Integrated digital diagnostics can support complex surgeries in many anatomic sites, and brain tumour surgery represents one of the most complex cases. Neurosurgeons face several challenges during brain tumour surgeries, such as differentiating critical tissue from brain tumour margins. To overcome these challenges, the STRATUM project will develop a 3D decision support tool for brain surgery guidance and diagnostics based on multimodal data processing, including hyperspectral imaging, integrated as a point-of-care computing tool in neurosurgical workflows. This paper reports the protocol for the development and technical validation of the STRATUM tool.

This international multicentre, prospective, open, observational cohort study, STRATUM-OS (study: 28 months, pre-recruitment: 2 months, recruitment: 20 months, follow-up: 6 months), with no control group, will collect data from 320 patients undergoing standard neurosurgical procedures to: (1) develop and technically validate the STRATUM tool and (2) collect the outcome measures for comparing the standard procedure versus the standard procedure plus the use of the STRATUM tool during surgery in a subsequent historically controlled non-randomised clinical trial.

The protocol was approved by the participant ethics committees. Results will be disseminated in scientific conferences and peer-reviewed journals.

NCT07036783.

Dyspnoea is an existentially burdensome symptom in patients with advanced and progressive diseases such as cancer, chronic obstructive pulmonary disease (COPD) and advanced heart failure. Recent studies have highlighted that symptomatic treatment of dyspnoea is often ineffective and may depend on the underlying disease. Immersive virtual reality (IVR) has emerged as a ‘digital therapeutic’ for conditions such as pain, anxiety, and dyspnoea. Brain functional MRI (fMRI) offers the opportunity to identify distinct patterns of dyspnoea. Current findings are mainly limited to healthy volunteers, but clinical data from patients with life-limiting conditions are needed. The aim of this study is to assess the feasibility of identifying dyspnoea patterns in different life-limiting conditions using fMRI and IVR.

This is an observational monocentric feasibility study, conducted in a tertiary university centre. Healthy volunteers and patients diagnosed with advanced cancer, COPD, or heart failure and suffering from persistent dyspnoea will undergo an fMRI of the brain using IVR. The primary outcome of feasibility will be evaluated using descriptive statistics. Secondary outcomes include analysis of fMRI patterns of dyspnoea across populations, patient-reported burden of participation, and correlation between dyspnoea and psychological symptoms. These preliminary data will help determine the sample size required for a future study evaluating differences in dyspnoea patterns. Exploratory comparison between the characteristics of all four groups will be assessed with Fisher’s test (for proportions) and either independent Student’s t-test or Mann-Whitney test, depending on distribution. Correlations between variables will be tested using the Pearson’s correlation coefficient. Statistical analysis will be performed using STATA.

This study protocol received ethical approval on 23 April 2025 from the Commission cantonale d’éthique de la recherche in the Canton of Geneva, Switzerland. The identification number is 2024-02289. Submission to peer-reviewed journals and presentation in international congresses for the dissemination of the study findings are planned.

Clinical Trials number is NCT07319039; Pre-results.

To assess health service use between days 43 and 365 postdelivery, comparing individuals with and without severe maternal morbidity (SMM).

Population-based cohort study.

Linked datasets from Population Data BC in British Columbia, Canada, April 2013–March 2021.

Postpartum individuals aged >18 years with a hospital or home delivery, with/without SMM occurring from 20 weeks’ gestation through 42 days post partum. Ectopic pregnancies, missing identifiers and maternal deaths at delivery or within 42 days post partum were excluded.

The primary outcome was high health service use, defined as being in the 95th percentile for use of one or more of the following non-obstetric visits: emergency department, hospitalisations and outpatient visits to a primary care physician or specialist—each occurring between 43 and 365 days after delivery hospitalisation discharge. Secondary outcomes included being in the 95th percentile for each visit type. Log binomial regression assessed the rate and risk of high health service use in SMM compared with non-SMM pregnancies, adjusting for confounders.

The cohort included 261 287 deliveries (5575 (2.1%) with SMM). Those with >15 visits within 43–365 days postdelivery were classified as having high health service use. SMM-affected individuals were twice as likely to have high health service use (9.2% vs 4.3%; adjusted relative risk (aRR)=1.96, 95% CI 1.78 to 2.17). Individuals with non-hypertensive cardiovascular SMM had markedly higher health service use (21.4% vs 4.3%; aRR=5.18, 95% CI 3.28 to 8.16). There was heterogeneity in the association between SMM and high health service use among those without versus with previous comorbidities, without versus with high service use in the 2 years prior to delivery, and without vs with preterm birth.

Our study revealed high health service use after SMM. These findings can help guide the development of standardised postpartum care pathways.

Childhood and adolescence are critical developmental periods marked by increasing physical inactivity, stress and mental health problems. TABATA training, a supramaximal form of high-intensity interval training, has been increasingly promoted as a time-efficient approach to improving health. However, evidence on its specific effects in children and adolescents remains limited, fragmented and not systematically synthesised. The objective of this review is to determine whether TABATA training improves physical fitness and mental health outcomes in children and adolescents aged 6–18 years.

We will perform a systematic review of experimental studies in the following databases: PubMed, Scopus, Cochrane Library and Web of Science. The initial literature search was conducted in May 2025, and the systematic review is expected to be completed by March 2026. Eligible studies will include multisession Tabata interventions defined as repeated 20 s high-intensity bouts with 10 s rest intervals, typically performed for 7–8 cycles per set, with or without multiple sets. Outcomes will include physical fitness indicators and mental health indicators. Study selection and data extraction will follow the Population, Intervention, Comparison, Outcomes, Study design framework and Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. The risk of bias will be assessed using the Cochrane Risk of Bias 2 tool for randomised trials and Risk Of Bias In Non-randomised Studies - of Interventions for non-randomised studies. When sufficient data are available, quantitative synthesis will be conducted using a three-level random-effects meta-analytic model to account for dependency among effect sizes and anticipated clinical and methodological heterogeneity across studies. Effect sizes for continuous outcomes will be calculated as standardised mean differences. Sensitivity analyses will be performed, and publication bias will be assessed using funnel plots when an adequate number of studies is available. Statistical analyses will be performed using R and Review Manager (RevMan) V.5.4, where appropriate.

The results of the systematic review will be disseminated via publication in a peer-reviewed journal and presented at a relevant conference. As we will not use individual patient data, ethical approval is not required.

CRD42025632986.

This study assessed the feasibility of implementing a phase 3 field-based clinical trial protocol to evaluate paediatric praziquantel (PED-PZQ) for the treatment of Schistosoma mansoni infection in children aged 3 months to 6 years in endemic areas of Brazil, focusing on operational aspects such as recruitment logistics, documentation management, investigational product handling and protocol adherence.

Pilot and feasibility study for a phase 3 clinical trial, comprising two components: a randomised, open-label, parallel-group, two-arm trial and a single-arm trial.

Conde, Bahia, Brazil, from December 2024 to January 2025.

Two trials aim to screen 5774 participants from three rural areas in Bahia and three in Sergipe, states in northeastern Brazil, and enrol 403 children eligible for either randomisation or allocation. Trial 1 will randomise (1:1 ratio) 240 children aged 4–6 years into the PED-PZQ treatment arm or the standard praziquantel (PZQ) 1. Trial 2 will enrol 163 children aged 3 months to 3 years, all receiving PED-PZQ. Both trials are open label. Eligible participants shall meet age criteria, test positive for S. mansoni and fulfil other inclusion criteria. In the first recruiting centre, Conde (Bahia), it was estimated that 650 participants would need to be screened for trial 1 and 552 for trial 2, assuming schistosomiasis prevalence of 5% and 4%, respectively. This pilot study reports on the first 60 participants enrolled.

The primary outcome of this pilot study is the feasibility of implementing the research protocol in a real-world field setting, focusing on key aspects such as study documentation challenges, participant safety, investigational medicinal product custody chain and protocol adherence. In addition to providing preliminary data on the parasitological cure rate, secondary outcomes include the prevalence of S. mansoni infection and the reduction in S. mansoni egg count (Kato-Katz method). Furthermore, the occurrence and severity of drug-related adverse events are monitored from drug administration to day 21 post-treatment, alongside changes in renal, hepatic and cardiac functions assessed through biochemical markers.

A total of 60 participants were recruited, and 55 provided stool samples for screening. The pilot phase demonstrated the feasibility of implementing the clinical protocol under field conditions, with successful completion of all planned procedures and minimal protocol deviations. Operational challenges were identified mainly in documentation processes, participant recruitment and investigational product management and were addressed through preventive and corrective quality assurance actions. The experience also highlighted logistical and infrastructural barriers typical of field-based trials in remote endemic areas, which informed adjustments for the subsequent phase 3 study. Preliminary parasitological results indicated an overall S. mansoni prevalence of 9.1% (5/55), with 21% in trial 1 and 2.8% in trial 2. All infected participants met the eligibility criteria, received treatment and completed follow-up. Four achieved a parasitological cure, and one case of treatment failure was observed (trial 1, PZQ group). Two mild adverse events (diarrhoea) were reported, with no serious complications or clinically significant changes in biochemical parameters.

This pilot study demonstrated the feasibility of implementing a field-based phase 3 clinical trial protocol for PED-PZQ in endemic areas of Brazil. The findings confirm that the protocol can be successfully applied in primary care settings, despite operational challenges related to recruitment, logistics and documentation. The study also provided preliminary evidence supporting the safety and effectiveness of the paediatric formulation and highlighted the need to revise prevalence assumptions to improve future screening strategies. Overall, the experience offers valuable insights to guide the large-scale phase 3 trial and supports the incorporation of PED-PZQ into national schistosomiasis control policies.

Brazilian Clinical Trials Registry; RBR-86kcy37.

Statins are a cornerstone of cardiovascular disease prevention yet remain underused among eligible patients. Clinical decision support systems embedded in electronic health records (EHRs) are commonly used to encourage guideline-concordant prescribing. Interruptive reminders (eg, pop-ups) may be effective but interfere with clinical workflows and contribute to alert fatigue. Non-interruptive alerts are less intrusive, but their effectiveness remains unclear. The Interruptive versus Non-Interruptive Reminders for Statin tHerApy in Primary Care (INIRSHA-PC) trial is designed to evaluate the comparative effectiveness of interruptive and non-interruptive reminders on statin-prescribing rates.

INIRSHA-PC is a single-centre, pragmatic, three-arm, parallel-group randomised controlled trial embedded in the EHR at Vanderbilt University Medical Center. The trial will enrol adults aged 18–74 seen in primary care who are eligible for, but not currently prescribed, statin therapy. The planned sample size is 3000 patients (1000 per arm). Enrolled patients will be randomised 1:1:1 to (1) interruptive reminder, (2) non-interruptive reminder or (3) no reminder (usual care). The primary outcome is statin prescription within 24 hours of enrolment. Secondary outcomes are statin prescribing within 12 months and low-density lipoprotein cholesterol levels measured between 30 days and 12 months after enrolment. Enrolment began on 14 August 2024. The study is expected to be completed on 19 November 2025.

The trial has been approved by the Vanderbilt University Medical Center Institutional Review Board with waiver of patient informed consent (IRB number: 240419). Results will be disseminated through peer-reviewed publication and presentation at scientific conferences.

NCT06456658.

Psychosocial safety climate (PSC) is increasingly recognised as an important organisational resource for promoting mental health at work and preventing psychosocial risks, which are aspects of work design, organisation and management that could threaten employees' psychological or physical well-being. While substantial theoretical and empirical evidence supports the role of PSC as a protective factor, limited research has explored how PSC can be deliberately and sustainably enhanced through organisational interventions. This scoping review aims to map PSC-related interventions, synthesise how PSC is conceptualised and operationalised, and identify elements that studies have reported as contributing to strengthening PSC.

This scoping review will follow established methodological frameworks and Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines to systematically identify and synthesise studies describing organisational interventions related to PSC. A comprehensive search strategy will be implemented across several databases, including MEDLINE, PsycINFO, Web of Science, ABI/INFORM and Business Source Premier. Eligible studies must describe, implement or evaluate interventions explicitly targeting PSC. Data on intervention types, mechanisms, outcomes and contextual factors will be extracted and narratively synthesised to address the descriptive research questions and map how PSC interventions have been conceptualised and implemented across organisational contexts. This protocol does not involve human participants. The review is not yet registered. Findings will inform future research and organisational practices related to PSC-focused interventions.

This review involves analysis of published literature only and does not require ethics approval. Findings will be submitted to a peer-reviewed journal and presented at relevant academic and professional conferences. Results will be reported in accordance with the PRISMA-ScR guidelines and will inform the development of future organisational interventions aimed at enhancing PSC.

Salivary gland carcinomas (SGC) are rare tumours. The term SGC is not more than an umbrella for a variety of histogenetically, morphologically and biologically distinct entities. Accordingly, SGCs have not been sufficiently investigated to date. Their rarity makes it difficult to reach high patient numbers for individual entities in clinical studies, leading to pooling patients with different histological subtypes to attain sufficient participants. The different histological subtypes of SGC differ significantly in their clinicopathological features, such as their grading, their occurrence and their outcome. SGCs are usually stratified into low-grade, intermediate-grade or high-grade tumours. In most kinds of SGC, specific targetable molecular markers are lacking. The inclusion of immunotherapy (IT), however, might improve the outcome of patients suffering from high-grade SGCs. In order to integrate IT as a therapeutic option for SGC and to facilitate therapeutic decisions based on tumour (immune) biology, predictive and prognostic immunological biomarkers are indispensable.

In this prospective study, 500 patients will be enrolled, who are distributed in three arms. The observational cohort includes patients with malignant salivary gland tumours, whereas patients with benign tumours of a salivary gland are grouped in the control group 1. In the control cohort, 2 patients do not have a salivary gland tumour but have a planned functional surgery of the nose or ear or a maxillofacial surgery. The local immune status from the tumour tissue and the microbiome will be sampled before treatment. In addition, the systemic immune status from peripheral blood will be analysed before and after surgery and after the adjuvant and definitive chemoradiotherapy, if applicable. Clinical baseline characteristics and outcome parameters will additionally be collected. Data mining and modelling approaches will finally be applied to identify interactions of local and systemic immune parameters and to define predictive and prognostic immune signatures based on the evaluated immune markers.

Approval from the institutional review board of the Friedrich-Alexander-Universität Erlangen-Nürnberg was granted in September 2023 (application number 23-292-B). The results will be disseminated to the scientific audience and the general public via presentations at conferences and publication in peer-reviewed journals.

NCT06047236.

Perioperative randomised controlled trials (RCTs) in liver transplantation are relatively infrequent. RCTs performed in this complex patient population need to be robustly conducted to maximise patient benefit and graft utility given the scarcity of donor organs. Recruitment challenges can compromise RCTs and studies in this population face unique challenges due to recipient illness severity, their comorbidities, demographics and the geographical constraints of specialist transplant centres. Emergency presentation and after-hours admission may further limit patients’ capacity or readiness to consider trial participation. This Study Within a Trial (SWAT) specifically explored motivators and barriers to recruitment in patients awaiting liver transplantation.

An observational mixed-methods ‘Study within a Trial’, nested within a feasibility RCT.

This study was dual centred at two Tertiary National Health Service Hospitals; The Royal Free Hospital, a liver transplant centre in North London and University Hospital Birmingham, a liver transplant centre in Birmingham.

Adults who were eligible for liver transplantation and recruitment into the associated RCT were eligible for inclusion into the SWAT.

Completion of an 18-question validated written questionnaire which explored motivation for accepting or declining participation in the RCT.

Through completion of the questionnaire, participants shared their perspectives on the RCT and their rationale for consenting or declining participation. Responses were analysed, providing feedback to the Trial Management Group (TMG) to refine recruitment strategies for future trials. An additional component, comprising interviews and audio recordings of recruitment consultations, was planned if the RCT recruitment rates fell below prespecified thresholds or concerns were raised by the RCT TMG, neither of which occurred.

84 completed questionnaires were received. Motivators included patients believing that the trial will benefit others, interest in helping with research, perception that benefits outweigh risks and belief that it offered the best treatment. Barriers included concerns about randomisation, feeling overburdened and a perception of lack of support from family or friends.

This is the first study exploring recruitment to a perioperative RCT involving patients undergoing liver transplantation. Key motivators were altruism and perceived safety, while barriers included concerns about randomisation and lack of family support. Future focus during recruitment should be on neutral patient-centred consultations, adequate information sharing, fostering of patient trust, improved explanation of randomisation and engagement of the patient’s support network.

NCT04941911 (Health Research Authority) and SWAT 152 (the Study With A Trial Database).

This scoping review aims to map evidence or literature on improvement strategies used by health leaders and professionals to strengthen the safety climate in the operating room.

A scoping review was performed on the basis of the method proposed by the Joanna Briggs Institute and applied to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews (PRISMA-ScR) extension.

16 academic and grey literature data sources were searched using search terms on 17 January 2025, namely, Medical Literature Analysis and Retrieval System Online via Pubmed, Latin American and Caribbean Literature on Health Sciences via the Virtual Health Library, Cumulative Index to Nursing and Allied Health Literature, Scopus, Web of Science, Embase, PsycINFO, Cochrane Library, WorldCat, Digital Library of Theses and Dissertations, Brazilian Association of Surgical Center Nurses, Center for Material and Sterilization and Anesthetic Recovery, Association of Portuguese Operating Room Nurses, Association of PeriOperative Registered Nurses, Institute for Healthcare Improvement, WHO and Agency for Healthcare Research and Quality.

Study selection, data extraction and synthesis were based on the following eligibility criteria based on the acronym PCC (participants, concept, context): participants (health leaders and professionals), concept (strategies to improve the safety climate) and context (operating room). This scoping review considered studies published from 2009 onwards.

Information on the objective, method and findings addressing improvement strategies employed to strengthen the safety climate in the surgical centre was retrieved. The findings are presented in tables and in a qualitative thematic summary.

A total of 26 studies were analysed, published between 2009 and 2024, with the USA as the country of origin of the publications with the highest number (11 studies). As for the methodological approach, intervention and quasi-experimental studies stand out. When the studies in this review were mapped, strategies that strengthened the safety climate in the operating room were identified and grouped into two main axes that are interrelated: communication tools and training programmes.

It is evident that the implementation of tools that promote communication and training programmes enhances safe surgical care, as they contribute substantially to the domains of the safety culture. The use of communication protocols in the operating room is recommended as a perioperative safety tool.

This scoping review adhered to a protocol previously published in this journal and that is registered on the Open Science Framework website (https://osf.io/zg8nu/).

To assess diagnostic concordance and reclassification following an India-led, multinational virtual multidisciplinary discussion (V-MDD) platform for interstitial lung disease (ILD).

Prospective, multicentre service-evaluation study.

Twenty-four Indian referral centres connected through a secure virtual platform, with international faculty participation from the UK, Greece and Sri Lanka.

A total of 127 anonymised ILD cases discussed across 29 V-MDD sessions (February 2024–February 2025). Each panel included ≥4 pulmonologists, two pulmonary pathologists, one of three rotating thoracic radiologists and one of two rheumatologists, along with international experts.

The cohort (mean age 52.6±16.1 years; 53.5% female (68/127)) most frequently presented with dyspnoea (82.6%) and cough (73.2%). Pre-V-MDD diagnoses included hypersensitivity pneumonitis (HP) and sarcoidosis as distinct disease entities, and usual interstitial pneumonia (UIP) and non-specific interstitial pneumonia (NSIP) as radiological patterns, along with connective tissue disease (CTD)-ILD and other ILDs. Concordance between pre- and post-V-MDD CT diagnoses was substantial (=0.658; 95% CI 0.562 to 0.754; p

The India-led, multinational V-MDD model demonstrated substantial diagnostic concordance and refined nearly one-quarter of ILD diagnoses. This virtual, scalable framework expands access to subspecialty expertise and offers a practical blueprint for standardising ILD care in resource-limited and cross-border settings.

Venous thromboembolism (VTE) is a common complication of traumatic brain injury (TBI) and is associated with increased morbidity and mortality. Low molecular weight heparin (LMWH) is recommended for prophylaxis against VTE after trauma but may increase the risk of progression of intracranial bleeding. Limited evidence exists to guide clinicians regarding the optimal timing of VTE prophylaxis in patients with acute TBI. This randomised controlled trial (RCT) will directly compare the safety and effectiveness of early versus delayed initiation of LMWH in patients with moderate to severe TBI.

The study design is a Bayesian adaptive RCT comparing early (within three calendar days of injury) versus delayed (after study Day 7) VTE prophylaxis with the LMWH, dalteparin. All patients receive sequential compression devices until study Day 8. The co-primary effectiveness outcome is the development of clinically important VTE at study Day 8. The co-primary safety outcome is the development of clinically important intracranial bleeding at study Day 8. Secondary outcomes are mortality and functional outcomes (Glasgow Outcome Scale Extended and EQ-5D) measured at study Days 30 and 180; clinically diagnosed VTE to Day 30 and progression of intracranial bleeding to Day 8.

This study has been approved through Clinical Trials Ontario’s streamlined ethics review process (board of record, Sunnybrook Health Sciences Centre) and all participating centres. It is conducted in accordance with the Declaration of Helsinki, Good Clinical Practice guidelines and Health Canada regulatory requirements. We anticipate that the trial will achieve wide dissemination through publication in a peer-reviewed medical journal and presentation at international conferences targeting the fields of critical care, trauma and neurosurgery. The results of this trial will help guide clinicians aiming to balance the risks and benefits of early anticoagulant prophylaxis after TBI and will inform guideline development.

NCT03559114.

This project aimed to assess the applicability of the National Institute for Health and Care Research (NIHR) tool to French academic studies and identify the carbon hotspots, with a view to discussing ways of mitigating their environmental impact.

Retrospective analysis.

A completed single-centre phase I haematology trial TOCILAM (NCT04547062) and a completed multicentre phase III in intensive care REMICRUSH (NCT03960801).

TOCILAM had a total number of 12 participants and REMICRUSH had a total number of 1150 participants.

Total carbon emissions from each trial and the hotspots of those emissions.

The carbon footprint of the TOCILAM and REMICRUSH studies was estimated at 3.2 and 5.8 tonnes of CO₂ equivalent, respectively. For these two studies, the hotspots were the Meetings and travel item followed by the clinical trial unit emissions.

The NIHR tool is easily applicable to the context of French academic clinical studies. The total estimated carbon footprint of the two clinical trials was generally lower than what has been reported in the literature for academic studies. However, areas for improvement have been identified.

Kerato-lenticule extraction (KLEx) is a refractive surgery technique that, in contrast with femtosecond laser-assisted in situ keratomileusis (FS-LASIK), does not require the creation of a flap to correct refractive defects. The potential advantages of this technique are related to the absence of a flap and its complications. On the other hand, FS-LASIK is the most widely practised refractive surgery worldwide, as it offers excellent visual outcomes and is currently the gold standard of refractive surgery. The objective of this study is to compare the effectiveness and safety of KLEx versus FS-LASIK as a treatment option in patients with myopia or myopic astigmatism.

This double-masked, parallel-group, single-centre randomised clinical trial will enrol 80 eyes from adults with myopia or compound myopic astigmatism within the ranges sphere –0.50 to –12.00 D and cylinder –0.50 to –6.00 D, recruited at the Instituto de Oftalmología Conde de Valenciana, Mexico City, Mexico. Participants will be allocated to KLEx or FS-LASIK and assessed at baseline and 1 day, 1 week, 1, 3, 6 and 12 months postoperatively. The primary outcome is uncorrected visual acuity at all postoperative visits. Secondary outcomes include postoperative spherical equivalent, best-corrected visual acuity (BCVA), loss of ≥2 BCVA lines, the proportion of eyes within ±0.50 D of the refractive target, corneal aberrations over a 5 mm pupil, epithelial changes and adverse events. Participants and outcome assessors will be masked to the assigned surgical technique.

Participant confidentiality will be maintained with the publication of results. This study was approved by the research and ethics committee of the Instituto de Oftalmología Fundación de Asistencia Privada Conde Valenciana (CI-017-2024). The study results will be disseminated in scientific articles published in peer-reviewed journals and presented through research posters at national and international conferences.

ClinicalTrials.gov registry (NCT06477081).

Interstitial lung diseases (ILD) associated with an underlying connective tissue disease (CTD), also known as a systemic autoimmune rheumatic disease or SARD, are chronic conditions with a tendency to progress. CTD-ILDs are increasingly diagnosed and pose an important global health challenge. This systematic review aims to provide an overarching evaluation of their epidemiology and disease burden in Asia. In this review, the term CTD-ILD will be used to denote all major forms of ILD arising in the context of a SARD.

This systematic review will adhere to the standards of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, including a flow diagram to depict the process by four independent reviewers that will assess titles and abstracts against the following predetermined criteria. A systematic review of the literature search published from 2000 to 2024 will be conducted using five electronic databases including PubMed/MEDLINE, Scopus, EMBASE, Cochrane Library and Web of Science. Publications that meet the inclusion criteria of this review will be subjected to a full-text review to extract relevant data. Collated data will be analysed and organised into categories based on the expected outcome and objectives. The quality of published evidence, including heterogeneity across studies, will be checked against PRISMA checklists and assessed by Newcastle-Ottawa Scale.

Ethics approval is not applicable for this study since no original data will be collected. The findings of this review will be disseminated through a peer-reviewed publication in a scientific journal and conference communications, with the aim of contributing insights to the field by identifying research gaps and informing clinical practice.

The protocol of this systematic review is registered with the National Medical & Research Register (ID-24–03600-GUB) and International Prospective Register of Systematic Reviews PROSPERO (CRD420251037095).

Delays in cancer diagnosis for patients with non-specific symptoms (NSSs) lead to poorer outcomes. Rapid Diagnostic Clinics (RDCs) expedite care, but most NSS patients do not have cancer, highlighting the need for better risk stratification. This study aimed to develop biomarker-based clinical prediction scores to differentiate high-risk and low-risk NSS patients, enabling more targeted diagnostics.

Retrospective and prospective cohort study.

Secondary care RDC in London.

Adult patients attending an RDC between December 2016 and September 2023 were included. External validation used data from another RDC.

The primary outcome was a cancer diagnosis. Biomarker-based risk scores were developed using Latent Class Analysis (LCA) and Least Absolute Shrinkage and Selection Operator (LASSO). Model performance was assessed using logistic regression, receiver operating characteristic curves (AUROC) and decision curve analysis.

Among 5821 RDC patients, LCA identified high white cell count, low haemoglobin, low albumin, high serum lambda light chain, high neutrophil-to-lymphocyte ratio, high serum kappa light chain (SKLC), high erythrocyte sedimentation rate (ESR), high C-reactive protein (CRP) and high neutrophils as cancer risk markers. LASSO selected high platelets, ESR, CRP, SKLC, alkaline phosphatase and lactate dehydrogenase. Each one-point increase in score predicted higher odds of cancer (LCA: AOR 1.19, 95% CI 1.16 to 1.23; LASSO: AOR 1.29, 95% CI 1.25 to 1.34). Scores ≥2 predicted significantly higher cancer odds (LCA: AOR 3.79, 95% CI 2.91 to 4.95; LASSO: AOR 3.44, 95% CI 2.66 to 4.44). Discrimination was good (AUROC: LCA 0.74; LASSO 0.73). External validation in 573 patients confirmed predicted increases in cancer risk per one-point LASSO score rise (AOR 1.28, 95% CI 1.15 to 1.42), with a borderline increase for LCA (AOR 1.16, 95% CI 1.06 to 1.27).

Biomarker-based scores effectively identified NSS patients at higher cancer risk. LCA captured a broader biomarker range, offering higher sensitivity, while LASSO achieved higher specificity with fewer markers. These scores may also help detect severe benign conditions, improving RDC triage. Further validation is needed before broader clinical implementation.

Cardiovascular diseases (CVDs) are the leading cause of death worldwide, making the development of self-management strategies crucial for preventing complications and improving clinical outcomes. This process involves symptom monitoring, treatment adherence, emotional management and a healthy lifestyle, among others. Reliable instruments are necessary to measure self-management, requiring robust psychometric properties. In this way, this COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN)-based systematic review aims to assess the quality of specific self-management instruments for adults with CVDs.

This systematic review will follow the COSMIN and be reported according to the Preferred Reporting Items for Systematic Review and Meta-analysis Protocol. Searches will be conducted in seven databases: MEDLINE, Web of Science, Scopus, PsycINFO, EMBASE and CINAHL. Additionally, a manual search will be performed on PROQOLID, PROMIS and The Medical Outcome Trust websites. Studies on the development and validation of patient-reported instruments measuring specific self-management for individuals with CVDs will be included, without language or date restrictions. The search will be performed in November 2025, with the final version of the review expected to be completed in October 2026. Data extraction will follow COSMIN recommendations. The Modified Grading of Recommendations, Assessment, Development and Evaluation approach will be used to determine the quality of evidence. Instruments will be categorised according to COSMIN recommendations. All steps will be conducted by two independent reviewers, with a third reviewer involved in case of discrepancies. Additionally, the content of the instruments will be analysed and linked to the International Classification of Functioning, Disability and Health, following international recommendations.

This study does not require ethics committee approval as it is a review of published data. The review results will be disseminated through peer-reviewed journal publications and presentations at scientific conferences.

CRD42024605969.

Telerehabilitation (TR) programmes are increasingly recognised for their feasibility and potential benefits, such as eliminating travel time, reducing costs and providing a more comfortable rehabilitation experience at home. However, the comparative efficacy of remote physiotherapy compared with traditional in-person sessions for individuals with Parkinson’s disease (PD) remains uncertain. This study aims to evaluate the effects of TR compared with in-person physiotherapy in individuals with PD, focusing on both motor and non-motor outcomes.

This is a randomised, single-blind clinical trial with a mixed-methods approach. A total of 22 individuals diagnosed with PD will be randomly assigned to one of two groups. The experimental group will receive TR, consisting of remote physiotherapy sessions conducted once a week for 1 hour over a 4-month period. The control group will receive the same interventions in person. Interventions will include global muscle strengthening exercises, balance training, gait and motor coordination exercises, and cognitive training. The primary outcome will be motor function, measured using part III of the Movement Disorder Society–Unified Parkinson’s Disease Rating Scale. Secondary outcomes will include cognition (Montreal Cognitive Assessment), gait (Functional Gait Assessment), mobility (Timed Up and Go Test) and quality of life (Parkinson’s Disease Questionnaire). Data will be analysed using repeated measures analysis of variance to compare outcomes between groups across four assessment points (baseline, midpoint, postintervention and 2 months follow-up). Additionally, a qualitative phase will explore participants’ perceptions and experiences regarding TR and in-person interventions, with assessments carried out 2 months after the completion of the 24-week interventions, through semistructured interviews that will be analysed using Bardin’s Content Analysis technique.

This protocol was approved by the Research Ethics Committee of the Federal University of Rio Grande do Norte (approval number: 5.553.701). All participants will provide written informed consent before inclusion. Results will be disseminated through peer-reviewed publications, scientific conferences and communication with participants and healthcare professionals.

RBR-6h5knrj.

First Nations communities in Canada are disproportionately impacted by prenatal opioid exposure (POE) and neonatal abstinence syndrome (NAS). In response, we developed a research partnership with 13 First Nations communities in Ontario. Phase I of the research project, initiated in 2018, included the development of mixed-methods reports on the impact of POE for each community. This protocol outlines the evaluation of phase II, during which nine communities individually co-designed and implemented community-specific knowledge mobilisation (KMb) plans informed by findings from phase I. The evaluation aims to assess advisory working group engagement, KMb implementation and perceived community-level impacts.

This mixed-methods evaluation integrates survey and qualitative data to assess First Nations-led KMb products and activities. The Public and Patient Engagement Evaluation Tool, a validated survey instrument, will be administered to advisory group members and analysed descriptively. Focus groups and interviews will be conducted to explore advisory working group members’ experiences and analysed using phenomenological methods. Qualitative findings will be mapped to the Engage with Impact framework to assess outcomes across engagement domains.

Ethics approval has been granted by Vancouver Island University. All community contacts and advisory working group members will provide informed consent prior to data collection. Phase II activities are governed by formal community agreements. In alignment with First Nations Principles of OCAP (Ownership, Control, Access and Possession), First Nations community partners retain ownership of their KMb products and are actively involved in the design, implementation and dissemination of the project evaluation. Results will be shared through peer-reviewed publications, community reports and knowledge-sharing events.

Monitoring physical rehabilitation is an essential component of patient recovery after knee arthroplasty. Monitoring can be remote, or clinic based. In India, unsupervised home-based physical rehabilitation is a common practice, but there is a lack of evidence to demonstrate the effectiveness of remote monitoring. Therefore, we developed and piloted a mobile application (TeleREhabilitation after knee ArThroplasty app) based on behaviour design thinking to support the recovery period. This trial aims to compare the effectiveness, acceptability, cost and safety of this app-supported home-based intervention against usual care using an open label, 1:1 individual randomised superiority trial at two tertiary care hospitals in India.

Consecutive adults undergoing partial or total, unilateral or bilateral knee arthroplasty who can use a smart phone will be invited to participate in this trial. Consenting individuals will be randomised to either an app-supported intervention or a usual home-based rehabilitation which typically consists of provision of oral or written instructions at discharge and follow-up check-up with the surgeon or physiotherapist at their discretion or as per individual need. We aim to recruit 300 individuals over a period of eighteen months. The primary objective is to compare patient-reported knee function between the two groups at 3 and 6 months postsurgery. Secondary objectives are to compare patient-reported outcomes (pain and activity), performance-based outcomes (lower limb strength and knee function), resource utilisation and quality of life. Fidelity of implementation, end-user experiences and challenges in implementing this intervention will be measured using both quantitative and qualitative methods. Quantitative data will be analysed in Stata, and group comparisons will be done using mixed effect linear regression. A mixed-methods approach will be used to analyse and interpret the process evaluation data. A modified intention-to-treat approach will be taken, which includes all those who were randomised irrespective of their adherence to trial protocol if they had at least one follow-up visit after enrolment.

The protocol has been approved by the ethics committees of the sponsor institute (The George Institute for Global Health) and the two clinical sites (All India Institute for Medical Sciences, Delhi & Indraprastha Apollo Hospitals, Delhi). The results will be disseminated via peer-reviewed publications, conference presentations and via plain language newsletters to the trial participants.

CTRI/2024/06/068838.