Frontotemporal dementia (FTD) remains challenging to diagnose owing to the marked clinical heterogeneity associated with the disease. This heterogeneity stems from the complex interplay of various clinical phenotypes, genetic mutations and underlying neuropathologies, such as TDP-43 and tau proteinopathies. Currently, there is no single confirmed biomarker that can reliably diagnose disease, specifically disease stage, disease subtype and underlying neuropathology. Recent research has indicated that neuroimaging techniques hold the most promise for the discovery of FTD biomarkers. We propose a protocol for a systematic review and meta-analysis to identify MRI and fluorodeoxyglucose positron emission tomography (FDG-PET) biomarkers associated with clinical, genetic and pathological subtypes of FTD. We aim to address the following research questions: can regional MRI volumetry and FDG-PET hypometabolism differentiate (1) FTD patients from healthy controls; (2) sporadic cases of FTD from healthy controls; (3) genetic cases of FTD (MAPT, GRN, and C9orf72 mutations); and (4) underlying neuropathology, specifically discriminating between tau- and TDP-43-based FTD?

Literature searches will be performed across three databases: Ovid Medline, Ovid Embase and Web of Science. Publications that have fewer than five participants, are non-human-based, not written in the English language or contain unpublished data will be excluded. Two independent investigators will screen and subsequently evaluate which publications to include. Should any disagreements arise, a third investigator will settle the discrepancy. After the random-effects meta-analysis has been used to extract and pool the data, I² analysis will be used to quantify heterogeneity.

Ethics approval will not be required for this research. On completion, the systematic review and meta-analysis will be published in a peer-reviewed journal.

CRD42024545302.

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.

Polysubstance use (PSU), particularly opioid-involved and stimulant-involved PSU, is a growing issue in the USA. PSU increases the risk of negative health consequences, including infectious diseases, worsening physical and mental health conditions, and overdose-related deaths. These consequences occur in the context of varying health risk behaviours, substance-related preferences, and treatment engagements among people with PSU. To inform improvements in prevention, harm reduction, and substance use disorder (SUD) treatment, additional research is needed to comprehensively understand the current context and drivers of PSU preferences, motivations, and behaviours.

Herein, we describe the protocol for a prospective cohort study designed to capture detailed patterns, profiles, and trajectories of PSU, with the aim of comprehensively examining the drivers of PSU behaviours and SUD treatment utilisation. Adults (ages 18–75; n=400) who engage in PSU will be recruited from healthcare institutions, an established participant database maintained by an adjacent SUD research team, and online advertisements. Study assessments will capture dynamic patterns, choice preferences, and motivators of PSU via behavioural economic (BE) measures, detailed Timeline Follow-Back (TLFB) interviews, and self-administered surveys. The assessment timeline will include a baseline survey and TLFB interview, weekly TLFB interviews for 4 weeks post-baseline, and follow-up surveys and TLFB interviews at 4-, 8-, and 12-months post-baseline.

The study is funded through the National Institutes of Health Helping to End Addiction Long-term (HEAL) initiative and was approved by the University of Michigan Medical Institutional Review Board. Findings will be disseminated to academic, clinical, and community partners through the Michigan Innovations in Addiction Care through Research and Education programme. Results from this study will inform actionable and practical insights relevant to the delivery of personalised care in the context of PSU.

About 30% of depressed patients suffer from a protracted course in which the disorder continues to cause significant burden despite treatment efforts. While originally developed for relapse prevention, mindfulness-based cognitive therapy (MBCT) has increasingly been investigated in depressed patients with such ‘difficult-to-treat’ courses. This is a protocol for an individual participant data (IPD) meta-analysis aiming to determine efficacy and potential moderators of MBCT treatment effects in this group based on evidence from randomised controlled trials.

Systematic searches in PubMed, Web of Science, Scopus, PsycINFO, EMBASE and the Cochrane Controlled Trials Register for randomised controlled trials were completed on 17 June 2024. Authors of identified studies have contributed IPD, and data extractions have been completed. An update search will be conducted immediately before the start of data analyses. We will investigate the following outcomes: (a) self-reported and observer-reported severity of depression symptomatology, (b) remission and (c) clinically meaningful improvement and deterioration. One-stage and two-stage IPD-MA will be conducted with one-stage models using the observed IPD from all studies simultaneously as the primary approach. One-stage IPD models will include stratified study intercepts and error terms as well as random effects to capture between-study heterogeneity. Moderator analyses will test treatment-covariate interactions for both individual patient-level and study-level characteristics.

The results will inform understanding of the use of MBCT in patients with current ‘difficult-to-treat’ depression and will contribute to arguments in favour of or against implementing MBCT as a treatment for this group. They will be published in a peer-reviewed journal and made available to stakeholders in accessible formats. No local ethical review was necessary following consultation with the Ethics and Governance Board of the University of Surrey. Guidance on patient data storage and management will be adhered to throughout.

CRD42022332039.

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.

Recently, legal questions have increasingly arisen in intensive care medicine (ICM), especially when it comes to end-of-life decisions. Still, for Europe, there is not much evidence about doctors’ situational legal knowledge and legal education during medical studies and further qualification. The present study was initiated to analyse these hitherto unexplored aspects in Germany.

A quantitative online survey has been performed among German intensive care physicians. The voluntary participants of the anonymous online survey were asked to answer legal questions related to end-of-life policies, informed consent, surrogate decision making or advance directives. We tested pure factual knowledge in five questions. The other five questions tested situational knowledge using case vignettes. Every question could be answered with ‘yes’, ‘no’ or ‘do not know’. Furthermore, the participants were asked to assess their subjective certainty on a Likert scale and to provide information about their professional experience (PE) and qualification.

All members of the two German professional societies for anaesthesiology who work in ICM were asked to take part in the survey.

952 completed questionnaires were analysed. 86% of the participants were specialists, and 56% held the additional qualification in ICM. 78% had more than 10 years of general clinical experience, and 62% had more than 5 years of experience in ICM.

On average, the participants answered the five facts–questions in 90.8% correctly. However, only 73.6% of the five case vignettes were answered correctly. Specialists, physicians with a lot of PE or physicians holding the additional qualification in ICM did not perform better than assistants or physicians with little PE.

German intensive care physicians have relevant gaps regarding situational legal knowledge, which are independent of their PE or qualification and persist. This may be due to difficulties in interpretation and implementation of law. Since these knowledge gaps can lead to liability and criminal prosecution, these gaps should be closed through awareness-raising and continuous education.

The global rise in the population aged over 65 has led to a corresponding increase in cognitive impairment diagnoses, with dementia as a predominant condition characterised by diverse aetiopathogenetic profiles. Behavioural and psychological symptoms of dementia (BPSD) encompass a range of psychiatric, behavioural and cognitive symptoms associated with cognitive impairment. BPSD significantly affects patients, caregivers and healthcare providers, often necessitating interventions like sedatives or physical restraints that may worsen patient outcomes. Emerging evidence underscores the need for innovative, non-pharmacological interventions to manage BPSD effectively.

The current study intends to investigate the feasibility and acceptability of customised, immersive virtual reality environments (iVRe) to reduce responsive behaviours among individuals with dementia. Building on prior findings demonstrating virtual reality (VR) potential in reducing anxiety and fostering positive emotional states, this pilot study assesses the feasibility, safety and user engagement of customised iVRe interventions.

A longitudinal, mixed-methods design will be employed, enrolling 20 elderly participants with varying levels of cognitive impairment from the APSP ‘Margherita Grazioli’ long-term care facility in Trento. Participants undergo three VR exposure sessions featuring tailored environments adjusted in real-time for visual and auditory preferences. Data collection integrates standardised self-report questionnaires, observational tools and clinical records. Measures include the Functional Assessment Staging Tool, Neuropsychiatric Inventory and Cohen-Mansfield Agitation Inventory, as well as tools assessing pain, anxiety and emotional states before, during and after VR sessions.

The study protocol has been approved by the Comitato Etico Territoriale della Provincia Autonoma di Trento per le Sperimentazioni Cliniche, Azienda Provinciale per i Servizi Sanitari—Trento, Italy (Rep. Int. 12090, 15 May 2025). All participants or their legal representatives will provide written informed consent prior to enrolment. Deidentified data will be securely stored on institutional servers at the Fondazione Bruno Kessler and the APSP ‘Margherita Grazioli’, curated in compliance with the General Data Protection Regulation, and retained for 3 years after study completion. Any data shared externally will be provided in fully anonymised form, and only for scientific purposes, subject to prior ethical and legal approval. Study findings will be disseminated through peer-reviewed publications, conference presentations and executive summaries shared with participating institutions and stakeholders.

NCT06693193.

Immunisation is one of the most valuable, impactful and cost-effective public health interventions which delivers positive health, social and economic benefits. Globally, 4 million deaths worldwide are prevented by childhood vaccination every year. In Ethiopia, despite huge progress being made, the routine immunisation coverage has never reached the targeted figures and planned goals. Pastoralist communities are often disproportionately under-vaccinated, and there is often a confluence of interrelated factors that drive this outcome. This study enables us to identify factors affecting immunisation service utilisation in the pastoralist communities of Ethiopia, which helps to design effective and context-specific interventions.

This study aims to explore the behavioural and social drivers (BeSDs) of routine immunisation among the communities with high numbers of zero-dose and under-immunised children in Afar, Somali and Gambella regions of Ethiopia.

A qualitative exploratory study was conducted in three selected regions of Ethiopia (Gambella, Somali and Afar) from 9 November 2023 to 30 December 2023. Purposive sampling was used. A total of 33 interviews were conducted in the three regions. Sample size was determined based on idea saturation. Data was collected using interview guides. The interview guide was developed after reviewing relevant literature, desk review and using the journey to health and immunisation framework. A separate interview guide was developed for the journey mapping exercise, in-depth interview, healthcare workers discussion guide, focus group discussion and observation. Data was analysed thematically.

Behavioural (lack of awareness, lack of reminder/forgetting, misperception about vaccines, negative previous experience, lost card and fear of post-vaccination adverse events).

Structural (language barrier, long distance from home to facility, high cost of transportation, long waiting time, limited training of healthcare professionals and incentives, inconvenient service hours, shortage of health professionals, disrespect by the healthcare provider), Socio-cultural (competing priorities, low community engagement, lack of decision-making autonomy, limited husband involvement, workload, rural residence and larger family size were the commonly mentioned barriers to routine immunisation uptake. On the other hand, structural (house to house visit by health extension workers, counselling about adverse events, presence of outreach service, affordability (free of charge)), behavioural and socio-cultural (knowledge of adverse event management, and respect from community) were enablers to routine immunisation service uptake in pastoralist communities.

The study found several individual and contextual factors affecting routine immunisation uptake in pastoralist communities. Context-specific and tailored interventions which address zero dose drivers should be designed so as to enhance vaccine uptake. The findings suggested the need to design context-specific interventions to address the aforementioned barriers to immunisation.

Haematological malignancies and their treatments are known for their significant adverse effects on health-related quality of life (QoL). During high-dose cytotoxic therapy in haematological intensive care units (HICU), adapted physical activity (APA) is recognised for its role in maintaining physical fitness and limiting fatigue. Psychological and emotional states are also impaired, with anxiety levels significantly increasing in this specific context. Limited information is available about this topic. However, APA has been shown to reduce anxiety in various populations, including oncological patients. Furthermore, adding new technology, such as exergaming or heart rate variability biofeedback (HRVB) relaxation tools, could be an effective way to regulate emotions during treatments while providing the health benefits of APA. APA, Exergaming and Relaxation by Biofeedback in Haematological Intensive Care Unit protocol is a randomised, controlled trial. Our study is designed to evaluate the effects of APA programmes during high-dose cytotoxic therapy in HICU on anxiety, fatigue level, functional capacities, immune system activity and global QoL. Additionally, we aim to analyse the added value of using specific devices, such as Exergaming and HRVB relaxation, on the aforementioned parameters. We expect a difference in effectiveness between the programmes concerning emotional regulation.

90 patients (18–75 years), with various forms of haematological malignancies admitted to HICU, with haematologist’s approval for APA, who have given their written informed consent, will be randomly allocated in a 1:1:1 ratio to three 3-week APA groups: APA only (APA), APA by exergaming (EXER), APA+Biofeedback relaxation (BIO) (30:30:30). APA sessions will consist of moderate aerobic training on cyclo-ergometer (classical stationary bicycle for APA, BIO and connected ergometer in EXER), three times per week. The HRVB training will consist of controlled breathing exercises with biofeedback of heart rate variability at the end of each APA session (BIO). The primary outcome is to evaluate the effect of three short APA programmes on state anxiety (Hospital Anxiety and Depression Scale and State and Trait Anxiety Inventory-YA (STAI-YA)). The secondary outcomes will assess the effects on fatigue (Multidimensional Fatigue Inventory–20), physical fitness (2-minute walk test; five-times sit to stand test), QoL (European Organisation for Research and Treatment of Cancer - Quality of Life Questionnary ; EORTC-QLQ-C30) and immune system functioning (blood samples). All of these assessments are evaluated initially (T0) and directly after intervention (T2).

Approval was obtained from the French South Mediterranean III ethical committee. Subjects are recruited after providing written consent after receiving the information provided by the investigator. According to French law and the French Data Protection Authority (Commission Nationale de l’Informatique et des Libertés ; CNIL), we are not authorised to publicly share individual participant data. The results of the Adapted Physical Activity, Exergaming and Relaxation by Biofeedback in Haematological Intensive Care Unit study will be disseminated through publication in peer-reviewed journals, presentations at scientific conferences and communication with stakeholders and participants.

French Sud Mediteranian III ethical committee and registered on ClinicalTrials.gov: NCT05475600.

To examine the impact of the extent of education and/or training on sex trafficking among healthcare, social and community service providers and the impact of education and/or training on their capacity to respond to sex trafficked persons.

Cross-sectional survey.

An anonymous, online survey assessing perceptions of, and capacity to respond to, sex trafficking was distributed between February and August 2023 via social media platforms and with professional healthcare, social service and community associations and organisations across Canada to share with their members.

553 healthcare, social and community service providers.

Seven 6-point Likert scale items were used, as part of a larger survey, to measure capacity to respond to sex trafficking. Specifically, respondents were asked to rate their awareness of red flags and capacity to identify, talk to, interview, enhance the safety of, provide appropriate resources or referrals for and collaborate with other professionals to support sex trafficked persons.

Although most respondents (86.8%) reported having received some education and/or training on sex trafficking, the vast majority (94.8%) believed that they would benefit from additional education and/or training. Compared with those with no previous sex trafficking education and/or training, those who received less than 5 hours of education and/or training (b=3.56, p

As the number of hours of education and/or training on sex trafficking increased, so did respondents’ capacity to respond to sex trafficked persons. These results highlight a need for more education and training to help build capacity among healthcare, social and community service providers in identifying sex trafficked persons and providing appropriate care. Appropriately trained service providers can better support sex trafficked persons’ complex needs and potentially mitigate adverse outcomes.

To determine the survival rate and prognostic factors associated with tuberculosis (TB) mortality in Medellín between 2018 and 2023.

Quantitative observational analytical study of a retrospective cohort.

Based on notifications made to the Public Health Surveillance System and managed by the Secretary of Health of Medellín—Colombia between 2018 and 2023.

A total of 11 202 individuals diagnosed with TB, aged between 1 and 103 years.

The Kaplan-Meier method was employed to determine survival and risk functions, as well as median survival. Crude HRs and adjusted HRs (aHRs) were estimated using Cox proportional hazards regression models.

A median overall survival of 1410 days (3.86 years) and an adjusted mortality rate of 40 cases per 100 000 population were estimated for the study period (6 years). Factors associated with TB mortality were age (>59 years) (aHR 5.53; 95% CI 3.17 to 9.65), renal disease (aHR 2.98; 95% CI 2.27 to 3.90), HIV infection (aHR 2.82; 95% CI 1.39 to 3.32) and cancer (aHR 2.56; 95% CI 1.95 to 3.34).

TB survival is influenced by age and comorbidities, indicating the need for targeted strategies to protect high-risk groups. Strengthening comprehensive TB control through timely diagnosis, integrated management of chronic conditions and patient-centred care is essential to reduce preventable deaths. Furthermore, improving case notification and follow-up through integrated information platforms will contribute to more effective public health interventions.

Coronary revascularisation practices have evolved over the last three decades. This study sought to examine the variations in percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) rates, alongside mortality from acute myocardial infarction (AMI) across a group of 16 high-income countries between 2006 and 2020.

Retrospective observational analysis using data from the Organisation for Economic Co-operation and Development (OECD) database between 2006 and 2020. Estimated annual percent change in revascularisation was analysed using Joinpoint regression model, and mortality rates were evaluated using the locally weighted scatterplot smoothing model.

Publicly available data on PCI and CABG procedure rates alongside AMI mortality rate from 2006 to 2020.

16 countries from the OECD database.

Not applicable.

Standardised PCI and CABG procedure rates and AMI age-standardised mortality rate (ASMR) from 2006 to 2020.

Over the 15 year period, 14.0 million PCI and 2.8 million CABG procedures were collectively recorded across 16 countries. PCI rates varied among nations, but from 2006 to 2020 increased in 11 of the 16 nations overall, led by Finland (+36.0%), Ireland (+34.5%) and France (+31.5%). Meanwhile, CABG rates declined in 14 out of the 16 countries, with Luxembourg (–71.3%), the UK (–62.6%) and Finland (–60.6%) experiencing the most substantial decreases. Throughout the study period, the PCI-to-CABG ratio increased, while AMI ASMR decreased consistently across all countries.

Despite evidence supporting CABG over PCI in specific scenarios, CABG rates have declined, and PCI rates have increased. Possible factors for this trend may include patient preference and advancement in interventional techniques. The varied use of PCI among these nations, alongside a sustained decline in AMI mortality rates, may be expected given the importance of optimal medical therapy in the management of ischaemic heart disease. The results further suggest the significance of factors beyond revascularisation in driving improved outcomes.