Multiple sclerosis (MS) is a common autoimmune illness that causes inflammation, demyelination and neurological damage. Symptom relief and immunotherapy are part of the treatment, but several healthcare barriers significantly influence outcomes and quality of life.

This study aimed to assess different aspects among patients with MS, such as their knowledge of the disease, access to care, medications’ beliefs and depression, and to evaluate any correlations between these variables and their impact on the presence of depression.

A cross-sectional study was conducted from May 2024 to October 2024 at Al-Basheer Hospital, King Abdullah University Hospital (KAUH), Princess Basma Teaching Hospital and the Multiple Sclerosis Society of Amman. 200 participants were recruited after confirming consent. Data were collected through face-to-face interviews using validated instruments, covering sociodemographics, beliefs about medicines, knowledge about MS, access to care and levels of depression.

This study involved 200 patients with MS with a median age of 36 years, mostly women (70.5%), non-smokers (65%) and insured (77.5%). The majority had high education (58%) but low income (67%), with a mean duration of MS disease of 7.8 years after diagnosis. The majority (79.5%) were unaware of their MS type. Beliefs about medications varied, with 22% accepting, 48.5% ambivalent, 14.5% sceptical and 15% indifferent. Disease knowledge was high, with patients recognising MS as an immune, non-contagious and non-curable disease that affects women more than men. Despite good access to care, a percentage of patients needed to travel long distances for care. Depression affected 58% of participants, and it was influenced by access to care, concerning beliefs, income and education. Other variables such as gender, health insurance, the duration of the disease and the necessity of medications had no significant influence.

In conclusion, patients with MS deal with various challenges, such as difficulties in accessing care, associated with psychological factors such as depression. Addressing these barriers by optimising patients' beliefs about medications, enhancing access to care and focusing on the level of knowledge of the disease is crucial for ensuring better and optimal treatment outcomes, as well as decreasing the risk of depression development.

Paediatric hospitalisation, encompassing the period from admission to discharge, often involves feelings of pain, fear and anxiety, primarily due to clinical diagnoses and, more significantly, discomfort and stress-inducing procedures. Numerous methodologies and interventions have been investigated and implemented to alleviate these phenomena during paediatric hospitalisation. Virtual reality (VR), for example, has demonstrated efficacy in pain relief for hospitalised children in recent studies. This systematic review, therefore, aims to identify and evaluate the effectiveness of VR in alleviating pain, fear and anxiety in hospitalised children undergoing painful procedures.

This systematic review and meta-analysis will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Protocols guidelines. A systematic search will be conducted in March and April 2025 across the following databases, with no restrictions on language or publication year: PubMed, Embase, Scopus, Web of Science, Cumulated Index in Nursing and Allied Health Literature, ClinicalTrials.gov and the Cochrane Central Register of Controlled Trials. Eligible studies will include randomised and quasi-randomised clinical trials involving children (aged 2–10 years) and adolescents (aged 10–18 years) who received VR interventions during painful procedures. Data will be managed and analysed using Review Manager software (RevMan 5.2.3). In cases of significant heterogeneity (I² > 50%), a random-effects model will be employed to combine studies and calculate the OR with a 95% CI. The methodological quality of the included studies will be assessed using the Cochrane Risk of Bias 2.0 tool, and the certainty of the evidence will be evaluated using the Grading of Recommendations, Assessment, Development and Evaluations framework.

This study will solely review published data; thus, ethical approval is not required. This systematic review is expected to provide subsidies, evidence and insights into the use of VR. It is also anticipated that the results will directly impact the improvement of care for these patients and the qualification of professional care.

CRD42024568297.

Millions of patients receive general anaesthesia every year with either propofol total intravenous anaesthesia (TIVA) or inhaled volatile anaesthesia (INVA). It is currently unknown which of these techniques is superior in relation to patient experience, safety and clinical outcomes. The primary aims of this trial are to determine (1) whether patients undergoing (a) major inpatient surgery, (b) minor inpatient surgery or (c) outpatient surgery have a superior quality of recovery after INVA or TIVA and (2) whether TIVA confers no more than a small (0.2%) increased risk of definite intraoperative awareness than INVA.

This protocol was co-created by a diverse team, including patient partners with personal experience of TIVA or INVA. The design is a 13 000-patient, multicentre, patient-blinded, randomised, comparative effectiveness trial. Patients 18 years of age or older, undergoing elective non-cardiac surgery requiring general anaesthesia with a tracheal tube or laryngeal mask airway will be eligible. Patients will be randomised 1:1 to one of two anaesthetic approaches, TIVA or INVA, using minimisation. The primary effectiveness endpoints are Quality of Recovery-15 (QOR-15) score on postoperative day (POD) 1 in patients undergoing (1) major inpatient surgery, (2) minor inpatient surgery or (3) outpatient surgery, and the primary safety endpoint is the incidence of unintended definite intraoperative awareness with recall in all patients, assessed on POD1 or POD30. Secondary endpoints include QOR-15 score on POD0, POD2 and POD7; incidence of delirium on POD0 and POD1; functional status on POD30 and POD90; health-related quality of life on POD30, POD90, POD180 and POD365; days alive and at home at POD30; patient satisfaction with anaesthesia at POD2; respiratory failure on POD0; kidney injury on POD7; all-cause mortality at POD30 and POD90; intraoperative hypotension; moderate-to-severe intraoperative movement; unplanned hospital admission after outpatient surgery in a free-standing ambulatory surgery centre setting; propofol-related infusion syndrome and malignant hyperthermia.

This study is approved by the ethics board at Washington University, serving as the single Institutional Review Board for all participating sites. Recruitment began in September 2023. Dissemination plans include presentations at scientific conferences, scientific publications, internet-based educational materials and mass media.

NCT05991453.

Osteoarthritis (OA) is a degenerative and progressive joint condition causing pain and disability. Physical exercise is recognised as the most effective intervention since individuals with this condition often experience muscle weakness, balance deficits and chronic pain. Additionally, knee osteoarthritis (KOA) is associated with central sensitisation, contributing to chronic pain conditions. Transcranial Direct Current Stimulation (tDCS), a non-invasive neuromodulation technique, has been employed to induce changes in pain perception by altering cortical excitability, potentially reducing chronic pain.

This is a protocol for a randomised controlled trial. Participants will be allocated to two groups: G1 (active tDCS combined with exercise) and G2 (sham tDCS combined with exercise). The intervention protocol will last for 5 weeks, with two sessions per week on non-consecutive days. Pain intensity will be assessed as the primary outcome using the Numeric Rating Scale (NRS). The sample size was calculated based on a minimum clinically important difference of 3 points on the NRS between groups, with a statistical power of 80% and a significance level of 5%. Secondary outcomes will include physical function and global perceived change.

This protocol was approved by the Research Ethics Committee of the Trairi School of Health Sciences, Federal University of Rio Grande do Norte (Approval Number: 6.801.827), and it is in accordance with the Declaration of Helsinki for human research. Results will be published in peer-reviewed journals and presented at scientific events. This trial is registered in the Brazilian Clinical Trials Registry.

Brazilian Clinical Trials Registry (RBR-5pb2g33).

Despite the abundant evidence showing the benefits of muscle-strengthening exercise (MSE), no epidemiological tool is available for assessing MSE among Indonesian university students. This study is the first to adapt the Muscle-Strengthening Exercise Questionnaire (MSEQ) from its original English version into another language, specifically Indonesian, incorporating cultural adaptations and to pilot test it to assess its validity and reliability among university students in Indonesia.

Translation and cultural adaptation, content validity studies, concurrent validity studies and reliability studies were conducted following COnsensus-based Standards for the Selection of Health Status Measurement INstruments guidelines. Content validation, conducted with three experts and nine university students, informed the development of the MSEQ Indonesian version. The concurrent validity study compared the results of measuring MSE frequency, intensity, duration and volume with those of the 7-day diary and relative handgrip strength with 22 respondents for concurrent validity against subjective measurement and 70 respondents for concurrent validity against objective measurement. For the reliability study, 39 respondents were asked to fill the MSEQ Indonesian version twice with a time interval of 7 days.

The study involved 143 participants, including experts and university students from three universities across two different islands in Indonesia.

Single administration MSEQ, consecutive administration MSEQ and 7-day diary recording resulted in 0%, 33.8% and 68.5% dropout rate, respectively. Moderate-to-strong correlations were observed between the results for the weekly frequency, duration, intensity and volume of MSE and those of the 7-day diary and hand grip strength. Test–retest reliabilities were good to excellent for machine weight, holistic and overall MSE but poor for bodyweight MSE. In assessing the target muscle group, the MSEQ Indonesian version showed good test–retest reliability for machine-weight MSE but poor-to-very good test–retest reliability for bodyweight, free weight and holistic MSE.

Our study demonstrated the acceptable validity and reliability of the Indonesian version of the MSEQ for assessing MSE among university students in Indonesia, not only by comparing each dimension of MSE with subjective measures but also by comparing MSE volume with objective measures. To enhance the generalisability of these findings, future studies should assess the MSEQ Indonesian version in diverse adult populations by considering dropout rates found by our study, ensuring its broader applicability and sample size adequacy.

Stroke is the second leading cause of death worldwide, with the greatest burden in low- and middle-income countries (LMICs). Haemorrhagic stroke or spontaneous intracranial haemorrhage (sICH), including intraparenchymal haemorrhage (IPH) and subarachnoid haemorrhage (SAH), has the highest mortality and morbidity. Local management practices for haemorrhagic stroke vary greatly between geographical regions. The Planetary Outcomes after Intracranial Haemorrhage study aims to provide a global snapshot of the patient characteristics, processes of care and short-term outcomes of patients being treated for sICH across high- and low-income settings. It will also describe variation seen in care processes and available resources and time delays to receiving care. A greater understanding of the current state of sICH care is essential to identify possible interventions and targets for improved standards of care in all settings.

We describe a planned prospective, multicentre, international observational cohort study of patients admitted to hospital for management of sICH. We will include patients of all ages presenting to hospital with imaging evidence of sICH (IPH, intraventricular haemorrhage and/or SAH). The study will collect patient, care process and short-term outcome data, following patients for up to 30 days (or until discharge or death, whichever occurs first). Any centre globally where patients with sICH are admitted and managed can participate, targeting a sample size of 712 patients. The study will recruit centres worldwide through pre-existing research networks and by dissemination through neurosurgical and stroke conferences and courses. Each participating centre will complete a site questionnaire alongside patient data collection.

The study has received ethical approval by the University of Cambridge (PRE.2024.070). Participating centres will also confirm that they have undergone all necessary local governance procedures prior to starting local data collection. The findings will be disseminated via open access peer-reviewed journals, relevant conferences and other professional networks and lay channels, including the study website (https://plotich.org/) and social media channels (@plotichstudy).

NCT06731751.

The mental health of people living with HIV (PLWH) is a growing concern globally, particularly in sub-Saharan Africa (SSA), where there is limited access to mental healthcare, with evidence showing high levels of depression, anxiety and neurocognitive disorders among this population. While Mental Health Disorders (MHDs) can impede HIV care and promote adverse health outcomes, there is limited literature on MHDs among PLWH. This scoping review will explore the existing literature on the burden and factors associated with MHDs among adults living with HIV in SSA.

Arksey and O’Malley’s methodological framework will guide the search of this scoping review. Relevant original research articles published in English from 1 January 2000 to 31 May 2025 on MHDs among PLWH in SSA will be identified through searches in the African Index Medicus, African Journal Online, PubMed and Embase databases. Four independent reviewers, working in pairs (one reviewer and one verifier), will screen the titles, abstracts and later the full texts, adopting the population, concept and context framework. Other coauthors will serve as tiebreakers whenever there is disagreement on the eligibility. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews flowchart will be presented. We will perform a narrative synthesis to report our findings.

This scoping review protocol does not require ethical approval, as it relies solely on publicly available existing data and does not involve human participants. We will disseminate the findings from this review through peer-reviewed publications and presentations at local and international conferences.

The protocol was registered in the Open Science Framework (https://osf.io/8ymqu).

The prevalence of HIV in adolescents is a major global health concern, and research into the influence of HIV on mental health outcomes in this demographic is ongoing. We will conduct a comprehensive systematic review of common mental health outcomes in adolescents with HIV infection (aged 10–24 years). Recognising the specific psychosocial issues that adolescents living with HIV infection are confronted with, this review aims to integrate existing research on the prevalence, risk factors and protective factors related to both positive and negative mental health outcomes in this population.

The following electronic databases will be searched for publications from 1959 up to December 2025: PubMed, PsycINFO, Global Health, Embase, African Journals OnLine and African Index Medicus. The review will focus on both positive and negative mental health outcomes: positive outcomes include resilience, subjective happiness and post-traumatic growth, whereas the negative outcomes include depression, anxiety, post-traumatic stress disorder, substance use disorder and suicidality. Peer-reviewed primary observational studies that report prevalence rates for common mental health outcomes outlined in the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, and the International Classification of Diseases, 11th Edition, their associated factors, as well as barriers to and facilitators of use of mental health support services among this population, will be included in the review. Google Scholar and ProQuest Dissertations & Theses Global as well as Electronic Theses and Dissertations from Ghana, South Africa, Uganda and Kenya, will also be searched for grey literature. The review will be limited to publications in English or French. To assess the methodological rigour of the selected studies, the Joanna Briggs Critical Appraisal Tools will be used. The synthesis will include a narrative summary and, if applicable, a meta-analysis of quantitative data depending on the extent of heterogeneity observed in the included studies. Subgroup analyses will be conducted to investigate differences in mental health outcomes by age, sex and socioeconomic position, where applicable. This systematic review will be reported in accordance with the PRISMA statement.

This review will use secondary data and does not require ethical approval. The findings will be shared through peer-reviewed publications and conference presentations. The emphasis will be on translating research findings into practical mental health interventions and HIV-specific support services for adolescents.

CRD42024568512.

Aphasia is a language impairment that affects one-third of people who experience a stroke. Aphasia can impact all facets of language: speaking, understanding, reading and writing. Around 60% of people with aphasia have persistent language impairments 1 year after their stroke, requiring ongoing healthcare and support. In recent years, the internet has become a key resource for the self-management of chronic health conditions. Navigating web content, however, requires language use, and as such, people living with aphasia are more likely to be excluded from digital health and support services. Web Content Accessibility Guidelines exist; however, they do not fully address the unique and diverse needs of people with aphasia, and a significant proportion of websites (over 90%) do not fully adhere to them. This protocol paper describes the first two stages of the Bridging the Digital Divide project, which aims to codesign and develop (a) a web-browser extension to re-render webpages to an ‘aphasia-friendly’ (accessible) format, (b) training tools to help users and health professionals customise the web-browser extension and (c) guidelines for developing communication-accessible websites.

The research will be conducted using experience-based codesign. In Stage 1a, focus groups will be held with (1) people with aphasia, (2) family members or significant others and (3) health professionals working with people with aphasia. Participants will be asked to share their experiences of accessing (or supporting a person with aphasia to access) healthcare, information and support services on the web. The nominal group technique (NGT) will be used to identify priorities for improving web accessibility for people with aphasia. Focus group data will be analysed using reflexive thematic analysis, and prioritisation data will be analysed using inductive qualitative content analysis. In Stage 1b, eight codesign workshops will be held with representatives of the three key stakeholder groups to iteratively codesign and develop a web-browser extension, training tools and guidelines to support web accessibility.

Ethical clearance for Stage 1a and Stage 1b of this project has been approved by the University of Queensland Human Research Ethics Committee (Stage 1a approval number: 2023/HE000528, Stage 1b approval number: 2024/HE000721). The outcomes of this research will be disseminated in peer-reviewed journals and presented at national and international conferences. A dissemination and celebration event will be held at the completion of the project.

High quality handover is critical for patient safety and care continuity. Existing practice is based on a weak evidence base in which the patient voice is poorly captured. The aim of this study was to identify outcomes of importance to patients, families and carers regarding interventions to improve in-hospital handover between healthcare practitioners.

A rapid systematic review of qualitative literature was carried out after prospective registration with PROSPERO and was reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Enhancing Transparency in Reporting the Synthesis of Qualitative Research guidelines.

The Ovid MEDLINE database was searched.

Qualitative or mixed-methods studies reporting patient, family or caregiver perspectives on in-hospital handovers were eligible for inclusion.

Synthesis was informed by the best-fit framework approach using a published taxonomy of handover-related outcomes and the Core Outcome Measures in Effectiveness Trials taxonomy. Outcomes were reported according to two distinct types of handover: bedside (patient-involved) and provider-focused (patient-uninvolved).

A total of 34 studies, including 1262 participants across a range of specialties and predominantly high-income settings, were analysed. 53 bedside and 31 provider-focused handover outcomes were identified according to four domains; adverse events, quality of patient care, quality of handover and patient/caregiver satisfaction. Bedside handover studies frequently reported outcomes relating to patient engagement and communication with healthcare staff. One study was carried out in a low income country; however, outcomes identified were broadly similar.

These findings expand the known outcomes for evaluating handover interventions and highlight the importance of prioritising the patient and public perspective in research. This work will contribute to developing a core outcome set for trials in surgical handover but can also be applied to handover practices for any other discipline within the hospital environment.

CRD42023493367.

This study aimed to investigate the characteristics and management of influenza-like illnesses (ILIs) in the outpatient and inpatient settings in Vietnam.

A cross-sectional, observational study.

We conducted a questionnaire survey of 407 individuals with ILI symptoms who presented to public community health centres and the paediatric ward of a public hospital in the city of Nha Trang, Khanh Hoa Province, Vietnam, from December 2022 to March 2023.

Not applicable.

No primary and secondary outcomes were pre-specified because this study was an explanatory study. The basic characteristics of the participants are presented using descriptive statistics. We conducted multivariable logistic regression analysis to examine the factors associated with the prescription of antibiotics to outpatients with ILIs.

A total of 198 outpatients and 200 inpatients were enrolled in the study. Most inpatients were children under 5 years of age and experienced longer illness durations and higher costs, with almost all patients receiving antibiotics. The rate of antimicrobial prescription for ILIs was 79.3% for outpatients and 99.5% for inpatients. The median health-related quality of life score of participants aged ≥18 years during illness was 0.796 (IQR 0.674–0.922). Logistic regression analysis indicated a negative association between a definite diagnosis of viral infection by rapid diagnostic test and outpatient antibiotic prescription (OR: 0.20, p=0.006).

This study underscores the widespread inappropriate antimicrobial use for ILIs in a community in Vietnam, which contributes to an avoidable economic and health burden. The results of this study suggest that implementing diagnostic tools may support antimicrobial stewardship efforts.

Non-communicable diseases (NCDs), such as diabetes, cardiovascular diseases and cancer, are major global public health concerns. Diet quality—particularly the consumption of ultra-processed foods—has been associated with increased risk of NCDs. Traditional cohort studies are often expensive and logistically complex. The NutriNet-Brasil cohort leverages a web-based approach, offering a cost-effective and practical solution for comprehensive data collection and long-term follow-up.

Recruitments began in January 2020 through mass media, social media campaigns and collaborations with health organisations. Eligible participants are adults (aged ≥18 years) living in Brazil with internet access. Participants complete self-administered online questionnaires covering dietary intake, health status and other health determinants. Dietary assessment is based on the Nova classification system, which categorises foods by their level of processing.

Over 88 000 participants have completed the initial questionnaire. The cohort is predominantly women (79.9%) and highly educated (67.9% had completed higher education). The web-based design enabled the development and application of innovative dietary assessment tools, including the Nova24h and the Nova24hScreener, specifically designed to evaluate food processing levels. These tools have shown good performance in capturing dietary patterns and are central to the cohort’s aim. The online platform facilitates efficient recruitment, data collection and participant retention.

NutriNet-Brasil is pioneering the development of web-based cohort methodologies and instruments tailored to food processing research. Future work includes leveraging collaborations with national and international research centres to conduct multidisciplinary analyses and inform public health policies.

Pharmacogenomic testing could potentially reduce the number of adverse drug reactions and improve treatment outcomes through tailoring treatment to an individual’s genetic makeup. Despite its benefits and the ambitions to integrate into routine care, the implementation of pharmacogenomic testing in primary care settings remains limited. This study aims to qualitatively explore the views of healthcare professionals (HCPs) and patients on implementing pharmacogenomic testing in the UK National Health Service (NHS) primary care setting and to estimate the cost-effectiveness of service-delivery implementation by comparing different HCPs’ models of care.

This study consists of three workstreams (WS). WS1 is semi-structured interviews with General Practitioners, pharmacists, nurses and patients (24 participants) to explore implementation issues, including the perceived barriers and facilitators to delivering a pharmacogenomic service. WS2 consists of focus groups (between 24–36 participants) with genomic experts to develop practical pharmacogenomic-guided clinical pathways for primary care. WS3 will estimate the cost-effectiveness of implementing pharmacogenomic testing when led by different HCPs incorporating parameters from the literature, expert opinions, as well as data from WS1 and WS2.

Thematic analysis will be used to analyse the qualitative data from WS1 and WS2, mapping findings onto the Consolidated Framework for Implementation Research domains, which will also be used as the theoretical framework. WS3 will be a decision-analytic model developed in Microsoft Excel to compare the cost-effectiveness of pharmacist-led, GP-led, nurse-led or multidisciplinary pathways.

This study has been approved by the NHS Health Research Authority and Health and Care Research Wales (24/PR/1088). Findings will be disseminated through peer-reviewed publications, conference presentations and engagement with NHS policymakers and Genomics England.

Most research on the relationship between diabetes and cognitive health has used data from high-income countries. This study described this relationship in India, the world’s most populous country.

Cross-sectional analysis of the baseline wave of the nationally representative Longitudinal Ageing Study in India, conducted from 2017 to 2019.

All 36 Indian states and union territories.

57 905 adults aged 45 years or older.

Scaled cognitive scores (mean of 0 and SD of 1) and cognitive impairment defined as a cognitive score 1.5 SD or below the age-matched and education-matched mean. Diabetes was defined as a self-report of a prior diabetes diagnosis made by a health professional or having a measured haemoglobin A1c ≥6.5%.

In age-adjusted and sex-adjusted models, people with diabetes had cognitive scores that were 0.24 SD higher (95% CI 0.22 to 0.26) and had a 1.2% (95% CI 0.6% to 1.7%) lower prevalence of cognitive impairment than people without diabetes. Differences persisted even when adjusting for demographic, socioeconomic and geographical characteristics. Rural versus urban residence modified the relationships of diabetes with cognitive score (p=0.001) and cognitive impairment (p=0.003). In fully adjusted models, rural respondents with diabetes had 0.05 SD (95% CI 0.03 to 0.07) greater cognitive scores and 1.6% (95% CI 0.9% to 2.4%) lower prevalence of cognitive impairment than those without diabetes. In urban areas, respondents with and without diabetes had similar cognitive scores and prevalence of cognitive impairment.

Middle-aged and older adults with diabetes living in India had better cognitive health than those without diabetes. Rural versus urban area of residence modified this relationship. Urban–rural differences, the nutrition transition and social conditions likely influenced the cross-sectional relationship between diabetes and cognitive health in India, leading to different associations than reported in other countries.

Acknowledging equality, diversity and inclusion (EDI) in research is not only a moral imperative but also an important step in avoiding bias and ensuring generalisability of results. This protocol describes the development of STAndards for ReporTing EDI (START-EDI) in research, which will provide a set of minimum standards to help researchers improve their consistency, completeness and transparency in EDI reporting. We anticipate that these guidelines will benefit authors, reviewers, editors, funding organisations, healthcare providers, patients and the public.

To create START-EDI reporting guidelines, the following five stages are proposed: (i) establish a diverse, multidisciplinary Steering Committee that will lead and coordinate guideline development; (ii) a systematic review to identify the essential principles and methodological approaches for EDI to generate preliminary checklist items; (iii) conduct an international Delphi process to reach a consensus on the checklist items; (iv) finalise the reporting guidelines and create a separate explanation and elaboration document; and (v) broad dissemination and implementation of START-EDI guidelines. We will work with patient and public involvement representatives and under-served groups in research throughout the project stages.

The study has received ethical approval from the Imperial College London Research Ethics Committee (study ID: 7592283). The reporting guidelines will be published in open access peer-reviewed publications and presented in international conferences, and disseminated through community networks and forums.

The project is pre-registered within the Open Science Framework (https://osf.io/8udbq/) and the Enhancing the Quality and Transparency of Health Research Network.

To determine if carer administration of as-needed subcutaneous medication for common breakthrough symptoms in people dying at home is feasible and acceptable in the UK, and if it would be feasible to test this intervention in a future definitive randomised controlled trial.

We conducted a two-arm, parallel-group, individually randomised, open pilot trial of the intervention versus usual care, with a 1:1 allocation ratio, using convergent mixed methods.

Home-based care without 24/7 paid care provision, in three UK sites.

Participants were dyads of adult patients and carers: patients in the last weeks of their life who wished to die at home and lay carers who were willing to be trained to give subcutaneous medication. Strict risk assessment criteria needed to be met before the approach, including a known history of substance abuse or carer ability to be trained to competency.

Intervention-group carers received training by local nurses using a manualised training package.

Quantitative data were collected at baseline and 6–8 weeks post-bereavement and via carer diaries. Interviews with carers and healthcare professionals explored attitudes to, experiences of and preferences for giving subcutaneous medication and experience of trial processes. The main outcomes of interest were feasibility, acceptability, recruitment rates, attrition and selection of the most appropriate outcome measures.

The secondary outcome measure was time to symptom relief, calculated using data items from the carer diary, after the patient had died.

In total, 40 out of 101 eligible dyads were recruited (39.6%), which met the feasibility criterion of recruiting >30% of eligible dyads. The expected recruitment target (50 dyads) was not reached, as fewer than expected participants were identified. Although the overall retention rate was 55% (22/40), this was substantially unbalanced (30% (6/20) usual care and 80% (16/20) intervention). The feasibility criterion of >40% retention was, therefore, considered not met. A total of 12 carers (intervention, n=10; usual care, n=2) and 20 healthcare professionals were interviewed. The intervention was considered acceptable, feasible and safe in the small study population. The intervention group had a considerably shorter time to medication administration than the usual-care group (median time to administer medication in intervention=5 min, usual-care=105 min). Intervention group carers felt confident in administering medication. Healthcare professional support was sought by intervention group carers in 24 out of 147 (16.3%) medication administration entries. The context of the feasibility study was not ideal, as district nurses were overstretched, unfamiliar with research methods and possibly not in equipoise. A disparity in readiness to consider the intervention was demonstrated between carers, who were uniformly enthusiastic, and healthcare professionals who were not. Findings confirmed methodological and ethics issues pertaining to researching the last days of life care.

The success of a future definitive trial is uncertain because of equivocal results in the progression criteria, particularly poor recruitment overall and a low retention rate in the usual-care group. Future work regarding the intervention should include understanding the context of UK areas where this has been adopted, ascertaining wider public views and exploring healthcare professional views on burden and risk in the NHS context. There should be consideration of the need for national policy and the most appropriate quantitative outcome measures to use. This will help to ascertain if there are unanswered questions to be studied in a trial.

ISRCTN11211024.

Over half of children and adolescents with attention-deficit/hyperactivity disorder (ADHD) have difficulties with emotion dysregulation (EDR) and/or sleep, yet the interrelations between emotional regulation and sleep are not well-characterised in this population. This systematic review will address the relationship between these difficulties and investigate whether specific aspects of EDR are more strongly related to sleep problems in youth with ADHD.

We will adhere to the Preferred Reporting Items for Systematic Reviews and Meta-analysis guideline for systematic reviews. A wide set of electronic databases will be searched for peer-reviewed quantitative studies investigating the relationship between EDR and sleep in children and adolescents (ages 5 to 18 years) with ADHD. In addition, the reference list of all studies will be searched for other relevant studies, and Scopus will be used to search for citations of the included studies. We will also contact experts in the field to request published and unpublished studies. The primary outcome will be the effect size of the relationship between EDR and sleep in children and adolescents with ADHD. We will look at EDR and sleep broadly and also consider the multifaceted nature of both terms. Secondary outcomes will include which facets of EDR and sleep have been measured and how they have been measured, developmental differences between children and adolescents with ADHD and how—and the extent to which—studies controlled for the use of CNS medications and cooccurring disorders in their study design and/or statistical analyses. The quality and risk of bias of the included studies will be assessed using the Mixed Methods Appraisal Tool.

This protocol is for a review of studies and does not involve any new data collection and therefore does not need ethical or human subjects approval. The results will be presented at international conferences and in a peer-reviewed journal.

CRD42024612984.

Amyotrophic lateral sclerosis (ALS) is a devastating illness that leads to muscle weakness and death usually within around 3 years of diagnosis. People with ALS (pwALS) often lose weight due to raised energy requirements and symptoms of the disease presenting significant challenges to taking adequate oral diet, with those who lose more weight being at a greater chance of earlier death. There is also some evidence to suggest that a higher calorie diet may benefit the disease course in pwALS, but further research is needed.

Two armed, parallel group, superiority, open labelled, randomised controlled trial, with internal pilot, to assess the effectiveness of an early high calorie diet on functional outcomes in ALS, comprising two treatment arms: (1) standard care, (2) standard care with additional active management using the OptiCALS complex intervention to achieve a high calorie diet (initially randomised 1:1, then 1:2 following a protocol amendment). Using a food first approach, pwALS will be encouraged and supported to follow a diet that meets an individualised calorie target from food before prescribing oral nutritional supplements. 259 pwALS will be recruited from up to 20 ALS centres across the United Kingdom and Ireland and followed up for a period of 12 months. Primary outcome is functional change measured over 12 months, using the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale. Secondary end points include measures of functional health, quality of life, calorie intake and weight, as well as time to gastrostomy and survival. A health economic analysis and process evaluation will also be undertaken. Participant recruitment is expected to complete in September 2025, and participant follow-up is expected to complete in September 2026. The results of this study are expected in March 2027.

The trial was approved by Greater Manchester—North West Research Ethics Committee, reference 20/NW/0334 on 8 September 2020. We will publish the study findings in peer-reviewed academic journals and present at local, national and international conferences where possible.

ISRCTN30588041.

Percutaneous coronary interventions (PCI) have become a cornerstone in the management of acute coronary syndromes (ACS), yet they carry risks of complications like stent thrombosis and reinfarction. Glycoprotein IIb/IIIa inhibitors, particularly tirofiban, have been employed as adjunctive therapies to reduce these risks. Despite its potential benefits, the use of tirofiban remains a subject of debate, with varying recommendations across major clinical guidelines.

We systematically searched five databases from 1 January 1992 to 1 April 2025, including Medline, Embase, Lilacs, Clinicaltrials.org and Cochrane Central Register of Controlled Trials (CENTRAL), in addition to three grey literature databases. Randomised controlled trials and cluster randomised trials investigating the use of intravenous or intracoronary tirofiban in patients with ACS, unstable angina or myocardial infarction were considered for inclusion. Only published studies in English, Portuguese, Spanish and French were included. Data selection and extraction will be performed independently by two researchers, with any inconsistencies resolved with consensus or by consulting a third senior researcher. The risk of bias will be assessed through the risk of bias measurement tool (Rob-2) for interventions and/or cluster trials by two researchers independently, and the overall certainty of evidence will be assessed by using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) tool. A meta-analysis will be carried out if there is sufficient homogeneity between studies, with subgroup analysis being performed if significant heterogeneity is detected. Additionally, a metaregression model will be conducted if sufficient data are available.

As this study involves secondary analysis of published data, ethics approval is not required. The results will be disseminated through peer-reviewed publication, conference presentations and will be shared with relevant clinical guideline committees.

CRD42024585252.

Excessive bleeding after childbirth (postpartum haemorrhage, PPH) affects 5% of births and causes 75 000 maternal deaths worldwide annually. It is the leading cause of direct maternal deaths globally and continues to be a major cause of mortality in the UK. Oxytocin is the standard first-line treatment for atonic PPH. The PPH rate is increasing, and this may be partially related to the overuse of oxytocics in labour. Laboratory studies on myometrium suggest that repeated use of oxytocics leads to the saturation of oxytocin receptors and reduced therapeutic efficacy of oxytocin. Carboprost (a prostaglandin analogue) is usually reserved for second-line management of atonic PPH. A systematic review comparing the efficacy of carboprost and conventional uterotonics for PPH prophylaxis found that carboprost was associated with less blood loss, but around 15% of women experienced side effects. The study’s aim is to compare intramuscular carboprost with intravenous oxytocin for the initial treatment of PPH. In addition, to assess the cost-effectiveness of both treatments, participants’ views on the two treatments and the consent process.

COPE is a double-blind, double-dummy, randomised controlled trial that aims to recruit 2000 women (1:1 allocation, stratified by mode of birth) across 20 hospitals in the UK. Due to the emergency nature of PPH, COPE uses a research without prior consent (RWPC) model. Randomisation and treatment will occur if eligibility criteria are met once bleeding starts. Postnatal consent will be sought for disclosure of identifiable data and continued follow-up. Clinical efficacy outcomes will be collected at 24 and 48 hours or at hospital discharge, if sooner. Questionnaires will also be collected at 24 hours and 4 weeks postrandomisation. Cost-effectiveness will be based on the incremental cost per quality-adjusted life-year, calculated from the perspective of the NHS and personal social services.

This study has been approved by the Coventry and Warwickshire Research Ethics Committee (REC) (18/WM/0227) and the Health Research Authority. Results will be disseminated via peer-reviewed publications.

ISRCTN16416766.