Each year, an estimated 1700 children should be diagnosed with cancer in western Kenya, with leukaemia making up nearly one-third of cases. However, far fewer are actually diagnosed, highlighting significant delays or errors in diagnosis. Flow cytometry, which the WHO considers essential for leukaemia diagnosis, remains underused across sub-Saharan Africa due to high costs, outdated equipment and a lack of trained personnel. In Kenya, decades-old cytometers have been adapted for leukaemia detection, but these systems are now outdated. Newer platforms, such as simplified single-tube multiparametric assays, provide a scalable and sustainable alternative. This study presents a protocol to evaluate the accuracy of diagnosis and the potential for implementing a streamlined flow cytometry assay using peripheral blood, supported by a regional educational initiative.

This prospective, mixed-methods implementation study has three aims: (1) to assess the concordance between the Beckman Coulter ClearLLab 10C gold standard 4-tube assay and the streamlined ClearLLab LS 1-tube assay using paired bone marrow and peripheral blood samples; (2) to evaluate the feasibility of peripheral facility referrals and transport logistics with couriered peripheral blood samples from referring sites across western Kenya; and (3) to measure training effectiveness and knowledge gain through a multimodal educational programme using the Project ECHO (Extension for Community Healthcare Outcomes) model. Up to 300 patients at Moi Teaching and Referral Hospital in Eldoret, Kenya, will be enrolled in Aim 1. A separate sample of 100 patients from peripheral facilities will be included in Aim 2. Surveys, knowledge assessments and structured interviews will be used to evaluate training impact under Aim 3. Diagnostic concordance, sensitivity, specificity and knowledge gain will be measured through appropriate quantitative and qualitative methods.

The protocol has received approval from institutional ethics committees at Moi University, MTRH and Indiana University. De-identified data will be analysed and shared through peer-reviewed publications, stakeholder presentations and educational platforms.

To investigate whether women who experienced pelvic girdle pain (PGP) during pregnancy were able to engage in meaningful activities at 4 months and 3 years post partum, and to identify factors associated with long-term functional outcomes.

Long-term follow-up of a randomised controlled trial comparing acupuncture and transcutaneous electrical nerve stimulation for pregnancy-related PGP.

Physiotherapy outpatient clinics in Sweden.

In total, 113 pregnant women with clinically verified PGP were randomised in the original trial; 86 participated in the initial study phase, 77 attended the 4-month follow-up and 57 completed the 3-year follow-up questionnaire.

The primary outcome was functioning, assessed using the Patient-Specific Functional Scale (PSFS). Secondary outcomes included self-reported PGP, overall functioning and the prognostic value of pelvic pain provocation tests at 4 months post partum for persistent PGP at 3 years.

3 years post partum, the mean PSFS score was 8.64, and 45.6% of the participants scored 10, indicating full return to baseline activities. In repeated linear regression analyses, estimated PSFS scores were approximately 3 points lower at baseline and post-treatment compared with the 3-year follow-up (both p

Most women with pregnancy-related PGP regained functioning by 4 months post partum, and this recovery was sustained at 3 years. The number of positive pelvic provocation tests at 4 months post partum predicted persistent pain at 3 years, suggesting potential prognostic value for identifying women at risk of long-term PGP and informing postpartum follow-up strategies.

In ‘FoU i Sverige’ (R&D in Sweden) No. 12726. https://www.researchweb.org/is/sverige/project/127261.

The aim of this study was to develop an educational video introducing an innovative panel survey approach to facilitate guideline panels in making inferences about patient values and preferences.

A user testing of the educational video through one-on-one interviews and iterative refinement of the video through brainstorming meetings.

Interviews and brainstorming meetings were conducted through Zoom.

The participants of the interviews include guideline panellists who had used the panel survey approach, and guideline panellists who had not used the approach but would or would not participate in a panel survey soon. The participants of the brainstorming meetings were a steering committee with expertise in guideline methodology and qualitative research.

The understandability and usefulness of the educational video.

We interviewed 18 guideline panellists from eight different guideline panels, all of whom carefully reviewed the video. Most participants found the video useful in explaining the panel survey approach and its role in incorporating patient values and preferences. Participants suggested improvements, including clarifying key concepts and using plain language instead of technical terminology to make the content more accessible. The major change the steering committee decided to make through brainstorming meetings was to add clarification, refine the wording and replace some text with animation.

User testing resulted in an improved educational video that is more useful and understandable for guideline panellists. Wider implementation of this resource has the potential to enhance the incorporation of patient values and preferences in guideline recommendations, supporting more patient-centred decision-making.

Diagnostic errors in primary care are common, particularly in the interpretation and follow-up of abnormal haemoglobin (Hgb) and estimated glomerular filtration rate (eGFR) results. These errors frequently result in missed or delayed diagnoses of serious conditions such as anaemia and chronic kidney disease. This protocol describes a stepped-wedge cluster randomised controlled trial designed to evaluate a novel, evidence-based, team-based intervention aimed at improving diagnostic safety and efficiency.

The study will be conducted across 12 University of Texas Physicians (UTPs) primary care clinics in Houston, Texas, USA. Adult patients (≥18 years) with newly identified abnormal Hgb or eGFR results will be eligible for inclusion. The intervention integrates automated tracking of abnormal laboratory results, nurse navigators to support patient follow-up and engagement, and clinical pathologists to provide diagnostic guidance to primary care providers. The primary outcome is diagnostic safety, defined as the proportion of patients who receive a correct diagnosis within 6 months. Secondary outcomes include diagnostic efficiency, appropriate test utilisation, cost-effectiveness, patient activation and implementation metrics such as acceptability, fidelity and sustainability. The study will also explore barriers and facilitators to successful implementation using mixed-methods evaluation.

This trial has been approved by the Institutional Review Board at The University of Texas Health Science Center at Houston. Study results will be disseminated through peer-reviewed publications and conference presentations, and findings will be reported to UTP leadership to inform potential system-wide implementation.

NCT05735314.

To explore differences in health-related benefit status over 3 years, focusing on patterns of sick leave, work assessment allowance and disability benefits, between people who underwent rehabilitation and a matched control group.

Prospective longitudinal multicentre cohort study using registry data over three consecutive years.

Secondary specialist rehabilitation services at 17 institutions across Norway.

Patients (n=2710), 42% with rheumatic and musculoskeletal diseases, aged 18–65 years referred for multidisciplinary rehabilitation at one of the participating institutions. They were propensity score matched with 37 760 controls from the national sick leave registry, based on sociodemographic factors and health-related benefit status.

Multidisciplinary rehabilitation programmes, commonly lasting 3 weeks (range: 1 week to 6 months), tailored to individual needs.

Days on health-related benefits (sick leave, work assessment allowance (WAA) and disability benefits) were quantified as lost workdays per month. Differences between groups were analysed using Generalised Estimating Equations across three consecutive years: the year before rehabilitation, the rehabilitation year and the year after rehabilitation.

The rehabilitation group had more days on health-related benefits per month than controls throughout the observation period. During the rehabilitation year, they had on average 1.7 more days on sick leave (95 % CI 1.3 to 1.9), 2.3 more WAA days (95% CI 1.9 to 2.7) and 0.2 more days on disability benefits (95% CI 0.1 to 0.3). In the year after rehabilitation, they had 0.6 fewer days on sick leave (95% CI –0.8 to –0.3), but 3.7 more days on WAA (95% CI 3.1 to 4.2) and 0.6 more days on disability benefits (95% CI 0.4 to 0.8). Patterns were similar for the subgroup with rheumatic and musculoskeletal diseases.

People undergoing rehabilitation had more days on health-related benefits and a greater increase in long-term benefits, even after matching, indicating a higher disease and support burden than controls. Tailoring interventions and health-related benefits is an essential aspect of rehabilitation for people with complex work participation needs. Future research should include longer observation periods to explore long-term outcomes of rehabilitation.

NCT03764982

Persons with serious mental illness (SMI) often have coexisting medical conditions and experience a significantly reduced life expectancy compared with the general population. Peer support is considered an effective care approach for this population, and with rapid technological advancements, digital peer support, such as the DigiPer mobile application, can be a feasible self-management tool for persons with SMI. The study aims to assess the feasibility of DigiPer for persons with SMI in the Norwegian community mental health service settings.

This feasibility study will incorporate both qualitative and quantitative methods. The study consists of three phases: (1) simulation-based training among peer support workers using qualitative individual interviews; (2) pre–post study of DigiPer among peer support workers and service users using quantitative questionnaires and (3) process evaluation for peer support workers and service users using qualitative individual interviews. Peer support workers (n=5) and service users with SMI (n=15) will be recruited to evaluate the feasibility of DigiPer.

Ethics approval was granted from the Regional Committee for Medical Research Ethics (reference no. 853041), along with an assessment of processing of personal data by the Norwegian Agency for Shared Services in Education and Research (reference no. 810990). Findings will be disseminated through peer-reviewed publications and presentations at relevant national and international scientific conferences.

We aimed to assess usage and explore factors influencing the suitability of British Medical Journal (BMJ) Rapid Recommendations—a set of international guidelines meeting standards of trustworthiness—for adaptation and implementation, further defined as implementability.

Qualitative descriptive study with a multimethod approach.

We used citation screening and a survey to identify groups that had used any of a sample of 14 BMJ Rapid Recommendations in adoption, adaptation, de novo guideline development or implementation.

12 participants from a range of country income levels were interviewed, using semistructured interviews.

Interviews were analysed using thematic analysis to identify themes related to implementability of the guidelines. We compared these findings with those from a critical appraisal conducted using three different appraisal tools.

BMJ Rapid Recommendations are used in high-income, middle-income and low-income countries. We identified 33 instances of use. Our thematic analysis of the interviews uncovered 14 challenges to implementability, categorised under perceived trustworthiness, comprehensibility and practical relevance. The critical appraisals gave the BMJ Rapid Recommendations high scores on validity, but low scores on implementability and measurability. The challenges found in the interviews were generally corroborated by the appraisals, but the comparison also exposed tensions such as the complex interaction between methodological rigour and perceived credibility, the balance between novelty and compatibility with current practice, and the difficulty of offering globally applicable yet locally practical guidance.

Implementability challenges may limit effective use of international guidelines globally. Recognising and reflecting on tensions between rigour, credibility and contextual feasibility may help improve their uptake and value. The next phase of this research will explore strategies to enhance guideline implementability during their development.

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.

Spinal cord injury (SCI) results in debilitating sensory, functional deficits and paralysis requiring neurorehabilitation solutions. In this regard, focal muscle vibration (FMV) is an emerging neuro-rehabilitation tool that uses mechanical vibration on muscles/tendons to stimulate underlying nerves and consequently modulate neural pathways. We conducted a systematic review to understand the exact effectiveness of FMVs on the sensorimotor function and mobility/strength in the SCI population.

Systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) approach.

PEDro, Springer, PubMed, Science Direct, Cochrane Library and Google Scholar were searched through 15 February 2025.

We included studies adhering to the following population–intervention–comparison–outcomes (PICO) elements. Population: SCI, intervention: FMV, comparison: unexposed controls, outcome: either of sensorimotor function or mobility and strength.

Two independent reviewers used standardised methods to search, screen and code included studies. Risk of bias was assessed using the Risk Of Bias In Non-randomised Studies - of Interventions (ROBINS-I) scale. Findings were summarised and a narrative synthesis is provided.

25 studies were included. 9 studies used FMV in the upper limb and 14 in the lower limb. The analysis includes 427 patients with SCI, with a focus on male, chronic SCI cases and a prevalence of North American studies.

Our systematic review of 25 studies, with 21 (84%) reporting positive outcomes, suggests that FMV may improve sensory perception, motor function, mobility and strength in individuals with SCIs, with benefits observed in both limbs. However, substantial heterogeneity in FMV parameters, study designs, participant characteristics and the high prevalence of serious/critical risk of bias (13/25 studies, 52%) limit definitive conclusions. Further research with optimised protocols, larger sample sizes and longitudinal designs is needed to confirm efficacy and establish clinical guidelines.

To partner with healthcare professionals and other stakeholders to identify top 10 research priorities within universal child and adolescent health promotion and disease preventive services.

The study used an adapted James Lind Alliance (JLA) approach. This included a priority setting partnership within the field of municipal health promotion and preventive services for children and adolescents, the gathering of research needs as reported by a national sample of healthcare professionals and other stakeholders and the sorting, evidence checking and final prioritisation of two top 10 lists corresponding with the two municipal service areas: (1) pregnancy care and child health centres 0–5 years and (2) school health service and youth health centres. The research needs were collected using an online survey asking: ‘In your opinion, what should scientific communities in Norway conduct research on to enhance child and adolescent health promotion and preventive services?’. Suggested needs framed as topics were sorted and categorised in Microsoft Excel. The digital survey Nettskjema was applied for final prioritisation by voting.

Municipal child and adolescent health promotion and disease prevention services in Norway.

Altogether, 1141 healthcare professionals and other stakeholders (government administrators and university staff).

The participants submitted a total of 1780 research needs. Following the steps of the JLA priority setting process, the two final top 10 lists were generated. The lists include research priorities relating to, for example, health literacy, mental health promotion, counselling and teaching, follow-up of children and families in vulnerable positions and interdisciplinary collaboration.

Research priorities for child and adolescent health promotion and preventive services were identified through structured user involvement of healthcare professionals and other stakeholders using the JLA framework. The two lists address key knowledge gaps and reflect current societal and professional challenges. The findings can enhance research relevance, foster collaboration and guide research and research funding.

Neurogranin (Ng) has a role in synaptic plasticity and is considered a biomarker of synaptic dysfunction, a process hypothesised to be important in delirium. Few studies examining Ng in delirium exist, with mixed findings. This study aimed to investigate associations between cerebrospinal fluid (CSF) Ng concentrations and delirium in acutely admitted hip fracture patients.

Cross-sectional study.

Acutely admitted orthopaedic patients with hip fracture recruited from four participating hospitals in eastern Norway, representing secondary and tertiary care settings.

This study included 392 hip fracture patients. All admitted hip fracture patients operated in spinal anaesthesia were, regardless of age, considered for inclusion.

An in-house ELISA was used to measure CSF Ng concentration in patients acutely admitted with a hip fracture (n=392). Delirium status was evaluated daily according to The Diagnostic and Statistical Manual of Mental Disorders, Fifth Editions criteria independently by two experienced geriatricians. A value > 3.44 on The Informant Questionnaire on Cognitive Decline in the Elderly was used as a surrogate marker of probable dementia.

180 patients (46 %) developed delirium and 70% of these had dementia. CSF Ng concentration did not differ significantly between those with and without delirium (176 pg/mL vs 164 pg/mL), with an estimated difference in medians of 12 (95% CI –5.8 to 29.8), p=0.185. Analyses adjusted for age, gender and dementia status did not show a statistically significant difference in Ng concentrations between the patients.

We did not find an association between delirium and CSF concentrations of Ng. This could imply that synaptic dysfunction and degeneration, involving Ng, are not key processes in the development of delirium. Further studies on other synaptic proteins are warranted to better explore synaptic dysfunction’s potential role in the pathophysiology of delirium.

Due to the documented benefits of peripheral resistance training (RT) and inspiratory resistance training, known as inspiratory muscle training (IMT), in patients with cardiovascular disease, both exercise forms are regularly used in cardiac rehabilitation. However, little is known about the haemodynamic responses to different intensities of dynamic RT, isometric RT, and IMT in patients with coronary artery disease (CAD). This study is designed to evaluate and compare the acute haemodynamic responses elicited by different RT and IMT modalities in patients with CAD.

This study design is a prospective, single-centre, randomised crossover trial. A total of 20 participants with CAD will be included. All participants will undergo four different exercise training interventions: IMT, isometric wall squat training (IWS), dynamic leg press training (DLP) and isometric handgrip training (IHG). For each intervention, participants will perform two intensity modalities in randomised order: IMT (low vs high), IWS (low vs moderate), DLP (low vs high) and IHG (low vs moderate). The primary outcomes are the acute exercise-induced haemodynamic responses (esp. systolic blood pressure, pulse rate, stroke volume, cardiac output) across the different exercise training interventions, as well as the changes in haemodynamic responses during the recovery phase for each intervention. Secondary outcomes include changes in tissue oxygen saturation, oxygen saturation, and perceived dyspnoea and exertion. The study period is planned for 2025.

The study has been approved by the Ethics Committee of the German Sport University Cologne (Ethical Approval Code: 209/24). The findings will be disseminated through international peer-reviewed publications. This study is supported by the Alexander von Humboldt Foundation via the partnership with the Coordenacão de Aperfeicoamento de Pessoal de Nível Superior (CAPES)(CAPES-Humboldt Research Fellowship for Experienced Researchers) and by research funding from Edwards Lifesciences LLC (Limited Liability Company).

German Clinical Trials Register DRKS00035668.

Engaging patients in surgical safety is challenging and has not been thoroughly investigated. Although surgical checklists and other safety protocols have been introduced across various surgical fields, preventable adverse events still occur, highlighting the need for additional research. A Patient’s Safety Checklist (PASC) has been developed and validated for use by surgical patients. Its effect on patient safety and patient outcomes is currently being investigated in a Stepped Wedge Cluster Randomised Controlled Trial (NCT03105713). In connection with this trial, we have examined elective patients’ experiences with using the PASC.

An exploratory qualitative study was conducted based on individual in-depth telephone interviews with 31 elective surgical patients. The interviews were carried out across three Norwegian hospitals including seven surgical specialties. The patients interviewed were part of the trial’s intervention arm and had used PASC. The interviews were transcribed verbatim, and reflective thematic analysis was applied.

Three themes were identified in the data: patient awareness, patient actions and utility value. Patients perceived PASC to increase awareness around surgical information, preparations, what to speak up about and which information to seek and repeat. This awareness led to a series of actions, such as ensuring medication control, optimising their own health, contacting healthcare professionals, asking questions, and for some no actions were needed. Patients perceived PASC to have high utility value for their surgical preparation.

The PASC enhanced patients’ involvement in surgical care and safety by ensuring they received systematic, accurate, clear, and understandable information and instructions throughout the surgical pathway. It is one of the few existing interventions that specifically focuses on assisting patients in preparing for surgery and managing their recovery. Further research is needed on the implementation of PASC and its adaptation to other clinical settings.

NCT03105713.

To map, summarise and analyse the methodologies of corneal nerve fibre imaging in studies using in vivo confocal microscopy (IVCM) in diabetes and assess the potential for standardising methods and reporting.

A scoping review was conducted using five databases, MEDLINE, Embase, Cochrane, Web of Science and Scopus, with search terms related to IVCM, diabetes and corneal nerves. Two researchers independently screened the studies for eligibility. Relevant data were extracted and systematically analysed.

Out of 1533 screened articles, 195 met the inclusion criteria. Spanning from 2000 to 2024, the studies showed high variability in image acquisition, image processing, image analysis and reporting detail. Most studies used laser scanning confocal microscopy, examining the central cornea in both eyes in patients with type 2 diabetes, manually selecting 3–6 images from each eye, and using ACCMetrics and CCMetrics for quantifying corneal nerve fibre length in mm/mm². Many studies lacked sufficient methodological details for reproducibility.

IVCM studies of corneal nerve fibres in diabetes show substantial methodological heterogeneity and inconsistent reporting, limiting reproducibility. We propose a guideline to support standardisation and improve the reliability of future research.

Histopathological evaluation of prostate biopsies using the Gleason scoring system is critical for prostate cancer diagnosis and treatment selection. However, grading variability among pathologists can lead to inconsistent assessments, risking inappropriate treatment. Similar challenges complicate the assessment of other prognostic features like cribriform cancer morphology and perineural invasion. Many pathology departments are also facing an increasingly unsustainable workload due to rising prostate cancer incidence and a decreasing pathologist workforce coinciding with increasing requirements for more complex assessments and reporting. Digital pathology and artificial intelligence (AI) algorithms for analysing whole slide images show promise in improving the accuracy and efficiency of histopathological assessments. Studies have demonstrated AI’s capability to diagnose and grade prostate cancer comparably to expert pathologists. However, external validations on diverse data sets have been limited and often show reduced performance. Historically, there have been no well-established guidelines for AI study designs and validation methods. Diagnostic assessments of AI systems often lack preregistered protocols and rigorous external cohort sampling, essential for reliable evidence of their safety and accuracy.

This study protocol covers the retrospective validation of an AI system for prostate biopsy assessment. The primary objective of the study is to develop a high-performing and robust AI model for diagnosis and Gleason scoring of prostate cancer in core needle biopsies, and at scale evaluate whether it can generalise to fully external data from independent patients, pathology laboratories and digitalisation platforms. The secondary objectives cover AI performance in estimating cancer extent and detecting cribriform prostate cancer and perineural invasion. This protocol outlines the steps for data collection, predefined partitioning of data cohorts for AI model training and validation, model development and predetermined statistical analyses, ensuring systematic development and comprehensive validation of the system. The protocol adheres to Transparent Reporting of a multivariable prediction model of Individual Prognosis Or Diagnosis+AI (TRIPOD+AI), Protocol Items for External Cohort Evaluation of a Deep Learning System in Cancer Diagnostics (PIECES), Checklist for AI in Medical Imaging (CLAIM) and other relevant best practices.

Data collection and usage were approved by the respective ethical review boards of each participating clinical laboratory, and centralised anonymised data handling was approved by the Swedish Ethical Review Authority. The study will be conducted in agreement with the Helsinki Declaration. The findings will be disseminated in peer-reviewed publications (open access).