OptiNeoCare: optimisation of routine care in the management of severe perinatal asphyxia in full-term or near-term newborns – study protocol for analysis of suboptimal care by confidential inquiries and e-self report

Introduction
Severe perinatal asphyxia at term or near term remains a critical public health issue, associated with high risks of neonatal death and hypoxic-ischaemic encephalopathy (HIE). Despite improved clinical guidelines, suboptimal care persists in many cases, and previous audits have demonstrated that up to 50% of asphyxia cases could be associated with suboptimal care. OptiNeoCare is a French study which aims to assess the prevalence and determinants of suboptimal obstetric and neonatal care and evaluate its potential impact on neonatal outcomes.

Materials and methods
This prospective, population-based observational study will include newborns ≥36 weeks’ gestation with severe perinatal asphyxia across 12 French perinatal networks (213 maternity units). Inclusion criteria comprise neonatal death or moderate/severe HIE with confirmed biochemical markers of asphyxia. Data will be collected prospectively from labour wards, transport teams and neonatal intensive care units using an electronic case report form, and the in-situ team will be invited to complete a morbi-mortality review (MMR). Approximately 336 cases will be included over 12 months, with 25% randomly selected for confidential enquiry by two experts. The quality of care will be assessed based on a structured classification of medical errors (diagnostic, therapeutic, preventive and systemic) by a panel of experts including an obstetrician or midwife and a paediatrician. Root cause analysis will identify determinants of suboptimal care. A concordance analysis will compare findings from MMRs and confidential enquiries. Statistical analysis will include multivariable logistic regression to explore associations between care quality and neonatal outcomes.

Ethics and dissemination
Ethical approval was granted by the Ethics Committee for Research in Obstetrics and Gynaecology. Informed non-opposition is required from participants. Results will be shared with participating centres, healthcare professionals and through scientific dissemination.

Trial registration number
ClinicalTrials.gov ID: NCT06322732.

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Coronary atherosclerosis screening in asymptomatic adults using coronary artery calcium for cardiovascular prevention: a systematic review of randomised controlled trials and prospective cohorts

Objectives
To review the available evidence of screening for atherosclerosis in adults in a primary prevention setting with coronary artery calcium scoring (CACS) on the impact on cardiovascular (CV) risk factor control, health behaviour and clinical events.

Design
Systematic review, reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

Data sources
We searched MEDLINE, Embase and Cochrane Central Register of Controlled Trials through 22 January 2025.

Eligibility criteria
We included randomised controlled trials (RCTs) and prospective cohorts, without language restrictions, comparing adults without cardiovascular diseases undergoing CACS to a control group that either did not undergo CACS or where the participants and physicians were blinded to its result. Outcomes included changes in CV risk factor control, CV therapy, changes in health behaviour at follow-up and clinical events (all-cause and CV mortality and non-fatal CV events).

Data extraction and synthesis
Two independent reviewers extracted data and assessed the risk of bias. Due to substantial heterogeneity among the included studies, a quantitative analysis was not possible.

Results
We identified seven RCTs and one observational study, with participants ranging from 56 to 43 447 with a total of 51 554. Populations were heterogeneous with a mean age range of 42–64 years, % women ranging from 21% to 100% and mean baseline CACS from 1.37 to >100 Agatston units. Interventions following CACS were also heterogeneous, ranging from simply communicating results to participants to initiating statin therapy for detectable CACS. One RCT demonstrated improvement regarding blood pressure (BP) (n=2137; change in systolic BP: CACS: –5 mm Hg; control: –7 mm Hg; p=0.02), several an improvement in blood lipids between groups (five studies, n=3693; eg, low-density lipoprotein (LDL) cholesterol: range –6.0 to –4.9 mg/dL). Results regarding CV medication (seven studies, n=51 104) were more discrepant, with some studies showing a decrease and others an increase in indication for or usage of CV medication. Three trials (n=3338) investigated adherence to CV medication, with only one showing increased adherence to statins (CACS: 63.3%; control: 45.6%; p=0.03). Five trials (n=3692) investigated behavioural changes, with one showing an increased motivation to change lifestyle (CACS: 94%; control: 62.8%; p=0.002) and another a higher adherence in self-reported physical activity (CACS: 96%; control: 59%; p

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Patient-Reported Experience Measures in Vascular Surgery Enhancement (PREMIERE) study: protocol for a mixed-methods study to develop and validate a vascular surgery-specific patient-reported experience measure

Introduction
Patient-reported experience measures (PREMs) capture patients’ healthcare journey experiences. No validated PREMs are specific to vascular surgery patients. This study aims to develop and validate a vascular surgery-specific PREM to assess patient experience and satisfaction.

Methods and analysis
Patient Reported Experience Measures In Vascular Surgery Enhancement Study is a two-phase multisite sequential mixed-methods study. The qualitative phase will develop a draft PREM; the quantitative phase will validate it. The study will be conducted across three major vascular units in Wales. Up to 40 patients and healthcare professionals will participate in the qualitative phase. Approximately 150–200 patients will be recruited for the quantitative validation. Inclusion criteria are: (1) age ≥18; (2) recent vascular procedure; (3) inpatient vascular care; (4) not cognitively impaired; (5) consent to participate and (6) English or Welsh proficiency. Primary outcomes will be construct validity and reliability. Secondary outcomes will include patient engagement, healthcare provider perspectives and health system impacts. Thematic analysis will be conducted using NVivo. Psychometric validation will include item analysis, internal consistency testing and factor analysis.

Ethics and dissemination
The study was approved by the London—Camberwell St Giles Research Ethics Committee, coordinated by the Health Research Authority and Health and Care Research Wales (REC reference: 24/PR/0522).

Trial registration number
NCT06363175.

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Influence of concurrent oral calcium carbonate supplementation on steady-state pharmacokinetics of once daily oral raltegravir in persons with HIV: a protocol for a prospective open-label non-randomised study in Canada

Introduction
Raltegravir is a potent HIV-integrase strand transfer inhibitor (INSTI). Despite its strong activity against HIV-1 strains resistant to other antiretroviral drug classes, it is usually used in combination with other antiretroviral drugs due to the empirical requirement for anti-HIV drug combinations to ensure effective anti-retroviral therapy (ART). As an early-arriving INSTI, raltegravir is clinically familiar for its safety, tolerability and treatment effectiveness. High-dose calcium carbonate formulated as an antacid (as opposed to a supplement formulation) taken orally together with raltegravir is known to reduce systemic raltegravir exposure due to chelation and reduced absorption. This study aims to assess the effect of daily calcium carbonate antacid as TUMS Ultra Strength (US) administration in lower doses, as currently used for oral calcium supplementation, on the steady-state pharmacokinetics (PKs) of once-daily oral raltegravir.

Methods and analysis
This is an open-label, three-treatment series in three periods in a single group, fixed-sequence PK study in 12 healthy adult volunteers with HIV on ART. Subjects will take 1200 mg of raltegravir single QD oral dose alone for 7 days (period one), then raltegravir 1200 mg with calcium carbonate 500 mg from day 8 to day 14 (period two) and raltegravir 1200 mg with calcium carbonate 1000 mg from day 15 to day 22 (period three). We will conduct serial PK sampling from observed dosing on days 7, 14 and 21, with 24-hour PK sampling scheduled for days 8, 15 and 22. Follow-up will continue until day 51.

Ethics and dissemination
This study will adhere to the ICH GCP Guidelines and the Declaration of Helsinki. Ethics approval was obtained from the Ottawa Health Science Network Research Ethics Board under study ID 20190750–01 hour. Informed consent will be obtained from all participants prior to enrolment. This protocol will be published in a peer-reviewed journal prior to the study’s completion and closure. Results generated from this activity will also be reported in a peer-reviewed journal.

Trial registration number
NCT04258475.

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[Articles] Intravascular lithotripsy for the treatment of calcified coronary lesions in individuals of advanced age: a post-hoc analysis of the multicentre, prospective BENELUX-IVL study

In patients of advanced age, IVL for calcified coronary lesions demonstrates a favorable safety and efficacy profile, with high technical success and low rates of device-related adverse events. Nonetheless, larger studies with extended follow-up are warranted to confirm these findings and establish long-term outcomes.

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Follow-up observation of eye movements in multiple system atrophy and Parkinsons disease: a cohort study

Objectives
We aimed to explore the changes in oculomotor deficiencies during the follow-up of patients with multiple system atrophy (MSA) and Parkinson’s disease (PD), and to investigate the value of dynamic eye movement examination in their differential diagnosis.

Design
This was a cohort study conducted from 2017 to 2023.

Setting
The Movement Disorders Clinic at a tertiary hospital in Beijing, China.

Participants
56 patients with PD and 13 patients with MSA from an initial cohort of over 1100 with parkinsonism were included in the final longitudinal analysis.

Outcome measures
Multisystem evaluations were performed at baseline. Videonystagmography (VNG) was repeated to assess oculomotor dysfunction at baseline and during follow-up. Abnormalities in the fixation and gaze-holding test, without-fixation test, reflexive and memory-guided saccade tests, smooth pursuit test and optokinetic test were qualitatively and quantitatively recorded and statistically analysed.

Results
The median follow-up time of MSA (16 months) was significantly shorter than that of PD (27 months). In MSA, the incidence of abnormalities in fixation and gaze-holding tests (0% vs 30.8%, p=0.030), reflexive saccade tests (46.2% vs 84.6%, p=0.039, with slow saccades increasing from 7.7% to 46.2%, p=0.027) and smooth pursuit tests (38.5% vs 76.9%, p=0.047) increased significantly from baseline to the end of follow-up. In PD, no significant changes were revealed during follow-up.

Conclusions
MSA exhibited more rapid and prominent changes in fixation and gaze-holding tests, reflexive saccades and smooth pursuit tests than PD. Dynamic observation of oculomotor function may aid in the differential diagnosis of Parkinson’s syndrome.

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Effects of febuxostat on heart failure patients with asymptomatic hyperuricaemia: a retrospective cohort study

Objectives
To investigate the effects of uric-acid-lowering therapy with febuxostat in asymptomatic hyperuricaemic patients with heart failure.

Methods
In this retrospective cohort analysis, we included consecutive hospitalised patients with heart failure and concomitant asymptomatic hyperuricaemia in Yangzhong People’s Hospital from 1 April 2018 through 1 April 2022. Febuxostat was used to lower serum uric acid. The primary endpoint was defined as a composite of cardiovascular death, recurrent hospitalisation and emergency room visit for cardiovascular (CV) reasons. Additional endpoints included changes in echocardiography measures, Kansas City Cardiomyopathy Questionnaire (KCCQ) scores and 6-minute walk test (6MWT) distance from baseline to the most recent clinic visit. Cox analysis was used to determine HR between febuxostat and the control group after adjustment for age, sex, body mass index, serum creatinine, atrial fibrillation and coronary heart disease and the Kaplan-Meier curve was used to describe survival.

Results
979 patients were included in the final analysis (505 in the febuxostat group vs 474 in the control group). In a follow-up duration of 16±9 months, uric acid was significantly lower in the febuxostat group compared with the control group (p

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Triangular perspectives of healthcare providers, patients and their families on ICU palliative care: a protocol for a systematic review of qualitative studies

Introduction
In the intensive care unit (ICU), palliative care encounters obstacles such as decision conflicts, psychological stress and cultural differences among patients, families and healthcare providers. The well-being and the care quality of patients are influenced by these factors. The highly technical and curative-focused environment of the ICU presents a challenge for palliative care without appropriate integration. Certainly, it is imperative to comprehend these issues and devise strategies to reconcile curative and palliative needs. This paper employs qualitative metaintegration to appraise the experiences and perspectives of palliative care in the ICU, emphasising its outcomes, barriers and the necessity of balanced care and treatment.

Methods and analysis
This study conducted a comprehensive search of both the published and unpublished literature (such as grey literature) from a variety of databases, concerning PubMed, Google Scholar, Cochrane Library, CINAHL, Web of Science, Embase, Scopus, PsycINFO, CNKI, Wanfang, CBM and VIP, up to 10 July 2024. The articles will be retrieved and incorporated into EndNote X9 to facilitate organisation. Two independent researchers will evaluate the studies using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Qualitative Research, and a third researcher will resolve all discrepancies. Data extraction and results synthesis will be performed independently based on the JBI qualitative data extraction tool. Finally, the ConQual method will be employed to estimate the calibre of the compiled results.

Ethics and dissemination
The systematic review was conducted without the necessity of obtaining ethical clearance from a research committee, as it analysed previously published studies that did not contain any personal identifying information of participants. The review’s findings were presented to key stakeholders and submitted for consideration in peer-reviewed journals.

PROSPERO registration number
CRD42024571594.

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Engagement of Indigenous peoples in commercial tobacco reform strategies: a scoping review protocol

Introduction
The tobacco and nicotine industry fuels tobacco-related addiction, disease and death. Indigenous peoples experience a disproportionate burden of commercial tobacco-related morbidity and mortality. Over the past two decades, significant progress has been made in reducing smoking prevalence among Indigenous peoples; however, smoking remains a leading contributor to the burden of death and disease. This review will summarise evidence on commercial tobacco resistance and/or eradication strategies, including policy reforms, in relation to Indigenous peoples across Oceania, the Pacific Islands and North America.

Methods and analysis
This review will follow guidelines from the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews and will be conducted in accordance with the Joanna Briggs Institute (JBI) methodology for scoping reviews. This review will consider academic and grey literature published since 1 January 2000. The following electronic databases will be searched for relevant primary research articles and commentaries: PubMed, Scopus, Informit, Web of Science and PsycINFO. Additional searches will be conducted in ProQuest to identify relevant grey literature. Papers will be screened by two reviewers to determine eligibility, followed by full-text data extraction. Findings will be synthesised descriptively for each review question and by region. Studies included in the review will be assessed against criteria for Indigenous engagement in research.

Ethics and dissemination
This protocol was led by Indigenous interests, needs and rights of Indigenous peoples, consistent with the United Nations Declaration on the Rights of Indigenous Peoples (UNDRIP), the WHO’s Framework Convention on Tobacco Control and ethical practice. This review was conceptualised with Indigenous leadership and through engagement, including but not limited to the Indigenous lived experience of the authors (MK, E-ST, HC, PNH, PH, SAM, AW, SW and RM). This review supports the global goal of eradicating commercial tobacco-related harms – reframing commercial tobacco use as a structurally imposed harm sustained by colonial and commercial forces rather than personal choice. Findings from this review will be shared with Indigenous partners and communities who requested this work and will be submitted for peer-reviewed publication.

Review registration
Open Science Framework https://osf.io/wxqcb

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Treatment and exercise strategies and their associations with pain and disability: a prospective cohort study of patients with long-lasting low back pain

Objectives
To describe self-reported treatment and exercise strategies among patients with long-lasting low back pain (LBP) 1 month after consultation at a specialised hospital-based Medical Spine Clinic and evaluate their associations with changes in pain and disability 1 and 3 months after consultation.

Design
Prospective cohort study using questionnaire data before consultation (baseline) and 1 and 3 months after consultation.

Setting
Specialised hospital-based Medical Spine Clinic, Denmark.

Participants
1686 patients with long-lasting LBP completed the baseline questionnaire; 908 patients responded at 1 month, of them 623 responded at 3 month.

Interventions
Patients were categorised by treatment (physiotherapy, chiropractic treatment, physiotherapy+chiropractic treatment and no recommended treatment) and exercise strategy (exercise continued, exercise ceased, exercise initiated and not exercising).

Primary and secondary outcome measures
Pain was assessed by the numeric rating scale (NRS: 0–10), and disability was assessed by the Oswestry disability index (ODI: 0–100).

Results
1-month postconsultation, half of the patients received no recommended treatment; most others received physiotherapy (42%). Nearly half of the patients continued exercise, 28% continued to be inactive, and 22% initiated exercise. For the population as a whole, pain changed by –0.74 (95% CI –0.90; –0.58) and –1.02 (95% CI –1.22; –0.83) points on the NRS at 1- and 3-month follow-up, respectively, and disability by –2.65 (95% CI –3.51; –1.78) and –4.48 (95% CI –5.59; –3.38) points on the ODI. Differences between treatment strategies were small. However, the two groups not exercising improved less compared with those who continued exercise when adjusted for age, sex and baseline level (order of magnitude from 0.07 to 1.18 points on the NRS and from 4.01 to 9.08 points on the ODI). For pain, these group differences were statistically significant at 1 month (p

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Azithromycin as adjunctive treatment for uncomplicated severe acute malnutrition (AMOUR): study protocol for a double-masked randomised controlled trial

Introduction
Amoxicillin is recommended for children with uncomplicated severe acute malnutrition (SAM). However, some trials have shown no difference in amoxicillin for nutritional recovery in children with SAM compared with placebo. In addition, amoxicillin treatment requires two times per day dosing for 7 days, which may influence adherence. Azithromycin is a broad-spectrum antibiotic that can be provided as a single dose and has reduced mortality in children aged 1–59 months when provided by mass drug administration. The AMOUR trial is designed to assess amoxicillin, azithromycin and placebo as part of outpatient treatment of uncomplicated SAM.

Methods and analysis
This double-masked randomised controlled trial will enrol 3000 children over 3 years in an individually randomised 1:1:1 allocation to azithromycin, amoxicillin or placebo arms and follow them for 12 months. Children eligible to enrol in the study will be aged 6–59 months and have uncomplicated non-oedematous SAM as defined by weight-for-height Z-score

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Rationale and protocol for a longitudinal cohort study of children with cerebral palsy in China assessing functional developmental trends, genetic aetiology and imaging

Introduction
Cerebral palsy (CP), the most common physical disability in children, imposes substantial economic and psychological burdens on families and society. The clinical management of CP remains challenging due to the limited efficacy of current treatments and the heterogeneity of its aetiologies and clinical presentations. This study aims to investigate the functional changes and identify influencing factors in Chinese children with CP. Through analysis of neuroimaging and genetic data, this study seeks to inform the development of preventive and therapeutic strategies and guide healthcare decision-making for this population.

Methods and analysis
This prospective cohort study aims to recruit 2051 children with CP across China. Baseline data will include demographic and clinical characteristics. Participants will undergo comprehensive assessments, including motor, cognitive, language, social, behavioural, nutritional, pain, sleep and quality-of-life domains, with regular follow-up evaluations. Trio whole-exome sequencing and detailed neuroimaging and musculoskeletal imaging will also be performed. This study will also assess caregivers’ quality of life and emotional burden. Mendelian randomisation will be adopted to evaluate genetic contributions to functional outcomes and their causal relationship with health metrics. Analytical methods will include correlation analysis, logistic regression (binary and multivariate), linear and non-linear mixed-effects models and structural equation modelling.

Ethics and dissemination
Ethics approval was granted by the Research Ethics Committee of Guangzhou Women and Children’s Medical Center (No.2023-346A01). All study procedures will adhere to the approved protocol. Study findings will be disseminated through peer-reviewed publications and conference presentations.

Trial registration number
ChiCTR2300079017.

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Efficacy of cashew nut protein immunotherapy: protocol for a single-centre randomised controlled trial in a Polish paediatric population

Introduction
The prevalence of food allergies, particularly IgE-mediated allergies, is rising in developed countries, with cashew nut allergy emerging as a significant public health concern due to its potential for severe anaphylaxis and frequent association with atopic disorders. Cashew nuts are among the most common allergens in Europe and Australia, often involving cosensitisation with pistachios, hazelnuts and other allergens. Diagnosis relies on clinical history, measurement of specific IgE (sIgE) levels, skin prick tests (SPT) and oral food challenges (OFCs). Current management strategies focus on allergen avoidance and emergency interventions, whereas oral immunotherapy (OIT) represents a promising approach to desensitisation. Recent studies, including the NUT CRACKER trial, have reported high desensitisation rates with cashew OIT, although these are associated with a risk of adverse events. This study introduces a novel randomised controlled trial aimed at evaluating the efficacy and safety of cashew immunotherapy in children.

Methods and analysis
This randomised, open-label, parallel-group trial, with a 2:1 allocation ratio, will be conducted at the Department of Paediatric Pneumology and Allergology, Medical University of Warsaw, Poland. Thirty-nine children, aged 4–17 years, with confirmed IgE-mediated cashew allergy via open OFC will be enrolled. Participants in the experimental group will undergo OIT, which involves gradually increasing doses of cashew protein up to a maintenance dose of 1200 mg. The duration of OIT will range from 12 to 60 weeks, depending on individual baseline tolerance. The control group will receive standard management, including strict cashew avoidance and emergency response strategies to accidental exposure, for 1 year.
The primary endpoint is to determine the proportion of participants tolerating a 4043 mg dose of cashew protein at the study’s end in the OIT group compared with the control group. Secondary outcomes include evaluating the safety profile of OIT, assessing changes in laboratory markers such as sIgE and IgG4 levels for cashew and the major cashew allergen Ana o 3, analysing basophil activation test responses and measuring changes in SPT wheal diameter at baseline and study completion.

Ethics and dissemination
The study has been approved by the Ethics Committee of the Medical University of Warsaw (approval number: KB/267/2023). Study findings will be published in peer-reviewed journals and presented at international conferences.

Trial registration number
NCT06328504.

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