Showing papers by "John F. Forbes published in 2022"

Common variants in breast cancer risk loci predispose to distinct tumor subtypes

Abstract: Abstract Background Genome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear. Methods Among 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes. Results Eighty-five of 173 variants were associated with at least one tumor feature (false discovery rate < 5%), most commonly ER and grade, followed by PR and HER2. Models for intrinsic-like subtypes found nearly all of these variants (83 of 85) associated at p < 0.05 with risk for at least one luminal-like subtype, and approximately half (41 of 85) of the variants were associated with risk of at least one non-luminal subtype, including 32 variants associated with triple-negative (TN) disease. Ten variants were associated with risk of all subtypes in different magnitude. Five variants were associated with risk of luminal A-like and TN subtypes in opposite directions. Conclusion This report demonstrates a high level of complexity in the etiology heterogeneity of breast cancer susceptibility variants and can inform investigations of subtype-specific risk prediction.

Implementation of clinical guidelines for osteoarthritis together (IMPACT): protocol for a participatory health research approach to implementing high value care

Abstract: The evidence-based interventions of exercise and education have been strongly recommended as part of prominent clinical guidelines for hip and knee osteoarthritis (OA) for more than ten years. Despite the wealth of strong evidence that exists, implementation in practice is sub-optimal. This paper describes the key methodologies used in the co-design, tailoring, and evaluation of the IMPACT project implementation strategies, to confront this problem across multiple levels (micro, meso, macro) in public and private healthcare settings in Ireland.Using a type III hybrid implementation-effectiveness design, a participatory, dynamic and iterative process will be used to tailor and evaluate multi-level implementation strategies using the following stages: 1) Co-design the implementation strategies with key stakeholders using best evidence, a theory-driven implementation framework (Consolidated Framework for Implementation Research), local context and expert consensus; 2) Pilot and evaluate the implementation strategies by training physiotherapists to deliver the evidence-based Good Life with osteoArthritis Denmark (GLA:D®) education and exercise programme using the implementation strategies, and conduct a mixed-methods process evaluation; 3) Adapt the implementation strategies based on implementation process evaluation indicators from stage two. The adapted strategies will be used for scale-up and sustainability in subsequent GLA:D® Ireland training programmes that will be rolled out nationally. Evaluation of effectiveness on patient and cost outcomes will continue up to 12 months post-programme delivery, using an online patient registry and pre-post design.This implementation science project aims to use participatory health research to address a gap in management of OA across public and private healthcare settings. This research has the potential to change practice and promote a policy of exercise and physical activity referral for chronic musculoskeletal disease that utilises community engagement effectively and enacts change 'together', with involvement of researchers, decision-makers, clinicians and patients.

Exploring the perspectives of people with stroke, caregivers and healthcare professionals on the design and delivery of a mHealth adaptive physical activity intervention: a qualitative study protocol

Abstract: Background: Despite recent advances in acute stroke intervention, secondary prevention strategies are lacking. Physical activity (PA) is the second-largest predictor of stroke and a cornerstone of secondary prevention therapies. Interventions to promote PA post-stroke include components aimed at reducing sedentary behaviour and increasing participation in lifestyle PA and structured exercise. Despite guidelines to adapt PA to individuals’ needs, there is no evidence on the empirical development of adaptive PA interventions post-stroke. This study will explore patient, caregiver and multidisciplinary healthcare professional perspectives on the design and delivery of adaptive, personalised PA interventions, delivered using a smartphone application, following mild-to-moderate stroke. Findings will directly inform the protocol of an experimental trial, using a novel adaptive trial design. Methods: A descriptive qualitative study will be undertaken to inform the design, delivery and subsequent acceptability of a smartphone application to reduce sedentary behaviour and promote PA post-stroke. Data will be collected via one-to-one interviews and focus groups and analysed according to a six-step thematic analysis. Findings will be reported in accordance with the consolidated criteria for reporting qualitative research (COREQ) checklist. One-to-one interviews and focus group interviews will be conducted with three stakeholder groups: 1) People post-stroke, who are independently mobile, without communication and cognitive deficits, living in the community, and without other diagnosed neurological conditions. 2) Caregivers (formal and informal) involved in post-stroke care. 3) Healthcare professionals who are members of multidisciplinary stroke teams. Ethics and dissemination: Ethical approval has been granted by the Faculty of Education and Health Sciences Research Ethics Committee at the University of Limerick [Ref: 2019_10_03_ EHS]. Findings will be shared locally with all stakeholder groups, submitted for publication, and will inform the protocol and conduct for a novel and flexible experimental trial, examining the effectiveness of an adaptive PA intervention post-stroke.