Childhood obesity has surged globally, leading to various metabolic comorbidities and increased cardiovascular risks. Early intervention in lifestyle and feeding practices during infancy is crucial to mitigate these risks. This study evaluates the efficacy of a mobile web app-based intervention tool, named the Feeding, Lifestyle, Activity Goals (FLAGs) to promote healthier eating behaviours and lifestyle habits in infants from birth to 12 months.

This two-arm randomised controlled trial will enrol 220 caregiver-infant pairs per arm at KK Women’s and Children’s Hospital, Singapore, with recruitment expected from January to December 2025. Eligible participants include women at ≥34 weeks’ gestation or up to 3 days post delivery with pre-pregnancy overweight/obesity (body mass index (BMI) >23 kg/m²) and/or a diagnosis of diabetes. Caregiver-infant pairs will be randomised to the FLAGs intervention or control group. Over 12 months, both groups will receive standard infant care. The intervention group will undergo regular assessments via the FLAGs web app built-in assessment tool, assessing infant feeding practices, sedentary behaviour and physical activity. The intervention group will also receive FLAGs personalised guidance and weekly digital nudges. Maternal and infant data will be collected at baseline and at 12 months. Primary outcomes are infant BMI, weight-for-length and body composition at 12 months. Secondary outcomes include lifestyle behaviours and eating habits assessed through validated questionnaires when the infants are 1 year old. We will perform both intention-to-treat and per protocol analysis.

Ethical approval has been obtained from the SingHealth Centralised Institutional Review Board (Ref: 2024/3224). Written informed consent will be obtained from all participants. Study findings will be disseminated via peer-reviewed publications and academic conferences, with de-identified data available on reasonable request. This trial is registered on ClinicalTrials.gov (ID: NCT06457750).

NCT06457750.

Colonoscopy is an essential procedure for the early diagnosis of colorectal conditions; however, over 60% of patients undergoing non-sedated colonoscopy report moderate to severe pain. This study aims to investigate the central analgesic mechanisms of transcutaneous electrical nerve stimulation based on wrist-ankle acupuncture theory (TENS-WAA). A multimodal approach combining electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) will be employed to assess pain-related brain activity, with artificial intelligence applied to model the relationship between objective neurophysiological signals and subjective pain experience.

This is a single-centre, randomised, double-blind, controlled trial involving 60 patients undergoing colonoscopy without anaesthesia. Participants will be randomly allocated (1:1) to either an electrical stimulation group receiving TENS-WAA or a sham stimulation group. EEG and fNIRS data will be acquired before, during and after the procedure. The primary outcome is the analysis of EEG-fNIRS signals to characterise cerebral responses associated with pain modulation. Secondary outcomes include patient-reported pain using the Visual Analogue Scale (VAS), total colonoscopy duration and the correlation between EEG-fNIRS indicators and VAS scores. A deep learning framework will be used to enhance pain prediction accuracy.

This study has received ethical approval from the Ethics Committee of Changhai Hospital, Shanghai (approval reference CHEC2025-006), and has been registered at ClinicalTrials.gov. Written informed consent will be obtained from all participants. Findings will be disseminated in peer-reviewed academic journals and at relevant scientific conferences, regardless of outcome, contributing to evidence-based, non-pharmacological pain management strategies.

ClinicalTrials.gov, NCT06813703.

Care pathways are crucial for patients with mental health disorders and should be designed to support integrated rehabilitation while reducing the burden of these disorders. The contemporary shift toward an outpatient follow-up model of care presents an opportunity to improve mental health care beyond the stagnation in advancements in pharmacological treatments. Various pharmacist-led interventions exist and can serve as levers to address ongoing challenges in mental health care pathways: they could help manage difficult transitions, ensure continuity between inpatient and outpatient care, and reduce high rehospitalisation rates. However, the contexts in which these solutions benefit patients and improve care outcomes remain unclear. Thus, the primary objective of this study will be to identify how pharmaceutical solutions contribute to improving mental health care pathways, what works, for whom and in what context. The secondary objective will be to identify the key outcomes currently used to evaluate the impact of pharmaceutical solutions on care pathways.

A systematic realist review will be conducted, following 5 iterative steps to synthesise heterogeneous evidence: (1) Scope definition with a general review of the literature and experts’ discussions, (2) Initial programme theory development based on the preliminary searches, (3) Systematic review for evidence, to refine and test initial programme theory across PubMed, Embase and Web Of Science, (4) Data extraction, including context-mechanism-outcome configurations, and evidence appraisal and (5) Data analysis, synthesis and refined programme theory construction with the realist logic. This process will involve consensus among expert researchers, incorporating insights from individuals with lived experience.

The final programme theory modelling will result in a new framework for pharmaceutical solutions applied in diverse mental health contexts. The findings of this systematic realist review could serve as a guide for implementing pharmaceutical solutions across healthcare settings, ensuring that interventions are evidence-based, contextually relevant and grounded in real-world needs.

As this realist review will collect previously published data and will not involve human or animal participants, no ethical approval is required. Since this manuscript is a review protocol, no datasets were generated or analysed. All data extraction forms will be made available as part of the publication of the realist review.

Systematic review registration PROSPERO 2025 CRD420251011954.

Dates of the study: September 2025 to September 2026.

This study explored how Structured Medication Reviews (SMRs) are being undertaken and the challenges to their successful implementation and sustainability.

A cross-sectional mixed methods online survey.

Primary care in England.

120 clinical pharmacists with experience in conducting SMRs in primary care.

Survey responses were received from clinical pharmacists working in 15 different regions. The majority were independent prescribers (62%, n=74), and most were employed by Primary Care Networks (65%, n=78), delivering SMRs for one or more general practices. 61% (n=73) had completed, or were currently enrolled in, the approved training pathway. Patient selection was largely driven by the primary care contract specification: care home residents, patients with polypharmacy, patients on medicines commonly associated with medication errors, patients with severe frailty and/or patients using potentially addictive pain management medication. Only 26% (n=36) of respondents reported providing patients with information in advance. The majority of SMRs were undertaken remotely by telephone and were 21–30 min in length. Much variation was reported in approaches to conducting SMRs, with SMRs in care homes being deemed the most challenging due to additional complexities involved. Challenges included not having sufficient time to prepare adequately, address complex polypharmacy and complete follow-up work generated by SMRs, issues relating to organisational support, competing national priorities and lack of ‘buy-in’ from some patients and General Practitioners.

These results offer insights into the role being played by the clinical pharmacy workforce in a new country-wide initiative to improve the quality and safety of care for patients taking multiple medicines. Better patient preparation and trust, alongside continuing professional development, more support and oversight for clinical pharmacists conducting SMRs, could lead to more efficient medication reviews. However, a formal evaluation of the potential of SMRs to optimise safe medicines use for patients in England is now warranted.

Endometriosis is a chronic condition affecting up to 11% of people presumed female at birth by the age of 44 years, characterised by the growth of tissue similar to the lining of the uterus on other organs. Endometriosis significantly impacts health-related quality of life (HRQoL) and imposes a substantial burden on both individuals and the healthcare system. International guidelines recommend the interdisciplinary management of endometriosis due to its significant biopsychosocial burden; however, research aimed at exploring psychological approaches for endometriosis is limited. This trial aims to evaluate the effectiveness of CodeEndo, an online co-designed interdisciplinary supportive care program, compared with a waitlist control (WLC), on HRQoL and biopsychosocial outcomes in people with a diagnosis of endometriosis.

A hybrid type 1 effectiveness and implementation randomised controlled trial (RCT) will be conducted. Eligible participants will be randomly allocated to either the CodeEndo program (n=176) or WLC group (n=176) for 8 weeks. The primary outcome will be HRQoL, and secondary outcomes will include psychological symptoms (anxiety, depression, stress), self-efficacy, menstrual, bladder and gastrointestinal symptoms, pain, fatigue, sleep, exercise, diet, symptom bothersomeness and physical and psychological well-being, measured at 8 weeks post-randomisation (T2) and 6-month follow-up (T3). Cost-effectiveness will also be examined. Longitudinal qualitative individual interviews (up to n=40) will be conducted with participants who complete the CodeEndo program to explore benefits, barriers and facilitators of ongoing use. Additionally, the CodeEndo program will undergo evaluation by a group of endometriosis healthcare providers, who will assess potential barriers and facilitators to its real-world implementation. Various process evaluation strategies will also be measured to inform future implementation. Data analyses will incorporate mixed-effects regression models on an intention-to-treat basis, cost-consequences and cost-utility, dietary and qualitative thematic analysis.

This protocol received ethics approval from Deakin University Research Ethics Committee (DUREC Ref: 2024-157). Dissemination is expected to include peer-reviewed journal articles, reports, conference presentations as well as websites or social media platforms of relevant chronic pain organisations. Participants will be sent a summary of trial results.

ACTRN12623000598684p.

Chronic venous disease, particularly lower extremity varicose veins (VVs) and incompetent perforating veins (IPVs), is a prevalent condition associated with significant morbidity, including venous ulcers and post-surgical recurrence. Current diagnostic modalities for IPVs—such as digital subtraction angiography, CT venography, magnetic resonance venography and conventional ultrasound—are limited by ionising radiation, operator dependency or inadequate spatial resolution. Ultrasound tomography (UT), an emerging automated 3D imaging technology, offers comparable resolution, wider field of view and reduced operator bias compared with conventional ultrasound. Preliminary studies suggest UT improves IPV detection rates, yet its diagnostic accuracy and clinical utility remain unvalidated in large-scale trials. This study aims to evaluate UT’s diagnostic performance and its impact on surgical outcomes in a paired-design and randomised controlled trial (RCT), addressing a critical gap in non-invasive venous assessment.

This study combines a paired diagnostic trial and a prospective, triple-blind RCT. In the paired trial (n=84), patients with VVs (Clinical-Etiological-Anatomical-Pathophysiological C2–C5) receive both conventional ultrasound and UT combined with Doppler examination to compare IPV detection sensitivity against surgical findings. The RCT (n=264) randomises patients to conventional ultrasound group (control group) or conventional ultrasound＋UT group (intervention group). After examination, all patients undergo standardised treatment (radiofrequency ablation with sclerotherapy and selective IPV ligation), with follow-up extending to 5 years. The primary endpoint is 1-year recurrence rates and secondary endpoints, including 3-month, 3-year and 5-year recurrence rates, as well as Venous Clinical Severity Scores, quality of life and Aberdeen Varicose Vein Questionnaire scores.

The study has been approved by the Ethics Committee of Shanghai Sixth People’s Hospital (approval number: 2024-132). Written informed consent will be obtained from each participant, and final results will be published in peer-reviewed journals.

The study has been registered on Chinese Clinical Trial Registry (http://www.chictr.org.cn), identifier: ChiCTR2500097289.

Chagas disease (CD) is one of the most neglected diseases in the world. In Latin America, CD is endemic in 21 countries, with an estimated 70 million people at risk of infection. Current treatments are limited to two nitroheterocyclic compounds: nifurtimox and benznidazole (BZN). Each has significant limitations, including long duration and safety concerns. However, data from recently completed studies suggest that reduced-duration regimens may be equally effective while enhancing safety.

NuestroBen is a phase III, randomised, multicentre clinical trial designed to assess whether shorter (2- and 4-week) regimens of BZN are non-inferior to the standard 8-week treatment. A total of 540 adult participants with no evidence of organ damage (the indeterminate form) or with mild cardiac progression (mild electrocardiographic alterations and without systolic dysfunction or symptoms), all in the chronic phase of CD, will be recruited at six study sites in Argentina and two study sites in Bolivia. Participants will be randomised to receive one of the two shortened regimens of BZN (300 mg per day for 2 or 4 weeks) or standard treatment (300 mg per day for 8 weeks). The primary endpoint is sustained elimination of parasitaemia from the end of treatment through 12 months of follow-up. Secondary endpoints will assess sustained clearance of parasitaemia at 1, 4, 6 and 8 months of follow-up from the end of treatment, drug tolerability and adherence to treatment. NuestroBen will also evaluate whether two shortened regimens of BZN improve drug tolerability and treatment adherence compared with the current standard treatment while maintaining efficacy in participants with the indeterminate form of CD or with mild cardiac involvement.

In Argentina, this study was approved by Fundación de Estudios Farmacológicos y Medicamentos ‘Luis M. Zieher’ for its conduct at the Instituto de Cardiología de Corrientes ‘Juana Francisca Cabral’ (reference: NuestroBen-2020/2021) and the Instituto Nacional de Parasitología ‘Dr. Mario Fatala Chaben’ (reference: NuestroBen-2020/2021) by Comité Institucional de Ética de Investigación en Salud for the Centro de Chagas y Patología Regional de Santiago del Estero (reference: NuestroBen-2020-088/2021), by Comité de Ética en Investigación for the Hospital de Infecciosas F.J. Muñiz (reference: NuestroBen-2020–4037) and the Hospital General de Agudos D.F. Santojanni (reference: NuestroBen-2020–4039) and by Comité de Bioética for the Fundación Huésped (reference: NuestroBen-2020/2021). In Bolivia, it was approved by Comité de Ética en Investigación en Salud from the Universidad Autónoma Juan Misael Saracho (reference: NuestroBen-2020/2025). All participants are asked to provide written informed consent to participate. Recruitment processes started in July 2023, and as of 15 June 2025, 140 participants have been recruited. Findings will be shared with Argentinian and Bolivian public health officials and with the Chagas and tropical medicine communities via international conferences. Findings will also be published in medical journals.

NCT04897516.

Diabetic retinopathy (DR) in pregnancy can cause blindness. National guidelines recommend at least one eye examination in early pregnancy, then ideally 3-monthly, through to the postpartum for pregnant women with pregestational diabetes. Here we examined adherence rates, barriers and enablers to recommended DR screening guidelines.

Cross-sectional survey study, as part of a larger prospective cohort study.

Participants were recruited from two tertiary maternity hospitals in Melbourne, Australia.

Of the 173 pregnant women with type 1 (T1D) or type 2 diabetes (T2D) in the main cohort study, with an additional four who participated solely in this survey study, 130 (74.3%) completed the survey.

This study calculated rates of adherence to guideline-recommended DR screening schedules and collected data on the enablers and barriers to attendance using a modified Compliance with Annual Diabetic Eye Exams Survey. Each of the 5-point Likert-scale survey items was compared between adherent and non-adherent participants using the Wilcoxon rank-sum test and logistic regression models were constructed to quantify associations as ORs.

A retinal assessment was undertaken at least once during pregnancy in 86.3% of participants, but only 40.9% attended during their first trimester and only 21.2% attended the recommended number of examinations. Competing priorities were the main barriers to adherence, with eye examinations ranked as the fourth priority (IQR 4th–5th) among other health appointments during pregnancy. Meanwhile, knowledge of the benefits of eye screening examinations, eye-check reminders and support from relatives was identified as enablers.

Despite the risk of worsening DR during pregnancy, less than half of the participants adhered to recommended screening guidelines, suggesting that eye health is not a priority. Proactive measures to integrate care are needed to prevent visual loss in this growing population.

This study aims to assess the feasibility of respondent-driven sampling (RDS) to recruit participants with recent abortion experiences in humanitarian contexts, and describe the composition of the study sample generated with this sampling method.

This was a three-phase mixed-methods community-engaged research study employing an exploratory and explanatory sequential approach. We conducted in-depth interviews, focus group discussions, an interviewer-administered questionnaire on abortion experiences and a health facility assessment.

Bidibidi Refugee Settlement, Uganda and Kakuma Refugee Camp, Kenya from November 2021 to December 2022.

Using RDS, we recruited 600 participants in Kakuma and 601 participants in Bidibidi with recent abortion experiences. In Kakuma, participants were primarily from Burundi, the Democratic Republic of the Congo and South Sudan; participants in Bidibidi were primarily from South Sudan. Most participants in both sites had completed at least some primary school and were not employed.

RDS recruitment dynamics: convergence and bottlenecks on key sociodemographic variables, recruitment and population homophily, reciprocity of social ties, success and experiences recruiting.

There were minor violations of RDS assumptions, particularly regarding assumptions of reciprocity of ties and seed composition independent of sample. In addition, there was a strong tendency of participants to recruit those from the same home country and living within the same camp zone. However, sample proportions for age, home country, marital status, zone of residence and student status reached equilibrium (stabilised) by around 500 participants at each site, and we were able to quickly attain the study sample size.

While the true representativeness of our sample remains unknown, RDS is a practical and effective recruitment method in humanitarian contexts for sensitive topics, particularly for research questions in which no data or sampling frames exist. However, attention to representativeness and community engagement is essential to optimising its application and ensuring success.

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.

To investigate the nutritional status and its influencing factors in elderly patients aged 60 years and above with malignant tumours.

A retrospective observational study.

The First Affiliated Hospital of Chengdu Medical College, a tertiary care hospital in Chengdu, China.

A total of 450 elderly patients with cancer (aged ≥60 years) admitted between January 1, 2022, and January 1, 2023. Patients were selected based on their clinical records, excluding those with communication disorders, mental illness or incomplete data.

Nutritional status was assessed using the Patient-Generated Subjective Global Assessment (PG-SGA). Participants were categorised based on the presence or absence of malnutrition. Multivariate logistic regression was used to identify independent risk factors for malnutrition.

Of the 450 patients included, 63.7% were male and 36.3% female, with a median age of 69 years. The prevalence of severe malnutrition was 46.4%. Univariate analysis showed significant associations between malnutrition and factors such as older age (p

Malnutrition is highly prevalent in elderly patients with cancer and is significantly associated with age, BMI, albumin levels and self-care ability. Early identification and targeted nutritional interventions may improve outcomes and quality of life in this population.

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

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

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

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

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

Postoperative pain is particularly pronounced in spinal surgery. Inadequate management of acute postoperative pain not only reduces patient satisfaction and delays recovery but also increases the risk of developing chronic pain. Local infiltration analgesia (LIA) is a widely used technique for perioperative pain management. However, even with the use of long-acting local anaesthetics, such as ropivacaine, postoperative analgesia often remains insufficient. Preliminary evidence suggests that combining diprospan, a mixture of betamethasone disodium phosphate and betamethasone dipropionate, with ropivacaine can significantly reduce analgesic requirements in the immediate postoperative period. However, concerns about steroid-related complications, including hyperglycaemia and surgical site infections, highlight the need to identify the minimum diprospan concentration to achieve a balance between efficacy and safety. This randomised, controlled, evaluator-blinded trial aims to investigate the dose-response relationship of diprospan as an adjunct to ropivacaine for LIA in spinal surgery to determine the minimum effective dose for effective and safe pain management.

This is a single-centre, randomised, evaluator-blinded, controlled, dose-mapping study in which subjects will be randomised in a 1:1:1:1:1 ratio to the control group or to receive diprospan at concentrations of 0.003%, 0.006%, 0.009% or 0.012%. Patients will receive either 0.5% ropivacaine alone or a corresponding dose of diprospan combined with 0.5% ropivacaine for LIA. All participants will be followed for a duration of 3 months. The primary outcome measure will be cumulative sufentanil consumption within the first 48 hours postsurgery. Secondary outcomes will include additional assessments of analgesia, steroid-related adverse events and other complications within the 3-month follow-up period.

This study protocol was approved by the Institutional Review Board of Beijing Tiantan Hospital (KY2024-365-02-1). Written informed consent will be obtained from all participants. The results will be submitted for publication in a peer-reviewed journal.

NCT06785350.

To quantify and describe the use of real-world data (RWD) in National Institute for Health and Care Excellence (NICE) oncology technology appraisal (TA) final appraisal determination documents.

A systematic literature review was conducted on pharmaceutical NICE oncology TAs published between April 2000 and March 2024 (covering financial years 2000/2001 to 2023/2024 inclusive) extracted on 22 August 2023 (2000/2001 - 2022/2023) and 8 August 2024 (2023/2024).

NICE TA final appraisal determination documents.

All pharmaceutical oncology TAs published between April 2000 and March 2024 (financial years 2000/2001 to 2023/2024) that did not go on to be terminated.

The data required for eligibility screening was extracted from an Excel file directly from the NICE website, where data related to each TA was extracted using an automated script derived from published sources. TAs were assessed based on prespecified review criteria covering whether an RWD submission was reported by the committee, and if so, which RWD sources were used, alongside the methods reported and any feedback from the committee regarding the use of RWD. Bias was not assessed as part of the study.

Of 310 TAs identified, 135 (48.0%) used RWD. A variety of RWD types were used, mostly from UK or US data sources. 47 TAs (34.8%) leveraged RWD from multiple sources. RWD was mostly used in comparisons of survival (41.5%), to inform utility values (26.7%) and to compare baseline characteristics (19.3%), with matched adjusted indirect comparisons (MAICs) and external control arms (ECAs), seen from 2015 and 2018, respectively. The committee expressed concerns around the RWD presented by the company in 53 TAs (39.2%), the most common being a lack of generalisability to the UK population and/or National Health Service practice and comprehensiveness of the RWD.

This study quantifies the increasing use of diverse RWD sources in NICE oncology TAs, as well as the shift towards more complex methods like MAICs and ECAs. The feedback of the NICE committee highlights key areas of improvement as the generalisability and maturity of the RWD presented.

Type 2 diabetes mellitus (T2DM) and osteoarthritis (OA) are globally prevalent chronic diseases that affect millions of individuals in ageing populations. Hip and knee replacements are well established and effective treatments in patients suffering from end-stage OA. Understanding how T2DM influences the outcomes of these surgeries is important for optimising patient care and improving surgical results. This study aimed to explore the association of T2DM with reoperation (regardless of the reason), adverse events (AEs) and mortality after primary hip and knee replacement surgery.

Observational study based on prospectively collected registry data analysed retrospectively.

Data from several Swedish national quality registers and health data registers were used to create a study database. 109 938 and 80 897 primary hip and knee replacements due to OA, performed between 2008 and 2019 (hip) and 2009 and 2018 (knee), were included in the study.

The risk of complications, such as reoperation, AEs and mortality, was investigated by estimating HRs using Cox regression, and OR using logistic regression, unadjusted and adjusted for confounding factors, such as patient characteristics, socioeconomic status and comorbidities, and mediators, such as surgical factors.

Adjusted multivariable Cox-regression analysis showed no T2DM-associated risk of reoperation after hip or knee replacement, adjusted HR 1.10 (95% CI 0.99 to 1.23) and 1.09 (95% CI 0.96 to 1.24), respectively, while T2DM was associated with increased risk of death after hip and knee replacement, adjusted HR 1.40 (95% CI 1.34 to 1.47) and 1.38 (95% CI 1.31 to 1.45). Adjusted logistic regression analysis showed T2DM-associated increase of reoperation within 90 days (OR 1.23 (95% CI 1.05 to 1.43)) and increased mortality within 90 days (OR 1.42 (95% CI 1.01 to 1.95)) following hip replacement; however, this was not the case after knee replacement, OR 1.08 (95% CI 0.85 to 1.36) for reoperation and OR 1.29 (95% CI 0.84 to 1.94) for mortality. Several factors closely linked with T2DM, such as body-mass index and comorbidities, were identified as important when assessing risk of reoperation and mortality. Regarding AEs within 30 and 90 days, very slight but not statistically significant T2DM-associated increases were seen after either hip replacement, OR 1.01 (95% CI 0.91 to 1.11) and 1.07 (95% CI 0.98 to 1.16) or after knee replacement, OR 1.05 (95% CI 0.93 to 1.17) and 1.08 (95% CI 0.98 to 1.19).

The observed risk of reoperation suggests that T2DM alone was not a strong justification to advise against hip or knee replacement in individuals with T2DM deemed eligible for joint replacement. The T2DM-associated increased mortality after hip and knee replacement is challenging to interpret, as T2DM itself without undergoing hip or knee replacement surgery is associated with increased mortality.

The TRAjectory of knee heaLth in runners (TRAIL) study is a prospective cohort study investigating the long-term knee health trajectories of runners with and without a heightened osteoarthritis risk. This study aims to describe the recruitment results and baseline characteristics of the TRAIL cohort.

Runners aged 18–50 years and running ≥3 times and ≥10 km per week on average in the past 6 months were eligible. Participants were recruited via running podcasts, running clubs and social media between July 2020 and August 2023. Data were collected at study enrolment and at a face-to-face baseline testing session, which occurred a median of 33 weeks (IQR 18 to 86 weeks) after enrolment. Follow-up data collection is ongoing.

Out of 462 runners who completed an online registration form, 268 runners enrolled, of which 135 had a history of knee surgery (46% females) and 133 were non-surgical controls (50% females). 60% of the surgery group had undergone anterior cruciate ligament reconstruction, 33% meniscus and/or cartilage surgery, and 7% other knee surgery. 54 participants previously enrolled were unable to continue in the study before attending baseline data collection. Of the 214 runners who remained in the study and attended baseline data collection, 108 had a history of knee surgery (49% females) and 106 did not have a history of knee surgery (51% females).

Participants will be followed for 10 years through ongoing patient-reported outcomes and continuous monitoring of training loads using wearable devices. At baseline, 4- and 10-year follow-up, knee MRI and knee-health patient-reported outcomes will be collected to evaluate structural and symptomatic knee osteoarthritis progression. Data will inform guidelines for safe running practices and rehabilitation post-knee surgery.

Artificial intelligence (AI) has the potential to revolutionise healthcare delivery, particularly in the domain of emergency medicine. With the rise of telemedicine and virtual care, AI-powered tools could assist in triage, diagnosis and treatment recommendations for patients seeking emergency care remotely. This systematic review aims to synthesise the current state of research on AI applications in virtual emergency care, identify key challenges and opportunities and provide recommendations for future research and implementation.

We will conduct a comprehensive search of multiple electronic databases (PubMed, Web of Science, Embase, CINAHL, MEDLINE, The Cochrane Library, Scopus) from each database’s inception to March 2025. The search will include terms related to AI, machine learning, deep learning, virtual care, telemedicine and emergency medicine. We will include original research articles, conference proceedings and preprints that describe the development, validation or implementation of AI models for virtual emergency care. Two reviewers will independently screen titles and abstracts, review full texts, extract data and assess risk of bias using the PROBAST (Prediction model Risk Of Bias ASsessment Tool) tool for prediction model studies, Cochrane Risk-of-Bias tool for randomised trials for randomised trials and Risk Of Bias In Non-randomised Studies of Interventions for non-randomised studies. Data synthesis will involve a narrative review of included studies, summarising key findings, methodological approaches and implications for practice and research. The results will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

No ethical approval is required for this systematic review as it will use only published data. The findings will be disseminated through publication in a peer-reviewed journal, presentations at relevant conferences and engagement with clinicians, health system leaders, policymakers and researchers. This review will provide a timely and comprehensive overview of the applications of AI in virtual emergency care to inform evidence-based guidelines, policies and practices for leveraging these technologies to enhance access, quality and efficiency of emergency care delivery.

CRD42025648202.

Globally, more than 700 000 people commit suicide annually. In Sweden, the yearly incidence ranges between 1000 and 1500 people, which is higher than the global average. The aim of this study is to estimate the economic burden related to indirect costs that suicide has imposed on Swedish society between 2010 and 2019.

National population-based cross-sectional study.

All suicides in Sweden between 2010 and 2019, using data from the Swedish National Cause of Death Registry.

Indirect costs associated with suicides, estimated using the human capital approach, including productivity loss over 1-year and lifetime horizons.

Between 2010 and 2019, 1406 to 1591 suicides occurred annually in Sweden, resulting in approximately 26 500 productive life years lost each year. In 2019, the productivity loss due to suicides was estimated at 44 million over a 1-year horizon and 935 million over a lifetime horizon. The corresponding per-person costs were 37 000 and 778 000, respectively.

This study provides valuable insights into the economic burden of suicide on Swedish society. It underlines the potential economic benefits of effective suicide prevention, aligning with previous research highlighting the substantial returns—both monetary and in terms of human well-being—that successful prevention strategies can yield.

Severe mental disorders are associated with increased risk of metabolic dysfunction. Identifying those subgroups at higher risk may help to inform more effective early intervention. The objective of this study was to compare metabolic profiles across three proposed pathophysiological subtypes of common mood disorders (‘hyperarousal-anxious depression’, ‘circadian-bipolar spectrum’ and ‘neurodevelopmental-psychosis’).

751 young people (aged 16–25 years; mean age 19.67±2.69) were recruited from early intervention mental health services between 2004 and 2024 and assigned to two mood disorder subgroups (hyperarousal-anxious depression (n=656) and circadian-bipolar spectrum (n=95)). We conducted cross-sectional assessments and between-group comparisons of metabolic and immune risk factors. Immune-metabolic markers included body mass index (BMI), fasting glucose (FG), fasting insulin, Homeostasis Model Assessment-Insulin Resistance (HOMA2-IR), C reactive protein and blood lipids.

Individuals in the circadian-bipolar spectrum subgroup had significantly elevated FG (F=5.75, p=0.04), HOMA2-IR (F=4.86, p=0.03) and triglycerides (F=4.98, p=0.03) as compared with those in the hyperarousal-anxious depression subgroup. As the larger hyperarousal-anxious depression subgroup is the most generic type, and weight gain is also a characteristic of the circadian-bipolar subgroup, we then differentiated those with the hyperarousal-anxious subtype on the basis of low versus high BMI (2 vs ≥25 kg/m², respectively). The ‘circadian-bipolar’ group had higher FG, FI and HOMA2-IR than those in the hyperarousal-anxious-depression group with low BMI.

Circadian disturbance may be driving increased rates of metabolic dysfunction among youth with emerging mood disorders, while increased BMI also remains a key determinant. Implications for assessment and early interventions are discussed.

Systemic therapies for advanced gastric cancer (GC), including chemotherapy, targeted therapy and immunotherapy, have evolved significantly in the past few years. The combination of immune checkpoint inhibitors (ICIs) and chemotherapy has become the standard first-line (1L) treatment for advanced gastric or gastro-oesophageal junction (G/GEJ) cancer, although there remains a need for improvement in efficacy. Fruquintinib, an oral and highly selective vascular endothelial growth factor receptor inhibitor, has shown a synergistic antitumour effect when paired with ICI or chemotherapy. Moreover, it has demonstrated a tolerable safety profile and high potential for synergy with chemotherapy or immunotherapy, suggesting that a combination of fruquintinib, sintilimab and oxaliplatin+capecitabine (CAPEOX) can be a promising treatment for locally advanced G/GEJ cancer. This phase 1b/2 study aims to investigate the safety and efficacy of the combination of fruquintinib, sintilimab and CAPEOX regimen as a 1L combination therapy for unresectable advanced or metastatic G/GEJ cancer.

The FUNCTION trial (NCT06329973) is a single-arm, prospective, multicentre, phase Ib/II clinical trial that will consist of a dose escalation phase and an expansion phase. The study is planned to be conducted at 16 public hospitals. A total of 70 participants will be enrolled, comprising nine in the dose escalation phase and 61 in the expansion phase. The dosing regimen during the dose escalation phase will include three different doses of fruquintinib (3 mg, 4 mg and 5 mg, per oral, once per day days 1–14) + sintilimab, 200 mg, intravenous, day 1 +oxaliplatin 130 mg/m², day 1, intravenous, + capecitabine 800 mg/m², per oral, twice daily, days 1–14, every 21 days. The recommended phase 2 dose (RP2D) and maximum tolerated dose will be determined in the escalation phase, and the RP2D will be used in the expansion phase. The primary endpoints will be the maximum tolerated dose and objective response rate; the secondary endpoints will include OS, progression-free survival, disease control rate, duration of response, surgical conversion rate and adverse events and identification of molecular biomarkers for efficacy. The results from this study will provide evidence for expanding the clinical applications of fruquintinib plus sintilimab and CAPEOX as a 1L combination therapy in metastatic or non-resectable, locally advanced G/GEJ cancer and lay the foundation for future large-scale clinical investigations.

This study will be conducted in full compliance with the ICH (The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, ICH) GCP (Good Clinical Practice, GCP) guidelines, the rules of the Declaration of Helsinki and ICH E2A (Clinical Safety Data Management: Definitions and Standards for Expedited Reporting) Guidelines . The study protocol has received approval from the Henan Cancer Hospital ethical committee (Approval No. 2023-237-002). Written informed consent will be obtained from all patients prior to enrolment. For patients who have the mental capacity for informed consent, their consent for participation will be sought and will not be overridden by their family members. For patients who have impaired cognition, informed consent will be sought from their legally acceptable representative. On completion of the analyses, the study findings will be disseminated locally and internationally through manuscript publications in peer-reviewed journals and conference presentations.

NCT06329973.