Sleep problems are an escalating global health concern, with prevalence estimates ranging from 8.3% to 45%. Physicians are disproportionately affected, with rates around 44% compared with 36% in the general population. In Bangladesh, reported rates range from 32% to 58%, with physicians being particularly vulnerable. Poor sleep among physicians is strongly linked to burnout, medical errors and increased mental health risks. Despite these serious implications, existing evidence from Bangladesh remains fragmented and inconsistent, limiting its utility for health policy and workforce interventions. This review therefore seeks to generate reliable pooled prevalence estimates and identify key determinants of sleep problems among Bangladeshi physicians.

The research team will search the PubMed, Scopus, Web of Science, EMBASE, PsycInfo, ProQuest Medical, CINAHL, Google Scholar and BanglaJOL electronic and regional databases following Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines for published studies from inception until 1 August 2025, using truncated and phrase-searched keywords, relevant medical subject headings and citation chaining from grey literature. Observational cross-sectional studies published within the predefined timeframe, using validated assessment tools, and published in English or other major international languages will be prioritised for inclusion. Review papers, case reports, case series, intervention studies, commentaries, preprints, meeting abstracts, protocols, unpublished articles and letters will be excluded. Two independent reviewers will screen the retrieved papers using the Rayyan web-based application, with any disagreements resolved by a third reviewer. Quantitative estimates of sleep problems, including prevalence, duration, quality and associated risk factors among Bangladeshi physicians will be extracted. A narrative synthesis and meta-analysis will be performed to assess the pooled prevalence using a random effects meta-analysis model. Forest and funnel plots will be generated for visualisation. Heterogeneity will be assessed using the I² statistic, with sensitivity or subgroup analysis conducted as required. The quality of included studies will be evaluated using Joanna Briggs Institute critical appraisal tools for observational study designs. All statistical analysis will be conducted using Jamovi V2.7.6, R V4.3.2 ‘meta’ packages and GraphPad Prism V9.0.2.

This review will synthesise evidence from existing published literature. While completing the findings, the findings will be submitted to an international peer-reviewed journal and disseminated through conferences, policy forums and stakeholders’ networks to inform future research and interventions.

CRD420251123294.

The global rise in the population aged over 65 has led to a corresponding increase in cognitive impairment diagnoses, with dementia as a predominant condition characterised by diverse aetiopathogenetic profiles. Behavioural and psychological symptoms of dementia (BPSD) encompass a range of psychiatric, behavioural and cognitive symptoms associated with cognitive impairment. BPSD significantly affects patients, caregivers and healthcare providers, often necessitating interventions like sedatives or physical restraints that may worsen patient outcomes. Emerging evidence underscores the need for innovative, non-pharmacological interventions to manage BPSD effectively.

The current study intends to investigate the feasibility and acceptability of customised, immersive virtual reality environments (iVRe) to reduce responsive behaviours among individuals with dementia. Building on prior findings demonstrating virtual reality (VR) potential in reducing anxiety and fostering positive emotional states, this pilot study assesses the feasibility, safety and user engagement of customised iVRe interventions.

A longitudinal, mixed-methods design will be employed, enrolling 20 elderly participants with varying levels of cognitive impairment from the APSP ‘Margherita Grazioli’ long-term care facility in Trento. Participants undergo three VR exposure sessions featuring tailored environments adjusted in real-time for visual and auditory preferences. Data collection integrates standardised self-report questionnaires, observational tools and clinical records. Measures include the Functional Assessment Staging Tool, Neuropsychiatric Inventory and Cohen-Mansfield Agitation Inventory, as well as tools assessing pain, anxiety and emotional states before, during and after VR sessions.

The study protocol has been approved by the Comitato Etico Territoriale della Provincia Autonoma di Trento per le Sperimentazioni Cliniche, Azienda Provinciale per i Servizi Sanitari—Trento, Italy (Rep. Int. 12090, 15 May 2025). All participants or their legal representatives will provide written informed consent prior to enrolment. Deidentified data will be securely stored on institutional servers at the Fondazione Bruno Kessler and the APSP ‘Margherita Grazioli’, curated in compliance with the General Data Protection Regulation, and retained for 3 years after study completion. Any data shared externally will be provided in fully anonymised form, and only for scientific purposes, subject to prior ethical and legal approval. Study findings will be disseminated through peer-reviewed publications, conference presentations and executive summaries shared with participating institutions and stakeholders.

NCT06693193.

Alcohol is consumed by an estimated 137.4 million people in the USA 12 years of age and older and, as a result, is estimated to have caused about 140 thousand deaths among people 20 to 64 years of age each year from 2015 up to and including 2019.

The proposed review of the evidence on alcohol’s impact on health aims to produce conclusions to inform the Dietary Guidelines for Americans, 2026–2030. A multi-method approach will be utilised to formulate conclusions on (i) weekly (ie, average) thresholds to minimise long-term and short-term risks of morbidity and mortality, (ii) daily thresholds to minimise the short-term risk of injury or acute illness due to per occasion drinking, (iii) alcohol use among vulnerable populations (eg, pregnant women) and (iv) situations and circumstances that are hazardous for alcohol use. To inform expert decisions, this project will also include a systematic review of existing low-risk drinking guidelines, a systematic review of meta-analyses which examine alcohol’s impact on key attributable disease and mortality outcomes, and of estimates of the lifetime absolute risk of alcohol-attributable mortality and morbidity based on a person’s sex and average level of alcohol use. The systematic reviews were designed in accordance with the preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P). The preliminary conclusions produced as a result of this project will undergo public consultation, and data from these consultations will be qualitatively analysed. The results of the public consultations will be used to further revise and refine the project’s conclusions.

The study was granted an ethics exemption as only secondary data sources and unidentifiable public consultation will be utilised. Systematic reviews are pre-registered with PROSPERO (registration numbers CRD42024584924 and CRD42024584948).

This project will establish a scientific consensus concerning alcohol’s impact on health. This consensus is imperative for informing the upcoming Dietary Guidelines for Americans, 2026–2030, and for better informing individuals about the health risks associated with alcohol use.

Depression, anxiety and stress are major contributors to the global burden of diseases. The ageing population faces an escalating burden of these conditions, and half of the cases are largely undiagnosed. Yet a paucity of epidemiological data limits understanding the full scope of the disease burden among older adults. This protocol outlines a systematic review to estimate the prevalence and incidence of anxiety, depression and stress among older people (60 years and above) and to identify contributing factors across South-East Asian countries.

A study protocol for a systematic review and meta-analysis has been registered in PROSPERO. The research team will systematically search, appraise and synthesise observational studies following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Comprehensive searches will be conducted from inception to May 2025 across PubMed (NCBI), MEDLINE (Ovid), Web of Science, Cochrane Library, Scopus (Elsevier) and PsycINFO (APA), supplemented by grey literature from government reports, the WHO Library and Google Scholar. Two investigators will independently screen titles and abstracts, review full-text articles published in the English language and extract data, with discrepancies resolved by a third reviewer. Methodological quality and risk of bias of the included studies will be assessed using standardised tools. Primary outcomes are the prevalence and incidence of depression, anxiety and stress. Secondary outcomes include variations in the prevalence and incidence of these conditions based on sociodemographic factors, as well as associated risk factors that differ across regional contexts. Data will be pooled via meta-analysis where feasible or narratively synthesised if heterogeneity precludes quantitative synthesis. The systematic review will provide a comprehensive understanding of the burden of anxiety, depression and stress among older people in South-East Asia. This novel evidence will guide policymakers and healthcare practitioners in developing targeted interventions and generating essential evidence for supporting policy development in the region.

Ethical approval will not be required as this study will not involve collection of original data. The findings will be disseminated through publications in a peer-reviewed journal and presentations at scientific conferences.

CRD42024609033.

To provide the first national estimate of syphilis prevalence among people who inject drugs (PWID) in Georgia, alongside updated HIV prevalence and associated risk behaviours, and to identify factors associated with infection.

Cross-sectional Integrated Bio-Behavioural Surveillance Survey conducted in 2022. Respondent-driven sampling was used to recruit PWID. Data were collected through standardised face-to-face interviews using structured questionnaires, and venous blood samples were collected for laboratory testing. HIV was diagnosed by serology, and syphilis was assessed using a two-step algorithm (Rapid Plasma Reagin screening with Treponema pallidum haemagglutination assay confirmation). Logistic regression models were applied to identify correlates of infection.

The study was conducted in community settings across seven major cities of Georgia that represent the main urban centres with large PWID populations. Survey implementation was supported by local peer-led and community-based harm reduction organisations with established trust and access to PWID networks, facilitating participant recruitment and ensuring feasibility.

HIV prevalence was 0.9% and syphilis prevalence 2.1%. Coinfection with HIV and syphilis was observed in 0.2% of participants. HIV infection was significantly associated with longer duration of injection drug use (adjusted OR (aOR) 0.2; 95% CI 0.5 to 0.9) and lack of access to HIV prevention services (aOR 2.8; 95% CI 1.1 to 7.8). Syphilis prevalence was significantly lower among PWID who had not had casual or paid sex in the past year (OR 0.06; 95% CI 0.02 to 0.2). Unsafe sexual behaviours were common: 25.8% reported sex with a casual partner in the past year, 12.3% reported a paid partner, and only around half used condoms consistently with these partners.

Despite a relatively low HIV prevalence, syphilis prevalence among PWID in Georgia highlights ongoing sexual risk behaviours. Current harm reduction programmes primarily address injection-related risks, with limited sexually transmitted infection (STI) prevention efforts. Expanding sexual health interventions within harm reduction services, including STI screening, structured counselling and safe sex education, is essential to reduce STI transmission and improve health outcomes among PWID.

Childhood cancer survivors (CCSs) experience educational disruptions during and following treatment, yet robust, longitudinal evidence on educational performance remains limited. We will investigate differences in educational outcomes between CCSs and non-cancer peers during primary and secondary school. We will also explore how sociodemographic factors and age at diagnosis contribute to potential differences in General Certificate of Secondary Education (GCSE) examinations, a critical indicator of future academic and employment prospects.

We will use the Education and Child Health Insights from Linked Data (ECHILD) to capture linked health and education data for children born in National Health Service (NHS)-funded hospitals in England. We will generate birth cohorts spanning September 1997 to August 2015 (estimated sample size: ~10 million), formed of pupils expected to have undertaken national curriculum assessments between academic years 2004/2005 and 2021/2022 including Key Stage (KS) 1, 2 and 4, corresponding to ages 7, 11 and 16 respectively. Cancer diagnosis will be identified from inpatient hospital records, using International Classification of Diseases, 10th Revision codes (ICD-10). We will investigate differences between CCS and their non-cancer peers in terms of their sociodemographic characteristics and describe trends in educational performances at all KSs, recorded Special Educational Needs and Disabilities (SEND) and school absences. Differences in KS4 (GCSE) performances between CCS and non-cancer peers will be quantified, according to and accounting for geographic region, sex, deprivation, ethnicity and birth characteristics. To assess whether cancer diagnosis disrupts academic trajectories, we will restrict analysis to those with KS2 attainment data and investigate KS4 performance. We will finally explore the influence of age at diagnosis on educational performance at KS4.

Ethics approval was granted by NHS Health Research Authority Research Ethics Committee (20/EE/0180). Findings will be shared with academics, policymakers, children and families affected by childhood cancer, and published in journals. Code/metadata will be shared on ECHILD GitHub repository.

Neutropenic fever (NF) has a crude mortality rate of 3–18%. International guidelines recommend that all patients with NF receive ultrabroad-spectrum antibiotics (UBSAs) within 1 hour of emergency department (ED) registration. However, over 70% patients presenting to hospital with suspected NF (sNF) cannot access absolute neutrophil count (ANC) result within 1 hour, do not have NF and do not require UBSAs. In ED and hospitalised patients with sNF, we hypothesise that the ASTERIC protocol effectively and safely reduces the use of UBSAs compared with standard care alone.

This pragmatic, parallel, multicentre, type 1, hybrid effectiveness-implementation, stepped-wedge, before-and-after, cluster randomised controlled trial aims to evaluate whether antibiotic prescribing can be safely reduced through implementing a multifaceted antibiotic stewardship intervention (ASTERIC) in adult patients with sNF presenting to EDs. The sNF was defined as a fever with a single oral temperature of ≥38.3°C (101°F) within 24 hours before ED registration or a temperature of ≥38.0°C (100.4°F) sustained over a 1-hour period, following last chemotherapy or targeted therapy within 6 weeks for any solid tumour, or in any period following therapies against leucaemia, lymphoma, myelodysplastic syndrome, aplastic anaemia, multiple myeloma or recipient of HSCT. The study will involve eight hospitals in Hong Kong with variable baseline practice. We will include 704 adult patients (352 patients in pre-implementation and post-implementation periods, respectively) with sNF (tympanic temperature ≥38.3°C) and 48 staff participants (6 staff participants in each hospital). Healthcare professionals will receive a multifaceted stewardship intervention consisting of risk assessment tools, fast-track ANCs, a decision tool for patient management and antibiotic use, supported by an educational package and staff interaction programmes (ASTERIC protocol). Patients’ blood ANC, and cancer therapy and chronic illness therapy scores will be measured. The RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) and Proctor conceptual frameworks will be followed for evaluation of implementation. The main outcome measures are the mean total dose of UBSAs prescribed in 7 days and serious adverse events at 30 days. Data analysis will incorporate intention-to-treat, per-protocol and as-treated analyses for service outcomes (effectiveness, safety, quality of life assessments and cost-effectiveness) and mixed methods for implementation outcomes, informed by the Theoretical Domains Framework. We expect that the study results will inform health policy with improvement in hospital services in treating stable sNF, evidenced by improved safe antibiotic stewardship, early antibiotic de-escalation and reduced costs and length of stay.

The institutional review boards of all study sites approved this study. This study will establish the ASTERIC protocol safely improves antibiotic stewardship and clinical management in adult patients with sNF. We will disseminate the findings through peer-reviewed publications, conference presentations and educational activities. All patients with sNF will be influenced by the new protocol which is agreed at hospital level. Randomisation is at hospital level, not patient level. Patient consent is sought for follow-up and data access, not for treatment. Staff consent is sought for interviewing.

NCT06794320.

Infant feeding practices in the first 2 years of life are linked to long-term weight trajectories. Despite the importance of obesity prevention interventions, there are no randomised controlled trials (RCTs) evaluating early childhood education and care (ECEC) and primary caregiver-targeted interventions on child weight and feeding outcomes.

To assess the efficacy of an 18-month digital health intervention (Tiny Bites) delivered to ECEC services and primary caregivers of children aged 4 to ≤12 months on child age-adjusted and sex-adjusted body mass index-for-age z-score (zBMI) relative to usual care control in the Hunter New England (HNE) region of New South Wales, Australia.

This type 1 hybrid cluster RCT will include up to 60 ECEC services and 540 children/caregiver dyads. The intervention supports ECEC services and caregivers to deliver recommended responsive feeding practices to infants. ECEC services will receive access to an online assessment platform, training and resources, and implementation support. Primary caregivers will receive text messages, monthly e-newsletters, online links and direct communication from ECEC services. We will assess the impact on child zBMI at 18-month follow-up. Secondary outcomes include duration of consuming any breastmilk, child diet and caregiver responsive feeding practices. We will also assess ECEC policy and practice implementation related to targeted feeding practices, programme cost effectiveness, adverse effects and engagement with the programme (ECECs and caregivers). For the primary outcome, between-group differences will be assessed for paired data using two-level hierarchical linear regression models.

Ethics approval has been provided by HNE Human Research Ethics Committee (HREC) (2023/ETH01158), Deakin University (2024-202) and University of Newcastle HREC (R-2024-0039). Trial results will be submitted for publication in peer-reviewed journals, presented at scientific conferences locally and internationally and to relevant practice stakeholders.

ACTRN12624000576527.

Type 2 diabetes (T2D) is a complex disease with a heterogeneous clinical presentation. Recently, five distinct clusters of T2D have been identified in the Emirati population of long-standing T2D with complications. This study aimed to validate these clusters in newly diagnosed T2D patients without any complications and determine whether severe and mild phenotypes are detectable early in the disease course.

Retrospective, cross-sectional, non-interventional study.

Primary healthcare centres in Dubai, UAE.

A total of 451 adults, including both Emiratis and expatriates, diagnosed with T2D in the last 5 years and without T2D-related complications at the time of visit, were enrolled. Patients with complications, incomplete clinical data or higher duration of T2D were excluded from the study.

Identification of distinct T2D clusters using machine learning-based clustering analysis. Five clinical variables: age at diagnosis, body mass index, glycated haemoglobin, fasting serum insulin and fasting blood glucose served as predictors. Overlap between clusters was assessed via the Silhouette Index and Bayesian probability.

Five clusters were identified, replicating prior findings: severe insulin-resistant diabetes (SIRD), severe insulin-deficient diabetes (SIDD), mild age-related diabetes (MARD), mild obesity-related diabetes (MOD) and mild early-onset diabetes (MEOD). As confirmed by a Silhouette Index and Bayesian probability of 1, 55.43% of the patients showed cluster-exclusiveness, while 44.56% of the cohort showed overlap between clusters. The highest overlap was recorded for mild forms of T2D in the order MOD>MARD>MEOD.

The study confirms that both severe and mild T2D phenotypes are present in newly diagnosed, complication-free patients, supporting the applicability of cluster-based classification early in disease. These results highlight the potential for personalised treatment strategies to optimise management and prevent complications. Future studies should investigate longitudinal outcomes and therapeutic response across clusters.

Deaths related to drug overdose and suicide in the USA have increased 500% and 35%, respectively, over the last two decades. The human and economic costs to society associated with these ‘deaths of despair’ are immense. Great efforts and substantial investments have been made in treatment and prevention, yet these efforts have not abated these increasing trajectories of deaths over time. The COVID-19 pandemic has exacerbated and highlighted these problems. Notably, some geographical areas (eg, Appalachia, farmland) and some communities (eg, low-income persons, ‘essential workers’, minoritised populations) have been disproportionately affected. Risk factors have been identified for substance use and suicide deaths: forms of adversity, neglect, opportunity indexes and trauma. Yet, the biological, psychological and social mechanisms driving risk are not uniform. Notably, most people exposed to risk factors do not become symptomatic and could broadly be considered resilient. Achieving a better understanding of biological, psychological and social mechanisms underlying both pathology and resilience will be crucial for improving approaches for prevention and treatment and creating precision medicine approaches for more efficient and effective treatment.

The State of Ohio Adversity and Resilience (SOAR) study is a prospective, longitudinal, multimodal, integrated familial study designed to identify biological, psychological and social risk and resilience factors and processes leading to mental health disorders, substance use disorders, substance overdose, suicide and associated psychological/medical comorbidities which reduce life expectancy and quality of life. It includes two nested longitudinal samples: (1) WD Survey: an address-based random population epidemiological sample of 15 000 individuals (unique households) representative of the state of Ohio assessed for psychosocial, psychiatric, behavioural health and substance use factors and (2) Brain Health Study: a family-based, multimodal, deep-phenotyping study conducted in 1200 families (up to 3600 persons aged 12–72 years) including MRI, electroencephalography, blood biomarkers and psychiatric diagnostic interviews, as well as neuropsychological, psychosocial functioning and family/community history, dynamics and support assessments. SOAR is designed to discover, develop and deploy advanced predictive analytics and interventions to transform mental health prevention, diagnosis, treatment and recovery.

All participants will provide written informed consent (or parental permission and assent for minors). The study was approved by The Ohio State University Institutional Review Board (study numbers 2023H0316 (Brain Health) and 2023H0350 (Wellness Survey). The Brain Health study was also approved by institutional review boards at each partnering institution involved in conducting participant assessments. Findings will be disseminated to academic peers, clinicians and healthcare consumers, policymakers and the general public, using local and international academic channels (academic journals, evidence briefs and conferences) and outreach (workshops and seminars).

Radioembolisation (RE) is gaining traction as a robust treatment option for patients with hepatocellular cancer (HCC) across all cancer stages. RE allows the delivery of targeted high-dose radiation directly to tumours, with relative sparing of the surrounding liver tissue. Traditionally, radiation has been delivered using ⁹⁰Yttrium ([⁹⁰Y]Y)-labelled microspheres, either glass or resin. The success of RE is dependent on the dose delivered to the tumour. When using [⁹⁰Y]Y microspheres, dose prediction is calculated through a ^99mTechnitium ([^99mTc]Tc)-macroaggregated albumin (MAA) scan, which allows the calculation of the dose to be administered to the tumour. However, [^99mTc]Tc-MAA is not a true surrogate of [⁹⁰Y]Y microspheres, and this will impact on the final dose delivered. [¹⁶⁶Ho]Ho, like [⁹⁰Y]Y, is a beta emitter but unlike [⁹⁰Y]Y also emits gamma-radiation, allowing for quantitative nuclear imaging. The primary aim of this pilot study was to investigate the safety and efficacy of dosimetry-based individualised ¹⁶⁶Holmium ([¹⁶⁶Ho]Ho-RE) in patients with HCC.

15 eligible participants will be recruited to receive [¹⁶⁶Ho]Ho-RE. The primary objective is to establish the toxicity profile of dosimetry-based individualised [¹⁶⁶Ho]Ho-RE. The secondary objective is to assess efficacy as measured by modified Response Evaluation Criteria in Solid Tumours (mRECIST) and Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 criteria. Additional exploratory objectives include quality of life assessment and identification of a radiomic signature of response. The results from this study will be combined with the prospective iHEPAR study to form a larger analysis.

The study has received approval from the East Midlands—Nottingham 1 Research Ethics Committee—approval number 23/EM/0239. The study will be performed in compliance with the Declaration of Helsinki and the principles of Good Clinical Practice. Signed informed consent will be obtained from each patient before study entry. The results will be disseminated through publication in a peer-reviewed scientific journal.

Clinicaltrials.gov NCT06302400.