Study protocol for a descriptive analysis of non-invasive prenatal testing uptake and performance in singleton and twin pregnancies using Ontario birth registry data

Introduction
Despite the availability of funded first-tier non-invasive prenatal testing (NIPT) for twin pregnancies in Ontario, Canada, research gaps persist regarding the feasibility and effectiveness of NIPT in this demographic. This protocol documents our planned comprehensive overview of twin data from the large Ontario provincial registry and evaluates the performance of NIPT among singleton and twin pregnancies.

Methods and analysis
We will conduct a descriptive study using routinely collected data housed in the Better Outcomes Registry & Network Ontario. The study population will include all singleton and twin pregnancies with an estimated date of delivery between 1 September 2016 and 31 March 2023. We will compare patient characteristics, NIPT uptake and test performance metrics (including sensitivity, specificity, positive predictive value and negative predictive value) between singleton and twin pregnancies. Subgroup analyses will be conducted, including assessment by the mode of conception, trimester of initial screening, age of the pregnant individual and eligibility for publicly funded first-tier NIPT.

Ethics and dissemination
This study has received approval from the Research Ethics Boards of the Children’s Hospital of Eastern Ontario (24/01PE) and the University of Ottawa (H-04-24-10309). Results will be disseminated through scientific conferences and publication in a peer-reviewed journal. By making our protocol and findings publicly available, we aim to establish a foundational reference for future investigations in Ontario. Additionally, we seek to support the design and implementation of further studies on NIPT in twin pregnancies in Canada and elsewhere.

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Exploring the causes of elevated kinesiophobia in post-coronary stenting patients: a qualitative analysis in a cardiac rehabilitation setting

Objectives
The primary aim of this study is to investigate the factors contributing to the development of kinesiophobia in patients following coronary artery stent implantation, integrating perspectives from both patients and healthcare professionals. The main hypothesis is that understanding and methods for effectively overcoming the fear of exercise and improving the effectiveness of cardiac rehabilitation require further exploration from both patient and professional viewpoints.

Design
This qualitative study used a semi-structured interview approach to gather data from participants.

Setting
The study was conducted at a hospital in Gansu province, China, focusing on the level of care provided to cardiac rehabilitation patients.

Participants
A total of 11 cardiac rehabilitation patients identified as having kinesiophobia (Tampa Scale for kinesiophobia Heart, TSK-SV Heart >37) through screening and nine healthcare professionals participated in the study. The selection criteria included patients undergoing cardiac rehabilitation and professionals involved in their care.

Results
The study identified a core theme, ‘Navigating Fear and Uncertainty’, encompassing five themes that elucidate how various factors contribute to the prevalent phenomenon of kinesiophobia among patients. These were further delineated into 11 subthemes: (1) physiological factors (fatigue, negative illness experiences), (2) psychological factors (hypervigilance, psychogenic anxiety and depression), (3) capacity factors (reduced physical abilities, lack of rehabilitation knowledge and skills), (4) motivational factors (low exercise self-efficacy, rehabilitation cognitive errors) and (5) support systems (primary caregivers, healthcare professionals and medical support). The results provide a qualitative understanding rather than quantitative measures, hence no CIs or statistical significance levels are provided.

Conclusions
The kinesiophobia observed in patients following coronary artery stent implantation stems from the combined influence of multiple factors, warranting early assessment and intervention by healthcare professionals. The study suggests that healthcare institutions should address the practical concerns faced by cardiac rehabilitation patients and enhance familial, medical and societal support systems to increase patient engagement and compliance with exercise rehabilitation. Further research is needed to develop and validate interventions based on these findings.

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[Articles] Cost-effectiveness of tuberculosis infection screening at first reception into English prisons: a model-based analysis

Universal tuberculosis screening and preventive treatment for new receptions into English prisons is not cost-effective by the usual threshold of £30,000. However, targeting high-risk groups could be cost-saving. Tuberculosis interventions should explore ways to reduce LTFU and extramural healthcare in order to meet the needs of those incarcerated while minimizing costs.

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Contrasting cultures of emergency department care: a qualitative study of patients experiences of attending the emergency department for low back pain in the UK

Objectives
This article aimed to explore patients’ experiences of attending the emergency department (ED) for low back pain (LBP) and provides a theoretically informed analysis of the ED cultures perceived by patients to inform their experiences of care.

Design
Multisite, cross-sectional qualitative interview study.

Setting
Four NHS Emergency Departments located in the UK.

Participants
47 adults (aged 23–79 years) who, in the past 6 weeks, had attended the ED for LBP (all types and durations). Purposive sampling was used to gain variation in the recruiting sites, and participants’ LBP and demographic characteristics.

Interventions
Data were collected using individual, semistructured, telephone interviews (median 45 min duration) which were audio-recorded and transcribed verbatim. Analysis was informed using reflexive thematic analysis and ideal type analysis. Cycles of inductive and deductive analysis were undertaken, with Bourdieu’s concepts of field and habitus employed to help explain the findings.

Results
We present three contrasting cultures of ED care for LBP, comprising (1) emergency screening only, (2) ‘cynicism and neglect’ and (3) appropriate and kind care. Taking each culture (field) in turn, we explore important differences in the content and delivery of care. Drawing on Bourdieu’s concepts of field and habitus, we consider the social and institutional norms and misrepresentations likely to underpin the thoughts and behaviours of ED staff (their habitus), and why these tended to vary based on where and by whom the patient was managed in the ED.

Conclusions
Strategies to improve patients’ experience need to review the social and institutional norms that underpin staff habitus, the assumptions informing these norms and the voices that validate and reproduce them.

ISRCTN registration number
ISRCTN77522923.

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Multiple chemical sensitivity (MCS) validity, prevalence, tools and interventions: systematic review protocol

Introduction
Multiple chemical sensitivity (MCS) describes reported adverse reactions to exposure to common chemical agents (solvents, odourants, air pollutants, material or substances) in low doses tolerated by most people. Symptoms involve more than one organ system and responses are triggered by multiple, chemically unrelated substances.

Methods and analysis
The systematic review will aim to answer six questions: Which definitions of MCS have been validated? What is the diagnostic performance of tools for identifying MCS? What is the prevalence and incidence of MCS? What is the empirical evidence that MCS is a distinct disorder? What is the empirical evidence for underlying biological mechanisms for MCS? What are the effectiveness and safety of treatment and management strategies for MCS?
We will conduct a comprehensive search in 22 multidisciplinary databases for primary and secondary research, research registries and clinical practice guideline repositories. We will reference-mine reviews and included studies, and confer with experts. Screening will be conducted in duplicate against prespecified eligibility criteria. Data abstraction will be pilot tested using detailed data abstraction forms to ensure accuracy and minimise ambiguity. Critical appraisal will be specific to the key question. We will synthesise data in comprehensive tables and figures. Where possible, meta-analysis will use random effects models to determine effect sizes.

Ethics and dissemination
This study was determined to be exempt from review (UP-22-00516). The results will be disseminated through a journal manuscript, and the data will be publicly accessible through an online data repository.

PROSPERO registration number
CRD420250645577.

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Assessment of the impact of multi-cancer early detection test screening intervals on late-stage cancer at diagnosis and mortality using a state-transition model

Objective
Multi-cancer early detection (MCED) tests are novel technologies that detect cancer signals from a broad set of cancer types using a single blood sample. The objective of this study was to estimate the effect of screening with an MCED test at different intervals on cancer stage at diagnosis and mortality endpoints.

Design
The current model is based on a previously published state-transition model that estimated the outcomes of a screening programme using an MCED test when added to usual care for persons aged 50–79. Herein, we expand this analysis to model the time of cancer diagnosis and patient mortality with MCED screening undertaken using different screening schedules. Screening intervals between 6 months and 3 years, with emphasis on annual and biennial screening, were investigated for two sets of tumour growth rate scenarios: ‘fast (dwell time=2–4 years in stage I) and ‘fast aggressive’ (dwell time=1–2 years in stage I), with decreasing dwell times for successive stages.

Setting
Inputs for the model include (1) published MCED performance measures from a large case-control study by cancer type and stage at diagnosis and (2) Surveillance, Epidemiology and End Results (SEER) data describing stage-specific incidence and cancer-specific survival for persons aged 50–79 in the US for all cancer incidence.

Outcome measures
We used the following outcome measures: diagnostic yield, stage shift, and mortality.

Results
Annual screening under the fast tumour growth scenario was associated with more favourable diagnostic yield. There were 370 more cancer signals detected/year/100,000 people screened, 49% fewer late-stage diagnoses, and 21% fewer deaths within 5 years than usual care. Biennial screening had a similar, but less substantial, impact (292 more cancer signals detected/year/100,000 people screened; 39% fewer late-stage diagnoses, and 17% fewer deaths within 5 years than usual care). Annual screening prevented more deaths within 5 years than biennial screening for the fast tumour growth scenario. However, biennial screening had a higher positive predictive value (54% vs 43%); it was also more efficient per 100,000 tests in preventing deaths within 5 years (132 vs 84), but prevented fewer deaths per year.

Conclusion
Adding MCED test screening to usual care at any interval could improve patient outcomes. Annual MCED test screening provided more overall benefit than biennial screening. Modelling the sensitivity of outcomes to different MCED screening intervals can inform timescales for investigation in trials.

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Survival status and predictors of mortality among patients with breast cancer in Ethiopia: a systematic review and meta-analysis

Objectives
This study aimed to evaluate survival outcomes and identify key mortality predictors among patients with breast cancer in Ethiopia.

Study design
A systematic review and meta-analysis.

Study participants
The study used 11 primary studies, involving a total of 4131 participants.

Data sources
We searched PubMed, Embase, Web of Science, Scopus and Google Scholar until 7 March 2025, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

Eligibility criteria for selecting studies
All observational studies that had reported the survival status and/or at least one predictor of mortality of women patients with breast cancer were considered.

Data extraction and synthesis
Three independent reviewers (HA, HKN and DGA) used a structured data extraction form to extract the data. To compute the pooled survival and mortality rates, the survival rates at different observation periods and the mortality rates reported in the included studies were extracted.

Results
Eleven studies were analysed. All studies were of good quality based on Newcastle-Ottawa Scale. However, heterogeneity was high (I² = 98.2%, p=0.00). Funnel plots showed significant publication bias. The Grading of Recommendations, Assessment, Development, and Evaluations assessment indicated moderate certainty for mortality rates and predictors, limited by heterogeneity and regional data gaps. The pooled mortality rate was 36% (95% CI: 25% to 46%). The survival rates at 1, 3 and 5 years were 85% (95% CI: 75% to 96%), 66% (95% CI: 48% to 84%) and 22% (95% CI: 1% to 43%), respectively. Key mortality predictors included advanced clinical stage (Adjusted Hazard Ratio (AHR): 4.14; CI: 2.53 to 6.78), rural residence (AHR: 1.65; 95% CI: 1.27 to 2.14), positive lymph node status (AHR: 2.85; 95% CI: 1.50 to 5.44), no hormonal therapy (AHR: 2.02; 95% CI: 1.59 to 2.56), histologic grade III (AHR: 1.76; 95% CI: 1.29 to 2.41), hormone receptor negativity (AHR: 1.54; 95% CI: 1.05 to 2.25) and comorbidities (AHR: 2.24; 95% CI: 1.41 to 3.56).

Conclusion
Breast cancer in Ethiopia poses a high mortality rate primarily due to late-stage diagnosis, rural residency, histologic grade III, positive lymph node status and comorbidities. To improve survival outcomes, it is crucial to expand access to early screening, particularly in rural areas, implement comprehensive treatment protocols and strengthen healthcare infrastructure to address these critical factors.

PROSPERO registration number
CRD42024575074.

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ASPirin for Acute Pneumonia in the elderlY (ASPAPY): protocol of a multicentre randomised double-blind placebo-controlled trial

Introduction
Acute pneumonia (AP) remains a leading cause of death in the older population. Excess risk of death after AP is partly due to cardiovascular (CV) events. We aim to evaluate whether aspirin at a preventive dose (100 mg daily) introduced at the acute phase of AP reduces 90-day mortality.

Methods and analysis
The ASPirin for Acute Pneumonia in the elderlY study is a phase III multicentre randomised double-blind, placebo-controlled, superiority clinical trial, which will investigate the efficacy and safety of aspirin in older patients with AP hospitalised in a French university and non-university hospitals. Patients will be randomised in a 1:1 ratio between two groups receiving daily either 100 mg of aspirin or a placebo, within 84 hours following radiologically proven AP diagnosis for 90 days. This study aimed at assessing the efficacy of aspirin on all-cause mortality after AP at 90 days (D90) (primary objective), D30 and D120 after randomisation, CV mortality, major adverse CV events (MACE) (ie, myocardial infarction, stroke, heart failure, new atrial fibrillation and pulmonary embolism, CV death and sudden death) incidence, length of intensive care unit and hospital stay, unscheduled rehospitalisation, dependence, overall and MACE-free survival, as well as safety outcomes (bleeding incidence). The sample size, calculated considering a 90-day mortality of 25% and a reduction of 10% in the aspirin group, a two-sided alpha risk at 5% and power of 80%, is 500 patients to prove the superiority of aspirin over placebo. To account for screening failures and consent withdrawals, 600 patients (300 per arm) will be included.

Ethics and dissemination
This study has full approval from an independent Ethics Committee. Participants will sign a written informed consent ahead of participation. Findings will be published in peer-reviewed journals and conference presentations.

Trial registration number
EU CTIS: 2024-510811-32-00.

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Serological screening for coeliac disease in an adult general population: the HUNT study

Background
A large proportion of individuals with coeliac disease (CeD) remain undiagnosed.

Objective
The aim of this study was to assess serological screening for CeD in the adult general population.

Design
The study was based on the fourth Trøndelag Health Study, a population-based study performed 2017–2019 in Nord-Trøndelag County, Norway, including 56 042 participants >20 years of age (54% participation rate). Serum samples were analysed with a dual antitransglutaminase 2 (TG2) IgA and IgG assay and seropositive participants were invited to endoscopy with duodenal biopsies. A CeD diagnosis was given if mucosal damage (Marsh grade 3) was found.

Results
Histological evaluation of 657 seropositive participants confirmed CeD in 423. The positive predictive value (PPV) of a positive TG2 IgA was 73.3% (95% CI 69.7% to 77.0%) for biopsy-confirmed CeD. TG2 IgA ≥10 times the upper limit of normal (ULN), as used in the no-biopsy approach in children, increased the PPV to 88.1% (95% CI 84.8% to 91.4%). Primary TG2 IgG response was found in 87 participants, five of whom had biopsy-confirmed CeD. One of the participants with CeD primarily responding with TG2 IgG was IgA deficient. The PPV of a positive TG2 IgG was 5.8% (95% CI 1.9% to 12.9%) and of TG2 IgG ≥10x ULN was 9.5% (95% CI 1.2% to 30.4%) for biopsy-confirmed CeD in TG2 IgA-negative individuals.

Conclusion
The TG2 IgA assay showed excellent abilities as a screening tool for CeD in the adult general population. However, the diagnostic accuracy of TG2 IgG was too poor for selectively identifying individuals with CeD.

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