Adolescent-onset type 2 diabetes (T2D) has increased in prevalence in recent decades. However, the efficacy of preventative interventions targeting health behaviours is limited, and key developmental factors that may influence effectiveness, such as executive functioning (EF) and stress, are often overlooked. Within-person fluctuations in EF and stress are linked to the adoption and maintenance of physical activity, a critical component of T2D prevention, yet little is known about the between- and within-person temporal variability of these constructs or their relationship with physical activity in adolescents at risk for T2D. Ecological momentary assessment (EMA) is ideal to capture these processes in real-time to inform intervention development and personalisation.

We will enrol a subset of participants from a larger intervention study involving assigned-female-at-birth adolescents aged 12–17 years, with elevated depression symptoms (CES-D≥21) and T2D risk (BMI≥85th percentile) and diabetes family history. Prior to the intervention, a minimum of 50 participants will complete a 7-day EMA protocol consisting of repeated daily gamified EF assessments and brief surveys about EF, stress and physical activity. Participants will simultaneously wear an activity monitor to provide objective measures of physical activity. Recruitment began in Spring 2024 and is ongoing. Multilevel models will be used to separate between- and within-person variability and to estimate short-term lagged within-person associations between EF/stress and subsequent physical activity across 15–60 min windows. Primary analyses are planned for Winter 2026.

The Colorado Multiple Institutional Review Board approved this study (COMIRB#22-0180). Findings will be disseminated in peer-reviewed journals and conference presentations.

NCT05543083.

Cardiovascular risk assessment and management in the paediatric population is a relatively uncharted territory. However, atherogenesis starts during childhood, making childhood and adolescence an important window of opportunity to prevent atherosclerotic cardiovascular disease (ASCVD) later in life. An emerging group at risk for early ASCVD are children with chronic conditions. This paper describes the rationale, design and methods for the Secondary Manifestations of ARTerial diseases in the Young with a chronic condition (SMART-Youth) study. This study aims to identify disease-associated and lifestyle-associated cardiovascular risk factors for preclinical atherosclerosis in children with a chronic condition. The results of this study may fuel development of tailored cardiovascular risk assessment and management strategies in children at-risk.

This is a prospective longitudinal cohort study including children aged 8–18 years with various chronic conditions (cystic fibrosis, juvenile idiopathic arthritis, systemic autoimmune disease, chronic kidney disease, primary immunodeficiency, autoinflammatory conditions, inflammatory bowel disease, congenital heart disease, premature birth, fetal growth restriction and children with persistent somatic symptoms) at the Wilhelmina Children’s Hospital of the University Medical Center Utrecht in The Netherlands. Assessment of cardiovascular risk factors includes blood pressure, body mass index, visceral and subcutaneous abdominal adipose tissue, nutrition, physical activity, stress, circulating lipids, HbA1c and C-reactive protein measurements. Preclinical atherosclerosis is measured by carotid intima-media thickness, carotid distension and carotid-femoral pulse wave velocity. These assessments are performed at baseline, 2-year follow-up and 17–18 years of age. Enrollment runs from August 2024 onwards, with a minimal study duration of 15 years and an estimated final sample of more than 2000 children. State-of-the-art regression-based methods will be used to examine the association of cardiovascular risk factors and preclinical atherosclerosis. Longitudinal data analysis methods will be used to model these associations over time.

Ethical approval was granted by the Medical Ethics Review Board of the University Medical Center Utrecht (NL84874.041.23). Written informed consent by participants and their parents is required for participation. Collected data will be made available to researchers upon reasonable request to the Steering Committee. Study findings will be disseminated through peer-reviewed publications, presentations at scientific meetings and meetings with patient organisations.

Bacterial translocation and gut dysbiosis are key drivers of systemic immune activation in decompensated cirrhosis, precipitating inflammatory complications such as acute-on-chronic liver failure (ACLF). Currently, no licensed therapies effectively restore intestinal barrier function or reverse dysbiosis in this vulnerable population. While previous studies have suggested benefits of faecal microbiota transfer (FMT) in hepatic encephalopathy or alcohol-associated hepatitis, data on its safety and immunomodulatory effects in decompensated cirrhosis with ascites are lacking. This Phase IIa trial (TransImmune) aims to evaluate the safety and tolerability of encapsulated FMT. Furthermore, it will assess feasibility, microbial engraftment and downstream effects on intestinal barrier integrity, as well as systemic and peritoneal inflammation.

This is a prospective, single-centre, randomised, double-blind, placebo-controlled Phase IIa pilot study. A total of 24 patients with decompensated cirrhosis and ascites will be randomised in a 1:1 ratio to receive either encapsulated FMT or placebo over three consecutive days. The investigational product, INTESTIFIX 001, is an encapsulated FMT preparation derived from rigorously screened healthy donors and manufactured under Good Manufacturing Practice (GMP) conditions with predefined release specifications, including minimum alpha-diversity QC criteria, manufactured by the Cologne Microbiota Bank (CMB). The primary endpoints are the occurrence of serious adverse events (SAE) up to the end of study (EOS) and the occurrence and severity of treatment-emergent adverse events (TEAE). Secondary endpoints evaluate signals of clinical efficacy, specifically: (1) systemic inflammation (white blood cell count, C-reactive protein, procalcitonin and IL-6); (2) gut inflammation (faecal calprotectin); (3) organ dysfunction (Child-Pugh, MELD and CLIF-SOFA scores); (4) quality of life (EQ-5D-5L and CLDQ) and (5) the number of antibiotic-free days. Patients will be monitored across five study visits up to 90 days.

The study was approved by ethics committee review and the German Federal Institute for Drugs and Medical Devices (BfArM). The trial is registered under EU CT no. 2023–5 07 790-18-00. The results of the study will be disseminated via peer-reviewed publications and at international conferences.

EU Clinical Trials Register: 2023-507790-18-00. Registered on 8 August 2024.

Suicide is a major public health concern and one of the leading causes of death among young people globally. Unemployment has been associated with an increased risk of suicide and suicidal behaviour through its effects on mental health, financial security and social well-being. In sub-Saharan Africa (SSA), high levels of youth unemployment, poverty and limited access to mental healthcare may further increase vulnerability to suicidal behaviour. This systematic review aims to synthesise evidence on the prevalence, associated factors and methods of suicide and suicidal behaviours among unemployed youth in SSA.

The review will be conducted and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Eligible studies will focus on unemployed youth aged 15–35 years residing in SSA countries and report on suicide, suicidal ideation, suicide attempts or completed suicide. Electronic databases, including PubMed, Web of Science, EBSCOhost, Scopus, ProQuest and Sabinet African Journals, will be searched using a comprehensive search strategy supplemented by backward and forward citation searching. Three reviewers will independently screen studies, extract data and assess methodological quality using appropriate critical appraisal tools. Prevalence estimates will be pooled using random-effects meta-analysis where appropriate. Associated factors will be synthesised narratively and organised according to the socioecological framework.

Ethical approval is not required as the review will use data from published studies and publicly available sources. Findings will be disseminated through publication in a peer-reviewed journal, conference presentations and engagement with relevant stakeholders. The review is expected to provide evidence to inform suicide prevention strategies, mental health interventions and employment-related policies targeting unemployed youth in SSA.

CRD42025642679.

Trauma, obstetric haemorrhage and severe anaemia lead to millions of deaths every year. Many of these deaths occur in regions known as ‘blood deserts’ where there is virtually no access to blood transfusions. A community or civilian walking blood bank (CWBB) is a low-resource strategy that can provide just-in-time, point-of-care tested blood transfusions in blood deserts when banked blood is not readily available and the alternative is almost-certain death. This protocol is designed to evaluate the effectiveness and implementation of a CWBB at Lodwar County Referral Hospital located in a blood desert in rural north-west Kenya.

We will use a mixed-methods approach relying on an implementation science design to evaluate effectiveness, acceptability, applicability and impact of a CWBB. The study will be conducted over 1 year in two parts: pre-emergency and post-emergency transfusion protocol (ETP) implementation. First, a previously developed ETP will be validated and finalised by key hospital stakeholders. Effectiveness will be assessed quantitatively and qualitatively. Prospective laboratory-based data collection will measure changes in blood ordering practices. We expect a sample size of approximately 140 (20/month) unmet blood transfusion requests, with 40 (5/month) of those being emergent (requiring blood in less than 2 hours). These cohorts will be compared pre-implementation and post implementation. Qualitatively, key informant interviews of hospital staff and the community will explore clinical blood demand and general understanding and perceptions about blood donation and transfusion. Lastly, we will determine the adaptability and scalability of a CWBB to other low-resource settings with in-depth interviews and a modified Delphi approach to achieve consensus regarding key components of a CWBB and its transferability to other settings.

Ethical approval was granted by the Strathmore University Institutional Scientific and Ethics Review Committee (SU-ISERC2234/24) and the Mass General Brigham (MGB) Hospital’s Institutional Review Board (#2024P001878; #2024P001879; #2024P001885; #2024P001887). The study team also secured a research licence from the National Commission for Science, Technology and Innovation (#168094) before initiating the study. Interviews will be voluntary and consent will be obtained prior to participation. Blood transfusion consent will be collected as per standard hospital process. The findings will be disseminated through academic publications, conference presentations and workshops, contributing valuable insights into emergency blood transfusion protocols. These findings will also be conveyed to Lodwar County Referral Hospital in order to facilitate quality improvement.

Cervical cancer remains a leading cause of morbidity and mortality among women in Ghana, yet screening coverage is extremely low and organised national programmes are limited. Although several studies have examined determinants of screening, no comprehensive synthesis has summarised the evidence to guide effective policy and intervention design.

To synthesise existing evidence on determinants of cervical screening in Ghana and identify opportunities to strengthen national screening strategies.

This is a systematic review conducted following Aromataris and Pearson’s methodology and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Searches across PubMed Central, CINAHL, Web of Science, Scopus and grey literature (January 2000–July 2025) identified studies reporting barriers and facilitators of cervical screening in Ghana. Risk of bias was assessed using standard appraisal tools.

This study was conducted in the context of Ghana.

Of 7833 records screened, 32 studies met inclusion criteria. Barriers to cervical screening spanned individual, interpersonal, health system, socio-cultural and structural factors, including poor knowledge, fear, limited access, financial constraints and social norms. Facilitators included knowledge and awareness, provider recommendation, social support, positive health perceptions, healthcare access and cost-related enablers. Overall, 23 studies were rated low risk of bias, while nine were rated moderate risk of bias.

Cervical screening behaviour in Ghana is influenced by structural, cultural, psychological and informational factors. The reviewed evidence suggests that these determinants do not operate in isolation but interact in ways that may vary across contexts and populations.

https://doi.org/10.17605/OSF.IO/M4XKT.

Elective non-emergent surgical wait times have increased across countries such as Canada, straining operating room (OR) resources and affecting patient outcomes and healthcare spending. Manual scheduling systems in Ontario orthopaedic centres create wide variations in wait times, with recent declines in meeting benchmark targets despite increased procedure volumes. Challenges stem from fragmented referral processes, outdated scheduling methods and resource constraints. Artificial intelligence and machine learning (ML) offer potential solutions for optimising scheduling; however, their implementation remains inconsistent. This study aims to identify determinants affecting the rollout of a new ML-driven automated scheduling system at a high-volume elective orthopaedic surgery centre.

A qualitative description approach supported by implementation science frameworks.

A high-volume elective orthopaedic surgery unit at a Canadian tertiary care centre.

17 individuals from clinical, administrative and leadership roles who were directly involved in surgical scheduling.

A new ML-driven automated surgical scheduling system.

Perceptions of the proposed new surgical scheduling system (barriers and enablers of implementation, recommendations for improvement).

Three main themes were identified, capturing challenges and enablers in the existing scheduling system: system functionality, process-related factors and resource constraints.

Participants described substantial inefficiencies in the existing manual scheduling system, including outdated software, fragmented information systems, inconsistent communication and resource constraints. Across interest-holder groups, there was broad but variable perceived support for a planned ML-enabled scheduling system, particularly for improving duration prediction, access to scheduling data and reporting, alongside concerns about system complexity, workflow fit, training and resource implications. Interest-holders emphasised the importance of user-friendly design, interoperability, responsive training, phased implementation and ongoing feedback.

This pre-implementation qualitative study identified significant process and resource limitations in manual orthopaedic surgical scheduling, but interest-holder support for a well-designed ML-driven system is strong. While participants anticipated potential benefits for scheduling accuracy, throughput and resource allocation, these perceived advantages will require meaningful user engagement, robust training, phased rollout and evaluation in subsequent implementation and outcome studies.

The Mental health care: Adverse Sequelae of COVID-19 study aimed to (1) compare the consequences of the COVID-19 pandemic for mental health services and people with pre-existing mental health conditions (MHCs) in six low- and middle-income countries and (2) identify good practice to mitigate these impacts.

An observational study, using a mixed-methods convergent design triangulating data from (1) semistructured interviews or focus groups and/or a self-completed survey, (2) routine service utilisation data, (3) local grey literature and (4) expert consultation.

The study was conducted in Chile, Ethiopia, Georgia, Nigeria, South Africa and Sri Lanka.

121 key informants.

We found clear evidence in all sites that the pandemic exacerbated pre-existing disadvantages experienced by people with MHCs and led to a deterioration in the availability and quality of care, especially psychosocial care. Alongside increased vulnerability to COVID-19, people with MHCs faced additional barriers to accessing prevention and treatment interventions compared with the general population. To varying extents, sites showed accelerated implementation of digital technologies, but with evidence of worsening inequities in access. In sites where primary care-based mental healthcare was more developed or prioritised, systems seemed more resilient and adaptive.

Our findings have the following implications. First, these mental health service reductions are clear examples of ‘structural stigma’, namely policy level decisions in healthcare which place a low priority upon services for people with MHCs. Second, integration of mental healthcare into all general healthcare settings is key to ensuring accessibility and parity of physical and mental healthcare. Third, digital innovations should be designed to strengthen and not fragment health systems. We discuss these findings in terms of anticipating such challenges for future pandemics and preparing layers of resilience.

The establishment of an effective strategy for recurrence prevention following curative treatment for hepatocellular carcinoma (HCC), including radiotherapy, remains a critical unmet clinical need. Despite favourable local control and safety profiles, recurrence after particle therapy remains a major challenge, highlighting the need for effective adjuvant strategies to improve long-term outcomes. The present phase Ib/II trial is designed to evaluate the safety and efficacy of atezolizumab plus bevacizumab (Atezo+Bev) administered after carbon-ion radiotherapy (C-ion RT) in patients with unresectable non-metastatic large HCC. This study aims to explore the potential of this multimodal approach as a novel adjuvant strategy to improve outcomes in patients at high risk of recurrence.

This is a phase Ib/II, single-arm clinical trial designed to evaluate the safety and efficacy of adjuvant Atezo+Bev following C-ion RT in patients with HCC. Eligible patients will be enrolled in the first registration phase. C-ion RT (60 Gy) will be administered over four consecutive treatment days ideally within one calendar week. Patients will receive a combination of atezolizumab (1200 mg) and bevacizumab (15 mg/kg) administered intravenously every 21 days for one treatment cycle. The primary endpoint of the phase Ib part is the proportion of patients with dose-limiting toxicity (DLT). DLT is defined as prespecified toxicities associated with the investigational drug among the adverse events that occurred from the start date of the investigational drug (Day 1) to Day 21. If there is one or fewer cases of DLT out of six cases, the trial will proceed to the phase II part. The primary endpoint of the phase II part is the 1-year recurrence-free survival rate.

This study was approved by the ethics committee of two participating institutions (Chiba University Hospital (approval No. 2024021) and National Institute for Quantum and Radiological Science and Technology, QST Hospital (approval No. C24-001)). Trial results will be reported in a peer-reviewed journal publication.

jRCT2031240284.