Strong primary healthcare enhances resource efficiency and resilience. Type 2 diabetes poses a growing global health challenge, with Argentina’s healthcare system struggling to detect and manage the disease effectively. Many patients bypass primary healthcare for secondary facilities, undermining continuity of care and increasing costs. Following a diagnostic process in collaboration with policymakers, we propose evaluating a redesigned primary care model consisting of codesigned evidence-based implementation strategies to improve type 2 diabetes management in Mendoza, Argentina.

This is an efficient, parallel-arm cluster randomised controlled Hybrid Type II trial with 12 clusters (administrative areas with 2–3 health facilities) allocated 1:1 to control (usual care) or intervention. In phase I, we will codesign, pilot and refine an implementation strategy package. In phase II, we will conduct the trial: 9-month baseline data collection, 15-month intervention and 6-month sustainability period. We will enrol a cohort of 396 patients with type 2 diabetes at primary healthcare centres and follow them for 12 months during the intervention and 6 months sustainment using routine clinical records and patient surveys. In phase III, we will conduct analysis, report and disseminate findings. The primary outcome will be a composite outcome including glycaemic control (glycated haemoglobin (HbA1c)

All study activities will comply with national and international ethics guidelines, presenting minimal risk to participants. The protocol was submitted and approved by the local independent ethics committee at the Mendoza Ministry of Health (Consejo Provincial de Evaluación ética en investigación en Salud-Provincial Health Research Ethics Review Board, Reference number: 149/2024). Facility-level permission will be obtained for participation and sharing of deidentified data. Written informed consent will be required from study participants, who will receive information on the study’s purpose, procedures, risks and benefits. Dissemination activities and outputs will include writing and submitting manuscripts for publication; writing policy briefs to support strategy implementation in other regions or countries; and tailoring outputs for patients, clinicians and researchers. We anticipate that improvements in disease management and patient experience will have clinical and economic benefits related to reduced usage of secondary-level and tertiary-level facilities, lower cost per visit and a reduced number of clinical events related to diabetes.

ISRCTN63277390.

A qualitative study was conducted in Catalonia (Spain), incorporating the views and opinions of relatives, healthcare professionals and patients on what they considered a ‘good death’. This study aimed to describe barriers, facilitators and unmet needs related to the achievement of a good death.

We recruited adult patients with advanced or chronic conditions, relatives and health and social care professionals involved in end-of-life processes of care, management or strategic planning. All participants took part in a qualitative study. The study was informed by phenomenological, hermeneutical and social constructivist perspectives and included 23 in-depth interviews and three focus group discussions with a total of 31 participants. Fieldwork was conducted between February and April 2022. Data were transcribed and analysed using qualitative thematic content and discourse analysis.

Six main themes were identified, comprising 17 subthemes. Facilitators and barriers related to achieving ‘a good death’ were categorised according to whether they occurred before death or during the dying process. Key facilitators include high-quality palliative care, open communication about death and the ability to choose the place of death. Key barriers included bureaucratic delays, inadequate resources, insufficient professional training and lack of respect for patients’ preferences and wishes.

Our study highlights the need to understand factors that facilitate or hinder the achievement of a good death and the quality of the dying process. Specifically, understanding individual preferences and unmet needs, enhancing communication, increasing awareness, reducing bureaucratic barriers and ensuring adequate resources are essential to support a more dignified end-of-life experience for patients, caregivers and healthcare professionals.

Cancer is the leading cause of death and morbidity among children and adolescents worldwide. Functionality-based interventions are relevant among children and adolescents with an oncological diagnosis, whence studies summarising evidence on this topic are needed. This systematic review will summarise evidence on the effect of interventions to improve functionality indicators among paediatric patients diagnosed with cancer.

This protocol will follow Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA)-Protocols reporting guidelines. The systematic review will be conducted according to the Cochrane Handbook and PRISMA 2020. Studies will be searched in MEDLINE (PubMed), Embase, Web of Science, CENTRAL, LILACS and PEDro. Additional searches will include Google Scholar, reference lists of included studies, relevant reviews and trial registries. Studies will be included if they implement a functionality-based intervention. They must evaluate effects among paediatric patients with an oncological diagnosis. Secondary outcomes will include health-related quality of life. There will be no limits to language or year of publication, and articles published in peer-reviewed journals will be accepted. Only randomised controlled trials will be included. Risk of bias will be assessed using the Cochrane Risk of Bias Tool 2. Two independent reviewers will select studies, extract data and assess risk of bias. A narrative synthesis and meta-analysis will be conducted if studies are clinically and methodologically homogeneous. Statistical heterogeneity will be assessed using Higgins’ inconsistency test (I^²). Meta-analysis may estimate combined effects using random-effects and the inverse variance method. The R statistical software will be used. The certainty of evidence will be evaluated for each outcome using the Grading of Recommendations Assessment, Development and Evaluation system.

This study used data from previously published studies, thus waiving submission to an Ethics Committee. Scientific dissemination strategies will include publication in peer-reviewed journals, conference presentations and workshops for the public.

CRD42024462833.

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.

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.

Encephalitis is brain parenchyma inflammation, frequently resulting in seizures which worsens outcomes. Early anti-seizure medication could improve outcomes but requires identifying patients at greatest risk of acute seizures. The SEIZURE (SEIZUre Risk in Encephalitis) score was developed in UK cohorts to stratify patients by acute seizure risk. A ‘basic score’ used Glasgow Coma Scale (GCS), fever and age; the ‘advanced score’ added aetiology. This study aimed to evaluate the score internationally to determine its global applicability.

Patients were retrospectively analysed regionally, and by country, in this international evaluation study. Univariate analysis was conducted between patients who did and did not have inpatient seizures, followed by multivariable logistic regression, hierarchical clustering and analysis of the area under the receiver operating curves (AUROC) with 95% CIs.

2032 patients across 13 countries were identified, among whom 1324 were included in SEIZURE score calculations and 970 were included in regression modelling. The involved countries comprised 19 organisations spanning all WHO regions.

The primary outcome was measuring inpatient seizure rates.

Autoantibody-associated encephalitis, low GCS and presenting with a seizure were frequently associated with inpatient seizures; fever showed no association. Globally, the score had limited discriminatory ability (basic AUROC 0.58 (95% CI 0.55 to 0.62), advanced AUROC 0.63 (95% CI 0.60 to 0.66)). The scoring system performed acceptably in western Europe, excluding Spain, with the best performance in Portugal (basic AUROC 0.82 (95% CI 0.69 to 0.94), advanced AUROC 0.83 (95% CI 0.72 to 0.95)).

The SEIZURE score performed best in several countries in Western Europe but performed poorly elsewhere, partly due to differing and unknown aetiologies. In most regions, the score did not reach a threshold to be clinically useful. The Western European results could aid in designing clinical trials assessing primary anti-seizure prophylaxis in encephalitis following further prospective trials. Beyond Western Europe, there is a need for tailored, localised scoring systems and future large-scale prospective studies with optimised aetiological testing to accurately identify high-risk patients.

Violence against women (VAW) is a public health, gender equality and human rights issue, with women with disabilities facing heightened risks due to intersecting discrimination. However, research on violence against people with disabilities often lacks sex-disaggregated data and primarily focuses on intimate partner violence, neglecting other perpetrators like family members or caregivers and leading to potential underestimation of its prevalence.

This protocol outlines the methods for a systematic review and meta-analysis to estimate the global prevalence of VAW with disabilities, focusing on intimate partner violence by intimate partners, domestic violence and sexual violence by any perpetrator. The review will adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and will include population-based quantitative studies focusing on women with disabilities aged 15 and older. 12 databases will be searched, and records will be screened by two independent reviewers. The risk of bias will be assessed. The global prevalence and pooled ORs comparing women with and without disabilities will be calculated.

Findings will contribute to global efforts in addressing VAW with disabilities, informing the development of targeted, evidence-based policies and programmes and ensuring that interventions are responsive to their specific needs and circumstances.

Ethics approval is not required, as this review analyses previously published data. Findings will inform ongoing World Health Organization (WHO)/Human Reproductive Programme (HRP) work on strengthening the measurement of VAW with disabilities and will be disseminated through a peer-reviewed publication, conference presentations and sharing with relevant organisations.

CRD42023427512.

To identify sex-specific patterns based on determinants related to sleep quality, using a representative sample of the Spanish adult population.

Cross-sectional, age-stratified and sex-stratified study.

Community-based assessments in two Spanish provinces (Salamanca and Ávila).

Adults aged 25–65 years (n=500), equally distributed by sex and five age strata, selected from the regional health-card database.

Objective sleep metrics from wrist actigraphy (time in bed, total sleep time (TST), sleep efficiency, wake after sleep onset, number/duration of awakenings, fragmentation/movement indices) and self-reported sleep quality (Pittsburgh Sleep Quality Index).

Standardised baseline assessments collected sociodemographic, clinical, mental-health and lifestyle variables using validated instruments. Actigraphy (ActiGraph GT3X+) recorded triaxial acceleration at 30 Hz over 5 days; data were aggregated in 60 s epochs (ActiLife). Sleep/wake was classified with Cole-Kripke and nocturnal episodes identified with Tudor-Locke before deriving sleep indices. Two-step cluster analysis was applied separately by sex.

Three clusters were identified for each sex, with age and educational level being the most influential factors. In men, the 65-year-old cluster with university education and lower anxious–depressive load showed the highest sleep efficiency (91.8±3.8%) and the lowest TST (351.7±74.8 min). In contrast, the 35-year-old cluster with middle or high school presented the lowest efficiency (88.3±10.0%) and higher TST (368.1±83.8 min). In women, the 55-year-old cluster with middle or high school and low emotional load showed the highest efficiency (93.6±2.8%), despite a reduced TST (352.0±79.7 min), while the 35-year-old cluster, with middle or high school and high levels of anxiety and depression, showed the worst efficiency metrics (89.5±3.9%) and a higher TST (394.8±67.3 min).

Sleep quality in Spanish adults is heterogeneous across sex-specific clusters shaped by age, education and mental-health burden. Cluster-based characterisation may support tailored public-health interventions.

NCT05324267.

A cancer diagnosis not only profoundly impacts individuals but also the very core of their families, reshaping their lives in many ways. However, there is a lack of focus on the well-being and health of the entire family across adult cancer research. This is concerning given that one-third of the Danish population will get a cancer diagnosis before the age of 75, suggesting that many Danes will become caregivers during their lifetime. In addition, identifying vulnerable families is challenging, and the determinant factors for their vulnerability are unknown.

The principal aim of this study is to investigate family health during cancer treatment. This will be done by gathering information on various parameters such as perceived support, quality of life and self-efficacy in patients with cancer and families across the cancer trajectory. Additionally, the study seeks to pinpoint particularly vulnerable families and investigate contributing factors to their vulnerability.

This mixed-methods study follows a sequential explanatory design, combining patient-reported outcomes in a longitudinal, prospective multicentre survey with interviews conducted with a nested sampling of the participants from the survey. A total of 240 patients diagnosed with prostate-, breast-, gastrointestinal- and lymphoma cancer, and designated adult family caregivers will be recruited from six different sites for the survey. Variables such as family health, needs and perceived support, quality of life, self-efficacy, depression, stress and resilience will be explored. Survey data will be collected at baseline, 3, 6, 12 and 18 months. The interviews (n=12–15) will be conducted twice with patients and caregivers jointly: once during the treatment phase (3 months) and once after completion of treatment (12 months). For the survey part, we estimated a sample size with 90% power and 5% significance to detect a minimal clinically important change in the Family Health Scale. Assuming an SD of 2x22 = 31, based on a cross-sectional SD of 22, 44 patients per group were required; to allow for dropout, 60 per group (240 total) were included. Patient and caregiver characteristics will be summarised descriptively. Longitudinal patient-reported outcomes will be analysed with linear mixed regression, separately for patients and caregivers. Changes will be reported as mean differences with 95% CIs and compared with published minimal clinically important differences or, if unavailable, 0.3xbaseline SD. For the qualitative part, thematic analysis by Braun and Clarke is chosen to extract data, identify patterns and analyse data and themes from the interviews. NVivo will be used for coding interview data.

The study will be conducted in accordance with the Helsinki Declaration. Measures will be taken to ensure confidentiality, data protection and participant safety throughout the study. The results will be published in peer-reviewed journals and conference presentations.

ClinicalTrials.gov: NCT06433349. Protocol version 2.0, June 2024.

Safety culture is essential to improving healthcare quality. Paediatric emergency departments are high-risk environments where evaluating safety culture helps identify areas for improvement. This study aimed to analyse the safety culture among professionals in paediatric emergency departments, according to job category and gender.

Multicentre cross-sectional study using the Hospital Survey on Patient Safety Culture (HSOPSC).

19 paediatric emergency departments, covering all levels of care.

1843 healthcare professionals were invited to participate; the response rate was 63.8%, and 33% of respondents were nurses. All clinical staff in paediatric emergency departments were eligible. Professionals from other specialties and non-clinical staff were excluded.

The primary outcome was the assessment of patient safety culture using the HSOPSC, following the methodology of the Agency for Healthcare Research and Quality. Secondary outcomes included comparisons by job category and gender, and an exploratory cluster analysis.

In terms of patient safety, the main strength was ‘teamwork within units’ (83.65% positive), while the main weakness was ‘staffing’ (61.92% negative). Patient safety was rated with an average score of 7.21 by the participants. Paediatricians rated ‘manager expectations’ significantly higher than nurses (p=0.023) and residents (p=0.026). Paediatricians gave more positive responses overall, with significant differences in ‘communication openness’, ‘feedback and communication’, ‘non-punitive response’ and ‘teamwork across units’, though none were classified as strengths. Cluster analysis showed that the group with more paediatricians identified more strengths and no weaknesses, while the group with more nurses and nursing assistants showed no strengths and significant weaknesses in ‘overall safety perception’, ‘staffing’ and ‘management support’.

Safety culture in paediatric emergency departments is acceptable, but still far from excellent, indicating ample room for improvement. Differences between professional categories, especially between paediatricians and nurses, highlight the need for targeted safety strategies and leadership involvement.

Eating disorders are complex mental health conditions characterised by pathological behaviours related to food intake, often accompanied by a chronic obsession with weight control. Their prevalence is increasing, with an earlier onset and greater severity among young people. Universal prevention, through multicomponent strategies that tackle modifiable risk factors, has emerged as a promising tool. This paper reports the study protocol designed to assess the effectiveness and cost-effectiveness of the PRETA (Prevención de los Trastornos de la Alimentación) programme in reducing the risk of eating disorders and related modifiable risk factors among preadolescents in the school setting.

The PRETA programme will be assessed by means of an open, community-based, multicentre, controlled trial using 1:1 matched-pairs cluster randomisation at the school level. Schools in Tenerife (Spain) will be assigned to the PRETA programme or a waitlist control group. Participants include 5th- or 6th-grade students (10–13 years old), their parents and teachers. The PRETA programme is a universal, school-based, multicomponent programme designed to reduce eating-disorder risk and modifiable risk factors. Its main component is an interactive online platform called e-PRETA, complemented by training sessions for families and teachers. e-PRETA includes nine 45-minute sessions addressing risk factors, such as dietary habits, beauty standards, media literacy, self-esteem, emotional regulation and social skills. A total of 1068 children from 12 schools will participate. The primary outcome will be the risk of developing eating disorders (Children’s Eating Attitudes Test-26 item version). Secondary outcome measures are body dissatisfaction (Adapted Contour Drawing Rating Scale), eating disorder traits (Eating Disorder Inventory-2), internalisation of appearance ideals (Sociocultural Attitudes Towards Appearance Questionnaire-4) and self-esteem (Rosenberg Self-Esteem Scale). Outcomes will be assessed at baseline and postintervention (3 months). Additional baseline covariates such as electronic device use, parental feeding attitudes, physical activity, sleep duration and screen time will also be collected. Programme effectiveness will be analysed using generalised mixed models. Cost-effectiveness will be assessed by comparing the incremental costs associated with the implementation of the PRETA programme with its estimated effectiveness.

Ethics approval has been obtained from the Ethics Committee for Research with Medicines at the University Hospital of the Canary Islands (CHUC_2021_78). Written informed consent will be obtained from the parents or legal guardians of all participants. Results will be disseminated through scientific publications and conferences.

NCT06792981.

To evaluate the cost-effectiveness of anti-vascular endothelial growth factor (VEGF) treatments for neovascular age-related macular degeneration (nAMD) using a value-based model that considers drug durability, dosing regimens and real-world administration strategies, including safe vial fractionation.

Model-based pharmacoeconomic analysis using data from randomised clinical trials and network meta-analyses. Analysis conducted from the payer perspective using cost data from the Spanish National Health System.

A model-based analysis compared five anti-VEGF agents—innovator and biosimilar ranibizumab, aflibercept 2 mg, brolucizumab and faricimab—across three dosing regimens: fixed, Pro Re Nata and Treat-and-Extend (TAE). Administration formats included single-use vials, prefilled syringes and vial fractionation (VF), with or without dead-space-free (DSF) syringes to minimise waste. The primary outcome was cost per optimal responder, defined as a patient gaining ≥15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, with and without adverse events. Cost-effectiveness was evaluated using Number Needed to Treat (NNT), Net Efficacy Adjusted for Risk-NNT (adjusted for safety) and incremental cost-effectiveness ratios. Secondary outcomes included the number of treated patients and optimal responders achievable within a fixed 1 000 000 budget.

The most cost-effective strategy was aflibercept 2 mg under a TAE regimen using DSF VF, with a total cost of 6214 per patient and a cost per optimal responder of 27 155. Under a fixed budget of 1 000 000, this approach allowed treatment of 160 patients, yielding 36 optimal responders. Faricimab with DSF VF ranked second, with a total cost of 5847 and a cost per optimal responder of 28 652, treating 171 patients and achieving 34 responders. In contrast, single-use vials without VF led to substantially higher total costs (eg, 11 305 for aflibercept TAE) and lower treatment capacity (eg, 88 patients treated).

This model demonstrates that combining durable agents, extended dosing intervals and optimised delivery strategies (eg, prefilled syringes and DSF VF) can substantially improve the cost-effectiveness and sustainability of anti-VEGF therapy in public health systems.

There is evidence that talking about the end of life with patients facing a life-threatening disease is not upsetting, and in fact, it may even be beneficial. However, both patients and health professionals can find it difficult to engage in these conversations. The aim of this clinical trial is to explore whether proactively inviting people with advanced cancer to share their thoughts about death and dying is distressing for them, comparing the impact with usual clinical practice (ie, a reactive approach to these issues).

A stepped-wedge cluster randomised controlled trial involving six palliative care units in Spain will be conducted. Each unit will recruit participants for both the experimental and control groups. Units will be randomised to determine the order in which they will begin implementing the intervention: GO-TaD (Give the Opportunity to Talk about Death thoughts). The trial will involve six sequences and seven periods (steps), with four patients per period (patients in each period will be different). The primary outcome will be emotional distress, assessed with the Detecting Emotional Distress scale. The following secondary variables will also be analysed: hopelessness, using the Beck Hopelessness Scale; quality of the patient–professional relationship, with the Patient–Doctor Relationship Questionnaire (PDRQ-9); and quality of life, with the Palliative Outcome Scale . The trial will follow the CONSORT extension for stepped-wedge cluster randomised designs. The primary analysis will include all eligible patients, applying mixed-effects regression models for binary results and mixed linear models for continuous data. Results will be reported as risk differences and ORs, with 95% confidence intervals. Analyses by sub-groups of interest (eg, age, gender, type of palliative care unit) will also be conducted. All analyses will be performed using R.

Ethical approval has been obtained from the researchers' university and all participating centres. Results will be disseminated through peer-reviewed open access publications, academic conferences and presentations to clinical audiences.

NCT06420609.

A synthesis and appraisal of the recommendations for biomarkers in practice guidelines concerning sepsis is required to consolidate evidence-based practice. We generated an evidence gap map (EGM) on the use of biomarkers for managing adults with sepsis.

Scoping review.

MEDLINE, Guidelines International Network, Pan American Health Organization, Trip Database and UpToDate were searched from 2016 to March 2025.

Guidance documents (GD) that searched at least one literature source and provided clinical recommendations for the use of biomarkers for the management (diagnosis and prognosis, including treatment response) of adults with sepsis.

Two reviewers independently applied the eligibility criteria and extracted data. We used the AGREE-II (Appraisal of Guidelines for Research and Evaluation) tool to assess the GD quality. GDs that scored ≥50% on the AGREE-II 'Rigour of development' domain were considered robust. We also applied the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system to evaluate if the recommendations were strong or conditional.

We found 10 GDs, with only half (4/8) having a robust methodology. There were 31 recommendations concerning biomarkers. Among these, 24 (77.4%) recommendations were about single biomarkers, with lactate (23; 74.2%) and procalcitonin (8; 25.8%) most frequently recommended. Biomarker testing focused on prognosis in 28 (90.3%) recommendations. Overall, 16 (51.6%) recommendations were graded strong and 13 (42.0%) were conditional, which we displayed in an EGM.

The methodology of GDs concerning adult sepsis was poor. Our review calls for more prudent use of biomarkers in specific prognostic scenarios and in combination with standard clinical assessments. Enhancing the methodological quality of future GDs is essential to generate more valid and robust recommendations for optimising patient care.