
Background Non-communicable diseases (NCDs) drive major mortality, morbidity, and economic loss in low- and middle-income countries. In Sri Lanka, NCDs account for over 80% of premature deaths, with cardiovascular disease, cancer, and diabetes being the leading causes. Methods This protocol describes a cluster randomized trial of Happy Village Plus, a community-based NCD prevention program that builds on the ongoing Happy Village initiative launched in 2017. The intervention uses a multilevel package of individual, group, community, and policy-oriented strategies tailored to local needs. It applies an adaptive implementation structure that is refined through community feedback and is supported by mediation and advocacy to link communities with stakeholders. The core components include health education, behaviorally informed approaches, and skills development targeting key risk factors, diet quality, physical inactivity, tobacco use, and alcohol use. Preparatory activities included volunteer training, stakeholder engagement, and community mobilization. Discussion The evaluation comprised two components. The quantitative trial assessed behavioral outcomes, fruit and vegetable intake, sugar-sweetened beverage consumption, overall diet quality, cigarette use, physical inactivity, cardiometabolic outcomes, blood pressure, blood cholesterol, fasting blood glucose, body mass index, and waist circumference. A qualitative process evaluation examines implementation and context, including norms, perceptions, social network development, acceptability, feasibility, barriers, and facilitators. This trial will generate robust evidence on the effectiveness and implementation of an adaptive village-level health promotion model for NCD prevention in Sri Lanka, with relevance for scalable and equitable approaches in similar settings. Trial Registration The clinical trial registration number is SLCTR/2023/005 (19-03-2023).
Background Autoimmune encephalitides are a group of neuroinflammatory disorders which are potentially treatable with immunotherapy. Corticosteroids are widely used, but the role of early intravenous immunoglobulin (IVIG) remains uncertain and has not been studied in a randomised control trial (RCT). ENCEPH-IG was designed to evaluate whether IVIG improved the outcome of autoimmune encephalitis in adults. Methods ENCEPH-IG was a UK multicentre, blinded superiority RCT of IVIG in adults with suspected autoimmune encephalitis. Patients were randomised 1:1 to receive IVIG or placebo, in addition to intravenous methylprednisolone followed by an oral prednisolone. The primary outcome was time to recovery, as defined by achieving a Glasgow Outcome Scale-Extended score of ≥5 on two consecutive assessments. Results The trial was terminated early because of slow site set-up and low recruitment. 21 patients were randomised; 10 received IVIG and 11 received placebo across 11 hospital sites. At 12 months, 10 patients (48%) achieved recovery (5 in the IVIG group and 5 in the placebo group). Median time to recovery was shorter in the IVIG arm (10 weeks [IQR 8–16]) than the placebo arm (20 weeks [IQR 16–32]). Serious adverse events (SAEs) affected 9/11 patients (82%) in the placebo arm, and 6/10 patients (60%) in intervention arm. The majority of SAEs were infections. Conclusion ENCEPH-IG could not determine the efficacy of early IVIG in autoimmune encephalitis in adults because of slower than expected recruitment and early trial termination. The impact of the COVID-19 pandemic on research infrastructure, differing IVIG availability across UK NHS sites and varying local practice affecting the degree of clinical equipoise all contributed to this. Future trials in autoimmune encephalitis should consider adaptive trial designs, allowing the assessment of multiple therapies, with agility to reflect the rapidly changing scientific advances in treatment, while retaining the power to assess clinically relevant outcome measures.
Introduction We describe a feasibility randomised controlled trial to determine if it is possible to implement a full cluster-randomised trial of a multi-component whole-school intervention aiming to improve the school climate. The Promoting Positive Adolescent Mental Health (PPAMH!) intervention will be adapted from an intervention previously trialled in India and Australia that reduced bullying, depression and risk behaviours among students. Methods We will randomise six secondary schools in Bradford in a feasibility trial. Three schools will receive the intervention and three will act as the ‘usual care’ control condition. We will collect quantitative and qualitative data on the implementation through activity logs and interviews with staff and well-being mentors. We will determine the feasibility of accessing and using routine education data and self-report mental health data as outcomes in the full trial. Results This study will provide information about the acceptability and feasibility of delivering and evaluating the school climate intervention in secondary schools. Conclusions This is the first study to deliver a promising whole school climate intervention in the UK. The results of this feasibility trial will inform the decision to embark on a full trial and further intervention adaptations as needed. Trial registration ISRCTN registry reference ISRCTN14856201.
Introduction Medicines are a key healthcare intervention. Medicines optimisation aims to ensure safe and effective use of medicines, with medication reviews a critical component. However, evidence around how reviews should be structured and delivered is limited. The Bristol Medication Review Toolkit comprises a review model and practical supporting materials to facilitate comprehensive, patient-centred, structured medication reviews. The BRISMED trial aims to evaluate the clinical effectiveness and acceptability of the Toolkit compared with standard general practice care. Methods BRISMED is a multicentre, open-label, cluster-randomised controlled trial, with two parallel groups. General practices within the Oxford RCGP Research Surveillance Centre (RSC) network will be selected to participate, representing 500 primary care networks (PCNs) in England. Randomisation will occur at PCN level. The intervention will take place at the practice level, with no patient-level recruitment. Practices will either undertake usual care (control group, 250 PCNs) or receive the BRISMED Toolkit (intervention group, 250 PCNs) over the same 12-month intervention delivery period. The primary outcome will be potentially inappropriate prescribing (PIP), defined as the proportion of patients with ≥1 STOPP/START indicator at 12 months (binary outcome per patient). Secondary outcomes will include additional prescribing metrics and healthcare utilisation. Outcomes will be determined using routinely collected electronic health data. The primary analysis will use mixed-effects logistic regression, on an intention-to-treat basis. A parallel mixed-methods process evaluation in a subset of practices will examine intervention implementation and provide context for interpretation of the trial findings, alongside a cost consequence analysis. Findings will be disseminated through publications, conferences and stakeholder engagement. Patients and the public will contribute throughout the study, supporting research delivery and dissemination. Ethics and registration The study has received approval from the West of Scotland NHS Research Ethics Committee 1 (reference 24/WS/0031). The trial is prospectively registered with ISRCTN (reference 12979016, registration date 3/6/2024).
Background Pulmonary Hypertension (PH) is a debilitating condition which can lead to avoidance of physical activity and reduced health-related quality of life (HRQoL). The Supervised Pulmonary Hypertension Exercise rehabilitation (SPHERe) multi-centre RCT found that remotely supervised online group exercise-based rehabilitation was safe and well tolerated, but not superior to a single one-to-one advice session for improving walking distance and HRQoL over 12 months. An embedded qualitative study aimed to explore participant and practitioner experiences of the trial and interventions. Design Qualitative process evaluation utilising semi-structured interviews. The framework method was used to analyse findings. Setting England and Scotland, UK. Participants Adults with PH living in the community. Results Twenty intervention participants, 20 usual care participants, and five intervention practitioners were interviewed. Barriers to participation in the SPHERe intervention group included finding time and being ill, whilst the dynamics of being in an online group were seen both as positive and negative. Enablers for participation included the support that came from a shared experience and a sense of belonging. Conclusion Despite a lack of clinical effectiveness, the SPHERe intervention was mostly well received by participants and practitioners. The main barrier was finding time to exercise. The main enabler was being in a group and the support this provided. Online group interventions should be considered important for future research and service models, whilst also appreciating the challenges associated with this mode of delivery.