Trends in high remnant cholesterol level and its risk factors among US adults using NHANES data from 1999 to 2020: a serial cross-sectional study

Objectives
To describe the trends in high remnant cholesterol (HRC) prevalence and identify its risk factors.

Design
A serial cross-sectional study.

Setting
Data from the National Health and Nutrition Examination Survey (NHANES) 1999–2020 were analysed.

Participants
A total of 24 658 adults aged ≥18 years with fasting total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) measured were included.

Outcome measure
Serum TC was measured using an enzymatic method. HDL-C and TG were quantified using photometry. Low-density lipoprotein cholesterol (LDL-C) was estimated by using the Sampson formula. Remnant cholesterol (RC) was defined as TC–HDL-C–LDL-C. HRC was defined as RC≥0.78 mmol/L.

Results
The multivariable-adjusted survey-weighted HRC prevalence decreased from 26.6% (1999–2002) to 13.7% (2015–2020) with a 5.4% reduction per year (plinear-trend

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Effectiveness of music with auditory beat stimulation in reducing state anxiety in Canadian students with trait anxiety: protocol for a randomised controlled trial

Introduction
Undergraduate students report a high level of trait anxiety, which is a risk factor for further psychological decline if unmanaged. Music-based interventions are cost-effective and have been found to improve indices of anxiety. More recently, music with auditory beat stimulation (ABS) has been shown to improve symptoms of anxiety to a greater extent than music alone. While there is limited empirical evidence, music interventions with ABS may also be effective at targeting neurophysiological markers of anxiety. The aim of this study is to evaluate the effectiveness of a novel music with ABS intervention on self-report and neurophysiological indices of anxiety in undergraduate students with trait anxiety. It is hypothesised that relative to a pink noise control, listening to music with ABS will lower self-reported anxiety, reduce salivary cortisol, increase heart rate variability, increase theta and alpha-band electroencephalography (EEG) power and decrease beta and gamma-band EEG power.

Methods and analysis
Fifty Canadian undergraduate students who self-report experiencing anxiety will be recruited for this two-arm randomised controlled trial. Participants will be randomised to a single music session with ABS or pink noise; each intervention ranges from 24 min to 27 min. Outcomes will be assessed at baseline and immediately following the intervention and will be self-reported anxiety and affect (the State-Trait Inventory of Cognitive and Somatic Anxiety and the Self-Assessment Manikin), salivary cortisol, heart rate variability measured by ECG and cortical measures of anxiety (measured by EEG). Repeated measures analyses of covariance will be performed to evaluate the effect of condition assignment on outcome measures.

Ethics and dissemination
This study will be conducted under the Declaration of Helsinki. This study was approved by the Toronto Metropolitan University Research Ethics Board (REB-2020-068) and registered on ClinicalTrials.gov (NCT05442086). The findings of this study will be published in a peer-reviewed journal.

Trial registration number
NCT05442086.

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Routine testing for group B streptococcus in pregnancy: protocol for a UK cluster randomised trial (GBS3)

Introduction
It is unclear whether routine testing of women for group B streptococcus (GBS) colonisation either in late pregnancy or during labour reduces early-onset neonatal sepsis, compared with a risk factor-based strategy.

Methods and analysis
Cluster randomised trial.

Sites and participants
320 000 women from up to 80 hospital maternity units.

Strategies
Sites will be randomised 1:1 to a routine testing strategy or the risk factor-based strategy, using a web-based minimisation algorithm. A second-level randomisation allocates routine testing sites to either antenatal enriched culture medium testing or intrapartum rapid testing. Intrapartum antibiotic prophylaxis will be offered if a test is positive for GBS, or if a maternal risk factor for early-onset GBS infection in her baby is identified before or during labour. Economic and acceptability evaluations will be embedded within the trial design.

Outcomes
The primary outcome is all-cause early (

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New Support for Old Medications in Resistant Hypertension

The term resistant hypertension has been variably applied to patients with high blood pressure (BP) since at least the 1960s. Specific definitions have evolved over time to align with advances in treatment and BP goals. In 2018, the American Heart Association updated its definition of resistant hypertension as uncontrolled BP levels (≥130/80 mm Hg) despite use of 3 different medication classes (typically a calcium channel blocker, renin-angiotensin system inhibitor, and diuretic) at maximal (or maximally tolerated) doses. Patients taking 4 or more medications regardless of BP control are also included in the definition. Determining true resistant hypertension requires the exclusion of white-coat hypertension (ie, uncontrolled clinic-measured BP, with either home or ambulatory readings at goal) and medication nonadherence. Resistant hypertension is a complex multifactorial condition, and it must be acknowledged that basing its definition on a specific BP threshold and number of drugs is inherently subjective in some regards.

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Morning vs Nighttime Hypertension Medication Dosing

Normal circadian rhythm of blood pressure (BP), defined as a BP decline of 10% to 20% at night, is an important predictor of cardiovascular health and an indicator of cardiovascular disease (CVD) risk when absent. For treatment of hypertension, it has been standard practice to dose antihypertensive medications in the morning to address higher daytime BP levels; the effects of altering timing of drug dosing on circadian rhythm have not been convincingly delineated.

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CT Scans Linked to More Cancer Cases Than Previously Estimated

Although computed tomography (CT) is a useful tool for detecting tumors and diagnosing other medical conditions, it exposes patients to ionizing radiation, a known carcinogen. If current CT practices persist, the scans could eventually account for an estimated 5% of new cancer diagnoses each year, a new risk model published in JAMA Internal Medicine found.

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Global prevalence of chronic kidney disease and associated risk factors in children and adolescents: protocol for a systematic review and meta-analysis

Introduction
While chronic kidney disease (CKD) is well characterised in adults, less is known about the prevalence of CKD in children and adolescents, where it is rare and associated with unique characteristics and implications for long-term health outcomes. This study protocol outlines a systematic review to assess the global prevalence of CKD in children and adolescents along with causes and associated risk factors. This is warranted to better characterise prevalence and to identify at-risk groups that would benefit from screening efforts. We will explore the risk and burden of CKD and its variations by sociodemographic characteristics (age group, race, sex/gender) and geographical regions (country, International Society of Nephrology region and income groups based on World Bank country classifications).

Methods and analysis
We will conduct a systematic review of studies reporting on the prevalence of CKD in children and adolescents following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols 2015 (PRISMA-P-2015) and the PRISMA 2020 methodological guidelines (PRISMA 2020). Searches will be undertaken in the following databases with the date range from 2000 to date: Ovid MEDLINE, Ovid Embase, CINAHL, Cochrane Library, ProQuest Dissertations & Theses Citation Index (via Clarivate), Web of Science Core Collection, Google Scholar and grey literature sites (registries, government reports) to identify studies that report on the prevalence of CKD in children and adolescents from ages 0 to 18. The primary outcome will be the global prevalence of CKD in children and adolescents. Secondary outcomes will include the causes of and risk factors for CKD, and examining differences and temporal trends in CKD prevalence across countries, geographical regions, income levels and sociodemographic characteristics.

Ethics and dissemination
No direct involvement with patient data will be used in this systematic review, as data will be obtained from previously published reports. Ethical approval is therefore not required. Our findings will be published in an open-access peer-reviewed journal and presented at scientific conferences.

PROSPERO registration number
CRD42024547467.

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Nursing research landscape in Malaysia: a systematic scoping review protocol on journal publications from 2015 to 2024

Introduction
The nursing profession has undergone significant evolution over the past century, shifting from a role traditionally viewed as an auxiliary to physicians to one of autonomous healthcare professionals equipped with specialised skills and expertise. This shift is driven by the increasing recognition of the importance of evidence-based practice in enhancing patient outcomes and advancing the field of nursing. Consequently, nursing research has emerged as a critical priority in the profession. This study seeks to explore the nursing research landscape in Malaysia, where data remain limited, by examining trends before, during and after the COVID-19 pandemic.

Methods and analysis
This scoping review will be conducted following the Arksey and O’Malley framework, using four electronic databases: PubMed, Scopus and CINAHL for journal articles published between 2015 and 2024, and Web of Science for conference proceedings from the same period.

Ethics and dissemination
The findings from this scoping review will provide an overview of the nursing research landscape in the Malaysian context, offering insights that could guide the future advancement of nursing research in the country. The results will be disseminated through submission to a peer-reviewed scientific journal for publication. Ethical approval is not required for this scoping review, as it involves the synthesis of data from available published literature.

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Trends in the prevalence of cardiovascular disease, defined as ECG abnormalities and/or self-reported events, in Mauritius between 1987 and 2021: analysis of data from seven large population-based surveys

Objective
To estimate the prevalence of coronary heart disease (CHD) in Mauritius. Over the last half century, rapid socioeconomic development has taken place in the multiethnic Mauritius. It is unclear if this is paralleled with an increasing prevalence of CHD.

Design
Repeated cross-sectional population-based studies.

Setting
Mauritius.

Participants
Seven population-based surveys were performed in Mauritius between 1987 and 2021. Altogether, 29 997 participants aged 35–74 years were included.

Measures
Except in 2004 and 2021, all participants were examined with an ECG. ECG changes were classified as ‘probable CHD’ and ‘possible CHD’ according to the Minnesota Code model. Participants were asked about previous myocardial infarction, stroke and angina pectoris as told by a doctor. An affirmative answer to any of these questions was labelled as the presence of cardiovascular disease (CVD). Since 2009, questions about previous coronary bypass surgery and percutaneous coronary intervention were included. The prevalence estimates were age and sex standardised to the 2008 Mauritian population. Multivariable logistic regression evaluated associations between traditional CVD risk factors and CHD.

Results
The prevalence (with 95% CI) of probable CHD according to ECG did not increase between 1987 and 2015, 1.6% (1.2–2.1%) and 1.9% (1.5–2.3%), respectively, whereas the prevalence of possible CHD decreased, 23.7% (22.3–25.1%) and 17.3% (16.2–18.3%), respectively. Self-reported CVD did not increase between 1987 and 2021. Male sex, diabetes, impaired glucose tolerance (IGT), hypertension, smoking and self-reported history of CVD were associated independently with probable CHD, whereas female sex, IGT, hypertension, high cholesterol and self-reported history of CVD were associated independently with possible CHD. Ethnicity did not associate with probable CHD but with possible CHD. Postload plasma glucose associated with probable and possible CHD.

Conclusions
The prevalence of probable CHD according to ECG and the prevalence of self-reported history of CVD did not increase in Mauritius. Traditional cardiovascular risk factors were associated significantly with the presence of probable and possible CHD.

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Mapping the use of extended reality (XR) in radiation oncology education: a scoping review protocol

Introduction
As the field of radiation oncology continues to evolve with rapidly advancing technologies, the need for innovative educational methods is critical. Extended reality (XR) technologies—including virtual reality, augmented reality and mixed reality—have emerged as transformative tools in medical education. While the potential of XR in healthcare education is recognised, there is a lack of comprehensive exploration specifically in the context of radiation oncology education. This scoping review aims to map the existing literature on XR technologies in radiation oncology training and education, identify barriers to their adoption and highlight opportunities for broader integration into curricula.

Methods
This scoping review will follow the Arksey and O’Malley framework with enhancements by Levac et al and will adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines. A comprehensive search will be conducted across databases, including MEDLINE, Scopus and Web of Science, to identify relevant studies on the use of XR technologies in radiation oncology education. Studies will be selected based on predetermined inclusion criteria using the population, concept, context framework. Data extraction will focus on the types of XR technologies used, educational settings, learning outcomes, barriers to adoption and methodologies for evaluating XR effectiveness. The results will be synthesised through descriptive statistics and qualitative thematic analysis. A consultation phase will engage experts to refine findings and ensure the practical relevance of the review.

Ethics and dissemination
This protocol does not require ethics approval at the current stage as it involves a scoping review of publicly available literature. Ethics approval will be obtained prior to initiating the consultation phase involving experts. Written informed consent will be obtained from all individual participants included in the study. The study will be conducted in accordance with relevant guidelines and regulations and was approved by the Chang Gung Medical Foundation Institutional Review Board on 13 May 2025 (ref.: 202500731B0). The findings of this review will be disseminated through peer-reviewed publications, conference presentations and tailored executive summaries aimed at educators, policymakers and stakeholders in radiation oncology education.

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What influences preparations of discharge documentation at patient discharge? An interview study with hospital health professionals based on the theoretical domains framework

Objectives
Poor quality handover instructions prepared by hospital staff have been identified as a key threat to safe discharges. To optimise patient safety, it is important to identify and understand the influences on how discharge documentation is prepared by hospital staff. The aim of this study was to systematically identify and explore important barriers and enablers to the preparation of high-quality discharge documentation by healthcare professionals (HCPs) for primary care teams at patient discharge.

Setting and participants
HCPs from different staff groups (doctors, nurses, pharmacists, occupational and physiotherapists) participated in online interviews.

Design
Semistructured interviews informed by the theoretical domains framework (TDF), to identify key influences on the preparation of discharge documentation. Anonymised transcripts were analysed thematically using a combined inductive-deductive approach. Themes were framed as influences on the preparation of discharge documentation. The likely importance of influences was decided through iterative team discussions structured on predetermined criteria. Criteria included whether the influence was an existing enabler, whether beliefs about the influences were expressed voluntarily and how often they were mentioned.

Results
12 HCPs were interviewed (5 junior doctors, 1 advanced nurse practitioner, 2 nurses, 1 occupational therapist, 1 physiotherapist and 2 pharmacists). Of 44 influences identified, 10 were deemed most important in the preparation of discharge documentation, spread across five TDF domains: knowledge (eg, lack of awareness of guidelines), skills (experience of hospital staff), social and professional role and identity (effective team communication), environmental context and resources (eg, software limitations) and social influences (eg, lack of feedback).

Conclusions
This study identified 10 important influences on how discharge documentation is prepared by hospital staff. These influences are potential targets for subsequent interventions to improve the quality of discharge documentation and patient safety during discharge.

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Implementing best practice for peripheral intravenous cannula use in Australian emergency departments: a stepped-wedge cluster-controlled trial and health economic analysis protocol

Introduction
Over one billion adults attend emergency departments (EDs) internationally every year, including 6.6 million in Australia. Up to half of these patients have a peripheral intravenous catheter (PIVC) inserted. Although healthcare workers believe that placing a cannula is helpful (‘just in case’), PIVCs often remain idle. PIVC insertion is painful for patients, takes clinicians’ attention away from other care, has adverse outcomes and causes major economic and environmental burden. Our aim is to codesign an implementation toolkit to reduce unnecessary PIVC insertions and improve other national quality indicators using an implementation science framework.

Methods and analysis
A stepped-wedge cluster-controlled trial will be conducted in nine ED sites (clusters) across Australia. The interventions will be codesigned with and adapted to sites based on local context. The interventions are evidence-based multimodal intervention (MMI) and aligned to the 2021 Australian Commission for Safety and Quality in Health Care National PIVC Clinical Care Standard. The Consolidated Framework for Implementation Research and Learning Health System will be used to guide implementation. Interventions will be phased across three steps (three sites per step), and each site will collect control and postintervention data using mainly routinely collected clinical data. Each site will be allocated to receive the intervention at one of three study steps. Implementation strategies will tailor broad clinician and consumer engagement, policy changes, education, audit and feedback and clinical champions, along with environment and equipment changes, to each site. The primary objective is to reduce the proportion of adult patients who have a PIVC inserted by 10%. We will evaluate the clinical, implementation and cost-effectiveness of the intervention.
Study findings will be used to conduct a health economic analysis, develop an implementation toolkit and inform a sustainable roadmap for national roll-out. This will meet the needs of a diverse range of EDs nationally and internationally.

Ethics and dissemination
The protocol was approved by the Monash Health Human Research Ethics Committee (HREC Reference Number: HREC/100808/MonH-2023-390692(v3)). The outcomes of this trial will be disseminated through peer-reviewed publications, conference presentations and communication with study partners and stakeholders including professional colleges and the Australian Commission for Safety and Quality in Health Care.

Trial registration number
Australian New Zealand Clinical Trials Registry registration number: ACTRN12623001248651. Date of registration: 1 December 2023. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=386256&showOriginal=true&isReview=true

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Indapamide or chlorthalidone to reduce urine supersaturation for secondary prevention of kidney stones: protocol for a randomised, double-blind, cross-over trial (INDAPACHLOR)

Introduction
Kidney stones constitute a major global healthcare problem and are characterised by high recurrence rates. Thiazide and thiazide-like diuretics (thiazides) have been the standard medical treatment for the prevention of kidney stone recurrence. This clinical routine has recently been challenged by the findings of the large NOSTONE trial that failed to show superiority of hydrochlorothiazide at doses up to 50 mg daily over placebo in preventing a composite of clinical or radiological recurrence in patients at high risk of kidney stone recurrence. If these results also apply to the longer-acting and more potent thiazides indapamide and chlorthalidone remains unknown. No head-to-head comparison of different thiazides for kidney stone recurrence prevention or for the established proxies of recurrence risk, urine relative supersaturation ratios, has ever been conducted.

Methods and analysis
INDAPACHLOR is a single-centre, randomised, double-blind, cross-over trial evaluating the efficacy of indapamide or chlorthalidone compared with hydrochlorothiazide in lowering urine relative supersaturation ratios for calcium oxalate and calcium phosphate in individuals with idiopathic calcium kidney stones. Participants will be allocated to indapamide 2.5 mg once daily, chlorthalidone 25 mg once daily and hydrochlorothiazide 50 mg once daily in a random sequence. The three consecutive active treatment periods of 28 days each will be separated by wash-out periods of 28 days. Inclusion criteria are age ≥18 years and ≥2 stone episodes in the last 10 years with calcium-containing kidney stones (containing ≥50% of calcium oxalate, calcium phosphate or a mixture of both). Patients with secondary causes of calcium kidney stones are excluded. The primary outcomes are the changes in the relative supersaturation ratios of calcium oxalate and calcium phosphate from baseline to day 28 of each treatment period. Secondary outcomes include changes in 24 hours urine and blood parameters from baseline to day 28 of each treatment period. The study targets enrolment of 99 participants to achieve 80% power for detecting a 20% reduction in the relative supersaturation ratios of calcium oxalate and calcium phosphate when treated with indapamide or chlorthalidone and hydrochlorothiazide.

Ethics and dissemination
The study was approved by the Ethics Commission Bern, Switzerland, and the Competent Authority Swissmedic. Results will be disseminated through peer-reviewed publications and conference presentations.

Trial registration numbers
ClinicalTrials.gov (NCT06111885) and Swiss National Clinical Trials Portal (SNCTP000006156).

Protocol version
Version 4.0, 29 November 2024.

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Efficacy of subanaesthetic esketamine on the prevention of postoperative delirium in older adult patients after cardiovascular surgery: protocol for a single-centre, randomised, double-blind, placebo-controlled trial (SEPDOC trial) in China

Introduction
Postoperative delirium (POD) is a common and serious complication in older adult patients undergoing cardiovascular surgery. Esketamine is known for its anti-inflammatory and neuroprotective properties. While it has shown preventive effects on POD in those not undergoing cardiovascular surgery, its efficacy in older adult patients undergoing cardiovascular surgery remains uncertain. Therefore, we herein aimed to evaluate the preventive effect of intraoperative subanaesthetic esketamine on POD in this specific population.

Methods and analysis
This single-centre, randomised, double-blind, placebo-controlled trial will enrol 778 patients aged 60–80 years undergoing open-heart cardiovascular surgery in China, from September 2023 to December 2025. The participants will be randomly assigned in a 1:1 ratio to the following groups: the esketamine group and the control group. In the esketamine group, esketamine (2 mg/mL) will be administered intravenously at a dosage of 0.3 mg/kg over 10 min following tracheal intubation, followed by a continuous infusion at 0.15 mg/kg/h until the end of the surgery. Patients in the control group will receive a placebo following the same dosage and regimen. The incidence of POD will be the primary outcome and will be assessed twice daily from the first to the seventh postoperative day. The postoperative sleep quality, duration of postoperative mechanical ventilation, and length of hospital and intensive care unit stay will be the secondary outcomes.

Ethics and dissemination
Ethical approval was obtained from the Institutional Review Board of Fuwai Central China Cardiovascular Hospital (No. 2023068). Public disclosure is guaranteed post-trial, and the results will be published in a peer-reviewed scientific journal.

Trial registration number
ChiCTR2300074395.

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Exploring facilitators and barriers in the financial model of hospitals: a qualitative case study on prehabilitation from the Netherlands

Objectives
To explore facilitators and barriers in the financial model of hospitals when a change in a care pathway is implemented.

Design
A qualitative research reported according to the Consolidated Criteria for Reporting Qualitative Research.

Setting
Five hospitals in the Netherlands, between February and September 2023.

Participants
28 interviewees with 7 different stakeholders: (director of) healthcare procurement, contracting manager, financial, business or project manager, physical therapist, board of Medical Consultant Group and surgeon.

Results
The absence of permanent funding in the hospital reimbursement model and the allocation of available resources in the internal hospital distribution model are the two most important barriers when implementing prehabilitation for patients with colorectal cancer. The main facilitator was found to be the internal provision of spare budget. Lump sum agreements are the preferred contract type because they may facilitate internal substitution of budgets according to need. Bundling primary and hospital care funding is recommended to overcome barriers in the financial model. Activity-based budgeting is the preferred budgeting method because budgets can be adjusted over time according to costs. Cost reduction can only be achieved when prehabilitation is offered to more patients. In addition to an appropriate financial model, preconditions like the involvement of a medical specialist and sense of urgency in the organisation should also be arranged.

Conclusions
The financial model of hospitals may affect the implementation of changes in care pathways. Despite barriers in both the reimbursement and the distribution model, it is possible to facilitate this transformation.

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