Oral HIV pre-exposure prophylaxis (PrEP) is a highly effective biomedical intervention for HIV prevention, but its access and utilisation are challenging, especially in high-burden settings such as Kenya. For potential PrEP users, long delays and repeated consultations with several providers are obstacles to both PrEP uptake and continuation. The One-Stop PrEP Care project aims to promote the use of PrEP among clients in the health system and enhance client satisfaction by reducing the waiting time.

We are conducting a 1:1 cluster-randomised trial to evaluate whether One-Stop PrEP Care achieves equivalent or better PrEP outcomes compared with the standard of care model in 12 high-volume HIV clinics in Kisumu County, Kenya. In the One-Stop model, all core PrEP components, including HIV risk evaluation, HIV testing and PrEP dispensing, are provided by one provider in a single consultation room. Programme data from ≥2400 new PrEP clients will be abstracted for 12 months each to obtain primary endpoints of PrEP initiation and continuation. Adherence will be assessed via blood drug level testing. A nested cohort of up to 300 PrEP clients will be enrolled and followed every 3 months to provide in-depth data on individual HIV prevention behaviour, risk perception and how they align PrEP use with perceived risk. We will also evaluate programme costs.

Ethical approval was obtained from the University of Washington Institutional Review Board (IRB) on 8 July 2022 (IRB ID: STUDY00015873) and the Kenya Medical Research Institute Scientific and Ethics Review Unit (SERU) with a letter dated 4 May 2023 (Ref: 4697). Project findings will be shared with stakeholders, including the Ministry of Health, County health officials and participants. Results will be disseminated through manuscripts, policy briefs and health meetings.

Plans for communicating important protocol modifications include timely notifications to all study team members and training on the changes, and updates to relevant stakeholders, including the two IRBs, through protocol amendment submissions.

V. 2.0 dated 21 May 2024.

NCT03194308.

This study aimed to evaluate the cost-effectiveness of integrating nutritional support into India’s National Tuberculosis Elimination Programme (NTEP) using the MUKTI initiative.

Economic evaluation.

Primary data on the cost of delivering healthcare services, out-of-pocket expenditure and health-related quality of life among patients with tuberculosis (TB) were collected from Dhar district of Madhya Pradesh, India.

Integration of nutritional support (MUKTI initiative) into the NTEP of India.

Routine standard of care in the NTEP of India.

Incremental cost per quality-adjusted life year (QALY) gained.

A mathematical model, combining a Markov model and a compartmental susceptible–infected–recovered model, was used to simulate outcomes for patients with pulmonary TB under NTEP and MUKTI protocols. Primary data collected from 2615 patients with TB, supplemented with estimates from published literature, were used to model progression of disease, treatment outcomes and community transmission dynamics over a 2-year time horizon. Health-related quality of life was assessed using the EuroQol 5-Dimension 5-Level scale. Costs to the health system and out-of-pocket expenditures were included. A multivariable probabilistic sensitivity analysis was undertaken to estimate the effect of joint parameter uncertainty. A scenario analysis explored outcomes without considering community transmission. Results are presented based on health-system and abridged societal perspectives.

Over 2 years, patients in the NTEP plus MUKTI programme had higher life years (1.693 vs 1.622) and QALYs (1.357 vs 1.294) than those in NTEP alone, with increased health system costs (11 538 vs 6807 (US$139 vs US$82)). Incremental cost per life year gained and QALY gained were 67 164 (US$809) and 76 306 (US$919), respectively. At the per capita gross domestic product threshold of 161 500 (US$1946) for India, the MUKTI programme had a 99.9% probability of being cost-effective but exceeded the threshold when excluding community transmission.

The findings highlight the potential benefits of a cost-effective, holistic approach that addresses socio-economic determinants such as nutrition. Reduction in community transmission is the driver of cost-effectiveness of nutritional interventions in patients with TB.

Sepsis is a major cause of death both globally and in the United States. Early identification and treatment of sepsis are crucial for improving patient outcomes. International guidelines recommend hospital sepsis screening programmes, which are commonly implemented in the electronic health record (EHR) as an interruptive sepsis screening alert based on systemic inflammatory response syndrome (SIRS) criteria. Despite widespread use, it is unknown whether these sepsis screening and alert tools improve the delivery of high-quality sepsis care.

The Sepsis Electronic Prompting for Timely Intervention and Care (SEPTIC) master protocol will study two distinct populations in separate trials: emergency department (ED) patients (SEPTIC-ED) and inpatients (SEPTIC-IP). The SEPTIC trials are pragmatic, multicentre, blinded, randomised controlled trials, with equal allocation to compare four SIRS-based sepsis screening alert groups: no alerts (control), nurse alerts only, prescribing clinician alerts only, or nurse and prescribing clinician alerts. Randomisation will be at the patient level. SEPTIC will be performed at eight acute-care hospitals in the greater New York City area and enrol patients at least 18 years old. The primary outcome is the percentage of patients with completion of a modified Surviving Sepsis Campaign (SSC) hour-1 bundle within 3 hours of the first SIRS alert. Secondary outcomes include time from first alert to completion of a modified SSC hour-1 bundle, time from first alert to individual bundle component order and completion, intensive care unit (ICU) transfer, hospital discharge disposition, inpatient mortality at 90 days, positive blood cultures (bacteraemia), adverse antibiotic events, sepsis diagnoses and septic shock diagnoses.

Ethics approval was obtained from the Columbia University Institutional Review Board (IRB) serving as a single IRB. Results will be disseminated in peer-reviewed journal(s), scientific meeting(s) and via social media.

ClinicalTrials.gov: NCT06117605 and NCT06117618.

To identify the patterns of tuberculosis (TB) notification rates and examine their relationship with social and economic determinants in Nepal between 2020 and 2023.

Cross-sectional study.

Nepal.

All TB cases across all ages.

Prevalence of TB cases.

This cross-sectional spatial analysis used the data set of the National Tuberculosis Control Centre, Nepal, covering the Fiscal Year (FY) 2020–2021 to 2022–2023. Moran’s I and Local Indicators of Spatial Association were employed to detect the spatial autocorrelation between the prevalence of TB and associated social and demographic factors.

The overall prevalence rate for TB in FY 2020–2021 was 98.08 per 100 000 population. This increased to 129.82 per 100 000 population in FY 2021–2022, followed by a slight decrease to 128.39 per 100 000 population in FY 2022–2023. The highest TB prevalence was observed in Kathmandu, with 146 cases per 100 000 population in 2020–2021, and in Dang district, the rate decreased from 215–191 per 100 000 population. We investigated the spatial patterns of TB prevalence and highlighted the geographic areas in each district in Nepal from 2021 to 2023 with Moran’s I of 0.558, 0.614 and 0.596, respectively. The consistent identification of High-High clusters in specific districts like Banke, Kapilbastu and Parsa across all 3 years periods highlighted persistent high-risk areas for TB transmission in Nepal.

This study emphasised the strong spatial associations and the complex, diverse aspects of TB transmission shaped by demographic and socioeconomic factors. Our results highlighted the need for tailored public health approaches that account for specific social determinants to address TB effectively.

Gambling is now widely acknowledged to be a major public health (PH) issue. The Office for Health Improvement and Disparities conservatively estimated that gambling harm is associated with an annual cost of £1.05–£1.77 billion in England alone. Marionneau et al have categorised gambling harms into seven themes: (1) financial, (2) relationship/conflict, (3) emotional and psychological (mental health), (4) health decrements (physical health), (5) employment/education, (6) cultural and (7) criminal activity. In this understanding, gambling harms are not restricted to individual experiences: they also impact families, the wider community and society, and hence they require a whole systems, PH approach, anchored in population-level interventions to reduce harms. We aim to identify the effects of interventional PH laws and regulations on the harms associated with gambling.

We limit our focus to interventional PH laws and regulations within a comprehensive search of scientific and legal databases, grey literature and books. Following Population, Intervention, Comparator, Outcome, Study, Timing inclusion criteria, evidence will be screened and appraised in Covidence by two reviewers (MF and TP). Included evidence will be analysed and synthesised using a narrative synthesis approach. Methodological quality will be appraised using the relevant risk of bias tool. Randomised controlled trials will be assessed using the Cochrane risk of bias tool (RoB2), Risk Of Bias In Non-randomised Studies - of Interventions (ROBINS-I) will be used for other non-randomised studies. Qualitative studies will be appraised using the EPPI reviewer software for systematic reviewing.

The review protocol is registered with PROSPERO (International prospective register of systematic reviews) at the National Institute for Health Research and the Centre for Reviews and Dissemination (CRD) at the University of York (CRD42024574502). We aim to define a theory of change and produce a context-mechanism-outcome framework with relevant experts using the findings. We plan to disseminate the findings through peer-reviewed publications, meetings with relevant experts and international conference presentations.

Adolescence is a time of rapid physical, social and psychological development and many risk factors for mental disorders have their roots in this age period. Primary prevention through school platforms has been extensively used and evaluated, but many interventions have poor uptake, high dropout and limited long-term sustainability. Mental health is a complex phenomenon and may be best supported through multicomponent interventions that more holistically consider inner, social and environmental levels. Character education-focused interventions are effective for improving adolescent psychosocial functioning and mental well-being. Therefore, an intervention that focuses on developing these strengths and is delivered within a school environment, through an adolescent-informed approach using creativity-focused components, has the potential to improve adolescent mental health and well-being.

This protocol describes the YiPEE cluster-randomised controlled trial with concurrent mixed-methods process evaluation and economic evaluation, which aims to determine the impact of a multilevel multicomponent intervention in schools in Chennai, Tamil Nadu, India. Clusters—defined as schools which include Grades 6–8 (ages 11–16 years), will be randomised to intervention (n=15) or control (n=15). The intervention consists of: an 8-week classroom-based component, a 12-week teacher-focused component and a board comprising members from across the whole school. All children attending Grade 7 (aged 12–15) will be exposed to the classroom component, and teachers who actively teach Grade 7 will be invited to participate in the teacher component. Within schools, students for the individual-level evaluation will be included if they are: (1) aged 12–15 years; (2) currently attending Grade 7; (3) competent to give consent and (4) have a legal guardian competent of giving consent. We aim to sample a minimum of 100 students from each school (n=3000). All teachers of Grades 6–8 will be recruited for the evaluation. The primary outcome is symptoms of anxiety and depression measured using an abbreviated version of the UNICEF MMAPP tool. The primary analysis will be intention-to-treat, comparing the mean change in mental health score between baseline and endline, between intervention and control clusters. In addition, we will record school monitoring data (student attendance, student grades). Individual interviews with students and teachers, focus group discussions with school staff, and ethnographic observations will provide data for the process evaluation. For the economic evaluation, the combined direct and non-direct costs will be compared with changes in mental health in the intervention arm.

The trial is approved by the Ethics Council of the Schizophrenia Research Foundation, India, with approval number EC/NEW/INST/2023/TN/0329. We plan to publish the main impact, process and economic evaluation results as academic publications in international peer-reviewed journals in 2026.

Clinical Trials Registry—India (CTRI/2024/07/070949).

Treating modifiable risk factors of dementia may prevent or delay dementia cases by up to 40%. The ‘Strategic Multimodal Intervention in at-risk Elderly Indians for Prevention of Dementia (SMRUTHI INDIA)’ study will be conducted to establish a trial-ready cohort of elderly Indians who are at high risk of developing dementia.

The main aim of the study is to create and study a cohort of individuals at high risk of dementia in rural India, where we can do multiple intervention trials. The study uses the ‘Cohort Multiple Randomised Controlled Trial’ (cmRCT) design, which combines a cohort study with in-built provisions to do multiple randomised controlled trials. A large rural cohort of size 10 000 (four zones of India, through established Indian Council of Medical Research - Model Rural Health Research Units) will be followed systematically with yearly neuropsychological evaluation for 5 years (the current funding supports first 3000 participants). The study also proposes to design a multimodal ‘care bundle’ for the prevention of dementia, which is culturally tailored and context-specific to the Indian population. This intervention will undergo testing for feasibility in the hospital setting at the central coordinating site through a pilot randomised controlled trial (6 months, 30 participants). In parallel, the care bundle will be culturally and linguistically adapted and pilot-tested in 20 participants in each zone. The final curated care bundle (first intervention that is planned) will then be tested for efficacy in phase 2 of the SMRUTHI INDIA cmRCT cohort.

The study has received ethical clearance at the central coordinating site and at each of the four clinical sites by the Institute Research Committee of each site. The outcomes of the study will be disseminated to various target audiences, including research participants, general public, scientific community and policy makers through national and international conferences and events, social media, various community engagement activities and publication in peer-reviewed journals.

The study protocol is registered in the Clinical Trial Registry of India (CTRI/2024/01/061172).

The selection of the optimal treatment strategy remains one of the most challenging decisions in the management of coronary artery disease (CAD). Surgical and percutaneous coronary revascularisation are two widely used treatments for managing CAD and can result in improved outcomes compared with medications alone. Current practice guidelines recommend revascularisation for multivessel CAD for most patients. However, there remains uncertainty about whether revascularisation or medical therapy is optimal for managing multivessel disease for many patients, especially, in the elderly and those living with multimorbidity. Also, there is limited understanding of patient preferences towards candidate treatment options for multivessel disease. This study aims to quantify and characterise heterogeneity in patient preferences towards treatment options for multivessel CAD.

We have designed and will administer a discrete choice experiment to elicit and quantify preferences of people with multivessel CAD towards revascularisation and optimal medical therapy for managing multivessel CAD. Multinomial logit mixed effects and hierarchical Bayes models will be used to model the association between the participants’ choices and the attributes and their different levels. The relative importance of the attributes will be assessed using the size of coefficients and marginal rate of substitution (MRS), a measure of the willingness to accept a trade-off among different options. Heterogeneity in patient preferences will be evaluated using latent class analysis.

Ethical approval for this study was granted by the University of Calgary Conjoint Health Research Ethics Board. Findings from this study will inform the development of clinical decision support tool that integrates patient preferences with clinical risk information to support patient-care provider discussion about optimal treatment for multivessel CAD management.

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality globally. Early diagnosis and intervention are crucial for preventing disease progression. The concept of early COPD is considered to represent the initial phase of the disease course. However, different terms are used, and a standardised definition is lacking. This has hindered research and clinical utility. This systematic review aims first to examine current early COPD research and outline the definitions and terms used to help reach consensus and direct future clinical research. Second, it will identify currently proposed markers and tools for predicting the progression of early COPD and the quality of evidence to help direct future research and facilitate the development of novel management strategies.

This study will search for all clinical studies on early COPD, using a standardised search strategy, searching CENTRAL (the Cochrane Library), MEDLINE (Ovid), PubMed, Scopus, Web of Science and Google Scholar. Titles and abstracts will be reviewed and compared against inclusion and exclusion criteria. Stage 1 of this review will assess the terms and definitions used for early COPD. Stage 2 will assess studies presenting additional markers or tools for predicting the progression of early COPD. Study quality will be assessed using a modified Downs and Black checklist for observational studies and the risk of bias (RoB) 2 tool for randomised controlled trials. This protocol has been registered in PROSPERO (CRD42025645320).

This systematic review will use freely available data within the literature and will not directly involve human participants; therefore, ethical approval is not required. The results of this systematic review will be prepared and submitted for presentation as conference presentation(s) and for publication as a peer-reviewed article.

CRD42025645320.

Mammographic screening identifies many women with small breast cancers with favourable biological features, which have an excellent prognosis. Some of these may never have become clinically apparent without screening and are commonly described as ‘overdiagnosed’ cancers. Despite this, all patients with screen-detected cancers are currently treated with surgical excision and sentinel lymph node biopsy, although this may represent overtreatment. There is, therefore, a need for less invasive approaches to reduce treatment burden for patients while maintaining current excellent oncological outcomes. Vacuum-assisted excision (VAE) may represent such an alternative treatment approach, and the SMALL (Open Surgery versus Minimally invasive-vacuum Assisted excision for smaLL screen-detected breast cancer) trial aims to investigate the use of VAE for the safe de-escalation of surgical treatment for such excellent prognosis invasive breast cancers.

SMALL is a prospective, multicentre, randomised phase III trial of VAE versus surgery in patients with small, biologically favourable screen-detected invasive breast cancer. SMALL has an innovative hybrid design with coprimary endpoints. These include a randomised non-inferiority comparison of surgical re-excision rates following initial treatment, and a single-arm analysis of local recurrence at 5 years following VAE. Secondary outcomes include complication rates, overall survival, quality of life and a health economic analysis. The trial includes a QuinteT Recruitment Intervention to support recruitment.

Ethical approval was obtained from the Office for Research Ethics (Northern Ireland) for all UK sites. Results will be submitted for publication in a peer-reviewed journal, presented, shared with patient partners and with relevant professional organisations to inform future guideline development for the management of screen-detected breast cancer.

ISRCTN12240119.

Childhood tuberculous meningitis (TBM) is a devastating disease. The long-standing WHO recommendation for treatment is 2 months of intensive phase with isoniazid (H), rifampicin (R), pyrazinamide (Z) and ethambutol (E), followed by 10 months of isoniazid and rifampicin. In 2022, WHO released a conditional recommendation that 6 months of intensified antituberculosis therapy (ATT) could be used as an alternative for drug-susceptible TBM. However, this has never been evaluated in a randomised clinical trial. Trials evaluating ATT shortening regimens using high-dose rifampicin and drugs with better central nervous system penetration alongside adjuvant anti-inflammatory therapy are needed to improve outcomes.

The Shortened Intensive Therapy for Children with Tuberculous Meningitis (SURE) trial is a phase 3, randomised, partially blinded, factorial trial being conducted in Asia (India and Vietnam) and Africa (Uganda, Zambia and Zimbabwe). It is coordinated by the Medical Research Council Clinical Trial Unit at University College London (MRCCTU at UCL). 400 children (aged 29 days to

Local ethics committees at all participating study sites and respective regulators approved the SURE protocol. Ethics approval was also obtained from UCL, UK (14935/001). Informed consent from parents/carers and assent from age-appropriate children are required for all participants. Results will be published in international peer-reviewed journals, and appropriate media will be used to summarise results for patients and their families and policymakers.

ISRCTN40829906 (registered 13 November 2018).