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Understanding the pathogenesis of uveitis in Ebola virus disease survivors: an observational cohort and cross-sectional study protocol for clinical, molecular virologic and immunologic characterisation

Por: Hartley · C. D. · Linderman · S. · Fashina · T. · Ward · L. · Drews-Botsch · C. · Pratt · C. · Kuthyar · S. · Fernandes · A. F. · Huang · Y. · Choo · C. · Nguyen · N. · Carag · J. · Morgan · J. · Kraft · C. S. · Hewlett · A. · Brett-Major · D. · Schieffelin · J. S. · Garry · R. F. · Grant
Introduction

The 2013–2016 Western African outbreak of the Ebola virus disease (EVD), the largest recorded outbreak since the discovery of Ebola virus (EBOV) in 1976, destabilised local health systems and left thousands of survivors at risk for postacute sequelae, including vision-threatening uveitis. In an EVD survivor with severe panuveitis, the detection of persistent EBOV in the aqueous humour, long after clearance of acute viremia, focused clinical and research attention on the host-EBOV interaction in the unique terrain of ocular immune privilege. Despite the recognition that uveitis is common and consequential in EVD survivors, our understanding of pathogenesis is extremely limited, including the contributions of viral persistence and ocular-specific and systemic immune responses to disease expression. In this study protocol, we outline a multifaceted approach to characterise EVD-associated intraocular inflammation, including the clinical phenotype and complications; the presence of EBOV (or EBOV RNA/antigen) in ocular fluids and tissues; and associated local ocular-specific and peripheral immune responses.

Methods and analysis

We use an observational cohort design, which includes EVD survivors and close contacts of EVD survivors (ie, no documented history of EVD), and we propose disease (clinical examination and imaging), as well as molecular, virologic and immunologic characterisation, to meet research objectives.

Ethics and dissemination

This study has received Institutional Review Board approval from University of Nebraska Medical Centre, Emory University and Sierra Leone Ministry of Health. Findings will be disseminated through peer-reviewed publications.

Percutaneous coronary intervention, coronary artery bypass grafting and mortality from acute myocardial infarction in EU15+ countries, 2006-2020: a secondary analysis of the OECD database

Por: Ojha · U. · Marshall · D. C. · Hammond-Haley · M. · Salciccioli · J. D. · Shalhoub · J. · Hartley · A.
Objective

Coronary revascularisation practices have evolved over the last three decades. This study sought to examine the variations in percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) rates, alongside mortality from acute myocardial infarction (AMI) across a group of 16 high-income countries between 2006 and 2020.

Design

Retrospective observational analysis using data from the Organisation for Economic Co-operation and Development (OECD) database between 2006 and 2020. Estimated annual percent change in revascularisation was analysed using Joinpoint regression model, and mortality rates were evaluated using the locally weighted scatterplot smoothing model.

Setting

Publicly available data on PCI and CABG procedure rates alongside AMI mortality rate from 2006 to 2020.

Participants

16 countries from the OECD database.

Interventions

Not applicable.

Main outcome measures

Standardised PCI and CABG procedure rates and AMI age-standardised mortality rate (ASMR) from 2006 to 2020.

Results

Over the 15 year period, 14.0 million PCI and 2.8 million CABG procedures were collectively recorded across 16 countries. PCI rates varied among nations, but from 2006 to 2020 increased in 11 of the 16 nations overall, led by Finland (+36.0%), Ireland (+34.5%) and France (+31.5%). Meanwhile, CABG rates declined in 14 out of the 16 countries, with Luxembourg (–71.3%), the UK (–62.6%) and Finland (–60.6%) experiencing the most substantial decreases. Throughout the study period, the PCI-to-CABG ratio increased, while AMI ASMR decreased consistently across all countries.

Conclusions

Despite evidence supporting CABG over PCI in specific scenarios, CABG rates have declined, and PCI rates have increased. Possible factors for this trend may include patient preference and advancement in interventional techniques. The varied use of PCI among these nations, alongside a sustained decline in AMI mortality rates, may be expected given the importance of optimal medical therapy in the management of ischaemic heart disease. The results further suggest the significance of factors beyond revascularisation in driving improved outcomes.

What are the exercise barriers, facilitators and preferences of community-dwelling older adults with heart failure with preserved ejection fraction? A qualitative best fit framework analysis

Por: Forsyth · F. · Hartley · P. · Mant · J. · Rowbotham · S. · Sharpley · J. · Wood · A. · Deaton · C.
Objectives

To establish, through patient and public involvement (PPI) events, the exercise barriers, facilitators and preferences of people with heart failure with preserved ejection fraction (HFpEF).

Design

Qualitative ‘best fit’ framework analysis was used to analyse field notes and transcripts collected during three patient and public involvement meetings and three workshops. The best fit framework was based on the COM-B model of behaviour change, which has identified that Capability, Opportunity and Motivation components are essential for Behaviour change. The Consolidated criteria for Reporting Qualitative research checklist was used to structure the report.

Setting and participants: Community dwelling older adults with HFpEF.

Results

24 people with HFpEF (n=16 female, 66%), 2 spouses and 2 people with chronic conditions participated in the PPI meetings and workshops. Multiple exercise-related capability (negative symptoms, functional ability, resilience and self-efficacy and knowledge and skill); opportunity (appealing components, optimal conditions, adequate support); and motivation factors (well-being, physical gains, goal achievement, sense of enjoyment) were identified as essential to facilitating change in exercise behaviours in people with HFpEF.

Conclusions

This study provides insight into capability, opportunity and motivation conditions that people with HFpEF feel are necessary to enable them to engage in exercise-related behaviour change. This work extends previous post hoc work by moving beyond identification of broad influencers that may enable or impede exercise intervention engagement, to identify intervention conditions necessary to affect change.

TRIAGE-GS: protocol for a randomised controlled trial of a genomics-first approach to rare disease diagnosis for patients awaiting assessment by a clinical geneticist

Por: Stanley · K. J. · Chisholm · C. · Gillespie · M. K. · Caluseriu · O. · del Signore · N. · Elango · S. · Hartley · T. · Hewson · S. · Kim · R. H. · McSheffrey · G. · Mendoza-Londono · R. · Sawyer · S. L. · Somerville · M. · Venkataramanan · V. · White-Brown · A. · Telesca · S. · Shickh
Introduction

Rare diseases (RD) are collectively common and often genetic. Families value and can benefit from precise molecular diagnoses. Prolonged diagnostic odysseys exacerbate the burden of RD on patients, families and the healthcare system. Genome sequencing (GS) is a near-comprehensive test for genetic RD, but existing care models—where consultation with a medical geneticist is a prerequisite for testing—predate GS and may limit access or delay diagnosis. Evidence is needed to guide the optimal positioning of GS in care pathways. While initiating GS prior to geneticist consultation has been trialled in acute care settings, there are no data to inform the utility of this approach in outpatient care, where most patients with RD seek genetics services. We aim to evaluate the diagnostic yield, time to diagnosis, clinical and personal utility and incremental cost-effectiveness of GS initiated at the time of referral triage (pre-geneticist evaluation) compared with standard of care.

Methods and analysis

200 paediatric patients referred to one of two large genetics centres in Ontario, Canada, for suspected genetic RD will be randomised into a 1:1 ratio to the intervention (GS first) or standard of care (geneticist first) arm. An unblinded, permuted block randomisation design will be used, stratified within each recruitment site by phenotype and prior genetic testing. The primary outcome measure is time to genetic diagnosis or to cessation of active follow-up. Survival analysis will be used to analyse time-to-event data. Additional measures will include patient-reported and family-reported measures of satisfaction, understanding and perceived test utility, clinician-reported measures of perceived test utility and management impact, and healthcare system utilisation and costs.

Ethics and dissemination

This study was approved by Clinical Trials Ontario. Results will be disseminated, at minimum, via peer-reviewed journals, professional conferences and internal reports to funding bodies. Efforts will be made to share aggregated study results with participants and their families.

Trial registration number

NCT06935019.

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