Environmental enteropathy (EE) is a syndrome affecting the gut characterised by villus blunting, reduced nutrient absorption and microbial translocation in children and adults experiencing a high burden of enteric infection due to inadequate access to clean water and sanitation.

We will conduct coordinated randomised controlled trials in six countries to determine if supplementation with indispensable amino acids (IAAs) can improve intestinal barrier dysfunction in six geographically diverse populations of 18–36 months old children with stunting or severe stunting. All trials will measure the same primary outcomes while secondary outcomes will be measured on a per-trial basis using standardised protocols across the project. The primary endpoint will be change in gut permeability as assessed by the lactulose/rhamnose ratio. Secondary endpoints include changes in amino acid and carbohydrate absorption using novel, isotope tracer tests. Other prespecified outcome measures include changes in EE biomarkers and child weight. IAA supplementation will be given daily for 28 days and evaluation of the major endpoints will be at baseline and after 28 days of supplementation.

Ethical approval will be obtained from the Research Ethics Committee at each participating site. Caregivers will provide written informed consent for each participant. Findings will be disseminated through peer-reviewed journals, conference presentations and face-to-face meetings with participant caregivers.

CTRI: CTRI/2024/06/069187 (India); ClinicalTrials.gov (NCT06617130, Malawi; NCT06676215, Philippines and NCT07256028, Morocco); Ongoing (Zambia); Ongoing (Morocco); PACTR: (PACTR202311714091884, Ghana).

Research on psychosocial interventions for dementia demonstrates increased rigour and robustness. However, if we are to influence practice, beyond results from randomised controlled trials, a variety of types and sources of evidence is needed. The Medical Research Council (MRC) framework offers a valuable guide for developing, evaluating and implementing complex interventions, to facilitate integration of research into practice. There is limited knowledge of how researchers design, evaluate and implement psychosocial intervention studies in dementia, using the MRC framework. This scoping review aims to: (1) identify the methodological and methods trends, use and gaps in the development, evaluation and implementation of psychosocial interventions for dementia, and (2) determine if and how the MRC six core elements were considered and applied in studies.

Six databases (Ovid MEDLINE, Embase, PsycINFO, CINAHL, Web of Science, Cochrane Library) will be searched for studies published from 2015 (when MRC process guidance was published) to 2025. Identified deduplicated citations will be imported into Covidence software, where up to 40% of title/abstracts will be double screened by independent reviewers. ASReview will be used to rank articles by relevance, with a stopping criterion of 250 consecutive irrelevant articles. Full texts will be reviewed by a single reviewer and those excluded will be checked by a second reviewer. Data extraction will include study aim/objective (ie, to develop/adapt; test feasibility/pilot; evaluate; implement); methodology and methods applied; information on which MRC six core elements were considered (yes/no), and if so, how they were addressed (ie, qualitative details). A narrative synthesis, alongside graphical representations (eg, table/bar charts/histograms), will be used to synthesise findings on methodologies and methods mapped onto the MRC framework.

This secondary analysis scoping review does not require ethics approval. Results will be disseminated through peer-reviewed publication(s), seminars, webinars, conferences, postgraduate dementia programmes, blogs, commissioner briefings and social media. The findings will provide a state-of-the-art overview of current practices; advance methods/methodology such as informing a Delphi consensus study on appropriate research approaches; and guide researchers in application of the MRC framework to widen the scope of dementia care evidence for practice improvements.

Submitted to Open Science Framework https://doi.org/10.17605/OSF.IO/S56NQ.

Hepatocellular carcinoma (HCC) recurs in most patients after curative treatment. Late recurrence (>2 years after curative treatment) typically indicates de novo tumours in the residual liver. Although contrast-enhanced computed tomography (CECT) and MRI are widely used for post-treatment follow-up, they each have limitations including radiation exposure, high cost and limited access. The abbreviated MRI using gadoxetic acid versus multiphasic CECT for detection of late recurrent HCC after curative treatment (AMRICT) trial aims to compare gadoxetic acid-enhanced abbreviated MRI using hepatobiliary phase imaging (HBP-AMRI) and multiphasic CECT for detecting late recurrent HCC after curative treatment.

This prospective multicentre intra-individual comparison trial will enrol 455 participants who have undergone surgical resection or local ablation for HCC and remained recurrence-free for over 2 years. Each participant will undergo two imaging sessions at 6±2 month intervals, using both HBP-AMRI and multiphasic CECT. The primary endpoint is the detection rate of all-stage HCC. The secondary endpoints include the false referral rate of all-stage HCC and detection and false referral rates of Barcelona Clinic Liver Cancer stage 0–A HCC and of stage 0 HCC. Structured imaging protocols and quality assessments will be implemented for both modalities.

This study was approved by the Institutional Review Boards of the three participating institutions (approval number: 2023–1630 (Asan Medical Center), H-2407-146-1556 (Seoul National University Hospital) and B-2410-929-401 (Seoul National University Bundang Hospital)) and registered at ClinicalTrials.gov (NCT06537193). Findings will be disseminated through peer-reviewed journals, scientific meetings, public forums and guideline updates.

ClinicalTrials.gov: NCT06537193. Participant enrolment began on 12 December 2024, and is ongoing.

This real-world study investigated the changes of lipid lowering therapy (LLT) usage in patients with high or very high cardiovascular (CV) risk in the UK and the group of all other European countries in the SANTORINI study up to 1 year from baseline and the impact this treatment had on the attainment of low-density lipoprotein cholesterol (LDL-C) risk-adjusted goals set by the National Institute for Health and Care Excellence (NICE) and those in the 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) dyslipidaemia guidelines.

Secondary analysis of the SANTORINI dataset (an international, prospective, observational, non-interventional study (NCT04271280)).

Primary and secondary care centres in the UK and the group of other European countries (Austria, Belgium, Denmark, Finland, France, Germany, Ireland, Italy, the Netherlands, Portugal, Spain, Sweden and Switzerland).

663 UK patients with high and very high CV risk were included in this analysis and 8502 from the group of other European countries. Of these, 380 UK patients and 6830 from the group of other European countries had LDL-C information available at baseline and 1-year follow-up.

The primary objectives were to describe patients’ lipid management, LDL-C levels at 1-year follow-up and their attainment of 2023 NICE (≤2.0 mmol/L) and 2019 ESC/EAS LDL-C 2019 guideline-recommended LDL-C goals (

Over the course of 1-year follow-up, the overall proportion of UK patients on no LLT reduced from 20.4% at baseline to 7.1%, similar to that observed in the group of other European countries (baseline–20.9%, 1 year–3.0%). The proportion of UK patients receiving LLT monotherapy increased from 74.8% at baseline to 84.9%, higher at both time points than that observed for the group of other European countries (baseline: 52.0%, 1 year: 55.0%). The use of any combination therapy increased slightly from baseline to 1 year in the UK overall cohort (4.9% vs 7.1%) and overall in the group of all other European countries, the cohort increased from baseline (27.1%) to 1 year (40.2%). Overall, mean (SD) LDL-C levels in the UK were 2.5 (1.2) mmol/L at baseline and 2.1 (1.0) mmol/L at 1 year and for the group of other European countries were 2.4 (1.2) mmol/L at baseline and 2.0 (0.9) mmol/L at 1 year. The overall proportions of UK patients achieving the UK NICE treatment goal and ESC/EAS 2019 guidelines at baseline versus 1-year follow-up were 40.3% vs 52.6% and 22.9% vs 32.9%, respectively; 21.1% and 30.9% of patients in the group of other European countries achieved the ESC/EAS 2019 guidelines at baseline and 1-year follow-up, respectively.

In this UK-focused analysis of the SANTORINI study, use of LLT increased modestly over 1 year, accompanied by a reduction in average LDL-C levels. However, mean LDL-C remained above the NICE goal, and attainment of both NICE and ESC/EAS LDL-C thresholds remained suboptimal. The findings highlight continued opportunities to optimise lipid management in UK clinical practice, including the potential for broader use of combination therapies.

To describe the epidemiology, ecological determinants and public-health response to a yellow-fever (YF) outbreak in Wa East District (WED), Ghana, and to identify operational gaps to strengthen surveillance and immunisation in high-risk rural settings.

A cross-sectional descriptive outbreak investigation integrating epidemiological, entomological, vaccination-coverage and community knowledge assessments, conducted under Ghana’s Integrated Disease Surveillance and Response framework.

WED, located in the Upper West Region of Ghana, is an agrarian, forest-fringe area bordering the Mole National Park, characterised by limited access to health services and seasonal nomadic movements.

All suspected YF cases (N=57) reported between epidemiological weeks 41–46 of 2021; 50 community respondents interviewed for knowledge and awareness and 52 households inspected for entomological indices.

Demographic and clinical characteristics of cases, spatial–temporal distribution, vaccination coverage, Aedes vector indices, community knowledge and awareness levels and response interventions.

A total of 57 suspected cases (33 males 24 females) were identified, of which 12 (21.1%) were laboratory-confirmed. The case-fatality ratio among confirmed cases was 33.3% (95% CI 9.7% to 65.1%). Most cases occurred in individuals aged 6–30 years and were clustered in the Ducie community. The epidemic curve, based on confirmed cases, showed a single focal wave between epidemiological weeks 41 and 46 of 2021, peaking in week 45 and declining thereafter following intensified outbreak response activities, particularly surveillance and risk communication. Routine YF vaccination coverage was 25% before the outbreak, increasing to 95% after the mass campaign. The district’s composite risk score was 83%, indicating very high transmission risk. Entomological indices (House Index=48.5%, CI=36.1%, Breteau Index=159.6) exceeded WHO thresholds, confirming intense Aedes proliferation. Community awareness was low, with only 22% recognising the viral cause, 16% identifying mosquitoes as vectors and 10% knowing that vaccination prevents YF.

The outbreak reflected the convergence of ecological vulnerability, low baseline immunity and poor community awareness. Sustained high routine immunisation, structured Aedes surveillance and continuous risk communication are essential to prevent recurrence and advance Ghana’s commitment to the WHO Eliminate Yellow Fever Epidemics strategy.

Enhancing Quality of Life for Individuals with Stroke (EQL-stroke) is an international, collaborative multiphase project aiming to strengthen supported self-management for older adults recovering from stroke at home in Sweden, Latvia and the Netherlands. Existing poststroke pathways may provide insufficient support for self-management during the transition from hospital to home, and there is limited evidence on interventions that integrate social networks and everyday environmental context.

EQL-stroke uses a participatory, multimethod design across three phases. Phase I generates knowledge through policy review, qualitative interviews and people–place mapping (~25 participants per country) and includes cross-cultural adaptation of the Collective Efficacy of Networks Scale. Phase II co-designs and specifies a tailored social network-informed supported self-management intervention (the Network-Based Intervention), including core components and principles for local adaptation (~15 participants per country). Phase III will recruit approximately 20–40 stroke survivors for a single-arm pilot feasibility study with an 8-week follow-up and embedded process evaluation to assess feasibility, acceptability and fidelity in routine practice.

Ethical approval has been obtained from the Swedish Ethical Review Authority (reg. no. 2025-00083-01), the Rīgas Stradina Universitāte Research Ethical Committee (reg. no. Rīgas Stradina Universitāte Research Ethical Committee) and the Research Ethics Committee of the Faculty of Spatial Sciences, University of Groningen (reg. no. 2025-07). Findings will be disseminated through peer-reviewed publications, stakeholder engagement activities and patient/public channels.

Inadequate emergence is a common postoperative complication in elderly patients following major abdominal surgery. This study was designed to determine its incidence, identify associated risk factors and characterise its clinical subtypes within this high-risk cohort.

This prospective single-centre cohort study was conducted at a comprehensive specialised tertiary care hospital in Northwest Ethiopia. Consecutive patients aged 65 years and older scheduled for elective major abdominal surgery under general anaesthesia were enrolled.

The primary outcome was the proportion of patients experiencing inadequate emergence.

A total of 388 patients were analysed. Inadequate emergence occurred in 21.9% of participants (95% CI 14.3% to 31.6%), with hypoactive emergence observed in 10.7% and emergence delirium in 11.2%. Multivariable logistic regression identified several independent predictors, including advanced age (adjusted OR (AOR)=1.9; 95% CI 1.5 to 8.2), preoperative anxiety (AOR=2.7; 95% CI 1.2 to 7.2), prolonged preoperative fasting (AOR=2.1; 95% CI 1.8 to 9.1), non-ketofol-based induction (AOR=3.4; 95% CI 1.6 to 6.3), absence of abdominal field block (AOR=4.2; 95% CI 4.0 to 9.6), substantial intraoperative blood loss (>1000 mL; AOR=1.9; 95% CI 1.2 to 7.6), postoperative nausea and vomiting requiring antiemetics (AOR=2.2; 95% CI 2.1 to 7.1) and presence of an indwelling urinary catheter (AOR=2.4; 95% CI 1.8 to 7.9).

Inadequate emergence occurred in approximately one in five elderly patients undergoing elective major abdominal surgery. Independent predictors included advanced age, major intraoperative blood loss, postoperative nausea/vomiting requiring antiemetics, non-ketofol-based induction, preoperative anxiety, absence of abdominal field block, presence of an indwelling urinary catheter and prolonged preoperative fasting.

Persistent fatigue is a frequent symptom in chronic medical conditions. Systematic reviews of non-pharmacological interventions for fatigue have identified interventions that are effective at reducing fatigue, but there is limited published evidence on the cost-effectiveness of these interventions.

To identify non-pharmacological fatigue interventions that have the potential to be cost-effective in patients with long-term medical conditions.

Decision analytic modelling with intervention costs estimated from staff time and quality-of-life outcomes mapped from a systematic review and network meta-analysis of fatigue outcomes.

UK National Health Service (NHS).

People with persistent fatigue associated with a chronic medical condition.

Non-pharmacological fatigue interventions versus usual care.

Net monetary benefit from a UK NHS and Personal Social Services perspective; quality-adjusted life years (QALYs) gained; intervention costs valued at 2022/23 prices; costs and benefits discounted at 3.5% per annum.

In the base-case analysis, expected costs from the probabilistic analysis for individual and group interventions were: £267 and £157 for physical activity promotion, £810 and £485 for cognitive behavioural therapy (CBT)-Fatigue and £462 and £214 for mindfulness. The expected QALYs gained were similar for mindfulness and physical activity promotion (0.061 and 0.060, respectively), but lower for CBT-Fatigue (0.045). All interventions provided positive incremental net monetary benefit (INMB) versus usual care when valuing a QALY at £20 000. However, since group interventions are less costly than individual ones, and we assumed equivalent clinical benefit, they are expected to provide greater INMB. These findings remained robust across different scenarios, except for CBT-Fatigue (individual), which had negative INMB in some scenarios.

There remains uncertainty regarding which intervention is most cost-effective due to limitations in the underlying evidence base. Future research is recommended to compare the cost-effectiveness of these interventions across a broad population with different chronic conditions.

With a prevalence of around 7.6%, developmental language disorders (DLDs) without comorbidities are among the most common and most frequently treated childhood disorders. Standard DLD therapy in Germany consists of individual therapy sessions once per week within speech–language therapy practices. In reality, these sessions only take place every 10–14 days on average. Online therapy may be beneficial but is not yet standard practice in Germany. Although DLD group therapy has been proven to be effective, it is rarely undertaken in Germany. The aim of this study is to compare the effectiveness of online DLD therapy for small groups of children with standard one-to-one therapy.

The effectiveness of two treatment settings is evaluated in 212 children with moderate-to-severe DLD (ages 3 years to 6 years 11 months) in the multicentre, block randomised controlled trial (RCT) THErapy ONline. Five centres in Germany participate. Children are randomly assigned to the intervention group (online interval-intensive therapy, IG1, n=106) or the control group (extensive standard in-person therapy, IG2, n=106). A speech and language assessment is conducted at baseline (study entry, T0), 12 months (T1) and 18 months (T2) after therapy start. The co-primary outcome parameters are the speech and language test scores of phonological speech sound production, expressive vocabulary, grammar production and language comprehension at T1. The secondary outcome parameters comprise two composite speech and language test scores at T1 and T2, including phonological working memory scores and the individual scores of the aforementioned tests at T2, as well as process evaluation parameters (time expenditure, resource utilisation, such as salary costs of speech–language therapists, additional costs of the online therapy, adherence to appointments and therapy acceptance).

This study has been approved by the Institutional Ethics Review Board of Westphalia-Lippe (2022-282 f-S). Parents provide written informed consent. Findings will be disseminated through presentations, peer-reviewed journals and conferences.

DRKS00030068

To evaluate the cost-effectiveness of early lead extraction (≤7 days post-admission) compared with delayed (>7 days) or no extraction for cardiac implantable electronic device (CIED) infections in the UK using a decision-analytic model from the NHS perspective.

A decision-tree model was constructed to simulate clinical and economic outcomes in adult patients with systemic or pocket CIED infections.

Secondary care hospital setting within the UK NHS.

A simulated cohort of adult patients with systemic or pocket CIED infections. Model inputs were sourced from published literature and NHS cost data (2023 £).

Early lead extraction (≤7 days after diagnosis/admission) compared with delayed extraction (>7 days) or no extraction.

Adverse events avoided and total healthcare costs over a 1-year time horizon; deterministic and probabilistic sensitivity analyses were conducted to assess model robustness.

Early extraction was both clinically and economically superior to delayed or no extraction. For systemic infections, early extraction reduced costs by £123 056 and avoided 9.0 adverse events per 100 patients, with mortality falling from 20.0 to 7.5 per 100 patients. In pocket infections, early extraction lowered costs by £104 904 and avoided 8.4 adverse events per 100 patients, with mortality decreasing from 12.4 to 0.9 per 100 patients. Sensitivity analyses confirmed the robustness of these findings, with antibiotic failure rates being the most influential parameter.

Early lead extraction for CIED infections is a cost-effective, dominant strategy in the UK, reducing mortality, adverse events and overall costs. These results strongly support guideline recommendations for prompt extraction and highlight the need for improved adherence to evidence-based management of CIED infections.

Maternal human milk feedings continue an offspring’s exposure to the programming stimuli of maternal metabolism during the postnatal period. While considerable research focuses on associations between in utero environments and offspring metabolic disease, few studies have been able to specifically measure how human milk composition modifies programming of children’s growth in conjunction with comprehensive measures of maternal glycaemia during pregnancy.

The Glycemia Range and Offspring Weight and adiposity in response To Human milk (GROWTH) Study is a longitudinal cohort enrolling women with a singleton pregnancy who (1) undergo serial testing of glycaemia during pregnancy and (2) are intending to provide their breast milk through direct breastfeeding or pumped milk as the primary nutrition for their infant. Enrolment started in October 2023 and is expected to be completed in December 2026. Key procedures include virtual lactation support visits, serial human milk sampling at three time points, maternal and infant blood sampling, serial maternal and child anthropometric measurements and diet assessment. After delivery, mother–child dyads are followed until children turn 2 years of age. The primary exposure variable is maternal glycaemia obtained from a fasting, 3 hour 100 g oral glucose tolerance test performed at 24–28 weeks of gestation, and the primary outcome measure is the composite of human milk linoleic and docosahexaenoic acid concentrations in milk samples collected at 1 month postpartum.

Lurie Children’s Hospital Institutional Review Board (IRB) provides central oversight of the GROWTH Study in conjunction with each participating centre’s IRB. The GROWTH Study data has the potential to inform perinatal health and future research in lactation and human milk science by providing comprehensive measures of human milk composition and early childhood growth and body composition parameters impacted by maternal metabolism in pregnancy.

To systematically identify and synthesise dengue management strategies, levels of implementation, management dimensions, key challenges and proposed solutions across health systems worldwide.

A scoping review following the Arksey and O’Malley framework and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews guidelines.

PubMed, Scopus, Web of Science, Embase and the Cochrane Library were searched for studies published between January 2003 and December 2024. Reference lists of included studies were also manually screened.

English-language, peer-reviewed articles and reviews focusing on dengue management strategies, challenges and solutions at any health system level were included. Studies without full-text access or outside the scope of dengue management were excluded.

Two reviewers independently screened studies and extracted data using a structured form. Extracted data were charted and synthesised using an inductive thematic approach to identify core strategy domains, implementation levels, challenges and solutions.

Of 4822 records identified, 34 studies met the eligibility criteria. Dengue management strategies were categorised into six domains: vector and environmental control; surveillance and early warning systems; vaccination; enhancement of diagnostic and treatment services; community participation and education; and governance with intersectoral coordination. Implementation occurred at community, municipal, national, regional and international levels. Key challenges were grouped into five domains: structural and resource-related; sociocultural; governance and policy; scientific and technological; and climate- and urbanisation-related factors.

Global dengue management is increasingly adopting integrated, multi-sectoral approaches. Effective dengue control requires strengthening health system infrastructure, institutionalising community engagement and leveraging scientific and technological innovations. Sustained political commitment, stable financing mechanisms and coordinated governance across sectors are essential for resilient and sustainable dengue control.