Immune checkpoint inhibitors (ICIs) have revolutionised cancer treatment through targeted disruption of the physiological pathways that maintain tissue tolerance, but which are co-opted by cancers to evade immunosurveillance. Thus, the resultant T-cell activity often causes immune-related adverse events including immune checkpoint inhibitor-induced inflammatory arthritis (ICI-IA). ICI-IA results in functional impairment that frequently persists, even after ICI discontinuation, with substantial quality-of-life impacts for cancer survivors.

A high-quality body of evidence to guide ICI-IA management remains an unmet need. Pharmacological treatment may be prolonged, typically begins with non-specific immunosuppression, including systemic steroids, and is usually only rationalised to more targeted therapy in resistant cases. Moreover, retrospective data suggest the high dose glucocorticoids sometimes used in new-onset ICI-IA may be associated with worse cancer outcomes.

Tumour necrosis factor (TNF) inhibition strategies are well established with excellent efficacy and safety profiles in ‘spontaneous’ inflammatory arthritides including rheumatoid and psoriatic arthritis. Mechanistic evidence from ex vivo and murine studies also supports the utility of anti-TNF therapy for steroid-refractory cases of ICI-IA. Although good clinical responses have been reported in this setting, the REACT trial (REmission induction of Arthritis caused by Cancer ImmunoTherapy) aims to provide randomised and robust clinical evidence for deploying targeted therapy earlier in ICI-IA management. It will test whether up-front anti-TNF therapy can more effectively and quickly control symptoms, reduce glucocorticoid exposure, prevent early ICI discontinuation and increase the frequency of drug-free ICI-IA remission.

REACT is a prospective, multicentre, open-label, superiority, two-arm, randomised controlled clinical trial to guide initial therapy for patients with ICI-IA. The trial will compare the current standard of care (initial prednisolone; Arm A) with the anti-TNF drug, adalimumab without glucocorticoids (Arm B).

The primary outcome is glucocorticoid-free arthritis remission rate at 24 weeks where remission is defined as: (i) No use of systemic or intra-articular glucocorticoids (except when used for adrenal insufficiency) within 4 weeks prior to assessment at 24 weeks; and (ii) absence of synovitis on clinical examination.

The protocol was approved by East Midlands—Leicester South Research Ethics Committee on 31-Oct-2024 (Ref: 24/EM/0202). Participants are required to provide written informed consent. The results of this trial will be disseminated through national and international presentations and peer-reviewed publications.

ISRCTN18217497.

Among the five hepatitis viruses, the hepatitis B virus (HBV) is a major cause of serious acute and chronic liver infections worldwide. The major public health impact of HBV infection arises from chronic liver disease, including cirrhosis and hepatocellular carcinoma, which predominantly affects young and middle-aged adults of both sexes. Therefore, preventive interventions focusing on mothers and infants are critical due to vertical and early childhood transmission dynamics.

HBV prevalence largely varies among pregnant women in Ethiopia because of multiple interrelated factors. This umbrella review will consolidate all existing systematic reviews and create a more reliable picture of HBV infection and its determinants among pregnant women in Ethiopia.

This umbrella review will be conducted according to Preferred Reporting Items for Systematic reviews and Meta-Analyses reporting standards. The review will focus on identifying and integrating evidence from eligible systematic reviews and meta-analyses, with methodological quality appraised using the MeaSurement Tool to Assess systematic Reviews instrument. A comprehensive literature search strategy will be developed using relevant Medical Subject Headings alongside free-text keywords. Electronic searches will be conducted in PubMed/MEDLINE, African Journals Online, Web of Science, Scopus and Google Scholar. Statistical heterogeneity among the included reviews will be quantified using the I² statistic. Data management and meta-analytic procedures will be performed using STATA version 17, and effect estimates will be presented with corresponding 95% CIs to determine statistical precision.

This review uses only published or publicly available data, so ethics approval is not required. Findings will be disseminated via peer-reviewed publications, conference presentations and shared with policymakers, healthcare partners, clinicians and patients to inform policy, enhance education and guide future research.

PROSPERO (CRD420251118982).

Indian immigrants experience significant dietary acculturation post-migration, shifting from traditional diets to more westernised eating patterns influenced by socioeconomic and environmental factors. This transition, often marked by increased processed food consumption and reduced intake of traditional staples, contributes to elevated risks of obesity and type 2 diabetes. Despite the growing Indian diaspora in Australia, Canada, New Zealand and the UK, the evidence on their dietary acculturation remains limited.

This review will adopt the Joanna Briggs Institute (JBI) methodology for scoping reviews. A three-step search strategy will be applied across databases including MEDLINE (via PubMed), CINAHL, Scopus and Web of Science. Google Scholar will be used as a supplementary search tool to identify additional relevant studies. The search will include peer-reviewed studies and grey literature published in English between 1 January 2000 and 22 May 2025. First-generation Indian immigrants of all ages will be included, while second-generation immigrants, refugee populations and studies linked to non-communicable disease interventions will be excluded. Screening will be conducted in Covidence by two independent reviewers, with discrepancies resolved by a third reviewer. Data will be extracted using a standard JBI tool, charted in tabular form, and synthesised narratively and thematically.

As this review will use published and publicly available data, formal ethics approval is not required. Findings will be disseminated through peer-reviewed publication, conference presentations and community engagement.

Parental psychological challenges and poor well-being are key factors in shaping both the quality of parent-child interactions and child development. Specifically, maternal psychological distress is a central determinant of child development. Elevated levels of distress in mothers are associated with poorer child cognitive, behavioural and social-emotional outcomes, with effects persisting into adolescence and adulthood. While this highlights the critical importance of early prevention and intervention efforts to support parents, postpartum mental healthcare remains limited, despite ongoing and evident needs.

This protocol outlines a 2-year longitudinal follow-up study investigating the impact of a secondary perinatal programme (ie, Toi, Moi, Bébé), completed by mothers during pregnancy, and its impact on children’s cognitive and social-emotional functioning at 24 and 48 months. Further, the study aims to explore whether maternal self-efficacy and emotion regulation may serve as potential mediators or moderators of the relationship between programme participation and child development outcomes. The research aims to leverage the Toi, Moi, Bébé programme, by recruiting mother-child dyads (n=250) in which the mothers participated in the programme during pregnancy. Mothers were randomly assigned to complete the parenting well-being intervention either independently or with added telephone support. Participants who consent will be invited to take part in a two-wave follow-up at 24 months (T1) and 48 months postpartum (T2). At both time points, mothers will complete demographic questionnaires and standardised measures assessing maternal well-being (Generalised Anxiety Disorder-7, Edinburgh Postnatal Depression Scale and Perceived Stress Scale), child cognitive functioning (Ages and Stages Questionnaire-3 and MacArthur-Bates Communicative Development Inventory), child social-emotional functioning (Ages and Stages Questionnaire, Social Emotional—second Edition-2 and Child Behaviour Checklist for Ages 1.5–5), maternal emotion regulation (Cognitive Emotion Regulation Questionnaire) and maternal self-efficacy (Parental Cognitions and Conduct Towards the Infant Scale & Me as a Parent Scale). Parents’ perceptions of their parenting experience will be measured using the Parental Reflective Functioning Questionnaire. Mother-child interaction, parenting quality and cognitive stimulation in the home environment will be measured using a brief virtual interview (StimQ₂-Toddler) and a naturalistic observation assessment (Parenting Interactions with Children: Checklist of Observations Linked to Outcomes). Using RStudio, linear mixed models will be used to assess the impact of the intervention (online intervention only vs only with telephone support) on child cognitive and social-emotional development at T1 and T2. In parallel, separate models will be conducted to examine associations between maternal emotion regulation and self-efficacy on the child development outcomes at the same timepoints. Exploratory analyses will be conducted to examine potential moderating effects of child sex and group assignment on the associations between maternal emotion regulation and self-efficacy and child developmental (cognitive and socioemotional) outcomes, using causal inference models.

The current study has been registered, reviewed and approved (MP-37-2025-10894) by the Research Institute of the McGill University Health Centre Research Ethics Board. Findings from this research will be disseminated through peer-reviewed open access publications, and presentations at national and international conferences.

NCT05110456.

To assess the impact of a National Enhanced Service (NES) incentive for weight management that financially rewarded practices for each eligible patient referred to a weight management programme.

Interrupted time-series analysis to examine the rate of weight management referral and weight management advice.

Primary healthcare records from January 2018 to December 2024 in the Oxford Clinical Informatics Digital Hub, covering 8.3 million patients in 1198 primary care clinics around England.

NES payments to practices for weight management were introduced in April 2021.

The rate of referral increased from 1 referral per 1000 patients per month before the incentive to around 4 referrals per 1000 patients per month afterwards. There was no evidence that the increase differed by age, gender, ethnic group or socioeconomic status. The occurrence of weight management advice was unchanged by the introduction of the NES and was at least three times more common than referral to weight management services.

The NES was associated with a fourfold increase in referrals to weight management services. However, clinicians are much more likely to offer advice rather than a referral to a weight management programme. There is a clear opportunity to improve outcomes for patients by encouraging greater use of referrals to effective weight management services in place of advice.

To investigate associations between body composition indices and metabolic status among normal-weight adults.

Cross-sectional study using data from the Tehran Lipid and Glucose Study (phaseVII: 2019–2021).

Primary care and community health services in an urban Tehran population.

1298 adults (40.5% men, 59.5% women), aged 18–80years, body mass index (BMI) 18.5–24.9 kg/m². Exclusions: known diabetes, cardiovascular disease, kidney failure, malignancy, pregnancy or lactation, diuretic or glucocorticoid use. Participants were classified as metabolically healthy normal weight (MHNW) or unhealthy (MUHNW).

The primary outcome was the association between body composition and anthropometric indices with metabolic status. The secondary outcome was identification of the strongest predictors of MUHNW. Body composition was assessed by bioelectrical impedance analysis to obtain fat mass (FM), body fat percentage (BFP), skeletal muscle mass percentage (SMM%), fat mass index (FMI), fat-free mass index, skeletal muscle indices and the fat-to-muscle mass ratio (FMR). Anthropometric measures included waist circumference (WC) and waist-to-hip ratio (WHR). Associations were examined using logistic regression adjusted for age, smoking and physical activity.

Mean age: 37.5±12.8 y; MUHNW participants were older than MHNW (44.5±13.2 vs 35.8±12.1 years, p

BMI, WC, WHR and body fat indices were positively associated with metabolically unhealthy status among normal-weight adults of both sexes. WHR was the strongest predictor, highlighting its value for identifying at-risk individuals where advanced body composition tools are unavailable.

To determine the prevalence of potentially inappropriate prescribing (PIP), potentially inappropriate medication (PIM), potential prescription omission (PPO), potentially harmful drug–drug interactions (PDDI) and identify associated factors among older Ethiopians.

Systematic review and meta-analysis

We searched PubMed, HINARI, Scopus and Web of Science databases to identify eligible studies published up to 31 October 2025.

Observational studies reported the prevalence of PIP, PIM, PPO and PDDI among older adults from any healthcare settings were screened.

Two independent reviewers selected studies, extracted data and assessed the risk of bias. The quality and risk of bias of the studies were assessed using the Newcastle-Ottawa scale and Hoy risk of bias tool, respectively, while the certainty of evidence of outcomes was assessed using Grading of Recommendations, Assessment, Development and Evaluation based on Cochrane recommendations. We used a random-effects model for analyses to estimate the pooled prevalence and associated factors. All data analyses were done using Stata V.17 software.

The national prevalence of PIP, PIM, PPO and PDDI was estimated as main outcomes. Variations were estimated based on regions, age groups, outcome evaluation tool, disease type and healthcare setting.

The review included 25 studies (n=5662 participants) for PIP or PIM, 14 studies (n=2706 participants) for PDDI and 6 studies (n=1342 participants) for PPO. The pooled prevalence estimate was 41% (95% CI 33% to 48%), I²=96.87% for PIP, 37% (95% CI 31% to 44%), I²=96.33% for PIM, 55% (95% CI 36% to 73%), I²=99.00% for PDDI and 14% (95% CI 6% to 24%), I²=95.07% for PPO. The majority of the studies have very good quality (very good=13, good=1, satisfactory=11 for PIP and PIM; very good=11, satisfactory=3 for PDDI; very good=6 for PPO) and low risk of bias (low risk=18, moderate risk=7 for PIP and PIM; low risk=12, moderate risk=2 for PDDI and low risk=6 for PPO), while all studies for each outcome have low certainty of evidence. Subgroup analyses revealed significant regional and contextual variations. Polypharmacy was significantly associated with PIP (OR=3.72, 95% CI 2.53 to 5.46, p2=69.56%), PIM (OR=4.20, 95% CI 2.91 to 6.06, p2=57.83%) and PDDI (OR=4.51, 95% CI 3.05 to 6.69, p2=0.00%), while hypertension (OR=2.46, 95% CI 1.38 to 4.36, p2=0.00%) was associated with PIP.

This review found a high prevalence of PIP, PIM, PDDI and PPO among older adults in Ethiopia, with notable heterogeneity across regions. Polypharmacy was associated with PIP, PIM and PDDI, while hypertension showed association with PIP. Despite generally good study quality, the certainty of evidence was low for the included studies due to the cross-sectional design nature, with high heterogeneity. Therefore, these findings should be interpreted cautiously. This study indicates a high burden of inappropriate medication prescribing and its associated factors, underscoring the importance of further robust studies to clarify prescribing practices and associated factors.

CRD42024556744.

This study intended to investigate barriers to implementing evidence-based intrapartum care during vaginal births, from maternity care providers’ point of view.

A descriptive qualitative study was conducted using in-depth interviews, with data analysed through thematic analysis.

The labour room of a major tertiary care hospital in Central Sri Lanka.

Purposively selected 17 maternity care providers including doctors, nurse managers, nurse-midwives and midwives.

Three major themes and twelve sub-themes were generated: (1) barriers related to care providers (lack of human resources, negative attitudes of care providers, poor relationship among care providers, poor relationship between women and care providers, lack of knowledge on evidence-based practice in childbirth care); (2) barriers related to organisational environment (gaps in management, heavy workload, inadequate physical resources, insufficient in-service training and lack of availability/use of updated guidelines) and (3) barriers related to women’s birth preparedness (women’s limited knowledge on childbirth and intrapartum practices and women’s limited engagement during labour and childbirth). Many maternity care providers perceived that prevailing challenges to implement evidence-based childbirth care were one of the major reasons that impacted the quality of current childbirth care in the labour room.

The findings showed that an integrative approach may be essential to address the diverse barriers to the implementation of evidence-based intrapartum care. It is necessary to engage healthcare administrators, healthcare professionals and care recipients to enhance the quality of current childbirth care in the setting through the successful implementation of evidence-based care.

There are approximately 700 000 autistic people in the UK, and autism is increasingly being diagnosed in adulthood. Diagnosis on its own does not provide adequate information to plan post-diagnostic support for autistic people, and clinicians often plan support without the use of validated standardised tools which may exacerbate inequities in care. This study will evaluate a novel strengths and needs assessment, based on the WHO’s International Classification of Functioning, Disability and Health CoreSet for Autism, for use in adult diagnostic services immediately on receipt of an autism diagnosis. Potential issues, including the length of the assessment, timing of delivery and selection bias, will be explored as part of the trial process evaluation.

A two-arm, multisite, randomised pilot trial design will be used to evaluate the ICF CoreSets for Autism Strengths and Needs Assessment in three diagnostic services in England. A total of 72 newly diagnosed autistic adults will be recruited across the three sites over a 6-month period and randomised into an assessment group (strengths and needs assessment plus standard care) and a treatment as usual group (standard care only). The assessment group will receive a summary report of their strengths and needs on completion of the assessment. Both groups will complete measures of mental health and quality of life at baseline and 3 months follow-up (Patient Health Questionnaire-9, Generalised Anxiety Disorder questionnaire-7, Recovering Quality of Life questionnaire-10, EuroQoL-5D). Acceptability and feasibility will be measured for the strengths and needs assessment and for trial procedures using standardised measures, progression criteria and qualitative data from clinician focus groups and interviews with a subsample of autistic participants. The study design and procedures are being co-produced with an autistic advisor/patient and public involvement lead and with a steering group of autistic adults.

This study was reviewed by the East Midlands—Nottingham 2 Research Ethics Committee and was given Health Research Authority approval on 18 March 2025 (REC reference:25/EM/0041). The results will be disseminated via reports to the funder (NIHR), a peer-reviewed journal paper and academic conferences. We will email a summary report of findings to study participants and will invite participants to an information dissemination event at the end of the study. Links to reports and a lay summary will be provided on the research group’s website: https://sharl.sites.sheffield.ac.uk/home

ISRCTN10283350.

Healthcare utilisation (HU) is key to improving the health of residents in urban informal settlements. This study aimed to explore household-level factors influencing HU among informal settlement households in Freetown, Sierra Leone.

Cross-sectional survey.

Three informal settlements (Cockle Bay, Dwarzark and Moyiba) in Freetown, Sierra Leone.

Primary data from 4871 households were collected during the Health and Wellbeing survey conducted between April and May 2023, targeting households with adults aged 18 years and older.

The primary outcomes were households HU both within and outside informal settlements. Household-level predisposing and enabling explanatory variables were derived from Andersen’s Behavioural Model of HU.

Disability in households increases HU within settlements (especially in Dwarzark, 13% and Moyiba, 10%) but is less likely outside. Households engaged in income-generating activities are more likely to seek healthcare within settlements, but 12% less likely outside in Cockle Bay and Dwarzark. Food insecurity decreases HU within Dwarzark (9%) and increases HU outside by 174% in Moyiba. Longer water fetching times and water shortages were associated with higher HU (between 6% and 16%) within settlements, especially in Cockle Bay and Dwarzark. Clean water sources (eg, piped dwelling, bowser, surface, bottled) were consistently associated with higher HU both within and outside settlements. Shared sanitation facilities (such as shared toilets) were positively associated with HU both within and outside settlements, particularly in Dwarzark and Moyiba. Households with income from fishing, informal salaried work and bike riding showed higher HU both within and outside settlements, especially in Dwarzark and Moyiba.

We identified strong settlement-specific patterns of household-level factors that influence HU both within and outside Freetown’s informal settlements. These findings provide a foundation for developing targeted policies such as strengthening local services, addressing affordability and accessibility barriers and supporting vulnerable occupation groups.

To identify the individual and community-level factors associated with barriers to accessing healthcare services among currently married women in Somalia.

A cross-sectional analysis using data from the 2020 Somalia Demographic and Health Survey.

Somalia.

A nationally representative sample of 30 311 currently married women aged 15–49 years with complete data on outcome and explanatory variables.

The primary outcome was ‘reporting at least one barrier to accessing healthcare’, a composite binary variable based on four specific problems: obtaining permission to go for treatment, getting money for treatment, distance to the health facility and not wanting to go alone.

A substantial majority (77.06%) of married women reported experiencing at least one barrier to accessing healthcare. Financial cost was the most common barrier (69.91%), followed by distance to health facilities (65.95%), reluctance to go alone (49.64%) and the requirement for permission (46.03%). Multilevel analysis confirmed that higher household wealth was strongly protective (richest vs poorest: adjusted OR (aOR)=0.27, 95% CI 0.24 to 0.32). Paradoxically, factors typically considered protective were associated with increased barriers: women with secondary education (aOR=1.19, 95% CI 1.00 to 1.41) and those with educated husbands (aOR=1.23, 95% CI 1.14 to 1.33) reported more obstacles. Similarly, urban residents faced higher odds of barriers than their nomadic counterparts (aOR=1.40, 95% CI 1.27 to 1.55). Significant regional disparities were evident, with community-level context explaining 26.30% of the total variance in reporting barriers.

Access to healthcare for married women in Somalia is predominantly hindered by economic, educational and community-level constraints. Targeted interventions addressing socioeconomic disparities, infrastructural deficits and specific community contexts are essential to alleviate these barriers.

Postoperative sleep disturbance (PSD) is a common complication following major surgery, occurring in 15%–72% of patients. PSD poses a significant threat to both postoperative recovery and long-term outcome, leading to elevated risks of cognitive decline, pain sensitivity and cardiovascular events in patients. The current pharmacological treatments for PSD are typically reactive, administered only after symptoms have manifested, highlighting a critical unmet need for effective prophylactic strategies during the perioperative period. Recently, an increasing number of studies have demonstrated the effect of esketamine on preventing PSD, but their findings are inconsistent. This protocol outlines a systematic review and meta-analysis to examine the effect of perioperative esketamine on the prevention of PSD.

A comprehensive search will be conducted in MEDLINE (via Ovid), EMBASE (via Ovid), the Cochrane Central Register of Controlled Trials (via Ovid), PubMed and Web of Science by two authors independently. The search terms will comprise indexed and free-text terms to encompass the concepts of esketamine and PSD. The primary outcome is the incidence of PSD at postoperative days 1, 3 and 7. Two authors will independently conduct study screening, data extraction and risk of bias assessment with the Cochrane Collaboration’s tool. RevMan V.5.4.1 and Stata V.17.0 software will be used to conduct the statistical analysis. Subgroup analysis, sensitivity analysis and assessment of publication bias will be performed to verify the strength of our conclusions. Finally, the Grading of Recommendations Assessment, Development and Evaluation approach will be used to recommend evidence quality.

Ethical approval is not required for this study. The findings will be presented at national or international conferences and submitted to a peer-reviewed journal.

CRD420251232636.

Status epilepticus (SE) in adults is a serious neurological emergency that can lead to high morbidity and mortality rates. Although functional outcomes are often assessed using general scoring systems, limited data on health-related quality of life (HRQoL) in patients admitted to intensive care units (ICUs) are still limited. Furthermore, comprehensive evaluations of patient-reported physical, cognitive, mental health and psychological outcomes are lacking in this population. POSEIDON 2 aims to assess HRQoL and cognitive, physical and psychological impairments at 3 and 12 months after ICU discharge following SE and quantify caregiver burden.

POSEIDON 2 is a prospective, multicentre, longitudinal study conducted in 19 French ICUs. The study combines data from the SE ICTAL Registry with data from patients who survived admission to the ICU for SE, who will be recruited for the study. The study also includes patient-reported outcome (PRO) data collected 3 (M3) and 12 (M12) months after discharge from the ICU using validated instruments. The Zarit scale will be used to measure the burden on caregivers at M3 and M12. The primary endpoint is the prevalence of overall HRQOL impairment at M3 and M12, as defined by dichotomous scores on the physical and mental components of the 36-Item Short Form Health Survey compared with those of the general population. Secondary endpoints include domain-specific impairments, such as cognitive function, dependence, mental health and patient experiences. The sample size has been calculated based on an estimated prevalence of 75% for HRQoL impairment, with a planned sample size of 140 patients.

The POSEIDON 2 study protocol received ethical approval from the ethics committee ‘Comité de Protection des Personnes Ouest VI’ on 5 October 2023 (#2023-A01223-42). The study is conducted in accordance with the Declaration of Helsinki, Good Clinical Practice and the regulatory requirements of France. Written informed consent is obtained from participants, who are able to decline participation or withdraw from the study at any time. Findings will be disseminated through publication in peer-reviewed journals and presentations at scientific conferences.

NCT06100978.

Common mental health outcomes among children in conflict with the law in correctional facilities in Africa are an under-researched area with significant public health implications. This review will synthesise available and accessible evidence on the prevalence and associated factors of common mental health outcomes among children in conflict with the law in Africa.

Comprehensive electronic searches will date from 01 January 2015 to 31 December 2025 and will be conducted in PubMed, Sabinet, Scopus, EBSCOhost, Web of Science and PsycINFO. Articles will be screened using defined inclusion and exclusion criteria and assessed for eligibility by three independent reviewers. Discrepancies will be reviewed by a ninth reviewer. The selection process of included articles will be reported by using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses will be used. The Mixed Methods Appraisal Tool will assess study quality, and data will be synthesised using meta-analysis or a narrative synthesis approach, depending on heterogeneity levels.

This study will not require ethical approval from an institutional review board, as it does not entail the direct collection of data from children in conflict with the law, nor does it pose any risk to their privacy. Once finalised, the full review report will be submitted for publication in a peer-reviewed journal. The key findings will also be shared at both local and international conferences, highlighting common mental health outcomes among children in conflict with the law.

CRD420251011484.

Losses of functional reserve across multiple physiological systems have been identified in frail patients, yet the exact aetiology of frailty remains unclear. Although strongly associated with chronological age, frailty often develops at a younger age in patients with organ failure. Frailty is prevalent in patients with kidney failure; however, individuals experience improvements in physical frailty measures following kidney transplantation. This makes younger patients with kidney failure a unique population for studying both the accelerated onset of frailty and its reversal. This research project aims to test the hypothesis that frailty secondary to organ failure and age-related frailty are associated with similar molecular and physiological measures.

This longitudinal study will recruit 150 patients in three groups. Group A (kidney transplant recipients aged ≥40 years; n=50) and Group B (patients aged ≥40 years active on the kidney transplant waitlist; n=50) will comprise younger adults with frailty from organ failure. Group C (adults aged ≥65 years (or ≥55 years for Aboriginal and Torres Strait Islander patients); n=50) will comprise older community dwellers. The primary outcome is the Frailty Index (FI). Secondary outcomes include the change in FI over time, and at baseline when considering various clinical metadata, immune parameters, kidney function and nutrition intake which will be measured at baseline and 12-month time points. Longitudinal changes in frailty will be analysed using linear mixed models with multiple testing corrections for false discovery rates.

Endocrine profiles and metabolomics, measures of immune function and microcirculatory dysfunction, will be measured by liquid chromatography-mass spectrometry and/or gas chromatography-mass spectrometry. The gut microbiome will be sequenced via shotgun metagenomics (Illumina NextSeq500, 150 bp paired-end, ³Gbp/sample). Circulating cell-free DNA/mitochondrial DNA will be quantified through droplet digital PCR. Microcirculation will be assessed via sublingual dark field videomicroscopy with glycocalyx markers measured by ELISA.

This study will be conducted with all stipulations of this protocol, and the conditions of the ethics committee approval. Ethical principles have their origin in the Declaration of Helsinki, all Australian and local regulations and in the spirit of the standard of Good Clinical Practice (as defined by the International Conference on Harmonisation). Organs/tissues will be sourced ethically and will not be sourced from executed prisoners or prisoners of conscience or other vulnerable groups.

Ethics approval was received by the Metro South Health Research Ethics Committee (HREC/2023/QMS/95392) and ratified by the University of Queensland.

Results will be disseminated through peer-reviewed publications, academic conferences, participant newsletters and health organisation collaboration.

Sarcopenia is characterised by loss of muscle mass and strength. Although ageing is the most likely risk factor of sarcopenia, sarcopenia is prevalent even in non-elderly people. Type 2 diabetes (T2D) is a risk factor for sarcopenia, as T2D shares with sarcopenia several aetiological factors. Meanwhile, gestational diabetes mellitus (GDM) is characterised by metabolic alterations that resemble those observed in T2D, including increased insulin resistance (present even in physiologic pregnancies). Hence, GDM presents two major risk factors for sarcopenia, that is, dysglycaemia and insulin resistance. Moreover, the number of pregnancies at age >40 years is increasing, which is in an age range in which sarcopenia prevalence is already not negligible. However, data on the prevalence of sarcopenia prevalence in GDM and its effect on pregnancy outcomes are limited. Thus, this study aims to evaluate the prevalence of sarcopenia in women with GDM (and in pregnant women without GDM), identify risk factors and determine its effect on delivery and maternal and fetal outcomes.

For this study, 100 each of women with and without GDM will be recruited. Women will undergo an oral glucose tolerance test within weeks 24–28 for possible GDM diagnosis (in weeks 16–18 for high-risk women). Muscle/physical performance tests will be conducted at weeks 28–32 for possible diagnosis of sarcopenia/presarcopenia. Cognitive function will also be assessed. For all women, information regarding pregnancy progression, along with any complications, will be collected. Collected data will be analysed according to the main objectives of the study: (i) determine the prevalence of sarcopenia/presarcopenia in pregnancy with and without GDM, (ii) identify factors associated with sarcopenia risk, (iii) determine the effect of sarcopenia/presarcopenia on pregnancy outcomes, (iv) explore the relationship between sarcopenia and cognitive function. Therefore, this study will provide information on sarcopenia/presarcopenia prevalence in GDM and, possibly, in pregnancy not complicated by dysglycaemia. Furthermore, the study will provide knowledge on the main factors associated with sarcopenia/presarcopenia in GDM/pregnancy. The identification of such factors will be relevant for an initial guidance for treatments that may prevent sarcopenia in GDM/pregnant women. This will become of even greater interest if sarcopenia/presarcopenia influences pregnancy outcomes, especially in GDM women.

The study protocol has been approved by the Comitato Etico Regione Toscana - Area Vasta Nord Ovest (CEAVNO) on 25 July 2024 and by the Local Ethics Committee of the Medical University of Vienna on 17 June 2024. Participants’ enrolment began in May 2025. The results of the study will be presented at national and international conferences and in peer-reviewed journals.

ClinicalTrials.gov Identifier: NCT06876090; Registration Date: 2025-03-14

This community-led research study protocol emphasises placing black youth impacted by the legal system, their families and their communities at the forefront of substance use treatment development research and decision-making. The study, the Cultural Adaptation of a Substance Use Treatment (CAST) Project, challenges traditional top-down approaches to treatment creation, advocating for a grassroots model that centres community knowledge, values and active participation.

The CAST project is a US-based mixed-methods study with an exploratory design that examines the impact of racial discrimination on substance use in black youth impacted by the legal system. The study participants are black youth impacted by the legal system (N=15), parents of black youth impacted by the legal system (N=10) and community members who serve black youth (N=10) (total N=35 study participants). Study participants from each group (youth, parents and community members) will participate in three separate focus groups, respectively, to provide feedback on the culturally responsive content needed to best support black youth impacted by the legal system around substance use and mental health. The eight-step Assess, Decision, Adaptation, Production, Topical Expert, Integration, Training, Testing framework will be used as a guide to inform adaptations to the Motivational Enhancement Therapy and Cognitive Behavioural Therapy (MET/CBT12) for black youth impacted by the legal system. Once the cultural adaptation process has been completed, the study will conclude with an open feasibility and accessibility trial of the culturally adapted MET/CBT12 manual. The primary outcomes of this study are the feasibility and acceptability of the culturally adapted manual, measured by treatment attendance and participant feedback. Secondary outcomes include reductions in substance use and discrimination distress, and improvements in mental health symptoms.

This study was approved by the Institutional Review Board (IRB) at the University of California, San Francisco (IRB Protocol Number: 23-40126). All study procedures will be conducted in accordance with the ethical standards outlined by the institutional review board. The results from this study will be shared through peer-reviewed publications, academic conferences, community forums and policy briefs to support broader implementation of culturally adapted adolescent substance use interventions that address discrimination-related stress and substance use among black individuals impacted by the legal system.

NCT06003725.