Sepsis, a life-threatening organ dysfunction caused by a dysregulated host response to infection, may benefit from immunomodulatory drugs. Nevertheless, numerous clinical trials of these drugs have failed to demonstrate efficacy, partly due to substantial heterogeneous treatment responses. Subgroup analyses from these trials are frequently employed to investigate different treatment effects across subgroups. However, which drugs might have different effects across subgroups and how credible these findings are have not been well summarised and evaluated. Additionally, the differences in the characteristics and results of subgroup analyses based on whether the primary trial’s main effect is statistically significant remain unclear. We will conduct a systematic review to comprehensively address these questions.

We will include randomised controlled trials (RCTs) evaluating immunomodulatory drugs for adult sepsis and exclude quasi-randomised trials, single-arm studies, animal research, conference abstracts, study protocols and non-English publications. To comprehensively search for subgroup analyses, we will search both RCTs and their published secondary analyses across PubMed, Embase, Web of Science, ClinicalTrials.gov and the Cochrane Library from their inception. Four reviewers will independently screen eligible studies and only one subgroup analysis will be selected for data extraction using standardised forms. The credibility of subgroup effects will be assessed using the Instrument for assessing the Credibility of Effect Modification Analyses. We will analyse the proportion and characteristics of subgroup analyses reported in trials. We will qualitatively summarise the results of subgroup analyses, focusing on findings with a subgroup-specific p value2 test or Fisher’s exact test, as appropriate.

No ethical approval is required because the data we will use do not include individual patient data. Findings will be disseminated through publication in a peer-reviewed journal.

CRD420251089737.

Gender, sex and ethnicity-sensitive approaches to psychosocial interventions for behavioural and psychological symptoms of dementia have been under-represented in the literature. Although the initial findings have revealed relevant differences with regard to sex, gender and ethnicity-sensitive approaches to those interventions. The GenderDem study aims to identify the top-10 research priorities in this context for future dementia care research.

The methodological approach in GenderDem is based on the James Lind Alliance Guidebook and the concept of priority setting partnerships. In this participatory research approach, people living with dementia, their caregivers (and/or their loved ones) and healthcare professionals will be actively involved in the study. As members of a steering group, they act as coresearchers in the GenderDem study. We aim to recruit a diverse group of people for the steering group by considering different factors, eg, gender identity, sex, ethnicity and age. Future research priorities will be identified through two rounds of online surveys to collect and rank research topics from additional participants (eg, people with dementia, caregivers and/or loved ones and healthcare professionals). Additionally, a literature review and a workshop will be carried out in parallel to consider the current state of the research and to finalise the top-10 research priorities.

An ethics application for conducting the two surveys and the workshop for this study has been approved by the German Society of Nursing Science (No. 25-029). Study participants will be informed in detail about the voluntary nature of their participation. Together with the coresearchers from the steering group, we will develop a dissemination plan that considers the different media consumption forms of the various groups. Additionally, we will disseminate our project results on an ongoing basis.

Type 1 diabetes is a chronic autoimmune disease, preceded by the presence of islet autoantibodies, a preclinical state defined as islet autoimmunity. Several environmental exposures have been associated with the initiation of islet autoimmunity but the triggers remain largely unknown. Rapid growth and weight gain during childhood are some of the exposures that have been proposed to promote islet autoimmunity. A high intake of protein and animal milks in early childhood is consistently associated with increased later obesity. Growth during early childhood is directly related to dietary intake and especially protein intake and this association has been linked to increased risk of islet autoimmunity and type 1 diabetes. The Intensive Dietary and Activity Counselling (IDAC) study aims to determine whether a healthy lifestyle counselling from age 3 months to age 2 years improves β-cell health in children with increased risk for islet autoimmunity.

The IDAC study is a randomised trial (1:1 allocation) with two parallel groups, aiming to enrol 1244 children at increased genetic risk of type 1 diabetes before the age of 4 months. Participants will be randomised to either the control or intervention group based on the child’s current breastfeeding status (currently breastfeeding or no longer breastfeeding). The intervention group will receive regular dietary and physical activity counselling. The primary outcome is β-cell health at 36 months, assessed by fasting and stimulated proinsulin-to-C-peptide ratio. Secondary outcomes include accelerated growth during infancy, overweight at 36 months, and time to development of persistent confirmed islet autoantibodies or type 1 diabetes. Growth measures, blood samples for serological markers, stool samples, dietary intake (nutrients and food group data) and questionnaire data will be collected regularly throughout the study period. Regression models will be used to estimate the effects of the intervention on the primary outcome.

The research protocol was approved by the Swedish Ethical Review Authority (dnr 2024-05217-01, 2024-08622-02, 2025-01759-02). Study findings will be presented at national and international conferences, submitted for publication in peer-reviewed journals, shared on social media and disseminated through patient-education materials.

NCT06670625.

This study investigated the knowledge and attitudes (KA) towards perioperative pulmonary embolism (PE) in patients undergoing major orthopaedic surgery, a population at particular risk.

A single-centre, cross-sectional study.

A tertiary care hospital in Shanghai, China.

454 patients scheduled for major orthopaedic surgery (Grade III or above) were enrolled between February and September 2024. Selection criteria included adult patients undergoing eligible procedures, while exclusion criteria encompassed cognitive impairment or refusal to participate. All enrolled participants completed the study.

The primary outcomes were the total scores on validated knowledge and attitude questionnaires. Secondary outcomes included the identification of demographic factors associated with these scores and the analysis of the direct relationship between knowledge and attitude using structural equation modelling (SEM).

The average knowledge score was 52.9% (23.82/45), indicating poor understanding. The average attitude score was 66.4% (29.88/45), indicating a moderate attitude. The multivariable analysis showed that a college diploma (OR=4.824, 95% CI 2.399 to 9.703, p

Patients undergoing major orthopaedic surgery possess poor knowledge but moderately positive attitudes toward PE. Educational level is a key factor influencing KA. Improving patient knowledge and attitudes is crucial for supporting informed surgical decision-making and enhancing perioperative self-management, though the complex relationship between knowledge and attitude warrants further investigation.

Some cancers are diagnosed late, making them harder to treat. People with an undiagnosed cancer may use over-the-counter medications to manage non-specific cancer-related symptoms that often mimic other more common, easily treatable conditions. Results from the original Cancer Loyalty Card Study (CLOCS) suggest there may be an increase in purchases of pain and indigestion medication 8–9 months before an ovarian cancer diagnosis. We aim to validate the CLOCS findings by exploring whether a significant change in medication purchases could be an indication for early signs of the following cancer types: oesophageal, stomach (gastric), colorectal (bowel), pancreatic, liver, bladder, endometrial, uterine sarcoma, ovarian and vulval, using data collected through store loyalty cards.

Using a retrospective case-control design, we aim to recruit 1450 participants with one of the cancers of interest (cases) and 1450 participants without cancer (controls) in the UK who (or whose household members) hold a loyalty card with at least one participating high street retailer. We will use pre-existing loyalty card data to compare past purchase patterns of cases with those of controls. To assess cancer risk in participants and their purchasing patterns, we will collect information on demographic characteristics, health risk factors, lifestyle habits and behaviours, family history of cancer and any symptoms experienced prior to diagnosis (cases) and in the last year prior to study recruitment (controls). In addition, cases will be asked about their cancer diagnosis.

CLOCS-2 was reviewed and approved by the East Midlands-Leicester South Research Ethics Committee (23/EM/0224). Study outcomes will be disseminated through peer-reviewed publications, conferences, presentations to the research communities as well as patients and the public, the study website and other social media outlets.

NCT06447064, CPMS58679; pre-results.

Cardiovascular disease (CVD) is the leading cause of death worldwide and is associated with a broad range of physical, emotional and social burdens. Existing tools such as Systematic Coronary Risk Evaluation and WHO CVD risk charts identify clinical risk factors but fail to capture patient-perceived burden and the risk of burden awareness. The Assessment of Burden of Chronic Conditions (ABCC)-tool, a validated, person-centred instrument, offers a more holistic approach. The aim of the current study is to develop and validate a new module within the ABCC-tool for patients with an elevated cardiovascular (CV) risk or CVD (cardiovascular risk management (CVRM) module).

A mixed-methods design was used across four phases and expert meetings to identify the items for the module. All phases took place in the Netherlands. Phase 1 (literature search) was performed in 2021, phase 2 (semistructured interviews) was completed between January and October 2021, phase 3 (survey) was completed in November 2023 and December 2024, and phase 4 (semistructured interviews) was completed in January 2025.

Phase 2 involved 14 experts by experience (patients with CVD or people at elevated risk) and 10 healthcare professionals in the field of CVD. Phase 3 included 86 healthcare professionals. Phase 4 included 12 experts by experience. In total, four expert meetings took place, attended by three experts by experience, nine healthcare professionals and seven researchers.

The module was refined iteratively, using qualitative and quantitative insights at each phase of development. The model was only finalised after thorough content validation.

No suitable patient-reported outcome measures (PROMs) focusing specifically on CVRM were identified in the literature. Interviews revealed significant burdens in terms of physical, emotional and social burdens. Feedback from expert meetings and validation rounds led to substantive refinement. The final module contains 10 items and was deemed valid by both experts by experience and healthcare professionals.

The CVRM module of the ABCC-tool has been systematically developed and validated in terms of content. The final module focuses on the multidimensional burden of CVD and dealing with its risk factors and aims to support self-management. The module complements existing risk assessment tools by focusing on the burden experienced by the patient and the burden resulting from risk awareness.

This trial investigates the efficacy of neoadjuvant therapy using rezvilutamide combined with androgen deprivation therapy (ADT), with or without docetaxel, in treating oligometastatic hormone-sensitive prostate cancer (omHSPC).

This prospective, open-label, multicentre trial aims to enrol 100 patients newly diagnosed with omHSPC (defined as ≤5 bone or lymph node metastases confirmed by conventional imaging, without visceral metastasis) who must express a desire to undergo surgery. All patients undergo a prostate-specific membrane antigen positron emission tomography/CT (PSMA-PET/CT) scan at enrolment or within 4 weeks before enrolment to assess and confirm the number of metastases at baseline. Scans should be performed before initiating ADT to avoid compromising test sensitivity. Then patients will be allocated into groups in parallel according to their own preferences: one group will receive an LHRH agonist or antagonist for 24 weeks to maintain continuous ADT or have undergone bilateral orchiectomy. Treatment with rezvilutamide will be maintained daily. The other group will be scheduled to complete up to six cycles of docetaxel within 24 weeks, with maintenance of continuous ADT and rezvilutamide for 24 weeks. Both groups will receive a conventional imaging evaluation at the 12th week. After neoadjuvant therapy, patients will undergo conventional imaging and a second PSMA-PET/CT assessment, followed by cytoreductive radical prostatectomy within the subsequent 6 weeks. After surgery, patients may choose to continue with ADT or rezvilutamide at their own discretion, until disease progression. The primary endpoint is pathological complete response, defined as the absence of residual viable tumour cells in the tumour bed on pathological evaluation of the postoperative specimen. Secondary endpoints include 1 year biochemical progression-free survival, overall survival, radiographic progression-free survival, time to prostate-specific antigen progression, quality of life scores (total and subscale) assessed using the Functional Assessment of Cancer Therapy-Prostate questionnaire, time to symptomatic progression, time to deterioration in Eastern Cooperative Oncology Group performance status, the interval from enrolment to an increase in score from baseline, the proportion of patients with a ≥30% reduction in prostate volume on imaging before cytoreductive surgery compared with pre-neoadjuvant therapy, minimal residual disease and major pathological response. The study plans to enrol a total of 100 patients. Patient recruitment for this study is scheduled to begin in May 2025.

This has been approved by the Ethics Committee in Clinical Research of the First Affiliated Hospital of Wenzhou Medical University (number KY2024-231). Results will be published in peer-reviewed publications.

This study is expected to provide prospective evidence on the feasibility and potential clinical value of rezvilutamide combined with ADT, with or without docetaxel, as neoadjuvant treatment for newly diagnosed omHSPC.

Chinese Clinical Trial Registry (ChiCTR2400093262).

To explore how Chinese patients with precancerous ear, nose and throat (ENT) lesions experience using artificial intelligence (AI)-driven chatbots for health-related information seeking, with particular attention to perceived benefits, challenges and influences on information-seeking practices.

Descriptive qualitative study.

Department of Otolaryngology, West China Hospital, Sichuan University, China.

12 adult patients with clinically diagnosed precancerous ENT lesions who had used AI-driven chatbots at least three times in the previous 30 days to seek health-related information about their condition were purposively recruited. Face-to-face, semistructured interviews were conducted between 11 October 2024 and 10 November 2024.

Interviews were analysed using Colaizzi’s method. Four themes were identified. First, participants described AI chatbots as an immediate and accessible source of health information, particularly when questions arose outside clinical encounters or during periods of uncertainty. Second, many reported moving away from conventional search engines towards conversational information seeking, valuing direct and synthesised responses over link-based retrieval. Third, participants emphasised that obtaining useful answers depended on learning to ask clear and specific questions, suggesting that effective prompting was an important user skill. Fourth, some participants perceived chatbot interaction as emotionally safer than asking healthcare professionals certain questions, particularly when they felt embarrassed, worried about asking repetitive questions or feared being judged.

Among this sample of Chinese patients with precancerous ENT lesions, AI-driven chatbots were perceived as a convenient and conversational supplementary source of health information. Participants valued their accessibility and interactional ease, but also indicated that their usefulness depended partly on users’ ability to formulate effective prompts. Some participants additionally perceived chatbots as a more comfortable channel for asking sensitive or basic questions. The findings suggest that AI chatbots may have a complementary role in patient information support, but further research is needed to evaluate response accuracy, safety and appropriate integration into clinician-led care.

Deep brain stimulation (DBS) for dystonia is effective but programming optimisation can take months. Local field potentials (LFPs) recorded by the Medtronic Percept device may provide biomarkers to guide stimulation. This study will prospectively evaluate whether chronic LFP profiles correlate with clinical outcomes and can inform DBS programming strategies.

LFP-DYT is a single-centre, multi-phase observational study at Newcastle upon Tyne National Health Service (NHS) Foundation Trust. An internal pilot (Cohort 1) will refine recording workflows, followed by Cohort 2 (traditional programming with LFP recordings) and Cohort 3 (LFP-informed programming). 20–25 adults with primary dystonia undergoing globus pallidus internus DBS will be recruited. The study combines chronic LFP sensing with neurophysiology (electromyography, electroencephalography), motor inhibition testing (stop-signal reaction time), patient-reported outcomes and wearable sensor monitoring (STAT-ON) to provide a comprehensive multi-modal assessment framework. Primary outcome: reproducibility of alpha–theta frequency LFP peaks and concordance with optimal stimulation site. Secondary outcomes include stimulation and medication effects on LFP profiles, clinical improvement (Toronto Western Spasmodic Torticollis Rating Scale-2 (TWSTRS-2), Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS)) and beta-band activity as a marker of stimulation-related bradykinesia. Analyses will be descriptive and exploratory. Feasibility outcomes, including recruitment rates, retention and data completeness, will inform design and power calculations for future multi-centre trials.

The study has NHS Research Ethics Committee approval from the East Midlands—Derby Research Ethics Committee (REC reference: 24/EM/0246; IRAS ID: 337426). All participants will provide informed consent. Data will be pseudonymised and stored on secure NHS servers. Results will be disseminated via peer-reviewed publications, conferences and participant summaries. De-identified data and analysis code will be available on reasonable request.

NCT07309133.

Behavioural and psychological symptoms of dementia (BPSD) affect up to 80% of people with dementia and pose significant challenges in the context of care. Psychosocial interventions have been recommended as first-line strategies, but the roles of aspects of sex, gender and ethnicity in this context remain underexplored. This umbrella review, which will be conducted as part of the GenderDem project, aims to synthesise existing reviews on psychosocial interventions for BPSD and to investigate the potential sex-, gender- and ethnicity-sensitive differences among them.

Our GenderDem project follows the methodology of the James Lind Alliance for Priority Setting Partnerships. As part of this approach, this participatory umbrella review actively involves people living with dementia, their caregivers and/or loved ones and healthcare professionals in examining the existing review literature.

Different types of reviews on this topic will be identified by reference to the databases MEDLINE (via PubMed), CINAHL (via EBSCO) and PsycInfo (via Ovid) databases. Two reviewers will independently screen titles, abstracts and full texts using Rayyan. Data will be extracted in line with the Criteria for Reporting the Development and Evaluation of Complex Interventions in healthcare: revised reporting guidelines, supplemented with items pertaining to gender, sex and ethnicity. The results will be summarised descriptively, and relevant intervention types (including whether sex/gender/ethnicity has been taken into consideration), the characteristics of the study populations, outcomes and research gaps will be highlighted.

Ethical approval is not required, as this umbrella review will include only data from published studies. The findings of this review will be disseminated through a publication in a peer-reviewed journal and conference presentations.

To identify key factors influencing the implementation of technology-enabled virtual wards (VWs), also known as hospital at home, drawing on the qualitative accounts of stakeholders involved in implementation, using the updated Consolidated Framework for Implementation Research (CFIR) as a guiding analytical framework.

Qualitative semi-structured interviews with implementation leads. All interviews were conducted online, using MS Teams or Zoom, between January–June 2024, and audio-recorded with consent. Audio-recordings were transcribed, anonymised and exported to NVivo V.12 Pro software for data management. The updated CFIR was used to guide thematic analysis of interview data.

Adult VW services in one regional health and social care system in North West England, UK.

Service implementation leads from 11 hospital sites providing adult VW services. Job titles and roles varied across sites and included both operational and clinical service leads.

20 interviews were conducted with 22 participants. Four implementation themes were identified: (1) complexity and adaptability: the ability to adapt the service to local conditions was valued by leads, but also contributed to wide variation in operational, clinical, workforce and digital components of VW models; (2) resource and infrastructure: workforce capacity was identified as a key implementation challenge along with information technology system capability and interoperability; (3) performance demands: leads were concerned that an excessive focus on bed numbers and occupancy levels, without accounting for patient acuity, could negatively affect implementation, straining the service and staff capacity; and (4) readiness for change: organisational and professional readiness for change was considered crucial for increasing referrals and enabling successful implementation, yet leads reported that the level of behavioural and cultural change required had been underestimated.

Implementation of a national VWs programme has resulted in wide service variation in one UK region, which raises questions about service equity and poses challenges for wider programme evaluation. Despite this variation, common factors found to help or hinder implementation have been identified. This study provides greater understanding of the factors that influence the implementation of VW services and outlines actionable insights to help refine VW strategies. These insights can support future planning and sustainability of technology-enabled inpatient-level care at home more widely.

Persons with childhood-onset intellectual or complex disabilities have an elevated probability of encountering delayed or erroneous diagnoses during hospital treatment. It is imperative to consider the possibility that mistreatment may worsen their health. Persons with intellectual disabilities face numerous challenges in accessing and using healthcare. These challenges include structural and communication barriers, as well as a dearth of competencies among health professionals in interacting with persons with intellectual disabilities. Nevertheless, there is a paucity of studies that analyse the challenges faced by persons with intellectual disabilities in hospital and even fewer that involve persons with intellectual disabilities in the research process. Therefore, the objective of the study described in this protocol is to identify the salient research questions for improving hospital care of adults with childhood-onset intellectual disabilities by collecting and prioritising the different perspectives of patients, caregivers and clinicians.

The study design is based on the Priority Setting Partnership procedure of the James Lind Alliance, encompassing four steps to identify and prioritise issues with patients, caregivers and clinicians. Initially, problems and issues pertinent to those affected are collated using an open online questionnaire and subsequently clustered into topics. In the second step, the topics are transformed into potential research questions and reviewed by available scientific literature. Subsequently, research questions that cannot yet be answered by current literature are prioritised by participants in a second online questionnaire. Finally, the 25 questions rated most relevant are to be discussed in a one-day workshop with participants reflective of all target groups. The salient 10 research questions are to be determined using nominal group technique.

The study has received a positive ethics vote from the Ethics Committee at the Ludwig Maximilian University of Munich in accordance with the Declaration of Helsinki on 21 March 2025 (reference 25-0106). This study’s findings will be shared in academic conferences and published in scientific peer-reviewed journals.

DRKS00037347.

The effect of early antiplatelet therapy on 30-day mortality after coronary artery bypass grafting (CABG) remains uncertain. This study aimed to evaluate the association between early antiplatelet therapy initiation and clinical outcomes in post-CABG patients.

A retrospective target trial emulation.

Single academic medical centre in Boston, Massachusetts, USA.

We included adult patients who underwent CABG and were admitted to the intensive care unit at Beth Israel Deaconess Medical Center between 2008 and 2022.

Patients were classified into the treatment group if they initiated antiplatelet therapy within 24 hours postoperatively; otherwise, they were assigned to the control group. To address immortal-time bias for the primary outcome of 30-day mortality, we used clone-censor-weighting. For the exploratory outcome of 30-day acute kidney injury (AKI) incidence, we employed inverse probability of treatment weighting to balance baseline covariates.

The analysis for 30-day mortality included 6887 patients. The mortality was 2.35% in the control group versus 1.44% in the treatment group, yielding an absolute risk difference of 0.90% (control group minus treatment group, 95% CI 0.09% to 1.72%). The difference in restricted mean time lost was 0.19 days (control group minus treatment group, 95% CI 0.03 to 0.36). For AKI incidence, 5543 patients were analysed. The incidence was 78.61% in the control group and 69.13% in the treatment group, with an absolute difference of 9.48% (control group minus treatment group, 95% CI 6.40% to 12.50%; p

In this target trial emulation, early antiplatelet therapy initiated within 24 hours after CABG was associated with lower 30-day mortality and a reduced incidence of postoperative AKI. These findings warrant confirmation in prospective randomised controlled trials.

Concept analysis is widely used in nursing to clarify key concepts, support theory development and improve conceptual consistency in research and practice. Although concept analysis studies have increased substantially, concerns remain regarding methodological heterogeneity and incomplete reporting. Based on preliminary scoping of the literature, no dedicated scoping review has yet mapped the broad landscape of concept analysis studies in nursing while also examining reporting completeness. This protocol describes a scoping review that will characterise methodological trends, identify recurrent reporting omissions and generate an evidence map to support future methodological work in this field.

This scoping review will follow established scoping review guidance and will be reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. Guided by the Population-Concept-Context framework, we will search major English-language and Chinese-language databases for nursing-related concept analysis studies. All concept analysis approaches will be considered eligible, provided the study explicitly reports analysing a nursing-related phenomenon. Two reviewers will independently screen records, assess full texts and chart data using a standardised extraction form. In parallel, reporting completeness will be examined using an author-developed, evidence-informed audit checklist. Findings will be synthesised using descriptive statistics and qualitative thematic analysis.

Ethical approval is not required because this review will synthesise data from publicly available sources. Findings will be disseminated through peer-reviewed publication and conference presentation. The review is expected to provide a structured overview of current concept analysis practices in nursing and to identify priority areas for improving reporting transparency in future methodological work.

China has the highest global burden of new cancer diagnoses and cancer-related mortality, with approximately 60%–85% of patients with advanced malignancies experiencing moderate-to-severe pain. Although the WHO’s analgesic ladder is widely implemented, approximately 20% of cancer-related pain remains refractory. This persistent pain is often further complicated by opioid-induced side effects and the risk of opioid use disorders. Methadone, a potent opioid with distinct pharmacokinetic and pharmacodynamic properties, has shown potential in managing refractory cancer pain; however, there is a lack of standardised and evidence-based protocols for methadone conversion, particularly in patients requiring high-dose opioids.

This multicentre, open-label randomised controlled trial will enrol 164 Chinese patients with cancer and oral morphine equivalent daily dose requirements of ≥300 mg. Participants will be randomised to receive either the 3 day switch (3DS) strategy or the National Comprehensive Cancer Network (NCCN)-recommended methadone conversion method. The primary endpoints include time to stable analgesia, methadone conversion efficiency and overall pain relief rate. Secondary endpoints will evaluate pain intensity, frequency of breakthrough pain, corrected QT interval changes, incidence of adverse events and health-related quality of life. This trial is designed to generate high-quality clinical evidence to inform methadone conversion strategies for patients with refractory cancer pain who are dependent on high-dose opioids. By addressing existing gaps in clinical practice and pharmacoeconomic decision-making, the study aims to support the development of standardised methadone protocols.

This study was approved by the Medical Ethics Committee of Zhejiang Cancer Hospital (approval number: IRB-2024-314(IIT)) on 3 April 2024 and registered with the Chinese Clinical Trial Registry (ChiCTR2400085332) on 5 June 2024. The outcomes will be disseminated through national and international presentations and peer-reviewed publications.

ChiCTR2400085332.