Novel linkage approach to join community-acquired and national data.

BACKGROUND: Community optometrists in Scotland have performed regular free-at-point-of-care eye examinations for all, for over 15 years. Eye examinations include retinal imaging but image storage is fragmented and they are not used for research. The Scottish Collaborative Optometry-Ophthalmology Network e-research project aimed to collect these images and create a repository linked to routinely collected healthcare data, supporting the development of pre-symptomatic diagnostic tools. METHODS: As the image record was usually separate from the patient record and contained minimal patient information, we developed an efficient matching algorithm using a combination of deterministic and probabilistic steps which minimised the risk of false positives, to facilitate national health record linkage. We visited two practices and assessed the data contained in their image device and Practice Management Systems. Practice activities were explored to understand the context of data collection processes. Iteratively, we tested a series of matching rules which captured a high proportion of true positive records compared to manual matches. The approach was validated by testing manual matching against automated steps in three further practices. RESULTS: A sequence of deterministic rules successfully matched 95% of records in the three test practices compared to manual matching. Adding two probabilistic rules to the algorithm successfully matched 99% of records. CONCLUSIONS: The potential value of community-acquired retinal images can be harnessed only if they are linked to centrally-held healthcare care data. Despite the lack of interoperability between systems within optometry practices and inconsistent use of unique identifiers, data linkage is possible using robust, almost entirely automated processes.

Conducting public involvement in dementia research: The contribution of the European Working Group of People with Dementia to the ROADMAP project.

BACKGROUND: Dementia outcomes include memory loss, language impairment, reduced quality of life and personality changes. Research suggests that outcomes selected for dementia clinical trials might not be the most important to people affected. OBJECTIVE: One of the goals of the 'Real world Outcomes across the Alzheimer's Disease spectrum for better care: Multi-modal data Access Platform' (ROADMAP) project was to identify important outcomes from the perspective of people with dementia and their caregivers. We review how ROADMAP's Public Involvement shaped the programme, impacted the research process and gave voice to people affected by dementia. DESIGN: The European Working Group of People with Dementia (EWGPWD) were invited to participate. In-person consultations were held with people with dementia and caregivers, with advance information provided on ROADMAP activities. Constructive criticism of survey content, layout and accessibility was sought, as were views and perspectives on terminology and key concepts around disease progression. RESULTS: The working group provided significant improvements to survey accessibility and acceptability. They promoted better understanding of concepts around disease progression and how researchers might approach measuring and interpreting findings. They effectively expressed difficult concepts through real-world examples. CONCLUSIONS: The role of the EWGPWD in ROADMAP was crucial, and its impact was highly influential. Involvement from the design stage helped shape the ethos of the programme and ultimately its meaningfulness. PUBLIC CONTRIBUTION: People with dementia and their carers were involved through structured consultations and invited to provide feedback on project materials, methods and insight into terminology and relevant concepts.

Valuing Alzheimer's disease drugs: a health technology assessment perspective on outcomes.

OBJECTIVES: Due to the nature of Alzheimer's disease (AD), health technology assessment (HTA) agencies might face considerable challenges in choosing appropriate outcomes and outcome measures for drugs that treat the condition. This study sought to understand which outcomes informed previous HTAs, to explore possible reasons for prioritizations, and derive potential implications for future assessments of AD drugs. METHOD: We conducted a literature review of studies that analyzed decisions made in HTAs (across disease areas) in three European countries: England, Germany, and The Netherlands. We then conducted case studies of technology assessments conducted for AD drugs in these countries. RESULTS: Overall, outcomes measured using clinical scales dominated decisions or recommendations about whether to fund AD drugs, or price negotiations. HTA processes did not always allow the inclusion of outcomes relevant to people with AD, their carers, and families. Processes did not include early discussion and agreement on what would constitute appropriate outcome measures and cut-off points for effects. CONCLUSIONS: We conclude that in order to ensure that future AD drugs are valued appropriately and timely, early agreement with various stakeholders about outcomes, outcome measures, and cut-offs is important.

Real-world evidence in Alzheimer's disease: The ROADMAP Data Cube.

INTRODUCTION: The ROADMAP project aimed to provide an integrated overview of European real-world data on Alzheimer's disease (AD) across the disease spectrum. METHODS: Metadata were identified from data sources in catalogs of European AD projects. Priority outcomes for different stakeholders were identified through systematic literature review, patient and public consultations, and stakeholder surveys. RESULTS: Information about 66 data sources and 13 outcome domains were integrated into a Data Cube. Gap analysis identified cognitive ability, functional ability/independence, behavioral/neuropsychiatric symptoms, treatment, comorbidities, and mortality as the outcomes collected most. Data were most lacking in caregiver-related outcomes. In general, electronic health records covered a broader, less detailed data spectrum than research cohorts. DISCUSSION: This integrated real-world AD data overview provides an intuitive visual model that facilitates initial assessment and identification of gaps in relevant outcomes data to inform future prospective data collection and matching of data sources and outcomes against research protocols.

Fine-mapping of retinal vascular complexity loci identifies Notch regulation as a shared mechanism with myocardial infarction outcomes.

There is increasing evidence that the complexity of the retinal vasculature measured as fractal dimension, Df, might offer earlier insights into the progression of coronary artery disease (CAD) before traditional biomarkers can be detected. This association could be partly explained by a common genetic basis; however, the genetic component of Df is poorly understood. We present a genome-wide association study (GWAS) of 38,000 individuals with white British ancestry from the UK Biobank aimed to comprehensively study the genetic component of Df and analyse its relationship with CAD. We replicated 5 Df loci and found 4 additional loci with suggestive significance (P < 1e-05) to contribute to Df variation, which previously were reported in retinal tortuosity and complexity, hypertension, and CAD studies. Significant negative genetic correlation estimates support the inverse relationship between Df and CAD, and between Df and myocardial infarction (MI), one of CAD's fatal outcomes. Fine-mapping of Df loci revealed Notch signalling regulatory variants supporting a shared mechanism with MI outcomes. We developed a predictive model for MI incident cases, recorded over a 10-year period following clinical and ophthalmic evaluation, combining clinical information, Df, and a CAD polygenic risk score. Internal cross-validation demonstrated a considerable improvement in the area under the curve (AUC) of our predictive model (AUC = 0.770 ± 0.001) when comparing with an established risk model, SCORE, (AUC = 0.741 ± 0.002) and extensions thereof leveraging the PRS (AUC = 0.728 ± 0.001). This evidences that Df provides risk information beyond demographic, lifestyle, and genetic risk factors. Our findings shed new light on the genetic basis of Df, unveiling a common control with MI, and highlighting the benefits of its application in individualised MI risk prediction.

Pre-existing diabetic retinopathy as a prognostic factor for COVID-19 outcomes amongst people with diabetes: A systematic review.

AIMS: Certain patients with Diabetes Mellitus (DM) have high risk for complications from COVID-19. We aimed to test the hypothesis that pre-existing diabetic retinopathy (DR), a microvascular disease, is a prognostic indicator for poor COVID-19 outcome in this heterogeneous population. METHODS: Seven databases (including MEDLINE) and grey literature were searched, identifying eligible studies using predetermined selection criteria. The Quality in Prognosis Studies (QUIPS) tool was used for quality assessment, followed by narrative synthesis of included studies. RESULTS: Eight cohort studies were identified. Three showed significant positive associations between DR and poor COVID-19 outcomes. The highest quality study, McGurnaghan, found increased risk of the combined outcome fatal or critical care unit (CCU)-treated COVID-19 with referable-grade DR (OR 1.672, 95% CI 1.38-2.03). Indirectly, four studies reported positive associations with microvascular disease and poorer prognosis. Variability between studies limited comparability. CONCLUSIONS: The current literature suggests an independent association between DR and poorer COVID-19 prognosis in patients with DM after controlling for key variables such as age. The use of standardised methodology in future studies would establish the predictive value of DR with greater confidence. Researchers should consider comparing the predictive value of DR and its severity, to other microvascular complications of DM.

Health Outcome Prioritization in Alzheimer's Disease: Understanding the Ethical Landscape.

BACKGROUND: Dementia has been described as the greatest global health challenge in the 21st Century on account of longevity gains increasing its incidence, escalating health and social care pressures. These pressures highlight ethical, social, and political challenges about healthcare resource allocation, what health improvements matter to patients, and how they are measured. This study highlights the complexity of the ethical landscape, relating particularly to the balances that need to be struck when allocating resources; when measuring and prioritizing outcomes; and when individual preferences are sought. OBJECTIVE: Health outcome prioritization is the ranking in order of desirability or importance of a set of disease-related objectives and their associated cost or risk. We analyze the complex ethical landscape in which this takes place in the most common dementia, Alzheimer's disease. METHODS: Narrative review of literature published since 2007, incorporating snowball sampling where necessary. We identified, thematized, and discussed key issues of ethical salience. RESULTS: Eight areas of ethical salience for outcome prioritization emerged: 1) Public health and distributive justice, 2) Scarcity of resources, 3) Heterogeneity and changing circumstances, 4) Knowledge of treatment, 5) Values and circumstances, 6) Conflicting priorities, 7) Communication, autonomy and caregiver issues, and 8) Disclosure of risk. CONCLUSION: These areas highlight the difficult balance to be struck when allocating resources, when measuring and prioritizing outcomes, and when individual preferences are sought. We conclude by reflecting on how tools in social sciences and ethics can help address challenges posed by resource allocation, measuring and prioritizing outcomes, and eliciting stakeholder preferences.

The effectiveness of portfolios for post-graduate assessment and education: BEME Guide No 12.

BACKGROUND: Portfolios in post-graduate healthcare education are used to support reflective practice, deliver summative assessment, aid knowledge management processes and are seen as a key connection between learning at organisational and individual levels. This systematic review draws together the evidence on the effectiveness of portfolios across postgraduate healthcare and examines the implications of portfolios migrating from paper to an electronic medium across all professional settings. METHODS: A literature search was conducted for articles describing the use of a portfolio for learning in a work or professional study environment. It was designed for high sensitivity and conducted across a wide range of published and unpublished sources relevant to professional education. No limits for study design or outcomes, country of origin or language were set. Blinded, paired quality rating was carried out, and detailed appraisal of and data extraction from included articles was managed using an online tool developed specifically for the review. Findings were discussed in-depth by the team, to identify and group pertinent themes when answering the research questions. RESULTS: Fifty six articles from 10 countries involving seven healthcare professions met our inclusion criteria and minimum quality threshold; mostly uncontrolled observational studies. Portfolios encouraged reflection in some groups, and facilitated engagement with learning. There was limited evidence of the influence of a number of factors on portfolio use, including ongoing support from mentors or peers, implementation method, user attitude and level of initial training. Confounding variables underlying these issues, however have not been fully investigated. A number of authors explored the reliability and validity of portfolios for summative assessment but reports of accuracy across the disparate evidence base varied. Links to competency and Quality Assurance frameworks have been demonstrated. There were conflicting reports about whether the different purposes of portfolios can be combined without compromising the meaningfulness of the contents. There was good evidence that the flexibility of the electronic format brought additional benefits to users, assessors and organisations, and encouraged more enthusiastic use. Security of data remained a high priority issue at all levels, and there was emerging evidence of successful transfer between electronic portfolio systems. CONCLUSION: The evidence base is extensive, but contains few high quality studies with generalisable messages about the effectiveness of portfolios. There is, however, good evidence that if well implemented, portfolios are effective and practical in a number of ways including increasing personal responsibility for learning and supporting professional development. Electronic versions are better at encouraging reflection and users voluntarily spend longer on them. Regular feedback from a mentor enhances this success, despite competing demands on users' time and occasional scepticism about the purpose of a portfolio. Reports of inter-rater reliability for summative assessments of portfolio data are varied and there is benefit to be gained from triangulating with other assessment methods. There was insufficient evidence to draw conclusions on how portfolios work in interdisciplinary settings.

What outcomes are important to patients with mild cognitive impairment or Alzheimer's disease, their caregivers, and health-care professionals? A systematic review.

INTRODUCTION: Clinical trials involving patients with Alzheimer's disease (AD) continue to try to identify disease-modifying treatments. Although trials are designed to meet regulatory and registration requirements, many do not measure outcomes of the disease most relevant to key stakeholders. METHODS: A systematic review sought research that elicited information from people with AD, their caregivers, and health-care professionals on which outcomes of the disease were important. Studies published in any language between 2008 and 2017 were included. RESULTS: Participants in 34 studies described 32 outcomes of AD. These included clinical (memory, mental health), practical (ability to undertake activities of daily living, access to health information), and personal (desire for patient autonomy, maintenance of identity) outcomes of the disease. DISCUSSION: Evidence elicited directly from the people most affected by AD reveals a range of disease outcomes that are relevant to them but are not commonly captured in clinical trials of new treatments.