Evaluation of contrast threshold measurements and simultaneous brightness ratios in the diagnosis of glaucoma

There is considerable dissatisfaction with the reliability and sensitivity of the methods used to assess the glaucomatous visual field. Two types of visual field test, which have been proposed as having potential in diagnosing glaucomatous visual field defects, have been modified and tested on a group of patients from a glaucoma clinic, a group of age-matched control subjects and a younger control group. 1. A grating pattern was generated using a laser interferometer which projected a large diameter image onto the retina independent of the subject's refractive error. The experimental set up which produced the most reliable and consistently low contrast threshold values in normal subjects was sought. The display characteristics which were examined included different orientations for the field quadrants as projected to the subject; stationary and flickering patterns using a variety of flicker generation methods; red and green light sources; and concentric or vertical sinusoidal grating patterns. Ultimately the optimal display was found to be a stationary image consisting of a green, vertical sinusoidal grating pattern. Arcuate regions of the visual field (at 10 to 20° from fixation) were stimulated in 4 distinct, obliquely oriented quadrants and a low spatial frequency (one cycle per degree) was chosen. 2. Normal limits were obtained from age-matched control subjects for comparison with the results for the patients from the glaucoma clinic. In the patient group, of the 13 who completed the test, 9 individuals were identified as abnormal with one or more of their contrast threshold scores exceeding that limit. The patients' Friedmann visual field plots were analysed and the amount of loss in each quadrant was quantified. There was a positive correlation between the quantified visual field loss and contrast threshold scores in 6 patients, a statistically borderline correlation in 2 patients and the absence of a correlation was found in 5 patient's results. The results for a subgroup of 6 visually abnormal eyes (not affected by glaucoma) excluded from the age-matched control group are also described. Their visual defects included mild cataract, amblyopia and retinal detachment. There were no clear abnormal results in 5 of the eyes in this group; however, in one subject with retinal scarring due to an infection, there was a distinct elevation of contrast threshold in the affected eye. Humphrey visual field plots were obtained for all but one of the age-matched control subjects. 3. Simultaneous brightness ratios (SBR) have previously been shown to provide an indication of'glaucomatous damage. The same subject groups as described above were tested. SBRs were obtained for central vision in both eyes of subjects (inter-ocular ratio). This technique was now extended for the first time to paired regions within each eye (intra-ocular ratios) producing 'nasal I temporal' and 'upper I lower' ratios. In each test the subject controlled the brightness ratio which was changed in a smoothly graduated and continuou8 way. The most effective procedure for recording repeatable SBRs was first explored, and it was determined that these could be best obtained by alternating the start point of the graduated filter position. For each subject, 5 ratios were obtained: inter-ocular SBR; upper I lower intra-ocular SBR for right eye and left eye; and nasal I temporal intra-ocular SBR for right eye and left eye. 4. Normal limits were obtained from age-matched control subjects for comparison with the results for the patients from the glaucoma clinic. In each of the 5 SBR tests carried out, these limits were wide, reflecting considerable variation in the normal results. Of the 14 patients who completed the tests, 5 were identified as abnormal by one or more of their SBRs being outside normal limits. Three of these were identified as abnormal by their inter-ocular SBRs alone, one was abnormal according to his upper I lower intra-ocular SBR alone and one patient had an abnormal inter-ocular SBR and an abnormal intra-ocular SBR. The corresponding regions of the patients' Friedmann visual fields were quantified, and these values were used to calculate visual field loss ratios. There was a positive correlation between the visual field loss ratios and SBRs in 3 patients, but no correlation in 11 patients. In the sub-group of 6 visually abnormal eyes without glaucoma, mild cataract appeared not to adversely affect SBR. Mean SBRs were normal in the subject with retinal detachment but there was evidence of an enhanced amount of variation in the readings. Two subjects with a damaged retina and one with an amblyopic eye did produce abnormal inter-ocular SBRs, with the normal eye being significantly more sensitive in both cases

Novel linkage approach to join community-acquired and national data

BackgroundCommunity 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.MethodsAs 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.ResultsA 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.ConclusionsThe 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

Valuing Alzheimer's Disease drugs:A health technology assessment perspective on outcomes

ObjectivesDue 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.MethodWe 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.ResultsOverall, 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.ConclusionsWe 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

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

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.</br

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

COVID-19 trajectories among 57 million adults in England: a cohort study using electronic health records

BACKGROUND: Updatable estimates of COVID-19 onset, progression, and trajectories underpin pandemic mitigation efforts. To identify and characterise disease trajectories, we aimed to define and validate ten COVID-19 phenotypes from nationwide linked electronic health records (EHR) using an extensible framework. METHODS: In this cohort study, we used eight linked National Health Service (NHS) datasets for people in England alive on Jan 23, 2020. Data on COVID-19 testing, vaccination, primary and secondary care records, and death registrations were collected until Nov 30, 2021. We defined ten COVID-19 phenotypes reflecting clinically relevant stages of disease severity and encompassing five categories: positive SARS-CoV-2 test, primary care diagnosis, hospital admission, ventilation modality (four phenotypes), and death (three phenotypes). We constructed patient trajectories illustrating transition frequency and duration between phenotypes. Analyses were stratified by pandemic waves and vaccination status. FINDINGS: Among 57 032 174 individuals included in the cohort, 13 990 423 COVID-19 events were identified in 7 244 925 individuals, equating to an infection rate of 12·7% during the study period. Of 7 244 925 individuals, 460 737 (6·4%) were admitted to hospital and 158 020 (2·2%) died. Of 460 737 individuals who were admitted to hospital, 48 847 (10·6%) were admitted to the intensive care unit (ICU), 69 090 (15·0%) received non-invasive ventilation, and 25 928 (5·6%) received invasive ventilation. Among 384 135 patients who were admitted to hospital but did not require ventilation, mortality was higher in wave 1 (23 485 [30·4%] of 77 202 patients) than wave 2 (44 220 [23·1%] of 191 528 patients), but remained unchanged for patients admitted to the ICU. Mortality was highest among patients who received ventilatory support outside of the ICU in wave 1 (2569 [50·7%] of 5063 patients). 15 486 (9·8%) of 158 020 COVID-19-related deaths occurred within 28 days of the first COVID-19 event without a COVID-19 diagnoses on the death certificate. 10 884 (6·9%) of 158 020 deaths were identified exclusively from mortality data with no previous COVID-19 phenotype recorded. We observed longer patient trajectories in wave 2 than wave 1. INTERPRETATION: Our analyses illustrate the wide spectrum of disease trajectories as shown by differences in incidence, survival, and clinical pathways. We have provided a modular analytical framework that can be used to monitor the impact of the pandemic and generate evidence of clinical and policy relevance using multiple EHR sources. FUNDING: British Heart Foundation Data Science Centre, led by Health Data Research UK

L’efficacité des portfolios pour l’évaluation et la formation pendant le cursus post gradué. Guide BEME No. 12

Contexte : Dans la formation post graduée en soins de santé, les port folios sont utilisés pour soutenir la pratique réflexive, pour fournir une évaluation sommative, pour faciliter les procédures de gestions des connaissances, et sont considérés comme un lien essentiel entre les apprentissages au niveau individuel comme au niveau des organisations. Cette revue systématique rassemble les preuves de l’efficacité des portfolios dans la formation post graduée en soins de santé et examine les implications de la migration du portfolio papier vers le port folio électronique dans tous les milieux professionnels. Méthode : Une revue de la littérature a été conduite sur les articles décrivant l’utilisation d’un portfolio pour l’apprentissage aussi bien dans le milieu du travail que dans celui de la formation professionnelle. Elle a été conçue pour avoir une haute sensibilité et a été conduite sur un large éventail de sources publiées ou non publiées relevant de la formation professionnelle. Aucune limite concernant la conception des études ou les résultats, ni le pays d’origine ou la langue n’a été définie. Une évaluation de la qualité, par paire, en aveugle, a été effectuée et l’évaluation détaillée de l’extraction de données à partir des d’articles inclus était gérée à l’aide d’un outil en ligne développé spécifiquement pour l’étude. Les résultats ont été discutés en profondeur par l’équipe, pour identifier et regrouper les thèmes pertinents afin de répondre aux questions de recherche. Résultats : Cinquante six articles de 10 pays impliquant sept professions de santé ont répondu à nos critères d’inclusion, et à un seuil minimal de qualité ; il s’agissait le plus souvent d’études observationnelles non contrôlées. Les portfolios encourageait la réflexion pour certains groupes, et facilitait l’engagement dans l’apprentissage. Il y avait des preuves limitées de l’influence d’un certain nombre de facteurs sur l’utilisation du portfolio, incluant un soutien continu par des mentors ou par des pairs, la méthode de mise en œuvre, le comportement des utilisateurs et le niveau de formation initiale. Un certain nombre d’auteurs ont exploré la fiabilité et la validité du portfolio pour l’évaluation sommative mais les rapports de fidélité variaient au travers de preuves disparates. Des liens vers des référentiels compétences et les cadres d’assurance qualité ont été démontrés. Il existait des rapports contradictoires pour savoir si les différents objectifs des portfolios peuvent être combinés sans compromettre la pertinence du contenu. Il existait des preuves concernant la flexibilité apportée par le format électronique des portfolios aux utilisateurs, aux évaluateurs et aux organisations, et encourageant une utilisation plus enthousiaste. La sécurité des données restait une priorité élevée à tous les niveaux et il y avait des preuves émergeantes de transferts réussis entre les systèmes électroniques de port folio. Conclusion : Les données probantes sont étendues mais contiennent peu d’études de haute qualité permettant de délivrer des messages généralisable sur l’efficacité des portfolios. Il y a néanmoins des bonnes preuves démontrant que s’ils sont bien mis en œuvre, les portfolios sont efficaces et utiles de plusieurs manières dont une augmentation de la responsabilité personnelle dans l’apprentissage et un accompagnement du développement professionnel. Les versions électroniques encouragent mieux la réflexion et les utilisateurs y passent volontairement plus de temps. La rétroaction régulière d’un mentor améliore cette efficacité, malgré l’aspect chronophage pour les utilisateurs et parfois un certain scepticisme sur les objectifs d’un portfolio. Les rapports de fidélité inter évaluateurs dans les évaluations sommatives des données du portfolio sont variés et il existe un bénéfice à trianguler avec d’autres méthodes d’évaluation. Les preuves étaient insuffisantes pour tirer des conclusions concernant la mise en place dans des contextes interdisciplinaires