dysfunction, manifesting as decreased blood pressure, aortic dilation and dissection, bladder enlargement, gut dilation, and hydronephrosis. In vivo base editing rescued these pathological abnormalities, normalizing smooth muscle function.Conclusions:This study demonstrates the effectiveness of adenine base editing to treat MSMDS and restore aortic smooth muscle function. By correcting theACTA2R179H mutation, the pathogenic phenotypic shift in SMCs was prevented, key aortic smooth muscle functions were restored, and life-threatening aortic dilation and dissection were mitigated in humanized mice. These findings underscore the promise of gene-editing therapies in addressing the underlying genetic causes of smooth muscle disorders and offer a potential transformative treatment for patients facing severe vascular complications.

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Exploring employee green behaviour in hospital settings: a scoping review protocol

Introduction
Hospitals have been identified as one of the drivers accelerating climate change, and in response, they have recently been incorporating environmentally sustainable goals into their organisations. Given the significant role that healthcare workers play in pursuing hospitals’ environmental goals through such actions as energy conservation and waste reduction, the scoping review is intended to comprehensively map and summarise the literature on these workers’ green behaviours within hospital settings.

Methods and analysis
The scoping review will follow Joanna Briggs Institute methodology and will report findings according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for Scoping Reviews checklist. A comprehensive search for relevant sources published from database inception through 31 January 2025 will be conducted across seven electronic databases (PubMed, Cumulative Index of Nursing and Allied Health Literature, Embase, Scopus, Web of Science, PsycINFO and Emerald Journals), using key terms such as “hospital,” “healthcare workers” and “green behavior”. We will include peer-reviewed journal articles focusing on healthcare workers’ green behaviours in hospitals and relevant grey literature in order to provide an extensive review. Articles that are not written in English or that are intervention-based will be excluded. The study selection process will be presented in a flow diagram, and the text will summarise the findings of eligible studies according to key characteristics.

Ethics and dissemination
The scoping review will not require ethical approval. The findings will be disseminated through publication in a peer-reviewed journal and conference presentation.

Trial registration number
This protocol has been registered with the Open Science Framework (https://doi.org/10.17605/OSF.IO/YU345).

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Scoping review protocol of the use of eye movement desensitisation and reprocessing in the treatment of birth trauma

Introduction
A traumatic childbirth can have severe negative effects on the mental health of the mother and can negatively impact the child and partner. Eye movement desensitisation and reprocessing (EMDR) is a psychological intervention used to treat symptoms of trauma. The National Institute for Health and Care Excellence guidelines for antenatal and postnatal mental health recommend that trauma-focused cognitive behavioural therapy or EMDR should be offered to women who suffer from post-traumatic stress disorder resulting from a traumatic birth. However, the use of EMDR for birth trauma has not been clearly outlined in the literature.

Objectives
The aim of this scoping review is to explore the extent of the currently available research and to identify knowledge gaps in the use of EMDR for treating birth trauma.

Methods and analysis
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews guidelines will be followed to provide a comprehensive scoping review of the use of EMDR for birth trauma. Several databases will be searched, such as PsychInfo, Pubmed, the Cochrane Library, Embase, Scopus and CINAHL, from the date the database was developed, until approximately August 2026. The grey literature sources will also be searched, and searches will be limited to include studies written in the English language. Two researchers will independently screen and extract data from both quantitative and qualitative studies, which meet the inclusion criteria. Data will be analysed in a descriptive and thematic manner. Data extraction may include study characteristics, data collection procedures, outcomes and results. Findings will be presented in tabular and narrative formats.

Ethics and dissemination
Ethical Approval is not necessary for this review, as only secondary data will be used. It is expected that the review will be disseminated at psychological conferences and in relevant journal articles.

Trial registration number
This scoping review protocol has been registered on Open Science Framework. The registration DOI is: https://doi.org/10.17605/OSF.IO/UJZ52.

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Application of distributional cost-effectiveness analysis methodology in real-world studies: a scoping review protocol

Introduction
Healthcare systems face the challenge of managing limited resources while addressing the growing demand for care and the need for equitable access. Traditional cost-effectiveness analyses focus on maximising health benefits but often fail to account for how these benefits are distributed across various populations, potentially increasing health inequities. As a result, there is increasing interest in distributional cost-effectiveness analysis (DCEA), which incorporates equity considerations by explicitly assessing how health outcomes and costs are shared among diverse populations. This scoping review explores the practical application of DCEA methodology in evaluating programs and interventions. We seek to learn more about the barriers to DCEA’s application, highlighting its practical challenges, limited use globally and the steps necessary to integrate equity more effectively into implementing and adopting programs and interventions into healthcare policy and resource allocation.

Methods and analysis
To evaluate the use of DCEA in the literature, a scoping review will follow Preferred Reporting Items for Systematic Reviews and Meta-Analyses—Scoping Review Extension guidelines. Systematic searches will be performed across scientific databases (MEDLINE, SCOPUS, BASE, APA Psych and JSTOR), grey literature sources (Google Custom Search Engine), and handsearching to identify eligible articles published from January 2015 to March 2025. No limits will be placed on language. Reviewers will independently chart data from eligible studies using standardised data abstraction. The collected information will be synthesised both quantitatively and narratively.

Ethics and dissemination
Formal ethical approval is not necessary as this study will not collect primary data. The findings will be shared with professional networks, published in conference proceedings and submitted for peer-reviewed publication.

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Application of distributional cost-effectiveness analysis methodology in real-world studies: a scoping review protocol

Introduction
Healthcare systems face the challenge of managing limited resources while addressing the growing demand for care and the need for equitable access. Traditional cost-effectiveness analyses focus on maximising health benefits but often fail to account for how these benefits are distributed across various populations, potentially increasing health inequities. As a result, there is increasing interest in distributional cost-effectiveness analysis (DCEA), which incorporates equity considerations by explicitly assessing how health outcomes and costs are shared among diverse populations. This scoping review explores the practical application of DCEA methodology in evaluating programs and interventions. We seek to learn more about the barriers to DCEA’s application, highlighting its practical challenges, limited use globally and the steps necessary to integrate equity more effectively into implementing and adopting programs and interventions into healthcare policy and resource allocation.

Methods and analysis
To evaluate the use of DCEA in the literature, a scoping review will follow Preferred Reporting Items for Systematic Reviews and Meta-Analyses—Scoping Review Extension guidelines. Systematic searches will be performed across scientific databases (MEDLINE, SCOPUS, BASE, APA Psych and JSTOR), grey literature sources (Google Custom Search Engine), and handsearching to identify eligible articles published from January 2015 to March 2025. No limits will be placed on language. Reviewers will independently chart data from eligible studies using standardised data abstraction. The collected information will be synthesised both quantitatively and narratively.

Ethics and dissemination
Formal ethical approval is not necessary as this study will not collect primary data. The findings will be shared with professional networks, published in conference proceedings and submitted for peer-reviewed publication.

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Scoping review protocol of the use of eye movement desensitisation and reprocessing in the treatment of birth trauma

Introduction
A traumatic childbirth can have severe negative effects on the mental health of the mother and can negatively impact the child and partner. Eye movement desensitisation and reprocessing (EMDR) is a psychological intervention used to treat symptoms of trauma. The National Institute for Health and Care Excellence guidelines for antenatal and postnatal mental health recommend that trauma-focused cognitive behavioural therapy or EMDR should be offered to women who suffer from post-traumatic stress disorder resulting from a traumatic birth. However, the use of EMDR for birth trauma has not been clearly outlined in the literature.

Objectives
The aim of this scoping review is to explore the extent of the currently available research and to identify knowledge gaps in the use of EMDR for treating birth trauma.

Methods and analysis
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews guidelines will be followed to provide a comprehensive scoping review of the use of EMDR for birth trauma. Several databases will be searched, such as PsychInfo, Pubmed, the Cochrane Library, Embase, Scopus and CINAHL, from the date the database was developed, until approximately August 2026. The grey literature sources will also be searched, and searches will be limited to include studies written in the English language. Two researchers will independently screen and extract data from both quantitative and qualitative studies, which meet the inclusion criteria. Data will be analysed in a descriptive and thematic manner. Data extraction may include study characteristics, data collection procedures, outcomes and results. Findings will be presented in tabular and narrative formats.

Ethics and dissemination
Ethical Approval is not necessary for this review, as only secondary data will be used. It is expected that the review will be disseminated at psychological conferences and in relevant journal articles.

Trial registration number
This scoping review protocol has been registered on Open Science Framework. The registration DOI is: https://doi.org/10.17605/OSF.IO/UJZ52.

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PREgnancy Care Integrating translational Science, Everywhere (PRECISE): a prospective cohort study of African pregnant and non-pregnant women to investigate placental disorders – cohort profile

Purpose
The PREgnancy Care Integrating translational Science, Everywhere Network was established to investigate specific placental disorders (pregnancy hypertension, preterm birth, fetal growth restriction and stillbirth) in sub-Saharan Africa. We created a repository of clinical and social data with associated biological samples from pregnant and non-pregnant women. Alongside this, local infrastructure and expertise in the field of maternal and child health research were enhanced.

Participants
Pregnant women were recruited in participating health facilities in The Gambia, Kenya and Mozambique at their first antenatal visit or at the time a placental disorder was diagnosed (Kenya and The Gambia only). Follow-up study visits were conducted in the third trimester, delivery and 6 weeks to 6 months postpartum. To elucidate the difference between pregnancy and non-pregnancy biology in these settings, non-pregnant nulliparous and parous women, aged 16–49 years, were recruited opportunistically primarily from family planning clinics in Kenya and Mozambique, and randomly through the Health and Demographic Surveillance System in The Gambia. Non-pregnant participants only had one study visit. Biological samples were processed rapidly and locally, stored initially in liquid nitrogen and then at –80°C, and details entered into an OpenSpecimen database linked to their social determinants and clinical research data.

Findings to date
A total of 6932 pregnant and 1825 non-pregnant women were recruited to the study, providing a repository of clinical and social data and a biorepository of 482 448 samples. To date, baseline descriptive analysis of the cohort has been undertaken, as well as a substudy on the prevalence of COVID-19 in the cohort.

Future plans
Analysis of data and samples will include an analysis of biomarker and social and physical determinants of health and how these interact in a systemic approach to understanding the origins of common placental disorders. The data from non-pregnant women will provide control data for comparison with the data from normal and complicated pregnancies. Findings will be disseminated to local stakeholders and communities through meetings and ongoing community engagement and globally by publication and presentations at scientific meetings.

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Assessment of the impact of multi-cancer early detection test screening intervals on late-stage cancer at diagnosis and mortality using a state-transition model

Objective
Multi-cancer early detection (MCED) tests are novel technologies that detect cancer signals from a broad set of cancer types using a single blood sample. The objective of this study was to estimate the effect of screening with an MCED test at different intervals on cancer stage at diagnosis and mortality endpoints.

Design
The current model is based on a previously published state-transition model that estimated the outcomes of a screening programme using an MCED test when added to usual care for persons aged 50–79. Herein, we expand this analysis to model the time of cancer diagnosis and patient mortality with MCED screening undertaken using different screening schedules. Screening intervals between 6 months and 3 years, with emphasis on annual and biennial screening, were investigated for two sets of tumour growth rate scenarios: ‘fast (dwell time=2–4 years in stage I) and ‘fast aggressive’ (dwell time=1–2 years in stage I), with decreasing dwell times for successive stages.

Setting
Inputs for the model include (1) published MCED performance measures from a large case-control study by cancer type and stage at diagnosis and (2) Surveillance, Epidemiology and End Results (SEER) data describing stage-specific incidence and cancer-specific survival for persons aged 50–79 in the US for all cancer incidence.

Outcome measures
We used the following outcome measures: diagnostic yield, stage shift, and mortality.

Results
Annual screening under the fast tumour growth scenario was associated with more favourable diagnostic yield. There were 370 more cancer signals detected/year/100,000 people screened, 49% fewer late-stage diagnoses, and 21% fewer deaths within 5 years than usual care. Biennial screening had a similar, but less substantial, impact (292 more cancer signals detected/year/100,000 people screened; 39% fewer late-stage diagnoses, and 17% fewer deaths within 5 years than usual care). Annual screening prevented more deaths within 5 years than biennial screening for the fast tumour growth scenario. However, biennial screening had a higher positive predictive value (54% vs 43%); it was also more efficient per 100,000 tests in preventing deaths within 5 years (132 vs 84), but prevented fewer deaths per year.

Conclusion
Adding MCED test screening to usual care at any interval could improve patient outcomes. Annual MCED test screening provided more overall benefit than biennial screening. Modelling the sensitivity of outcomes to different MCED screening intervals can inform timescales for investigation in trials.

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Exposure to Multiple Metals and Cerebral White Matter Hyperintensity in Chinese Population: A Cross-Sectional Study

Stroke, Ahead of Print. BACKGROUND:Evidence about the impact of multiple metal exposure on brain neuroimaging metrics remains limited. We aim to investigate the effects of single and mixed metal exposure on white matter hyperintensities (WMHs).METHODS:This cross-sectional study included 1183 subjects without stroke history from the META-KLS (Multi-modality Medical Imaging Study Based on Kailuan Study), which is an existing prospective cohort in Tangshan, China. Plasma metal levels, including Mg, Ca, V, Mn, Co, Ni, Cu, Zn, As, Se, Rb, Cs, Tl, Pb, and Cd, were measured using an inductively coupled plasma mass spectrometer. Ordinal and binary logistic regression models were used to examine the effects of metal exposure on the WMH burden, deep white matter hyperintensity, and periventricular white matter hyperintensity. All metal concentrations were naturally log-transformed to reduce skewness and were analyzed as both continuous and tertile forms. Weighted quantile sum regression, quantile-based g-computation model, and Bayesian Kernel Machine Regression were used in the metal mixture analysis.RESULTS:Compared with the first tertile, the adjusted odds ratios and 95% CIs for the WMH burden in the third tertile were 1.57 (1.05–2.34) for As, 2.01 (1.28–3.18) for Cu, 1.68 (1.14–2.50) for V, 1.61 (1.07–2.44) for Cs, and 1.56 (1.04–2.34) for Tl (allPfor trend

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