Postextubation swallowing disorders (SD) are common in the intensive care unit (ICU) and are associated with severe complications, including aspiration pneumonia, a three-fold increase in reintubation risk and higher mortality. While fibreoptic endoscopic evaluation of swallowing (FEES) and videofluoroscopy are gold standards for diagnosis, they are often impractical or impossible to perform on intubated patients. The use of ultrasound offers a non-invasive, bedside alternative to evaluate the musculoskeletal structures involved in swallowing. The Echographie Identifier les troubles de Déglutition Acquis en Réanimation (EIDAR) study aims to evaluate the diagnostic performance of pre-extubation ultrasound in identifying patients at risk of SD following mechanical ventilation.

This prospective, monocentric diagnostic study conducted at the Dijon University Hospital ICU will include 100 adult patients ventilated for ≥48 hours. The primary outcome is the presence of SD, defined as a Penetration-Aspiration Scale score >2 during a FEES procedure performed 3 to 24 hours postextubation and independently assessed by an otolaryngologist blinded to index test results. Pre-extubation cervical ultrasound (Index Test) will be performed within 3 hours prior to extubation and measure hyoid bone ascension (primary variable of interest), geniohyoid muscle surface area and digastric muscle cross-sectional area. The diagnostic performance of cervical ultrasonographic parameters will be assessed using their discriminative capacity via a receiver operating characteristic curve. The feasibility of the ultrasound procedure in a critical care setting will also be assessed.

The study received a favourable opinion from the independent ethics committee CPP Ouest III and is registered with the French health authority ANSM (national agency on safety in medicine and health products). It is conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. Participants or their proxies provide free and informed oral consent. Results will be submitted for publication in peer-reviewed medical journals and presented at international conferences.

RCB 2023-A00461-44 and NCT05922085

Non-specific low back pain (NSLBP) is one of the leading causes of disability worldwide. Emerging evidence suggests that altered diaphragmatic function may be associated with lumbar pain, impaired trunk stabilisation and functional disability. Manual diaphragmatic techniques have been proposed as an intervention to modulate diaphragmatic tension, mobility and neuromyofascial relationships; however, their effectiveness has not yet been synthesised using rigorous systematic review methods.

This protocol follows Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidance and has been prospectively registered in PROSPERO. Randomised controlled trials evaluating manual techniques specifically applied to the diaphragm in adults with NSLBP will be eligible. The primary outcomes will include pain intensity and functional disability; secondary outcomes will include lumbar mobility, respiratory function, quality of life and adverse events. Searches will be performed in PubMed/MEDLINE, Cochrane CENTRAL, PEDro, CINAHL, Scopus, Embase and clinical trial registries without language or date restrictions. Two reviewers will independently perform study selection, data extraction and risk-of-bias (RoB) assessment using the Cochrane RoB 2 tool. Where appropriate, a random-effects meta-analysis will be conducted; the certainty of evidence will be evaluated using the Grading of Recommendations, Assessment, Development and Evaluation approach. Substantial clinical and methodological heterogeneity is anticipated across trials, which may limit the feasibility of quantitative data pooling.

As this study uses data from previously published trials, ethical approval is not required. Findings will be disseminated through peer-reviewed publication, conference presentations and a plain-language summary for clinical stakeholders.

CRD420251172616.

Stakeholder involvement in research processes is widely recommended to enhance the relevance, quality and uptake of research findings. However, existing studies highlight persistent challenges in engaging family caregivers in co-design research. This gap may result in research outcomes that fail to reflect family caregivers’ needs and preferences, contradicting the core purpose of co-design. Therefore, the aim of this systematic review is to synthesise the available evidence on family caregivers’ experiences of involvement in co-design research and to generate evidence-based strategies to support effective engagement.

This systematic review will be conducted using a meta-aggregative approach, following the Joanna Briggs Institute’s (JBI’s) Manual for Evidence Synthesis. Systematic searches will be conducted in PubMed, CINAHL, Scopus, Web of Science and PsycINFO, with no date restrictions. Preliminary searches were performed in EMBASE between September and October 2025. Qualitative primary studies that explore family caregivers’ experiences of involvement in co-design research will be included. Study selection and quality appraisal will be performed independently by two researchers using predefined protocols, disagreements will be resolved through discussion with a third reviewer. After calibration, a single reviewer will extract the data using a customised data extraction template with the dataset distributed among the authors. The first author will then review all extractions. Data will be analysed following JBI’s meta-aggregative method, and results will be presented in narrative summaries, tables and diagrams. The findings will inform strategies for stakeholder involvement in future co-design research. Family caregivers and co-design researchers will be involved in reviewing and revising generated recommendations to enhance their relevance and practical utility.

This protocol does not involve human participants. The findings of this review will be submitted for publication in a peer-reviewed journal and presented at relevant scientific conferences and meetings.

CRD420251229190.

Artificial intelligence (AI) is rapidly evolving, offering an expanding suite of capabilities that go beyond the traditional focus on prediction and classification. Generative AI (GenAI) and agentic AI could create transformative practices to support real-world evidence (RWE) generation for health research by streamlining studies, accelerating insights and improving decision-making. However, there is no published overview available describing the range of applications in RWE generation. This review aims to describe where and how genAI and agentic AI are applied across the domains of healthcare research tasks for RWE generation. Additionally, to map applications by tasks and methods across the product lifecycle continuum, and to identify emerging gaps and opportunities.

This Living Scoping Review (LSR) will include studies reporting an application and/or evaluation of genAI or agentic AI applied to one or more RWE generation research tasks. Searches will be conducted in Embase, MEDLINE and additional sources (eg, grey literature). Citations will be independently screened by two human senior reviewers for a substantive training dataset and a commercially available screening algorithm (Robot Screener) will complete screening with a human reviewer. The LSR will include reports of studies (primary or reviews) describing and/or evaluating the application of any genAI model for RWE generation in healthcare, in English, published from 1 January 2025 to the date of search. Data will be extracted from all studies included in the LSR by one independent senior reviewer using a piloted template, with 10% quality check by a second senior reviewer. Descriptive statistics will be used to summarise the applications of genAI per RWE research task, and the results of genAI evaluations. Thematic analysis will be used to describe genAI application patterns, trends, gaps and opportunities. The LSR protocol and reports will be updated annually, and findings will be published on a publicly available website (eg, ISPE—the International Society for Pharmacoepidemiology).

Ethical approval is not required due to use of previously published data. Planned dissemination includes peer-reviewed publication, presentation and short summaries.

Sodium-glucose cotransporter (SGLT) inhibitors have shown substantial benefit in reducing cardiovascular and kidney events across diverse clinical populations, but the underlying physiological mechanisms remain unclear. However, existing mechanistic studies on renal and cardiovascular haemodynamics show variability in design, have limited statistical power and yield inconsistent outcomes, thus limiting the ability to draw generalisable conclusions. To address this gap, we conducted a systematic review and proposed the first meta-analysis to aggregate individual participant-level data from mechanistic studies to identify consistent physiological patterns and enhance understanding of the therapeutic effects of SGLT inhibition.

Gold-standard measured glomerular filtration rate (mGFR) was selected as the primary outcome for this systematic review, which aimed to identify all completed mechanistic studies investigating the effects of SGLT inhibition. Electronic databases including Ovid MEDLINE; Ovid Embase; Cochrane Database of Systematic Reviews; and Cochrane Central Register of Controlled Trials were searched using a detailed search strategy. In total, 24 studies (n=1296) were identified. This systematic review was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Key variables including demographics, medical history, concomitant medications, vital signs, mGFR, renal haemodynamics, urine and plasma biochemistry, tubular sodium handling, echocardiography, cardiac output monitoring, arterial stiffness and fluid volume will be extracted. A one-stage individual participant data meta-analysis under a Bayesian framework will be conducted, using hierarchical models to simultaneously analyse data from all eligible studies. The risk of bias due to missing results will be assessed. Sensitivity analyses and subgroup evaluations will be incorporated to explore sources of heterogeneity and assess robustness of findings.

Ethics approval was obtained from University Health Network, Toronto, Canada. Findings from the Mechanisms of SGLT Inhibitor Action and Physiological Mediators (MOSAIC) meta-analysis will be published in peer-reviewed journals and results will be disseminated at scientific conferences.

CRD420251001413.

To assess human papillomavirus (HPV) vaccine awareness and uptake among caregivers in rural Indigenous communities in Guatemala and to identify sociodemographic predictors of vaccine unawareness and non-uptake.

This cross-sectional survey was conducted across 12 rural Indigenous communities in Guatemala’s Central Highlands. Using a community-engaged research approach, trained multilingual health workers administered surveys in Spanish, Kaqchikel or K’iche’. Eligible participants were adults who served as primary caregivers to children. The survey assessed HPV vaccine awareness, vaccine attitudes and uptake among those with daughters aged 8 or older. Logistic regression was used to examine predictors of vaccine unawareness and bivariate analysis explored differences in vaccine uptake.

Among 602 participants (92.5% identified as Indigenous), 95% expressed willingness to vaccinate a child against cervical cancer, yet only 56% had heard of the HPV vaccine. Of the 175 participants with eligible daughters, only 33.7% reported vaccination. Indigenous identity, older age and illiteracy were significantly associated with HPV vaccine unawareness. Speaking an Indigenous language at home was associated with greater awareness. Departmental differences were significant: participants from Sololá were more likely to be unaware of the vaccine, while those from Sacatepéquez had higher awareness and uptake. Community partners noted that access to information, geographic connectivity and social desirability may influence both awareness and response accuracy.

Despite strong willingness to vaccinate, significant knowledge gaps persist among Indigenous caregivers. Tailored, community-informed education strategies—delivered through trusted channels and adapted linguistically and culturally—are urgently needed to increase awareness and uptake of the HPV vaccine in underserved Guatemalan communities.

Binge drinking in the previous month was reported in 23.5% of US adults, and 28.1 million adults met criteria for Alcohol Use Disorder (AUD) in 2023. Individuals with AUD face increased risks of oral health problems, including caries, periodontal disease and mucosal lesions. Poor oral hygiene, nutrition and dental care all contribute to these conditions, but individuals with AUD are often under-represented in oral health surveys. Understanding relationships between oral health behaviours, attitudes and general health is crucial for designing future interventions. This pilot aims to explore the relationship between oral and systemic health in subjects with AUD, focusing on oral health behaviours, salivary biomarkers and clinical phenotype, including systemic biomarkers of inflammation, to inform future research on oral–systemic interactions in AUD.

This protocol has two parts. Part 1 involves cognitive interviews to assess the content validity and interpretability of the Oral Health Behaviours Assessment (OHBA) questionnaire. Part 2 will collect biological and behavioural data from treatment-seeking patients with AUD and matched controls (age, sex and smoking status), including saliva, blood, dental exams, and health behaviour and symptom measures. Inpatients with AUD will provide biospecimens and answer symptom severity questionnaires at admission and again at the dental exam visit (7–12 days later), while controls will provide a single set of measures at their dental exam visit. Oral health will be assessed through structured dental and periodontal examinations, radiographs and validated questionnaires (including the OHBA). Additional data will include alcohol use history, psychiatric and medical history assessments, dietary recall, and measures of stress, sleep and mood to capture potential moderators of oral–systemic relationships. Biomarkers of inflammation and stress will be quantified from saliva and blood using immunoassays. Primary outcomes will compare oral health, salivary biomarkers and clinical measures between AUD and controls, while secondary outcomes will evaluate within-subject changes in patients with AUD during inpatient treatment and early abstinence.

This clinical protocol was approved by the National Institutes of Health Institutional Review Board (IRB #002005). Prior to enrolling, participants will be informed of the study purpose, risks and benefits, and study procedures, and evaluated for understanding prior to signing consent. Part 1 of the protocol is currently active and recruiting participants for cognitive interviews. The study findings will be disseminated through journals and conferences related to addiction medicine, psychology, immunology, neuroscience and dentistry. We expect the results of the pilot study will inform future research on oral health and salivary bioscience while also providing treatment-seeking patients with AUD targeted information on the importance of oral health behaviours for maintaining oral and systemic health.

NCT06684483; preresults.

To implement an overview of reviews that discuss the current state of syntheses (such as systematic reviews) of only observational studies on health risk behaviours (HRBs), including smoking, alcohol intake, poor sleep, poor quality diet, common mental health problems (depression and anxiety), and glycated haemoglobin (HbA1c), while excluding synthesis of clinical trials.

Overview of reviews or umbrella review following Preferred Reporting Items for Overviews of Reviews (PRIOR) guidelines.

PubMed, Scopus, Web of Science, PsycINFO-PsychArticles and Epistemonikos, searched from January 2013 to 30 June 2025.

We included systematic reviews and meta-analyses of observational studies that assessed the relationship between HRBs—including smoking, alcohol intake, poor sleep, poor quality diet, physical activity and common mental health problems such as depression and anxiety—and HbA1c. Reviews of clinical trials were excluded.

We synthesised systematic reviews and meta-analyses on the above topic from five databases following the PRIOR protocol. Two independent reviewers screened titles, abstracts and full texts using standardised methods. Data extracted included study design, exposures, outcomes and population characteristics. Risk of bias was assessed using the AMSTAR-2 tool. Overlap across reviews was evaluated using the corrected covered area metric.

Eight systematic reviews were included in the final synthesis, encompassing a total sample size of around 307 019 individuals. The study highlights a significant paucity of systematic reviews of observational studies in this area, with no reviews on alcohol and exercise. The existing evidence on poor sleep, poor quality diet and smoking points towards these HRBs leading to worse HbA1c. A bidirectional relationship was found between depression and HbA1c.

This umbrella review highlights the significant association between HbA1c and key health risk factors underscoring the importance of observational studies, highlighting their ability to capture real-world conditions and complex interactions. While in agreement with existing study designs, this review provides convergent evidence of the critical role of HRBs in managing HbA1c levels.

Preventable hospital patient harm events disproportionally affect certain patient populations. For some, harm extends beyond physical injury to include cultural, emotional or spiritual impacts. While these disparities are linked to socio-demographics (eg, race, education), they are driven by structural factors (eg, procedures and policies). Patient safety monitoring systems (eg, incident reporting, patient concerns) were not originally designed to identify equity-related harms and may inadvertently obscure or reinforce the injustices they should address. This study will examine how equity is currently considered within hospital incident reporting and patient concerns systems across Canada and will identify opportunities to strengthen these systems’ responsiveness to inequities in patient safety.

This 3-year exploratory sequential mixed-method study began in September 2024. Phase one involves qualitative interviews with patient safety and equity leads, patients/families/caregivers and leaders of innovative initiatives to explore current practices, gaps and innovations in how equity-related factors are identified and addressed within incident reporting and patient concerns systems. Findings will inform Phase 2, a modified Delphi process with patient safety and equity experts and persons with lived experience of equity-related harm events to refine and reach consensus on key equity-promoting features, considerations and recommendations for these systems. In Phase 3, consensus items will be used to develop a national cross-sectional survey assessing the extent to which equity is integrated into hospital incident reporting and patient concerns systems in Canada. A patient advisory committee will inform data collection, interpretation of findings and dissemination.

Ethics approval has been received for Phase 1, with subsequent approvals to be sought for later phases. Dissemination plans include peer-reviewed publications, presentations at international conferences and knowledge exchange activities to inform patient engagement, the design of incident reporting and patient concerns systems and policy development.

Despite a lack of evidence relating to effectiveness and safety, the use of apps in the field of mental health is increasing due to their ease of use and accessibility. The aim of the EvalDepApps project is to develop and validate an assessment tool for evaluating depression management apps based on scientific evidence, expert judgement and end-user needs.

The purpose of this study was to determine the most relevant criteria for evaluating apps intended to manage depression through consensus-based assessment.

A total of 43 individuals were invited to participate in an online modified Delphi study of 51 criteria identified from the literature. In Round 1, participants rated criteria according to relevance and three levels of consensus were defined: high level when ≥80% of respondents scored the criterion at 5 or 6; medium when 60%–79% of respondents scored the criterion at 5 or 6 and low when

The response rate was 59.0% (26/43) in Round 1 and 53.4% (23/43) in Round 2. In Round 1, 24 criteria (47.1%) attained the maximum level of consensus, 20 (39.2%) the medium level and 7 (13.7%) the lowest level. In Round 2, 4 out of 20 criteria (20.0%) attained the maximum consensus. Participant comments reinforced the relevance of the selected criteria. The final list consisted of 28 criteria, the majority relating to Safety and Privacy and Clinical Effectiveness (25.0% each), followed by Usability and Functionality (17.9%).

By prioritising criteria relating to data safety and clinical effectiveness, participants in this study emphasised that the assessment of apps for depression management must take both these aspects into full consideration. Despite some limitations of the study (eg, lack of participant sociodemographic data and its implications for generalisation, not face-to-face inter-round), the results of this study will enable the EvalDepApps project to develop an assessment tool for depression management apps that incorporates the most relevant criteria.

EvalDepApps will support healthcare professionals and users in identifying safe, effective and user-friendly depression management apps.

Knee osteoarthritis (OA) is a leading cause of disability in older adults, with health and economic impacts. Despite pharmacological advances, exercise continues to be a fundamental pillar in the management of OA, with lower limb strength training showing significant benefits. Virtual reality (VR)-based interventions have emerged as innovative tools, providing immersive environments to facilitate functional movement exercises. VR offers pain relief, improved functionality and reduced fall risks, although its efficacy in OA management requires further exploration. The main aim of the study is to assess whether a VR-based intervention provides superior improvements in pain, stiffness, physical function and movement biomechanics compared with conventional therapeutic exercise in adults aged 60 years and older with knee OA.

This is a protocol for a randomised controlled trial comparing the effects of immersive VR interventions with conventional therapeutic exercises in individuals aged 60 years and older with knee OA. Participants are allocated 1:1 to experimental (VR) and control groups. The VR intervention involves 18 supervised sessions over 8 weeks, using Meta Quest 3 goggles to perform functional movements in virtual environments. The control group follows standard therapeutic exercise protocols per Osteoarthritis Research Society International guidelines. Outcomes include OA-related symptoms, kinematic performance, pain intensity, kinesiophobia and fall risk. Secondary measures assess cybersickness, depressive symptoms, medication use and comorbidities. Assessments occur at baseline, ninth week, sixth and ^12th months. Data analysis employs intention-to-treat principles, leveraging descriptive statistics, t-tests and multiple imputations for missing data.

This study was approved by the A Coruña-Ferrol Research Ethics Committee (reference: 2023/557), under the Galician Health Service. All participants will be required to provide written informed consent prior to their inclusion in the study. Participant data will be pseudonymised and securely stored. Additionally, anonymised datasets will be deposited in open-access repositories (Zenodo).

NCT06362785.

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.