Interstitial lung diseases (ILDs) represent a heterogeneous group of disorders, which have in common persistent inflammation and/or pulmonary fibrosis, involving mainly but not exclusively the interstitium. This results in restrictive ventilatory physiology and limited respiratory reserve. Patients with ILD can have frequent exacerbations of their disease, with subsequent acute respiratory failure that may require admission to the intensive care unit (ICU). The diagnosis and management of ILD in the ICU presents unique challenges due to the paucity of evidence supporting survival benefits of organ support in this cohort of patients.

This systematic review will be reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, and the protocol will follow the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guideline. MEDLINE, Embase, Emcare and CENTRAL will be searched for studies published from inception to 2026, involving adult patients with ILD requiring invasive mechanical ventilation (IMV), with or without comparison to non-invasive respiratory support such as high-flow oxygen, non-invasive ventilation (NIV), continuous positive airway pressure or bilevel positive airway pressure. Eligible studies will include randomised controlled trials and observational studies (cohort and case–control) in adults with ILD and acute respiratory failure requiring IMV in the intensive care setting. Case series with fewer than 10 patients, non-human or in vitro studies and studies involving perioperative lung transplant or lung cancer as the primary diagnosis will be excluded. The primary outcomes assessed will be in-hospital and 1-year mortality, and secondary outcomes will include ventilator-free days, ICU and hospital length of stay, NIV failure, reintubation and postdischarge respiratory outcomes where available. Where feasible, meta-analysis will be conducted using a random-effects model. Heterogeneity will be assessed using the I² statistic. Prespecified subgroup analyses will be performed, including ILD subtype (eg, idiopathic pulmonary fibrosis (IPF) vs non-IPF), presence of pulmonary hypertension, timing of IMV initiation (early vs late), baseline lung function (forced vital capacity ≥50% vs

This systematic review will be based on published data, and as such, no ethical approval is required. Findings from this study will be disseminated through peer-reviewed publications as well as presentations in healthcare-based settings.

CRD420251265836.

To examine the prevalence and sociodemographic factors associated with tobacco smoking, smokeless tobacco and dual use among adults in Ghana using the 2022 Demographic and Health Survey (GDHS).

Ghana, nationwide sample of males and females aged ≥15 years.

This was a cross-sectional secondary analysis of the 2022 GDHS.

A representative sample of 22 058 individuals (females, 15 014 aged 15–49; males, 7044 aged 15–59)

Current tobacco smoking, smokeless tobacco use and dual use.

Prevalence for smoking, smokeless tobacco and dual use was 4.7 (4.1–5.4), 1.6 (1.3–2.0) and 0.6 (0.4–0.9) among males and 1.0 (0.8–1.3), 0.08 (0.05–0.1) and 0.1 (0.05–0.1) among females, respectively. Among males, smoking was associated with higher age (30–44 years: AOR: 2.3, 95% CI 1.7 to 3.1; 45–59 years: AOR: 2.6, 95% CI 1.8 to 3.7). Higher education was protective for both sexes [(males: AOR: 0.4, 95% CI 0.2 to 0.8) and (females: AOR: 0.4, 95% CI 0.2 to 0.8)] compared with their counterparts who had no education. Males in the Coastal zone had higher odds of use (AOR: 1.8, 95% CI 1.3 to 2.3) compared with males in the Middle zone, while females in the Northern/Savanna zone had lower odds of tobacco use (AOR: 0.5, 95% CI 0.3 to 0.8) compared with the Middle zone. Being Christian was associated with lower odds of smoking among males (AOR: 0.3, 95% CI 0.2 to 0.5) compared with others, while being Mole-Dagbani ethnic is associated with higher odds of smoking among females (AOR: 3.0, 95% CI 1.7 to 5.4).

The study provides the first national analysis across Ghana’s 16 regions and investigates patterns of smoking, smokeless tobacco and dual tobacco use. While tobacco use in Ghana remains predominantly smoked and male-driven, the divergent patterns of use across educational, regional and ethnic groups, especially the emerging risk among females, represent a significant public health shift that demands focused gender-sensitive tobacco control interventions.

Atosiban may confer therapeutic benefits to specific subpopulations in assisted reproductive technology. The Phase I Atosiban study indicated potential improvements in live birth rates among women with previous implantation failure undergoing frozen-thawed blastocyst transfer who exhibited abnormal uterine contractions, although these findings did not reach statistical significance. Therefore, further investigations are warranted to thoroughly elucidate the efficacy of atosiban and to evaluate whether uterine contractions can serve as a reliable biomarker for its targeted application.

This is a single-centre, randomised, triple-blind, placebo-controlled trial aiming to enrol 792 infertile women aged 20–40 years with a history of at least one previous embryo implantation failure and abnormal uterine contractions prior to single blastocyst-stage embryo transfer. Eligible participants will be randomly assigned in a 1:1 ratio to receive either intravenous atosiban or a placebo before embryo transfer. The primary outcome is live birth rate, with secondary outcomes encompassing various pregnancy and perinatal parameters. Randomisation will be stratified by age and transfer type. Intention-to-treat analysis will be performed using generalised linear models. The trial will be monitored by an independent data and safety monitoring committee, including one interim analysis.

This study has been approved by the Institutional Ethics Committee of Northwest Women’s and Children’s Hospital (No. 2025-058-02). Written informed consent will be obtained from all participants. The study results will be disseminated at scientific conferences and published in peer-reviewed journals.

NCT07185230.

Mycoplasma pneumoniae (MP) is a major cause of community-acquired pneumonia in children. In East Asia, the prevalence of macrolide-resistant MP (MRMP) has surged, leading to treatment failures and prolonged illness. While doxycycline is an effective alternative, its use in young children has historically been limited due to concerns about tooth discolouration. This study aims to evaluate the efficacy and safety of doxycycline compared with azithromycin as a first-line treatment for children with pneumonia suspected of MRMP infection.

This is a multicentre, randomised, open-label, parallel-group superiority trial conducted at 14 tertiary hospitals in South Korea. A total of 208 children (aged 3–17 years) with pneumonia and confirmed or suspected MP infection will be randomised 1:1 to receive either doxycycline (4 mg/kg/day in two divided doses for 7–14 days) or azithromycin (10 mg/kg on day 1, then 5 mg/kg on days 2–5) (). Randomisation will be stratified by age (3–7 years vs 8–17 years). A standardised ‘rescue therapy’ protocol ensures patient safety by allowing control group patients to switch to doxycycline if no clinical improvement is observed within 48–72 hours. The primary outcome is the defervescence rate within 72 hours after randomisation. Secondary outcomes include treatment failure rate, length of hospital stay, symptom duration and adverse events. Safety assessment will specifically include tooth discolouration evaluation at Day 28, focused on children aged

This study has been approved by the Institutional Review Boards (IRB) of all participating centres. Written informed consent will be obtained from parents or legal guardians, and assent will be obtained from children aged 7 years and older. Results will be disseminated through peer-reviewed publications and conference presentations.

NCT07306234.

Infections are a leading cause of non-relapse mortality following chimeric antigen receptor T-cell therapy (CAR-T) and bispecific antibody (BsAb) therapies. However, infection data from clinical trials are often incomplete, lack pathogen-level detail and rarely capture late infectious complications. This CAR-T treatment in Lymphoma: Analysis of Risk of Infection following Therapy (CLARITY) study aims to generate real-world, longitudinal infection data with extended follow-up to characterise infection timing, including late events and inform risk prediction in patients with lymphoma and myeloma receiving novel immunotherapies.

CLARITY is a multicentre observational cohort study across six Australian centres enrolling adults treated with CAR-T or BsAb therapies. A co-designed REDCap (Research Electronic Data Capture) instrument captures infections classified as microbiologically defined, clinically defined or fever of unknown origin, using internationally standardised definitions. Patients were enrolled between 2019 and 2023, with at least 2 years follow-up per patient, allowing time-updated data on immunosuppressive exposures, haematological recovery and prophylaxis. Multivariable regression and landmark analyses will estimate infection incidence and identify dynamic risk factors over time. Incidence rate ratios will assess prophylaxis effectiveness. Data integrity is supported by central adjudication and site-level audits.

The study has received a waiver of consent (HREC/PMCC/89002) and was co-designed by haematology and infectious diseases investigators. Findings will be disseminated through peer-reviewed publications, scientific meetings and national guideline committees to inform infection prevention and late effects surveillance in immunotherapy-treated populations.

Obesity is a global public health issue, with its effects a particular issue in Kuwait. Advances in pharmaceutical treatment (eg, glucagon-like peptide-1s) offer an effective solution, with the magnitude of weight lost something to celebrate. However, this level of weight loss also results in dramatic reductions in lean mass, reflecting loss of muscle mass and muscle strength which can predispose people to sarcopenia. This is a particular issue in people with type 2 diabetes in Kuwait, where the prevalence of muscle weakness is extremely high. Solutions to mitigate this loss of muscle mass and strength are needed, with a pragmatic resistance exercise intervention and increasing dietary protein intake having potential. This trial aims to determine whether resistance exercise and/or protein intake can preserve muscle mass and improve physical function in people with obesity initiating semaglutide/tirzepatide therapy.

This single-centre, 6-month, randomised controlled trial at Dasman Diabetes Institute will enrol 232 adults with obesity, randomised (1:1:1:1) to control, resistance exercise, protein supplementation or combined resistance exercise and protein in conjunction with semaglutide or tirzepatide therapy. Resistance exercise will be home-based and involve three sessions per week, progressing from one to three sets targeting major muscle groups. Protein supplementation will target 1.6 g/kg/day via dietary adjustment and protein products. Assessments at baseline and 6 months will include MRI measured quadriceps cross-sectional area (primary outcome), plus measures of secondary outcomes of MRI measured liver fat content and stiffness and intramuscular fat, body composition (dual energy X-ray absorptiometry), strength, physical function, dietary assessment, physical activity levels, sleep patterns, quality of life, glycaemic control and metabolic biomarkers.

The study has received ethical approval from the Dasman Diabetes Institute Ethical Review Committee (HR-RA-2025-01, 19 February 2025) and is registered at ClinicalTrials.gov (NCT06885736, 26 June 2025). Written informed consent will be obtained from all participants, with no financial compensation provided. Data will be reported in accordance with Consolidated Standards of Reporting Trials (CONSORT) guidelines, ensuring participant anonymity. Findings will be disseminated through peer-reviewed publications and presentations at national and international conferences.

NCT06885736.

To develop an empirically grounded, activity-based tariff framework for Hospital at Home (HaH) services using time-driven activity-based costing (TDABC) and micro-costing to support transparent and equitable reimbursement for acute elderly care delivered at home.

Microcosting study embedded within a randomised controlled trial (RCT) comparing HaH with conventional hospital admission in Denmark.

Three municipalities in the Central Denmark Region in collaboration with emergency department physicians at a regional hospital.

A consecutive subsample of 107 elderly acute patients enrolled in the RCT between June 2022 and February 2024. Resource use for HaH activities was measured prospectively using microcosting logs, time-motion observations and administrative records.

Empirically derived tariffs per HaH visit (first and subsequent) calculated using an eight-step TDABC framework incorporating process mapping, resource identification, capacity cost rates and time equations. Sensitivity analyses tested robustness to variation in key cost drivers.

The mean total tariff was 338.89 (95% CI 310.94 to 351.49) for first visits and 207.81 (95% CI 200.70 to 215.69) for subsequent visits, including treatment and transport components. Staff time was the principal cost driver, while equipment, overhead and travel reimbursement had smaller effects. The framework accommodates variation in staffing, geography and visit intensity and can be used to estimate total costs across diverse HaH pathways.

A transparent and reproducible tariff-development framework for HaH services was established using TDABC and microcosting. The model aligns reimbursement with actual resource use and care complexity and provides a transferable template for economic evaluation and operational planning.

NCT05360914.

Induction of labour (IOL) is a commonly performed obstetric intervention, particularly when delivery is deemed more beneficial than continuing the pregnancy due to maternal or fetal indications. When the cervix is unfavourable for delivery, cervical ripening is performed prior to IOL. A wide variety of mechanical, pharmacological and combination methods are used, but the optimal approach balancing efficacy, safety and patient experience remains uncertain. Conventional aggregate data (AD) meta-analyses lack individual-level data, limiting exploration of patient-level factors for personalised medicine and do not address concerns about the trustworthiness of data presented in peer-reviewed randomised controlled trials (RCTs). This protocol describes an individual participant data (IPD) network meta-analysis (NMA) designed to evaluate and rank cervical ripening methods for IOL using only high quality, trustworthy data.

We will identify eligible parallel-group RCTs enrolling pregnant women with a singleton, cephalic fetus at ≥34 weeks’ gestation requiring cervical ripening, through comprehensive searches of Ovid MEDLINE, Embase, Emcare, Scopus, Cochrane Pregnancy and Childbirth Register, WHO International Clinical Trials Registry Platform, clinicaltrials.gov and reference lists of prior reviews. The interventions we consider will be selected via Delphi consensus with international clinical experts. Eligible trial investigators will be invited to contribute de-identified IPD; AD will be used if IPD is unavailable. Trials will be assessed for trustworthiness using the Trustworthiness in RAndomised Clinical Trials checklist and the IPD Integrity Tool, with only eligible studies included in the primary analysis. All statistical analyses will follow a pre-specified statistical analysis plan (SAP) finalised before any analyses are conducted. A two-stage, contrast-based, frequentist IPD-NMA will compare cervical ripening methods for three co-primary outcomes: vaginal birth, composite adverse perinatal outcomes and composite adverse maternal outcomes. Subgroup analyses will assess effect modifiers (eg, parity, age and previous caesarean), with treatment rankings presented using the surface under the cumulative ranking curve and rank-heat plots. Sensitivity analyses will examine the impact of bias, missing data and population criteria.

This study has been approved by the Monash University Human Research Ethics Committee (No. 48189). IPD will be de-identified and securely transferred for storage on a Monash University-hosted shared network drive. Findings will be disseminated via peer-reviewed publications, conference abstracts and the Cervical Ripening for Induction of Labour Collaborative Evidence Network Meta-Analysis (CIRCLE-NMA) website (https://circlenma.com). Patient and public involvement will guide the communication and interpretation of results.

CRD420251077464.

To evaluate the cost-effectiveness of the levonorgestrel intrauterine system (LNG-IUS) compared with hysteroscopic niche resection (HNR) for women with niche-related postmenstrual spotting.

Economic evaluation from a healthcare perspective, conducted alongside a randomised controlled trial with 12 months of follow-up.

A single-centre study at a university hospital in Shanghai was carried out between October 2019 and January 2021.

A total of 208 women aged 18–48 years with niche-related spotting who were suitable for a HNR, defined as a residual myometrium of at least 2.2 mm confirmed by MRI.

Participants were randomly assigned to LNG-IUS insertion (n=104) or HNR (n=104).

The primary outcome was reduction in postmenstrual spotting at 6 months, defined as ≥50% decrease in spotting days compared with baseline. Cost-effectiveness was expressed as incremental cost-effectiveness ratios (ICERs), calculated by dividing cost differences in effective rate and spotting days.

Mean costs (diagnostic, examination, surgical) were compared between groups using Student’s t-test, standardised to 2019 price levels. Uncertainty around cost-effectiveness was assessed with non-parametric bootstrapping and cost-effectiveness acceptability curves.

At 6 months, 78.4% (80/102) of women in the LNG-IUS group and 73.1% (76/104) in the HNR group reported improvement in spotting symptoms (RR 1.07, 95% CI 0.92 to 1.25). Spotting reduction was greater with LNG-IUS (0.0 days, IQR 0.0 to 2.8) compared with HNR (2.0 days, IQR 0.8 to 4.3; p

LNG-IUS is highly cost-effective compared with HNR for the treatment of niche-related postmenstrual spotting at 6 months. These findings support LNG-IUS as first-line therapy for niche-related spotting in women with a residual myometrium ≥2.2 mm.

ChiCTR1900025677.

Nigeria has one of the highest maternal mortality burdens globally. Improving maternal outcomes requires a better understanding of how women experience care across pregnancy, childbirth and the postnatal period. This study explored women’s maternal healthcare experiences across the perinatal continuum in Nigeria, with a focus on how challenges emerge and interact over time.

Longitudinal qualitative study using patient journey mapping.

Public primary, secondary and tertiary healthcare facilities in Abuja, Nigeria.

12 pregnant women were purposively sampled. Each woman participated in two rounds of in-depth interviews: once in late pregnancy and again 2–6 weeks postpartum. All participants completed both interview rounds.

Data were collected through 24 semistructured in-depth interviews conducted longitudinally to capture changes in women’s experiences before and after childbirth. Interview guides were informed by existing maternal health frameworks. Transcripts were analysed using reflexive thematic analysis and organised across five stages of the maternal healthcare journey: Awareness, Consideration, Access, Treatment and Recovery.

This study introduces a five-stage framework: Awareness, Consideration, Access, Treatment and Recovery, to comprehensively explore maternal healthcare experiences. The findings reveal systemic inefficiencies at every stage of the pregnancy journey, from limited awareness of pregnancy test kits to unreliable booking systems and inadequate postpartum mental health support. This study highlights how early-stage barriers cascade into later phases, unlike traditional research that focuses only on clinical interactions. This study emphasises the importance of maternal care accessibility and recovery support, moving beyond a treatment-centric lens. 

This study presents a transformative framework for understanding maternal healthcare as a continuum of interconnected experiences. The research offers actionable insights to enhance maternal health outcomes through stage-specific strategies. The globally adaptable framework provides policymakers and healthcare practitioners with a roadmap to improve maternal healthcare systems in Nigeria and beyond. This holistic approach lays the foundation for reducing maternal mortality while ensuring equitable care for all.

Group A Streptococcus (Strep A) causes a wide spectrum of diseases, ranging from pharyngitis and impetigo to severe invasive infections and immune-mediated conditions such as acute rheumatic fever, rheumatic heart disease and acute post-streptococcal glomerulonephritis. Contemporary data on the global burden of Strep A diseases are lacking. The proposed study aims to use administrative data from numerous jurisdictions to estimate age-specific incidence or prevalence of Strep A diseases, with an emphasis on severe clinical endpoints. Depending on the availability of data, a secondary objective will be to estimate the economic burden of Strep A diseases.

This population-based descriptive study will use routine health data obtained from different low-income and middle-income and high-income countries through international research collaborations to estimate the country-level and global burden of Strep A diseases. Data will be primarily obtained and collated from hospital or national health laboratory databases for individuals across all age groups, along with emergency department, primary care and microbiological datasets where available. Strep A disease endpoints will be identified using International Classification of Diseases 10th Revision or other relevant coding systems and microbiological diagnosis. Age-specific incidence and prevalence rates will be computed using population denominators, and country-level age-adjusted rates will be applied to standard global reference populations to estimate the number of cases globally.

Ethical approval to conduct this study was obtained from the Human Research Ethics Committee at the University of Western Australia (reference: #2024/ET000401) and governance approval was obtained from The Kids Research Institute Australia. The findings from this study will be published in peer-reviewed journals and presented at Strep A Vaccine Global Consortium collaborative meetings.

Despite advances in maternity care, stillbirth remains a major burden. It disproportionately affects black and Asian mothers, those with obesity and women over the age of 35 years. Induction of labour may benefit these women, but there is no clear evidence to guide recommendations on optimal timing of induction because of variations in the intervention and insufficient power in primary trials for rare outcomes such as stillbirth and perinatal mortality, or to assess whether effects differ by maternal characteristics. We will conduct an individual participant data (IPD) meta-analysis of randomised trials to assess the overall and differential effect of induction of labour, according to timing of induction and maternal characteristics, on adverse perinatal and maternal outcomes. We will also rank induction of labour timing strategies by their effectiveness to inform clinical and policy decision-making.

We will identify randomised trials on induction of labour by searching MEDLINE, CINAHL, EMBASE, BIOSIS, LILACS, Pascal, SCI, CDSR, ClinicalTrials.gov, ICTRP, ISRCTN registry, CENTRAL, DARE and Health Technology Assessment Database, without language restrictions, from inception to June 2025. Primary researchers of identified trials will be invited to join the OPTIMAL Collaboration and share the original trial data. Data integrity and trustworthiness assessment will be performed on all eligible trials. We will check each study’s IPD for consistency with the original authors before standardising and harmonising the data. Study quality of included trials will be assessed by the Cochrane Risk of Bias tool. We will perform a series of one-and-two-stage random-effects meta-analyses to obtain the summary intervention effect on composite adverse perinatal outcome (stillbirth, neonatal death or severe morbidity requiring admission to neonatal unit) with 95% CIs and summary treatment–covariate interactions (maternal age, ethnicity, parity, socioeconomic status, body mass index and method of conception). Heterogeneity will be summarised using tau², I² and 95% prediction intervals for effect in a new study. Sensitivity analysis to explore robustness of statistical and clinical assumptions will be carried out. Small study effects (potential publication bias) will be investigated using funnel plots.

The study is registered on PROSPERO (CRD420251066346) and ethics approval is not required. We will disseminate findings widely to women, healthcare professionals and policymakers through academic, professional bodies and social media channels, and in peer-reviewed journals to achieve impact.

CRD420251066346.

To test the feasibility of identifying and quantifying resource use for a Hospital-at-Home (HaH) model in Danish municipalities, we used a micro-costing approach. Additionally, we aimed to generate a transparent activity and time dataset. This dataset will support subsequent tariff development with time-driven activity-based costing and feed into the economic evaluation of an ongoing randomised controlled trial (RCT).

Prospective pilot feasibility study.

Three municipalities in the Central Denmark Region in collaboration with emergency department specialists and general practitioners.

56 elderly acute patients treated in HaH during the pilot phase.

Feasibility of micro-costing data collection (completeness, consistency and acceptability to staff) and descriptive resource-use quantities by activity and provider group. No price assignment or cost estimates are reported.

Patients received a mean of 3.8 HaH treatment days with 7.8 acute team visits and 3.9 municipal-staff visits per treatment course. The acute team spent a mean of 742 min per patient across treatment activities, communication, documentation and transport, while municipal care staff recorded a mean of 213 min. Intravenous medicine administration and vital sign assessments were the most frequent activities. Data completeness and consistency improved over time through co-design and feedback.

Detailed resource-use measurement using provider logs was feasible in a municipal HaH model and produced an activity and time dataset suitable for tariff development. Findings are context-specific and not generalisable due to the small sample. The micro-costing log refined through the pilot will be applied in an RCT, where time and activity data will be used to construct a tariff using time-driven activity-based costing.

Pain in patients with rheumatoid arthritis (RA) is an unmet clinical need. Targeting joint inflammation with disease-modifying antirheumatic drugs has not resulted in the anticipated reduction in pain for many patients. This can partly be explained by the concept of central sensitisation whereby spinal and supraspinal pathways have a lower threshold of activation, leading to increased perception of pain. Synovial stromal cells, such as fibroblasts, are also thought to play a role through peripheral sensitisation of nerves in the joint. Synovial fibroblasts are known to produce pro-algesic mediators such as interleukin 6 and nerve growth factor at the messenger RNA level. These pro-algesic mediators could activate sensory nerve fibres that send signals from the joint to the spinal cord, thereby driving persistent pain in RA. The purpose of this study is to evaluate which pro-algesic mediators are produced by lining versus sub-lining fibroblasts and whether the level of these mediators correlates with clinical measures of pain in patients with RA.

FiND-Pain RA is a multicentre observational study which will recruit 50 patients with seropositive RA who attend the rheumatology department of Guy’s and St Thomas’ Hospital, London, and the Nuffield Orthopaedic Centre, Oxford. Clinical examination, pain-focused patient-reported outcome measures, ultrasound examination and ultrasound-guided synovial biopsy of the knee will be performed. The levels of known and putative pro-algesic mediators will be measured in fibroblasts from the lining and sub-lining layer of the synovium. The location and spatial morphology of sensory nerve fibres and their proximity to lining and sub-lining fibroblasts will be characterised. The primary outcome will be to determine whether the knee pain scores of participants correlate with the level of leukaemia inhibitory factor, a novel putative pain-mediator expressed in sub-lining fibroblasts. The secondary outcomes will be to determine whether other pro-algesic mediators produced by lining or sub-lining fibroblasts correlate with clinical measures of pain and to assess the location and proximity of sensory nerve fibres to lining versus sub-lining fibroblasts.

The study is a sub-study of the PUMIA (Pain Phenotypes and their Underlying Mechanisms in Inflammatory Arthritis) study, which has been approved by the Bromley Research Ethics Committee (REC: 21/LO/0712). The findings of this study will be disseminated through open-access publications, as well as scientific and clinical conferences.

Patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA) are considered to have a symptomatic venous thromboembolism (VTE) risk of 1.0%–1.5% despite thromboprophylaxis. Fast-track treatment protocols have substantially lowered the VTE risk in most patients. Hence, the majority of patients may be unnecessarily exposed to the burden and risk of thromboprophylaxis. On the contrary, there are still patients with a high VTE risk who develop VTE despite thromboprophylaxis. Thus, tailored thromboprophylaxis treatment may potentially reduce both VTE and bleeding risk.

The DISTINCT (inDividual, targeted thrombosIS prophylaxis versus the standard ‘one-size-fits-all’ approach in patients undergoing Total hIp or total kNee replaCemenT) trial is a national, multicentre, randomised, multiarm, open-label trial. The main objective is to study whether tailored thromboprophylaxis reduces the occurrence of symptomatic VTE (primary outcome) and major bleeding (primary safety outcome) within 90 days after THA/TKA in comparison with standard thromboprophylaxis. Patients with a low, intermediate or high predicted VTE risk (based on the Thrombosis Risk Prediction following total hip and knee arthroplasty score (TRiP(plasty) score)) will be included in the DISTINCT-1, DISTINCT-2 or DISTINCT-3 studies, respectively. In the DISTINCT-1 trial, 3478 patients will be randomly allocated to receive either in-hospital thromboprophylaxis or standard prophylaxis. In the DISTINCT-2 cohort study, 2500 patients will receive standard prophylaxis. In the DISTINCT-3 trial, 4100 patients will be randomly allocated to receive either 6 weeks of high-dose thromboprophylaxis or standard prophylaxis. Standard prophylaxis consists of a low dose of any approved thromboprophylactic agent for 4 weeks. We hypothesise that (1) the efficacy of in-hospital only thromboprophylaxis is non-inferior in preventing VTE and equally safe compared with standard prophylaxis in patients with a low VTE risk (DISTINCT-1) and (2) prolonged high-dose thromboprophylaxis is superior in preventing VTE as compared with standard prophylaxis in patients with a high VTE risk (DISTINCT-3). Patients with intermediate VTE risk will be observed to evaluate VTE and bleeding rates (DISTINCT-2).

The protocol has been approved by the Medical Research Ethics Committee Leiden-Den Haag-Delft, EU-trial-number 2023-510186-98. Study results will be disseminated through peer-reviewed journals and during international conferences.

NCT06581965.

Breast cancer is the most common cancer among women globally. While the impact of lifestyle factors like smoking and obesity on breast cancer risk and survival is well documented, the effect of working conditions is not fully understood. Moreover, breast cancer can reduce employability, making it crucial to identify factors that facilitate return to work and improve life satisfaction. Since breast cancer is affected by sleep and lifestyle, which are related to working conditions, understanding how they affect breast cancer outcomes is key. This study aims to explore the relationship between working conditions and breast cancer outcomes, including incidence, mortality and survival within a causal framework. Our specific aims are to understand the relationship between (1) working conditions and occupational groups and breast cancer outcomes, including the extent to which sleep, lifestyle and breast cancer screening uptake explain these relationships and (2) prediagnosis working conditions, sleep and lifestyle and their effect on return to work and life satisfaction among breast cancer survivors.

We will use data from the UK Biobank, a large-scale cohort study with data on 273 825 women between 40 and 69 years old at baseline, followed from 2006 to 2022. The data has been linked with death and cancer registries and includes 8309 incident breast cancer cases. To quantify the effect of working conditions on breast cancer outcomes (aim 1) and their effect on return to work and life satisfaction (aim 2), we will implement g-methods to estimate the average causal effect and employ counterfactual-based mediation analysis to quantify how much mediating factors, such as sleep and lifestyle, explain this effect.

UK Biobank received ethical approval from the North West Multi-Centre Research Ethics Committee. No further ethical approval was required for the proposed research project. In line with the two aims, four original research manuscripts will be published in open-access peer-reviewed journals to disseminate the findings. In addition, findings will be disseminated at international conferences and scientific meetings.

As the opioid crisis continues, people who use drugs (PWUD) experience a disproportionate burden of both HIV and overdose, driven by increased injection-related HIV outbreaks and an opaque and rapidly evolving drug market, respectively. Pre-exposure prophylaxis (PrEP) for HIV and point-of-care drug checking services are underused yet potentially impactful interventions to address the harms of the opioid crisis. Implementing such interventions using known strategies to enhance client engagement and reduce access barriers, such as street outreach, mobile services and peer navigation, can optimise intervention and maximise their impact.

The Substance Checking Outreach and PrEP Engagement (SCOPE) Study is a non-randomised clinical trial evaluating the impact of the Check It intervention, a mobile community PrEP and drug checking intervention in Baltimore, Maryland, USA. SCOPE will recruit a cohort of 500 PWUD at risk for HIV through street-based recruitment methods. Cohort members will be followed semi-annually for 18 months. The primary study outcomes are engagement with the PrEP continuum of care and the number of non-fatal overdoses. We will use both random effects models and marginal structural models to estimate the effects of Check It on participant engagement on the PrEP continuum and the number of non-fatal overdoses over time.

Study procedures have been approved by the Johns Hopkins Bloomberg School of Public Health Institutional Review Board. Risks to participants are low, with the most serious risk being potential data confidentiality breaches. This risk was minimised through the use of secure data storage platforms with limited user access. Study findings will be disseminated through peer-reviewed manuscripts, academic presentations, and reports and fact sheets designed for lay audiences.

This study was registered with clinicaltrials.gov (study ID: NCT05977881; Protocol ID: 00017498).