Direct-acting antivirals are highly effective in curing hepatitis C virus (HCV) infection but linkage to care remains a barrier to population-wide treatment. Hospitalisation for any cause may be an opportunity to identify candidates for treatment. Here, we present the test characteristics of an electronic medical record (EMR) alert system to identify hospitalised patients with HCV infection.

We created two alerts based on HCV antibody and RNA values and HCV-specific International Classification of Diseases codes: an ever-alert designed to detect patients with any history of HCV infection (resolved or active) and an active-alert designed to only detect active infections. We performed manual chart review of alerted patients to determine positive predictive value (PPV). We reviewed consecutively hospitalised patients to determine sensitivity.

Two affiliated academic tertiary care hospitals in Baltimore, Maryland, USA.

Primary and secondary outcome measures: PPV and sensitivity of the alerts for patients with active HCV infection.

Hospitalised adults (aged ≥18 years).

During 12 weeks in 2022 and 2023, the ever-alert fired for 1218 hospitalisations. The ever-alert detected 438 active infections among 1218 alerted hospitalisations (PPV 36.0% (95% CI 33.3% to 38.7%)) compared with 415 active infections among 591 alerts (PPV 70.1% (95% CI 66.4% to 73.8%)) for the active-alert. Both alerts detected 37 of 44 active cases (sensitivity 81.4% (95% CI 70.6% to 92.1%)) among 1115 consecutively hospitalised patients.

The active-alert demonstrated a higher PPV than the ever-alert with a negligible decrease in case detection and similar sensitivity for active infection.

The active-alert may represent an efficient method of identifying candidates for HCV linkage to care using hospital EMR data. Future directions include deploying the active-alert with a formal linkage to care team.

To apply the Haddon Matrix framework (HM) to examine factors associated with the severity of paediatric road traffic injuries (RTIs) in Ghana.

Prospective hospital-based cross-sectional study. Variables were organised according to the three domains of the HM framework. Three negative binomial regression models were developed to identify the best-fitting model for predicting paediatric RTI severity

Three teaching hospitals in the Northern, Ashanti and Central Regions of Ghana.

A total of 484 consecutive children and adolescents aged 0–18 years presenting to the emergency department with RTIs between 18 September 2023 and 30 September 2024 were included. Data were collected using interviewer-administered questionnaires and medical record reviews.

The primary outcome was injury severity measured using the Injury Severity Score, an anatomical measure based on the sum of the squared Abbreviated Injury Scale scores for the three most severely injured body regions.

The third model (variable selection threshold p≤0.1) demonstrated the best predictive model for paediatric RTI severity, with the lowest Akaike Information Criterion and the highest log-likelihood. Increased injury severity was independently associated with self-reported frequent alcohol use (β=1.54, p=0.016), Harmattan weather conditions (β=0.21, p=0.024), afternoon crashes (β=0.17, p=0.041) and referral cases (β=0.28, p=0.003). Whereas single bicycle crashes (β=–1.58, p=0.011) and walk-in hospital visits (β=–1.09, p=0.026) were associated with lower injury severity.

The HM identified modifiable environmental, behavioural and health system factors associated with paediatric RTI severity. Interventions targeting alcohol use, Harmattan-related road safety, timely referral and prehospital care may reduce injury severity among children in Ghana.

The PREgnancy Care Integrating Translational Science, Everywhere (PRECISE)-DYAD Study is a prospective observational cohort designed to investigate health outcomes among mother-child pairs (dyads) over the first 3 years of life in two contexts from sub-Saharan Africa. The primary objective of the study was to explore the effects of selected placenta-related complications, such as pregnancy hypertension, fetal growth restriction and preterm birth, on (1) Child health and development, and (2) Women’s health and well-being, including outcomes after stillbirth.

The PRECISE-DYAD Study enrolled women (and their children) originally recruited into the PRECISE pregnancy cohort study in The Gambia and Kenya between July 2021 and April 2024. Participants were seen at 6 weeks to 6 months, 12 months, 24 months and 36 months postpartum. Clinical and health data, including anthropometry and diet, were collected for both mothers and children. Mother assessment included a cardiology assessment and collection of data about symptoms of COVID-19 infection. In a subset of participants, mothers were asked about their mental health, their healthcare costs during and after pregnancy, and experiences of care during labour and childbirth/delivery. Additionally, a personal environmental exposure assessment was performed for a subset of the cohort by collecting air and water quality data alongside geographical, demographic and behavioural factors. Child development was assessed using neurodevelopmental assessments, home environment evaluation and quality of life measures. Biological samples were collected from mothers and children, processed promptly and biobanked locally. Sample data were entered into an OpenSpecimen database and linked to each individual, as well as to their corresponding social determinants and clinical data.

A total of 2980 women and 2909 children completed at least one PRECISE-DYAD Study visit. The biorepository contains 108 897 biological samples from mothers and children. Baseline descriptive analysis of the cohort is reported here.

Analysis of data and samples will include biomarker studies, social determinants of health and epidemiological investigations. These analyses will explore how placenta-related complications and environmental exposures, such as nutrition and air quality, interact to shape maternal health, mental well-being, subsequent pregnancies and mother-child interaction, as well as child growth and neurodevelopment through early childhood. Additional work will examine the biological pathways linking these exposures to outcomes and the impacts of caring for children with moderate-to-severe disabilities on maternal well-being. Findings will be disseminated through scientific publications, conference presentations, engagement with local stakeholders and continued community outreach.

Glucocorticoid (GC) bridging therapy is recommended in patients with rheumatoid arthritis commencing a disease-modifying anti-rheumatic drug (DMARD). It is not clear whether GC therapy is better administered intramuscularly or orally and at what dose level. The aim of the LEADER trial is to identify the most effective and safest way of using steroids in patients with uncontrolled RA who are starting a DMARD.

A multicentre, randomised, open-label, four-arm, parallel-group clinical trial with an internal pilot phase, economic evaluation and qualitative study of acceptability. Participants will be randomised to one of four arms: arm A, 30 mg oral prednisolone tapering over 6 weeks; arm B, 15 mg oral prednisolone tapering over 4 weeks; arm C, Intramuscularly 120 mg methylprednisolone; and arm D, Intramuscularly 80 mg methylprednisolone. Participants will be assessed at baseline (pre-GC intervention), 4, 12 and 24 weeks. The primary outcome measure is the mean DAS(CRP)–28 over 12 weeks. The primary comparison will be according to route of administration (oral vs intramuscular GC treatment) with secondary comparisons within route of administration to provide evidence of dose effectiveness. Toxicity will be measured using the Glucocorticoid Toxicity Index, a clinical outcome assessment and early morning cortisol level. LEADER will be conducted in ~30 sites delivering NHS care, recruiting a sample size of 448. Economic evaluation will compare cost-effectiveness within a trial and over a lifetime horizon from the English National Health Service perspective.

The LEADER trial received MHRA and Leicester Central Research Ethics Committee ethics approval (REC reference: 24/EM/0277, IRAS 1010280), opened to recruitment on Protocol Version 4.0 and is currently recruiting on Protocol Version 5.0. Participants will provide written informed consent in accordance with the Declaration of Helsinki and applicable regulatory requirements. Trial results will be disseminated via presentations at national and international meetings, published in open-access journals and to patients.

ISRCTN32090559.

To estimate the cost-effectiveness of immediate septoplasty compared with 6 months of medical management with the option for delayed septoplasty in individuals with nasal obstruction associated with septal deviation.

Economic evaluation alongside a multicentre, open label, randomised controlled trial.

17 otolaryngology clinics in the UK, recruiting from January 2018 to December 2019.

Adults aged≥18 years with symptoms of nasal obstruction associated with septal deviation with at least moderate symptoms of nasal obstruction (score>30 on the Nasal Obstruction and Symptom Evaluation scale).

Participants were randomised to receive either septoplasty within 12 weeks of recruitment or 6 months of medical management (nasal steroid and saline spray) with the option for delayed septoplasty.

Incremental cost per quality-adjusted life year (QALY) gained at 12 months. A UK National Health Service perspective was adopted, and surgery costs were estimated using a tariff and micro-costing. QALYs were estimated based on responses to the Short Form-36 (SF-36). Seemingly unrelated regression was used to estimate incremental costs and QALYs. A model-based analysis was used to extrapolate costs and effects to 24 months. Sensitivity analyses were used to illustrate uncertainty.

In the within-trial analysis, immediate septoplasty was on average more costly (mean difference (95% CI) £1193 (£1018 to £1368)) and more effective (mean difference (95% CI) 0.044 QALYs (0.03 to 0.06)) when compared with 6 months of medical management with the option for deferred septoplasty. Immediate septoplasty had an incremental cost per QALY gained of £27 114 in the base case analysis, which decreased to £16 682 when micro-costing was used to estimate surgery costs. Immediate septoplasty had a 15% and 78% probability of being considered cost-effective at a £20 000 threshold for an additional QALY, respectively. In the model-based analysis, immediate septoplasty remained more costly and more effective than 6 months of medical management with the option for deferred septoplasty but had a 99% probability of being considered cost-effective at a £20 000 threshold for an additional QALY.

Over a 24-month time horizon, immediate septoplasty would be cost-effective in the management of deviated nasal septum.

ISRCTN16168569.

Knee osteoarthritis is a leading cause of pain and disability and frequently results in total knee arthroplasty (TKA). Decisions about surgery and postoperative management rely largely on subjective pain scales and patient-reported outcome measures (PROMs), and 10–15% of patients remain dissatisfied after TKA despite technically successful surgery. Evidence suggests that pain is partly reflected in peripheral immune signalling, yet this neuroimmune interface has not been studied in patients with joint pain due to knee osteoarthritis. This study will explore whether peripheral immune responses (interleukin-1 beta, IL-1β) are associated with pain and may serve as objective pain biomarkers in patients with painful knee osteoarthritis compared with pain-free controls and how these markers relate to pain and psychological (anxiety, depression and pain catastrophising) PROMs. This will be the first study to correlate pain markers (peripheral immune responses) with subjective pain levels in orthopaedic patients with symptomatic knee osteoarthritis.

This is a protocol for a prospective cross-sectional matched-subject observational study. We will include 20 adults undergoing unilateral primary TKA for painful advanced knee osteoarthritis, their contralateral pain-free knees as internal controls and 20 age and sex matched healthy controls without joint pain or functional limitation. All participants will undergo standardised clinical assessment and complete pain and psychological PROMs. In patients with TKA, venous blood will be collected pre-operatively. During TKA surgery, synovial fluid will be aspirated from the painful operated knee and the contralateral pain-free knee. Healthy controls will provide a single venous blood sample at a hospital visit. Peripheral blood mononuclear cells and synovial fluid mononuclear cells will be stimulated ex vivo with toll-like receptor 2 and 4 agonists to quantify IL-1β release. In parallel, hyperspectral imaging will characterise unstimulated immune cell phenotypes. Multivariable statistical and machine-learning approaches will relate biomarker profiles to pain and psychological PROMs.

The study has been approved by the Southern Adelaide Local Health Network (SALHN) HREC (references: 2024/HRE00253, SSA 2024/SSA00641). Written informed consent will be obtained from all participants. Study results will be disseminated through peer-reviewed publications and presentations at national and international scientific conferences.

ACTRN12626000084381.

Ophthalmic complaints account for a substantial proportion of presentations to emergency and acute eye care services, yet initial assessment or referral is frequently performed by non-ophthalmologist healthcare professionals. Previous single-centre studies suggest that one-third of referrals are incorrectly diagnosed, potentially delaying appropriate management of vision-threatening conditions. However, the overall magnitude of diagnostic error and patterns of misdiagnosis across healthcare settings remain unclear. This study aims to systematically review and synthesise the evidence on the diagnostic concordance of ophthalmic referral diagnoses made by non-ophthalmologists in acute eye care.

A systematic review and meta-analysis will be conducted following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols) guidance and registered with PROSPERO. MEDLINE (Ovid), Embase (Ovid) and the Cochrane CENTRAL database will be searched from inception to April 2025. Studies evaluating the diagnostic accuracy of referrals made by non-ophthalmologist healthcare professionals in emergency or acute eye care settings will be included. Two reviewers will independently screen studies, extract data and assess risk of bias using the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies-2) framework adapted for referral-diagnosis studies. The primary outcome will be diagnostic concordance between referral and final ophthalmologist diagnosis. Where appropriate, pooled concordance proportions will be synthesised using a random-effects meta-analysis. Condition-specific 2x2 diagnostic accuracy analyses will only be undertaken where valid binary target conditions and sufficient denominators are reported. Heterogeneity will be assessed using Cochran’s Q test and the I² statistic with subgroup analyses exploring differences by referring clinician type and anatomical location of ophthalmic pathology.

Ethical approval is not required for this study as it will synthesise data from previously published studies; findings will be disseminated through publication in a peer-reviewed journal and presentation at relevant academic conferences.

CRD420261352717.

People with severe mental illness (SMI) engage in less physical activity (PA) and more sedentary behaviour (SB) than the general population, contributing to poorer physical health outcomes in this population. Therefore, the aim of this study was to evaluate the feasibility of a multi-component behaviour change intervention called Walking fOR Health (WORtH), delivered by community mental health teams, aimed at increasing PA and reducing SB compared with a one-off education session in people with SMI.

Feasibility randomised controlled trial (RCT).

Study recruitment and intervention delivery took place within four community mental health teams in the UK and Ireland.

Eligible participants had a diagnosis of a SMI and no contraindications to participating in physical activity. Fifty-four participants (25 male, 29 female; mean age 51.6 years) were recruited.

Participants were randomised to the 13-week WORtH intervention, comprising education, activity tracking and health coaching or an education-only control.

Feasibility outcomes included recruitment, retention, adherence and acceptability. Clinical outcomes included device-measured (Axivity AX3) and self-reported PA and SB, body anthropometry, physical function and mental well-being.

This feasibility study met 90% target recruitment and 94% of participants provided follow-up data. Adherence to allocated intervention and engagement with all core intervention components was >80%. Qualitative feedback indicated high levels of satisfaction. Valid device-measured moderate-vigorous PA (MVPA), the intended primary outcome for a definitive trial, was obtained from 90% of participants at baseline and 75% of participants at post-intervention. Point estimates indicated a mean increase of 8.6 min/day of MVPA in the intervention group (baseline 54.7 min/day (95% CI 39.5 to 70.0); follow-up 63.3 min/day (95% CI 50.1 to 76.4)) and of 1.0 min/day in the control group (baseline 42.1 min/day (95% CI 24.6 to 59.6); follow-up 43.1 min/day (95% CI 29.6 to 56.5)).

The results of this study support the feasibility of the WORtH intervention in adults with SMI, and findings will be used to optimise the design of a definitive RCT.

NCT04134871.

A proportion of patients hospitalised for COVID-19 acquire the disease during their hospital stay, underscoring the risk of hospital-acquired COVID-19 (HA-COVID-19). This risk is presumed to be high, given how commonly and intensely air and surfaces within hospitals are reportedly contaminated with SARS-CoV-2. However, the true extent of HA-COVID-19 worldwide remains unknown, with limited understanding of factors that influence its occurrence and how these have evolved over time. This review will therefore aim to estimate the pooled prevalence of HA-COVID-19 among hospitalised COVID-19 patients globally and investigate differences by country, type of hospitals, medical specialty, length and timing of studied periods.

A systematic review and meta-analysis will be conducted adhering to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. MEDLINE and PubMed Central (via PubMed), Scopus, Embase (via Ovid), the Web of Science Core Collection as well as websites of public health agencies (PHA) will be searched until 1 July 2026. All journal articles and sources from PHAs reporting any primary data on the prevalence of HA-COVID-19 will be included. Methodological quality will be assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Studies Reporting Prevalence Data. The primary outcome will be the global prevalence of HA-COVID-19. Data synthesis will include random-effects proportional meta-analysis. Estimates will be presented with two-sided 95% CIs and heterogeneity assessed using the I² statistic.

Ethical approval is not needed as no original data will be generated. This review will be published in an international, peer-reviewed journal.

CRD420251136884.

Randomised controlled trials (RCTs) are essential to determine intervention effectiveness yet they often fail to capture how and why interventions succeed or fail in different contexts. Embedding a process evaluation alongside a clinical trial allows exploration of implementation processes, intervention fidelity and contextual influences. The CANFit trial is a basket-design RCT evaluating a personalised, remotely delivered exercise intervention for people diagnosed with breast, lung and bowel cancer with increased risk of recurrence. This embedded process evaluation aims to understand how individual, team and organisational factors influence intervention delivery and uptake.

A concurrent, mixed-methods process evaluation will be conducted using a hybrid type 1 design. Data will be collected from multiple sources, including participant and trainer questionnaires, semi-structured interviews, intervention adherence logs, trainer diaries and observations. Five core implementation outcomes, guided by Proctor’s framework—acceptability, appropriateness, fidelity, penetration and sustainability—will structure the evaluation. Quantitative data will be analysed descriptively and qualitative data will undergo framework analysis using both deductive and inductive coding. Data integration will occur through a convergent mixed-methods approach, using context-mechanism-outcome (CMO) configurations to refine programme theory.

Ethical approvals were obtained through Hull York Medical School (ID: 23/SS/0060) and the UK NHS Health Research Authority (ID: 327663). All participants will provide informed consent before taking part. Data will be handled according to General Data Protection Regulation and University of Hull data management policies. Findings will be disseminated through peer-reviewed publications, conference presentations, stakeholder reports and lay summaries for participants and the public.

ISRCTN97662203.

To examine whether multiparous women have more or less folic acid uptake than primiparous women.

Preconceptional, periconceptional and postconceptional folic acid use among all pregnant women and high risk pregnant women.

Systematic review and meta-analysis.

MEDLINE-Ovid, CINAHL Ultimate, Scopus and ProQuest Medical.

Observational epidemiological studies comparing folic acid use between primiparous and multiparous women, published in English from January 1994 to June 2024.

Two reviewers screened all papers meeting the eligibility criteria. One reviewer completed data extraction and assessed study quality using an adapted version of the Newcastle-Ottawa Scale. Three other reviewers independently assessed 10% of the studies as a quality check. Random-effects (DerSimonian and Laird) meta-analyses combined results for each outcome. Heterogeneity, risk of publication bias and certainty of evidence were assessed.

Of the 10 982 records identified, 81 studies involving 826 855 women were included in the review. 27 studies were conducted in Europe, 22 in Asia, 11 in North America, 7 in Africa, 7 in Australia, 5 in the Middle East and 2 in South America. Multiparous women were consistently less likely to take folic acid before and during pregnancy than primiparous women. For preconceptional use, the odds were 29% lower among multiparous women (adjusted OR (aOR): 0.71; 95% CI 0.64 to 0.78; n=25 studies; I²=88.67%), and 58% lower in multiparous high-risk women (aOR: 0.42, 95% CI 0.27 to 0.64; n=3 studies; I²=27.28%). For periconceptional use, the odds were 32% lower among multiparous women (aOR: 0.68; 95% CI 0.63 to 0.74; n=28 studies; I²=85.46%). Postconception, the odds were 21% lower among multiparous women (aOR: 0.79; 95% CI 0.74 to 0.85; n=33 studies; I²=85.91%). By the second trimester, there was no significant difference between the two parity groups (aOR: 0.96; 95% CI 0.87 to 1.05; n=4 studies; I²=0.00%). The certainty of evidence was low for preconceptional, periconceptional and postconceptional uptake due to heterogeneity, and moderate for preconceptional uptake among high-risk women.

Multiparous women were less likely to take folic acid preconceptional, periconceptional and postconceptionally, despite their previous pregnancy experience. Barriers to folic acid supplement uptake among multiparous women need to be identified, and strategies to address them in preconception, antenatal and interconception care should be investigated.

CRD42024553241.