A healthy diet is a crucial component for adolescents’ health and wellbeing. Current literature surrounding dietary intake and its effect on cognition, mental health and wellbeing has mainly focused on children, not adolescents. This review aims to synthesise findings from studies that explore the relationship between dietary intake and cognition, mental health and wellbeing in the adolescent population.

Electronic searches will date from 1 January 2000 to 7 October 2024 and will be conducted in CENTRAL, MEDLINE/PubMed, CINAHL via EBSCOHOST, ERIC, British Education Index, Child and Adolescent Studies, Education research complete, Psychology and Behavioural Sciences Collection, Social Policy and Practice Embase, and APAPsychINFO via OvidSP. Articles will be screened using defined inclusion and exclusion criteria and assessed for eligibility by five independent reviewers. Discrepancies will be reviewed by a third reviewer. The selection process of included articles will be reported by using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram. A narrative summary will be used to report and synopsise the extracted data.

This systematic review does not require ethical approval. The dissemination strategy for this review comprises peer-reviewed publications, public health conference presentations and providing a valuable reference for healthy-food interventions in school and community-based settings as well as identifying gaps in the current literature and informing policy and practice.

CRD42025633083.

Cisplatin is a widely used chemotherapeutic anti-cancer drug. However, high-dose cisplatin is also known for its dose-limiting toxicities, including irreversible cisplatin-induced hearing loss (CIHL). Sodium thiosulphate (STS) can bind to cisplatin to form an inactive and harmless complex. A topical application is desired, allowing cisplatin to retain its systemic anti-cancer effect.

The SOUND trial is an investigator-initiated randomised controlled multicentre phase III trial to study the efficacy of transtympanic administration of STS against CIHL in a cohort of 100 patients with head and neck cancer treated with cisplatin at a dose of ≥200 mg/m². Each subject will receive transtympanic STS injections in one ear, chosen by randomisation, before each cisplatin infusion. The contralateral ear serves as an internal control. The primary objective is efficacy (ie, clinically relevant benefit) of transtympanic STS injections against CIHL, defined as a difference in threshold shift of ≥10 decibels between baseline and 3 months after treatment in favour of the STS-treated ear. Secondary objectives include the difference in mean threshold shifts on frequencies essential for speech and extended high frequencies, as well as the difference between both ears in the gradation of hearing loss as defined by ototoxicity grading scales.

The medical ethics committee in the Netherlands approved the trial (Clinical Trials Information System (CTIS) 2023-503313-30-00). The results will be disseminated through the CTIS and peer-reviewed scientific journals.

CTIS 2023-503313-30-00 approved by Medical Research Ethics Committee NedMec.

Heart failure (HF), chronic kidney disease (CKD) and atherosclerotic cardiovascular disease (ASCVD) are highly prevalent conditions that often coexist. Using electronic health records (EHRs), we evaluated the 1-year risk of all-cause death, major cardiovascular and kidney events in patients with HF, CKD, ASCVD and with combinations of these conditions, compared with an unselected control population aged ≥75 years.

Retrospective cohort study based on EHR data.

Integrated primary and secondary health unit located in the North of Portugal. Eligible adult patients were identified using EHRs from 2008 to June 2022.

Eight cohorts were defined: (1) control: patients with ≥75 years; (2) ASCVD alone; (3) HF alone; (4) CKD alone; (5) cardiorenal syndrome (CRS): combined HF+CKD; (6) atherosclerotic HF: combined ASCVD+HF without CKD; (7) atherosclerotic CKD: combined ASCVD+CKD without HF and (8) combined ASCVD+CRS. The risk of these conditions was compared with controls using propensity score age-sex matching. We identified 19 129 patients with ASCVD alone, 13 640 patients with HF alone, 40 545 with CKD alone and 10 499 with CRS. The control group comprised 36 532 patients aged 75 years or older.

The primary outcome was all-cause mortality. The main secondary outcomes were cardiovascular death, HF hospitalisations and end-stage renal disease.

The 1-year mortality rate was 0.65% in the control cohort, 5.6% for patients with ASCVD alone, 6.05% for patients with HF alone and 3.53% for patients with CKD alone. Adjusted risk of all-cause death was significantly increased in the ASCVD-alone (HR: 8.42, 95% CI 7.12 to 9.95), HF-alone (HR: 9.19, 95% CI 7.75 to 10.9) and CKD-alone (HR: 5.35, 95% CI 4.62 to 6.19) cohorts, compared with control population; however, patients with the combination of all three conditions (ie, ASCVD+CRS) had the highest mortality risk (HR: 14.18, 95% CI 11.62 to 17.3). A similar association pattern was observed for cardiovascular death, HF events and end-stage renal disease.

Our results support the concept of an atherosclerotic cardiorenal phenotype, with a very high risk of mortality, cardiovascular and renal adverse events. Implementation strategies are required to target these conditions simultaneously.

Glioblastoma multiforme (GBM) is an aggressive primary brain tumour associated with a poor prognosis despite standard-of-care treatment, including surgical resection, radiotherapy and temozolomide (TMZ) chemotherapy. Certepetide (also known as LSTA1, CEND-1) is an investigational tumour-penetrating peptide that facilitates the extravascular delivery and intratumoural penetration of co-administered immune/chemotherapeutics; however, it has not yet been evaluated in clinical trials for the treatment of intracranial malignancies.

LSTA1-GBM-2A is an exploratory phase 2a, double-blind, placebo-controlled, randomised, proof-of-concept investigator-initiated trial assessing the safety, tolerability and preliminary efficacy of certepetide in combination with standard-of-care TMZ, compared with TMZ with a matching placebo, in subjects with newly diagnosed GBM.

The trial is funded by Lisata Therapeutics, sponsored by Tartu University Hospital and conducted at hospitals in Estonia and Latvia. Subjects are randomised in a 2:1 ratio. Following initial surgery and radiotherapy with concurrent TMZ, the subjects receive intravenous certepetide or placebo alongside six cycles of adjuvant TMZ treatment. The primary endpoint is overall survival. The target number of subjects is 30. The first subject was recruited in January 2024, and accrual is ongoing.

This study was approved by the Republic of Estonia State Agency of Medicines (17 October 2023) and the State Agency of Medicines of the Republic of Latvia (1 February 2024). The results of this study will be published in peer-reviewed journals and reported at academic conferences.

2023-506813-23-00.

Early childhood—specifically, the period from 0 to 6 years of age—is a critical time in children’s lives with rapid growth in their cognitive, social and emotional development. This period has also been shown to be the most effective time for early interventions. The use of artificial Intelligence (AI) for supporting early child development is increasing alongside the rapid advancement of technology. AI can be used directly by children (eg, for implementing adaptive technologies), by individuals who interact with children (eg, educators, parents, nurses), and by individuals indirectly supporting early child development (eg, early childhood researchers or policy analysts). This scoping review will provide a roadmap for relevant stakeholders on how AI has been applied within and across different contexts to support infants and young children’s development, as well as the most predominant AI technologies used across various contexts.

The current study follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Review The search syntax will be applied in PsycINFO, ERIC, Education Source, CINHAL, MEDLINE, Embase and IEEE Xplore. The purpose of this study is to curate and synthesise academic papers to examine the application of AI for supporting the development of children between birth and age 6 years of age. Studies with children or individuals who work directly or indirectly with children will be included. Part of the abstract and full-text screening will be conducted by two researchers, with discrepancies being resolved by the lead authors. In addition, AI will be used to help with study screening and data extraction once confirmed to be reliable (Cohen’s kappa >0.80). Thematic and content analyses will be conducted to identify the types of AI products used and their applications in different contexts, the most predominant AI products used within and across each context, as well as how children’s developmental outcomes are impacted by the use of these AI products. Where applicable, visualisations such as tables, graphs and figures will be used to synthesise the data across contexts and AI products used to support early development of young children.

This study aims to identify the key factors driving excessive alcohol and salt consumption in Ghana, both of which are modifiable risk factors for diseases such as cardiovascular conditions and cancers. Using the socio-ecological model (SEM), we qualitatively examine stakeholder perspectives to gain a comprehensive understanding of the influences contributing to these unhealthy consumption patterns.

A qualitative study was conducted using semi-structured interviews. Transcripts were analysed thematically, with identified drivers mapped onto the corresponding levels of influence within the SEM.

The study included 21 purposively sampled stakeholders from government and academic institutions in Ghana, including policymakers, practitioners and researchers.

Drivers of excessive salt and alcohol consumption were identified across all five levels of the SEM. At the intrapersonal level, disregard for health risks was a key factor. Community-level drivers included easy access to unhealthy foods and cultural norms promoting alcohol use at social events and salt in traditional dishes. At the societal and policy levels, inadequate regulation of the alcohol and food industries was found to reinforce lower-level drivers, further encouraging unhealthy consumption.

This study highlights the multilevel influences on alcohol and salt consumption, emphasising the interactions across SEM levels. It highlights that addressing unhealthy consumption is not solely a matter of personal responsibility, demonstrating that societal and policy factors play a significant role in shaping health and dietary behaviours. The findings underscore the need for comprehensive public health strategies that address influences at multiple levels to effectively reduce excessive alcohol and salt intake.

Providing care in a patient’s preferred language improves health outcomes and patient satisfaction. In Ontario, access to French-speaking physicians (FSPs) is estimated using FSP-to-Francophone population ratios and compared with total physician-to-total population ratios. This approach fails to consider the fact that FSPs also serve non-Francophone patients and that Francophones must compete with the entire population to access FSPs. As a result, this approach inaccurately suggests that Francophones have better access to language-concordant care than Anglophones/Allophones. We propose a novel approach to address this issue, enabling unbiased comparisons of access to language-concordant care across linguistic groups.

This secondary analysis of publicly available data containing linguistic variables for the Ontario population (Statistics Canada, 2021 Census) and for family physicians (FPs) (College of Physicians and Surgeons of Ontario, January 2024) calculated competition-adjusted ratios and probabilities of accessing language-concordant care.

Ontario, Canada.

Census and publicly available data on FPs (ie, those providing comprehensive family medicine care to the community) and the Ontario population were obtained.

Province-wide, the crude ratio of FSPs per 1000 Francophones was 3.46. After adjusting for competition, the ratio of FSP per 1000 population was 0.12, compared with a general physicians-per-1000 population ratio of 1.05. Anglophones/Allophones attached to a FP have a 100% probability of receiving care in English compared with an 11.4% probability for Francophones to receive care from a FSP. Expressed otherwise, Anglophones/Allophones are 8.8 times more likely to receive language-concordant care (ie, care in English) than Francophones.

Although crude physician-to-population ratios overestimate Francophones’ access to FSPs, competition-adjusted ratios and probabilities demonstrate that they are much less likely to access language-concordant care than Anglophones/Allophones. This novel approach has equity implications for health human resources planning and can be applied to other linguistic minority groups and healthcare providers.

The teaching profession plays a crucial role in society. From educating and forming future generations to fulfilling various administrative tasks and managing expectations and experiences that reach beyond the classroom—teachers face immense demands on their time, energy, and emotional resources. Consequently, they are subject to high work burden. This is reflected in the high prevalence of burnout, anxiety, and depression among teachers. A scoping review of factors associated with these outcomes in teachers is required to inform the further development of preventive occupational medicine strategies. In this scoping review, we aim to (i) identify and (ii) appraise the factors (eg, workplace, environmental, lifestyle, psychological) associated with burnout, anxiety, and depression specific to secondary school teachers and to (iii) synthesise the findings from the perspective of preventive occupational medicine.

The scoping review will be performed following the PRISMA extension for Scoping Reviews guidance. A systematic literature search will be conducted in the Medline, Web of Science Core Collection, PsychInfo, and Cochrane Library databases using search terms pertinent to secondary school teachers as the population of interest and depression, anxiety, and burnout as the outcomes of interest. Returned articles from the database search published pre-2017 will be excluded for the following reasons; namely, (a) that current literature will more closely reflect the current demands of the teachers, (b) the timing fits with recent systematic reviews highlighting burnout, anxiety, and depression as major problems among teachers, and (c) it facilitates feasibility of review in terms of the volume of studies. Remaining records will then be deduplicated and screened against predefined eligibility criteria that also add focus on teachers and these outcomes. Relevant data concerning factors associated with burnout, anxiety, and depression in teachers will be extracted and mapped. A narrative appraisal of included studies will be employed that will be specific to the validity of the results regarding factors (exposures, mediators, effect modifiers) that may affect the outcomes of interest (as opposed to more generic appraisal of the entirety of individual articles). Findings will be narratively synthesised from the perspective of preventive occupational medicine.

Formal ethical approval is not required as primary data will not be collected in this study. The findings of this study will be disseminated through peer-reviewed publication, conference presentation, and condensed summaries for key stakeholders and partners in the field (including teachers, schools, and governing bodies).

The protocol was registered on the Open Science Framework on 26.06.2025 and can be identified using the following link: https://doi.org/10.17605/OSF.IO/BKX56.

Hospital falls persist as a major threat to patient safety. This study aimed to develop an interprofessional reference standard to prevent, manage and report hospital falls.

A Delphi consensus methodology, informed by the Conducting and Reporting Delphi Studies guideline, was used to design the reference standard. An interprofessional expert panel (n=47) of health professionals, researchers, policymakers and consumers participated in three Delphi rounds. Following the review of clinical guidelines, an e-Delphi survey was developed and piloted to derive 60 initial items for the standard. Two iterative rounds of e-Delphi surveys were distributed via Research Electronic Data Capture and included free-text questions and 9-point Likert scales. An online consensus meeting followed, to ratify the final standard.

In the first Delphi round, there was over 80% agreement for 44/60 items to be included in the reference standard. This increased to 48/60 items in Round 2. At the final consensus meeting, 12 items still did not reach consensus for inclusion and one was added, yielding 49 items. Items that replicated text according to falls with injury/without injury were combined, resulting in 42 items in the final reference standard. Agreed items included: (1) brief screening of falls risk on hospital admission; (2) comprehensive falls assessment for inpatients who are older, frailer or have complex conditions; (3) single interventions (such as environmental adaptations and exercise); (4) multifactorial interventions; (5) education of patients, families and staff; (6) optimising local falls hospital policies, procedures and leadership capability; (7) optimising documentation and reporting; (8) improving accreditation processes; (9) workforce redesign to augment falls education. Items that did not reach agreement (n=12) pertained to alarms, bed rails, grip socks, artificial intelligence, volunteers and care bundles.

This new reference standard provides a checklist for staff, patients, managers and policymakers to reduce unwanted variations in prevention, management and reporting of hospital falls.

ANZCTR 386960

Suicide is a leading cause of preventable death worldwide. Evidence supports the impact of providing active contact for individuals who have attempted suicide. The current systematic review and meta-analyses aim to investigate the effects of suicide prevention strategies implemented through remote and synchronous technology-based interventions.

Systematic review, narrative synthesis and meta-analysis.

Electronic databases (PubMed, PsycINFO, Scopus and Web of Science) and grey literature sources (ClinicalTrials.gov and Google Scholar) were searched until December 2024.

Eligible articles assessed suicide prevention interventions for participants over 12 years with prior suicidal behaviour. Eligible study designs included randomised controlled trials and non-randomised clinical trials published in English or Spanish.

Screening, selection process, data extraction and risk of bias assessment were performed independently by two reviewers. Data on suicide-related factors and adherence to treatment were extracted. Meta-analyses were conducted to determine effect sizes (Hedges’ g) for suicidal ideation, risk ratios (RR) for suicide attempts and Peto odds ratios (OR) for suicide. Heterogeneity was assessed using the Cochrane’s Q test, tau² statistic and I² value. Publication bias was investigated employing funnel plots and Egger’s test.

A total of 28 studies, comprising 10 015 participants in the intervention group and 10 726 in the comparison group, were included in the systematic review and meta-analyses. Synchronous remote-based interventions were effective in preventing repeated suicide attempts at 1 month (RR 0.73, 95% CI 0.62 to 0.85, I²=0.0%, Q=0.70, tau²=0.00), 6 months (RR 0.56, 95% CI 0.34 to 0.95, I²=85.4%, Q=54.92, tau²=0.36) and 12 months (RR 0.68, 95% CI 0.49 to 0.96, I²=87.6%, Q=72.63, tau²=0.27). Additionally, these interventions were associated with a reduction in suicide-related deaths at 18 months (Peto OR 0.18, 95% CI 0.08 to 0.44, I²=0.0%, Q=0.03, tau²=0.00). Effects on suicidal ideation were not statistically significant at any time point (Hedges’ g –0.07 to –0.28, I²=0.0 to 69.3%, Q=1.16 to 7.38, tau²=0.00 to 0.14).

Synchronous remote-based interventions demonstrate a potential benefit in preventing suicide attempts and deaths by suicide and may serve as an adjunct to usual treatment; however, the effect on suicidal ideation appears limited. The observed heterogeneity warrants caution when interpreting these findings. Future research should prioritise methodological enhancements to improve the quality and consistency of evidence, as well as investigate the mediating processes underlying their effectiveness in reducing suicidal behaviour.

CRD42021275044.

This study explored how Structured Medication Reviews (SMRs) are being undertaken and the challenges to their successful implementation and sustainability.

A cross-sectional mixed methods online survey.

Primary care in England.

120 clinical pharmacists with experience in conducting SMRs in primary care.

Survey responses were received from clinical pharmacists working in 15 different regions. The majority were independent prescribers (62%, n=74), and most were employed by Primary Care Networks (65%, n=78), delivering SMRs for one or more general practices. 61% (n=73) had completed, or were currently enrolled in, the approved training pathway. Patient selection was largely driven by the primary care contract specification: care home residents, patients with polypharmacy, patients on medicines commonly associated with medication errors, patients with severe frailty and/or patients using potentially addictive pain management medication. Only 26% (n=36) of respondents reported providing patients with information in advance. The majority of SMRs were undertaken remotely by telephone and were 21–30 min in length. Much variation was reported in approaches to conducting SMRs, with SMRs in care homes being deemed the most challenging due to additional complexities involved. Challenges included not having sufficient time to prepare adequately, address complex polypharmacy and complete follow-up work generated by SMRs, issues relating to organisational support, competing national priorities and lack of ‘buy-in’ from some patients and General Practitioners.

These results offer insights into the role being played by the clinical pharmacy workforce in a new country-wide initiative to improve the quality and safety of care for patients taking multiple medicines. Better patient preparation and trust, alongside continuing professional development, more support and oversight for clinical pharmacists conducting SMRs, could lead to more efficient medication reviews. However, a formal evaluation of the potential of SMRs to optimise safe medicines use for patients in England is now warranted.

The TRAjectory of knee heaLth in runners (TRAIL) study is a prospective cohort study investigating the long-term knee health trajectories of runners with and without a heightened osteoarthritis risk. This study aims to describe the recruitment results and baseline characteristics of the TRAIL cohort.

Runners aged 18–50 years and running ≥3 times and ≥10 km per week on average in the past 6 months were eligible. Participants were recruited via running podcasts, running clubs and social media between July 2020 and August 2023. Data were collected at study enrolment and at a face-to-face baseline testing session, which occurred a median of 33 weeks (IQR 18 to 86 weeks) after enrolment. Follow-up data collection is ongoing.

Out of 462 runners who completed an online registration form, 268 runners enrolled, of which 135 had a history of knee surgery (46% females) and 133 were non-surgical controls (50% females). 60% of the surgery group had undergone anterior cruciate ligament reconstruction, 33% meniscus and/or cartilage surgery, and 7% other knee surgery. 54 participants previously enrolled were unable to continue in the study before attending baseline data collection. Of the 214 runners who remained in the study and attended baseline data collection, 108 had a history of knee surgery (49% females) and 106 did not have a history of knee surgery (51% females).

Participants will be followed for 10 years through ongoing patient-reported outcomes and continuous monitoring of training loads using wearable devices. At baseline, 4- and 10-year follow-up, knee MRI and knee-health patient-reported outcomes will be collected to evaluate structural and symptomatic knee osteoarthritis progression. Data will inform guidelines for safe running practices and rehabilitation post-knee surgery.

We evaluated the performance of risk models that incorporate ambulatory ECG data and clinical information for prediction of healthcare expenditures related to heart failure (HF) and stroke events in treated and untreated patients.

A retrospective cohort study of Medicare patients who underwent Zio XT ambulatory monitoring in the USA was conducted between 2014 and 2020.

14-day ambulatory ECG data and claims data were evaluated in the study sample which included 89 923 patients in the HF hospitalisation group, 75 870 in the new-onset HF group and 90 159 in the stroke hospitalisation group. Predictive models for new-onset HF, HF hospitalisation and stroke hospitalisation were generated using LASSO Cox regression with ambulatory ECG variables and components of the CHA₂DS₂-VASc. For each outcome, we scored patients using standardised linear predictors from three composite risk models, and we evaluated the association between risk score and total Medicare cost.

The following hazard ratios per one SD increase in the new risk score were observed for the model that included all CHA₂DS₂-VASc components and ECG variables: HF hospitalisation in treated 2.94, 95% CI 2.75 to 3.15; new-onset HF in treated 1.84, 95% CI 1.75 to 1.93; HF hospitalisation in untreated 3.51, 95% CI 3.23 to 3.82; and new-onset HF in untreated 1.92, 95% CI 1.85 to 2.00. Risk scores generated by the model were also predictive of Medicare cost in both treated and untreated patients, with patients in the high-risk category for all outcomes having the greatest Medicare costs during 1 year of follow-up.

Integrating arrhythmia data from ambulatory ECG monitoring into clinical risk models allows for better prediction of healthcare utilisation and cost in both treated and untreated patients at high risk for HF and stroke events.

Ebola virus disease remains a significant public health concern. For protection from Ebola virus, the main target populations are epidemiologically identified and often include healthcare workers and refugees. These target populations are also routinely offered vaccines for other vaccine-preventable diseases. However, concomitant use of rVSVG-ZEBOV-GP with other vaccines is not recommended, given the absence of data regarding its reactogenicity and antigen-specific immunogenicity profile when co-administered. The EbolaCov trial aims to inform whether rVSVG-ZEBOV-GP can be administered concurrent to a Pfizer–BioNTech COVID-19 booster dose without an unacceptable increase in reactogenicity and/or loss of humoral immunogenicity to Ebola vaccine antigen.

This is a single-centre, randomised, single-blinded, vaccine safety and immunogenicity study in healthy adults living in Rwanda. Seventy-two participants will be randomised in a 1:1 ratio to two study groups, the first receiving rVSVG-ZEBOV-GP with a placebo, the second group receiving rVSVG-ZEBOV-GP concurrently with a Pfizer–BioNTech COVID-19 booster dose. The primary outcome measures are quantitative serum anti-glycoprotein (GP) antibody responses, as measured by ELISA, 28 days after vaccination, and frequency and severity of adverse events in the 7 days following vaccination. Secondary outcome measures include day 28 and day 180 serum anti-GP and serum SARS-CoV-2 anti-spike protein-specific geometric mean antibody titres.

This trial was approved by the Rwanda National Ethics Committee (reference 442/2024) and the University of Birmingham (reference ERN_2661-Jun2024). All participants were required to provide written informed consent in accordance with good clinical practice. Dissemination of results will be through conference presentations and peer-reviewed publications.

Pan African Clinical Trials Registry (PACTR202407764378004) and ClinicalTrials.gov (NCT06587503)

This review aims to map oral health plans, programmes and policies worldwide in countries with universal health coverage.

This protocol describes a scoping review that will follow the Joanna Briggs Institute methodology and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Scoping Review checklist, guided by the PCC framework: Population—countries with universal health coverage (78 globally recognised); Concept—oral health plans, programmes and policies; Context—integration into health systems. Searches will be conducted in MEDLINE (PubMed), Scopus, Web of Science, Embase, Health System Evidence and Epistemonikos, with no restrictions on date, language or study type. Grey literature will be accessed through Google Scholar, OpenThesis and the Brazilian Digital Library of Theses and Dissertations. Official documents from ministries of health and international bodies, including the WHO and the International Monetary Fund, will also be reviewed. Two independent reviewers will screen titles and abstracts; a third will resolve disagreements. Eligible records will undergo full-text review. Data will be extracted into predefined categories reflecting health system components: population, structure, services, governance and oral health indicators. Results will be presented using tables, charts and figures to illustrate strategies and innovations.

This review does not involve primary data collection and does not require ethical approval. Results will be disseminated through a peer-reviewed publication and presentations at academic conferences and scientific events.

Open Science Framework (DOI 10.17605/OSF.IO/RCP8N).

Current treatments for alcohol use disorders (AUD) have limited efficacy. A previous 28-day pilot trial of N-acetyl cysteine (NAC) vs placebo found NAC to be feasible and safe, with evidence of improvement on some measures of alcohol consumption. Thus, the primary aim of the NAC-AUD study is to examine the therapeutic and cost-effectiveness of NAC vs placebo in improving treatment outcomes for AUD. We will also examine the (i) effect of NAC vs placebo on mood, markers of liver injury, cognition and hangover symptoms; and (ii) predictors of any response.

This double-blind trial will randomise participants with AUD to a 12-week regimen of either NAC (2400 mg/day) or placebo. All participants will receive medical management. The primary drinking outcome will be the number of heavy drinking days (HDDs) per week, validated by phosphatidylethanol (PEth). Secondary alcohol-related outcomes will include standard drinks per drinking day (SDDD) per week and absence of any HDDs. Other secondary outcomes will include markers of liver injury, depression, anxiety, craving, hangover symptoms, cognition and blood oxidative stress markers. We will also examine the cost-efficacy of NAC vs placebo.

Ethics approval for the study has been granted by The Sydney Local Health District Ethics Review Committee (X21-0342& HREC2021/ETH11614). There are no restrictions on publication from the sponsor or other parties.

NCT05408247.

Elevated lipid profiles increase the risk of atherosclerotic cardiovascular disease (ASCVD), a leading cause of mortality worldwide. Despite the availability of lipid-lowering therapy (LLT), adherence to therapy and achievement of Low-Density Lipoprotein Cholesterol (LDL-C) target levels remain suboptimal. Coronary artery disease (CAD) presents substantial public health challenges, with LDL-C goal attainment rates reported to be between 30.0% and 54.0%. The EDHIPO MARCA (Evaluación De adherencia a la terapia HIPOlipemiante en pacientes de Muy Alto Riesgo CArdiovascular) study aims to evaluate LDL-C target achievement among Colombian patients with CAD.

This is a retrospective and multicentre study aiming to evaluate LDL-C target achievement within 12 months of coronary angiography across multiple Colombian institutions. Data will be retrospectively extracted from medical records corresponding to the years 2011, 2012, 2016, 2017, 2021 and 2022, which were selected to correspond with the European Society of Cardiology/European Atherosclerosis Society guideline updates. Inclusion criteria included patients ≥18 years old with confirmed CAD and LDL-C reports recorded during outpatient follow-up. The study will evaluate a minimum sample size of 5000 patients, with data collected through medical records and managed using the REDCap platform. Statistical analyses will be conducted to assess LDL-C target achievement, associated factors and temporal trends using mixed-effects models. Uncertainty will also be explored through sensitivity analysis. The EDHIPO MARCA study will provide key insights into LDL-C target achievement in Colombia, contributing to both regional and global CAD management. Its findings will be used to help shape public health policies and serve as a foundation for future prospective research and interventions aimed at mitigating the burden of cardiovascular disease.

This study was approved by the Comité de Ética en Investigación Biomédica of Fundación Valle del Lili, the coordinating institution and creator of the study protocol. Each participating centre will obtain approval from its local ethics committee prior to data collection. Data will be collected in a de-identified manner, ensuring confidentiality. In accordance with Colombian Resolution 8430, this study is classified as 'no-risk', and informed consent was not required. The findings will be disseminated through scientific events and published in international peer-reviewed journals to contribute to cardiovascular disease management and public health policies.

Flexible bronchoscopy (FB) is widely used for diagnostic and therapeutic procedures in pulmonary medicine. However, FB can cause respiratory and haemodynamic complications, especially in patients with pre-existing lung and/or cardiovascular comorbidities. Despite the range of oxygenation and ventilatory approaches available to prevent these risks, evidence regarding their real-world application and clinical impact is limited. The OxyFOB study aims to assess the prevalence and outcomes of various oxygenation and ventilatory support strategies used during FB across Europe.

The OxyFOB study is a large, prospective, international, observational cohort study which aims to involve over 10 000 FB procedures across European centres. Eligible participants include all adults undergoing FB for diagnostic, therapeutic or procedural indications. Data are collected via a standardised electronic case report form and encompass demographic information, procedural details and clinical outcomes. The primary endpoint is the prevalence of oxygenation and ventilatory support strategies: conventional oxygen therapy, high-flow oxygen therapy, continuous positive airway pressure, non-invasive ventilation and invasive mechanical ventilation. Secondary outcomes include periprocedural respiratory and haemodynamic events, patient comfort, dyspnoea and postprocedural complications. Statistical analyses include descriptive statistics, subgroup comparisons and multivariate logistic regression.

The study has received ethical approval from the coordinating centre (protocol n. 22/2022 on the 20 January 2022, by the ‘Comitato Etico Sezione Area Centro - Regione Calabria’) and all participating sites. Informed consent is given from all patients or their legal representatives. Findings will be disseminated through peer-reviewed publications and presentations at international meetings. Data will be managed and made available on reasonable request to support further research.

ClinicalTrials.gov ID: NCT05681962. Registered January 2023.

Muscle-invasive bladder cancer (MIBC) is an aggressive type of cancer. About 50% of patients will die from the disease within 5 years despite radical treatment. This implies that in many patients, the disease has already spread at the time of radical treatment, even though imaging shows no signs of metastasis. We hypothesise that the standard local staging method, transurethral resection of the bladder tumour (TURBT), is partly responsible for tumour cell spread. Furthermore, TURBT (and re-TURBT in many patients) contributes to a significant delay to definitive therapy. The aim of this randomised study is to determine whether multiparametric MRI (mpMRI) of the bladder, in combination with a single outpatient bladder tumour biopsy for histological confirmation, is a safer, faster, less costly and, therefore, more cost-effective diagnostic pathway than TURBT to detect or rule out MIBC.

BladParadigm is a two-arm multicentre randomised controlled trial (RCT) conducted in the Netherlands. Over a 3-year period, patients with clinically suspected MIBC without evidence of metastases will be recruited and randomised 1:1 to either TURBT or 3-Tesla mpMRI with same-day outpatient bladder biopsy. The Vesical Imaging Reporting and Data System (VI-RADS) will be used to standardise mpMRI reporting. Patients will undergo definitive treatment based on the results of the TURBT or mpMRI. The study is powered to demonstrate that the mpMRI-based strategy is at least non-inferior to standard TURBT in patients treated with radical cystectomy alone, assuming a relative hazard of 0.55. The required sample size is 360 patients (180 TURBT, 180 mpMRI). The primary outcome is 2-year progression-free survival. Progression will be assessed by imaging, according to the current standard of care. Secondary outcome measures are time to definitive treatment, quality of life (EuroQol 5D-5L), healthcare costs and cost-effectiveness.

This study has received ethical approval from the Medical Ethical Committee Oost-Nederland (NL83685.091.23). All participants will provide written informed consent prior to inclusion. Findings of this study will be disseminated through peer-reviewed, open-access publications, presentations at scientific conferences and stakeholder briefings.

NCT05779631.

To assess atrial fibrillation (AF) burden, symptoms and quality of life (QoL) in endurance athletes with paroxysmal AF.

Prospective cohort study.

Otherwise healthy endurance athletes with paroxysmal AF in Norway, Australia and Belgium. The current study presents baseline measurements collected before the intervention of a randomised controlled trial on effects of individually tailored training adaptation.

AF burden (percentage time in AF) was measured by insertable cardiac monitors (Confirm Rx, Abbott). AF-related symptoms and QoL were assessed using the Atrial Fibrillation Effect on QualiTy-of-Life Questionnaire (AFEQT) with any score

43 athletes (age 57±10 (mean±SD), range 33–75 years, 3 women) were included. The athletes were monitored for 50±18 days. Median AF burden was 0.18% (IQR 0%–2.6%). Out of 29 athletes with at least one AF episode, 21 (72%) had AF episodes >60 min. 13 athletes (30%) had AFEQT overall score 60 min were associated with reduced QoL (mean AFEQT score 78 vs 90, p=0.001 and 78 vs 90, p=0.001, respectively). There were large individual variations between the athletes concerning AF burden, symptoms and QoL.

Although most athletes were still competing, more than half had troublesome symptoms. One-third had reduced QoL, which was associated with higher AF burden and longer duration of AF episodes. Variations between the athletes highlight the need for individually tailored AF management in athletes with paroxysmal AF.

NCT04991337.