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Background: Improving data access, sharing, and linkage across local authorities and other agencies can contribute to improvements in population health. Whilst progress is being made to achieve linkage and integration of health and social care data, issues still exist in creating such a system. As part of wider work to create the Cambridge Child Health Informatics and Linked Data (Cam-CHILD) database, we wanted to examine barriers to the access, linkage, and use of local authority data.Methods: A systematic literature search was conducted of scientific databases and the grey literature. Any publications reporting original research related to barriers or enablers of data linkage of or with local authority data in the United Kingdom were included. Barriers relating to the following issues were extracted from each paper: funding, fragmentation, legal and ethical frameworks, cultural issues, geographical boundaries, technical capability, capacity, data quality, security, and patient and public trust.Results: Twenty eight articles were identified for inclusion in this review. Issues relating to technical capacity and data quality were cited most often. This was followed by those relating to legal and ethical frameworks. Issue relating to public and patient trust were cited the least, however, there is considerable overlap between this topic and issues relating to legal and ethical frameworks.Conclusions: This rapid review is the first step to an in-depth exploration of the barriers to data access, linkage and use; a better understanding of which can aid in creating and implementing effective solutions. These barriers are not novel although they pose specific challenges in the context of local authority data. [ABSTRACT FROM AUTHOR]

Visual impairment has emerged as a potential modifiable risk factor for dementia. However, there is a lack of large studies with objective measures of vision and with more than 10 years of follow-up. We investigated whether visual impairment is associated with an increased risk of incident dementia in UK Biobank and European Prospective Investigation into Cancer in Norfolk (EPIC-Norfolk). In both cohorts, visual acuity was measured using a "logarithm of the minimum angle of resolution" (LogMAR) chart and categorized as no (≤0.30 LogMAR), mild (>0.3 to ≤0.50 LogMAR), and moderate to severe (>0.50 LogMAR) impairment. Dementia was ascertained through linkage to electronic medical records. After restricting to those aged ≥60 years, without prevalent dementia and with eye measures available, the analytic samples consisted of 62 206 UK Biobank and 7 337 EPIC-Norfolk participants, respectively. In UK Biobank and EPIC-Norfolk, respectively, 1 113 and 517 participants developed dementia over 11 and 15 years of follow-up. Using multivariable Cox proportional-hazards models, the hazard ratios for mild and moderate to severe visual impairment were 1.26 (95% confidence interval [CI]: 0.92-1.72) and 2.16 (95% CI: 1.37-3.40), in UK Biobank, and 1.05 (95% CI: 0.72-1.53) and 1.93 (95% CI: 1.05-3.56) in EPIC-Norfolk, compared to no visual impairment. When excluding participants censored within 5 years of follow-up or with prevalent poor or fair self-reported health, the direction of the associations remained similar for moderate impairment but was not statistically significant. Our findings suggest visual impairment might be a promising target for dementia prevention; however, the possibility of reverse causation cannot be excluded. [ABSTRACT FROM AUTHOR]

Background: Exploring the domains of cognitive function which are most strongly associated with future dementia may help with understanding risk factors for, and the natural history of dementia.Objective: To examine the association of performance on a range of cognitive tests (both global and domain specific) with subsequent diagnosis of dementia through health services in a population of relatively healthy men and women and risk of future dementia.Methods: We examined the association between performance on different cognitive tests as well as a global score and future dementia risk ascertained through health record linkage in a cohort of 8,581 individuals (aged 48-92 years) between 2004-2019 with almost 15 years follow-up (average of 10 years) before and after adjustment for socio-demographic, lifestyle, and health characteristics.Results: Those with poor performance for global cognition (bottom 10%) were almost four times as likely to receive a dementia diagnosis from health services over the next 15 years than those who performed well HR = 3.51 (95% CI 2.61, 4.71 p < 0.001) after adjustment for socioeconomic, lifestyle, and biological factors and also prevalent disease. Poor cognition performance in multiple tests was associated with 10-fold increased risk compared to those not performing poorly in any test HR = 10.82 (95% CI 6.85, 17.10 p < 0.001).Conclusion: Deficits across multiple cognitive domains substantially increase risk of future dementia over and above neuropsychological test scores ten years prior to a clinical diagnosis. These findings may help further understanding of the natural history of dementia and how such measures could contribute to strengthening future models of dementia. [ABSTRACT FROM AUTHOR]

Background: The current evidence for higher physical activity and better cognitive function and lower risk of dementia is strong but not conclusive. More robust evidence is needed to inform public-health policy. We provide further insight into discrepancies observed across studies, reporting on habitual inactivity including that during work.Methods: We examined cross-sectional and prospective relationships of physical inactivity during leisure and occupation time, with cognitive performance using a validated physical-activity index in a cohort of 8585 men and women aged 40-79 years at baseline (1993-1997) for different domains using a range of cognitive measures. Cognitive testing was conducted between 2006 and 2011 (including a pilot phase 2004-2006). Associations were examined using multinomial logistic-regression adjusting for socio-demographic and health variables as well total habitual physical activity.Results: Inactivity during work was inversely associated with poor cognitive performance (bottom 10th percentile of a composite cognition score): odds ratio (OR) = 0.68 [95% confidence interval (CI) 0.54, 0.86], P = 0.001. Results were similar cross-sectionally: OR = 0.65 (95% CI 0.45, 0.93), P = 0.02. Manual workers had increased risk of poor performance compared with those with an occupation classified as inactive. Inactivity during leisure time was associated with increased risk of poor performance in the cross-sectional analyses only.Conclusions: The relationship between inactivity and cognition is strongly confounded by education, social class and occupation. Physical activity during leisure may be protective for cognition, but work-related physical activity is not protective. A greater understanding of the mechanisms and confounding underlying these paradoxical findings is needed. [ABSTRACT FROM AUTHOR]

Background: Heavy drinkers of alcohol are reported to use hospitals more than non-drinkers, but it is unclear whether light-to-moderate drinkers use hospitals more than non-drinkers. Objective: We examined the relationship between alcohol consumption in 10,883 men and 12,857 women aged 40–79 years in the general population and subsequent admissions to hospital and time spent in hospital. Methods: Participants from the EPIC-Norfolk prospective population-based study were followed for ten years (1999–2009) using record linkage. Results: Compared to current non-drinkers, men who reported any alcohol drinking had a lower risk of spending more than twenty days in hospital multivariable adjusted OR 0.80 (95%CI 0.68–0.94) after adjusting for age, smoking status, education, social class, body mass index and prevalent diseases. Women who were current drinkers were less likely to have any hospital admissions multivariable adjusted OR 0.84 (95%CI 0.74–0.95), seven or more admissions OR 0.77 (95% CI 0.66–0.88) or more than twenty hospital days OR 0.70 (95%CI 0.62–0.80). However, compared to lifelong abstainers, men who were former drinkers had higher risk of any hospital admissions multivariable adjusted OR 2.22 (95%CI 1.51–3.28) and women former drinkers had higher risk of seven or more admissions OR 1.30 (95%CI 1.01–1.67). Conclusion: Current alcohol consumption was associated with lower risk of future hospital usage compared with non-drinkers in this middle aged and older population. In men, this association may in part be due to whether former drinkers are included in the non-drinker reference group but in women, the association was consistent irrespective of the choice of reference group. In addition, there were few participants in this cohort with very high current alcohol intake. The measurement of past drinking, the separation of non-drinkers into former drinkers and lifelong abstainers and the choice of reference group are all influential in interpreting the risk of alcohol consumption on future hospitalisation. [ABSTRACT FROM AUTHOR]

Background: Cognition covers a range of abilities, such as memory, response time and language, with tests assessing either specific or generic aspects. However differences between measures may be observed within the same individuals. Objective: To investigate the cross-sectional association of cognitive performance and socio-demographic factors using different assessment tools across a range of abilities in a British cohort study. Methods: Participants of the European Prospective Investigation of Cancer (EPIC) in Norfolk Study, aged 48–92 years, underwent a cognitive assessment between 2006 and 2011 (piloted between 2004 and 2006) and were investigated over a different domains using a range of cognitive tests. Results: Cognitive measures were available on 8584 men and women. Though age, sex, education and social class were all independently associated with cognitive performance in multivariable analysis, different associations were observed for different cognitive tests. Increasing age was associated with increased risk of a poor performance score in all of the tests, except for the National Adult Reading Test (NART), an assessment of crystallized intelligence. Compared to women, men were more likely to have had poor performance for verbal episodic memory, Odds Ratio, OR = 1.99 (95% Confidence Interval, 95% CI 1.72, 2.31), attention OR = 1.62, (95% CI 1.39, 1.88) and prospective memory OR = 1.46, (95% CI 1.29, 1.64); however, no sex difference was observed for global cognition, OR = 1.07 (95%CI 0.93, 1.24). The association with education was strongest for NART, and weakest for processing speed. Conclusion: Age, sex, education and social class were all independently associated with performance on cognitive tests assessing a range of different domains. However, the magnitude of associations of these factors with different cognitive tests differed. The varying relationships seen across different tests may help explain discrepancies in results reported in the current literature, and provides insights into influences on cognitive performance in later life. [ABSTRACT FROM AUTHOR]

The European Prospective Investigation of Cancer (EPIC) is a 10-country collaborative study in which EPIC-Norfolk is one of the UK centres. EPIC-Norfolk examined 25 639 men and women resident in East Anglia (aged 40-79 years), between 1993 and 1997. The EPIC collaboration was set up to examine the dietary determinants of cancer, but the remit in the EPIC-Norfolk cohort was broadened from the outset to include determinants of other health conditions and chronic diseases. EPIC-Norfolk completed a third round of health examinations (EPIC-Norfolk 3 or 3HC) in December 2011, on 8623 participants in the age range 48-92 years. EPIC-Norfolk focused on objective measures of cognitive function, physical capability and visual health, adapting this existing mid-life cohort to the current need to investigate healthy and independent living for ageing societies. With a wealth of longitudinal data and a biobank (including DNA) collected at up to three separate time points, EPIC-Norfolk offers the unique opportunity to investigate the association of lifestyle and biological factors, including genetic exposures, with a range of health outcomes in middle and later life. Information for data access can be found on the study website, details as given in this cohort profile. [ABSTRACT FROM AUTHOR]

We envisage the development of new Brain Health Services to achieve primary and secondary dementia prevention. These services will complement existing memory clinics by targeting cognitively unimpaired individuals, where the focus is on risk profiling and personalized risk reduction interventions rather than diagnosing and treating late-stage disease. In this article, we review key potentially modifiable risk factors and genetic risk factors and discuss assessment of risk factors as well as additional fluid and imaging biomarkers that may enhance risk profiling. We then outline multidomain measures and risk profiling and provide practical guidelines for Brain Health Services, with consideration of outstanding uncertainties and challenges. Users of Brain Health Services should undergo risk profiling tailored to their age, level of risk, and availability of local resources. Initial risk assessment should incorporate a multidomain risk profiling measure. For users aged 39–64, we recommend the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) Dementia Risk Score, whereas for users aged 65 and older, we recommend the Brief Dementia Screening Indicator (BDSI) and the Australian National University Alzheimer's Disease Risk Index (ANU-ADRI). The initial assessment should also include potentially modifiable risk factors including sociodemographic, lifestyle, and health factors. If resources allow, apolipoprotein E ɛ4 status testing and structural magnetic resonance imaging should be conducted. If this initial assessment indicates a low dementia risk, then low intensity interventions can be implemented. If the user has a high dementia risk, additional investigations should be considered if local resources allow. Common variant polygenic risk of late-onset AD can be tested in middle-aged or older adults. Rare variants should only be investigated in users with a family history of early-onset dementia in a first degree relative. Advanced imaging with 18-fluorodeoxyglucose positron emission tomography (FDG-PET) or amyloid PET may be informative in high risk users to clarify the nature and burden of their underlying pathologies. Cerebrospinal fluid biomarkers are not recommended for this setting, and blood-based biomarkers need further validation before clinical use. As new technologies become available, advances in artificial intelligence are likely to improve our ability to combine diverse data to further enhance risk profiling. Ultimately, Brain Health Services have the potential to reduce the future burden of dementia through risk profiling, risk communication, personalized risk reduction, and cognitive enhancement interventions. [ABSTRACT FROM AUTHOR]

We envisage the development of new Brain Health Services to achieve primary and secondary dementia prevention. These services will complement existing memory clinics by targeting cognitively unimpaired individuals, where the focus is on risk profiling and personalized risk reduction interventions rather than diagnosing and treating late-stage disease. In this article, we review key potentially modifiable risk factors and genetic risk factors and discuss assessment of risk factors as well as additional fluid and imaging biomarkers that may enhance risk profiling. We then outline multidomain measures and risk profiling and provide practical guidelines for Brain Health Services, with consideration of outstanding uncertainties and challenges. Users of Brain Health Services should undergo risk profiling tailored to their age, level of risk, and availability of local resources. Initial risk assessment should incorporate a multidomain risk profiling measure. For users aged 39–64, we recommend the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) Dementia Risk Score, whereas for users aged 65 and older, we recommend the Brief Dementia Screening Indicator (BDSI) and the Australian National University Alzheimer's Disease Risk Index (ANU-ADRI). The initial assessment should also include potentially modifiable risk factors including sociodemographic, lifestyle, and health factors. If resources allow, apolipoprotein E ɛ4 status testing and structural magnetic resonance imaging should be conducted. If this initial assessment indicates a low dementia risk, then low intensity interventions can be implemented. If the user has a high dementia risk, additional investigations should be considered if local resources allow. Common variant polygenic risk of late-onset AD can be tested in middle-aged or older adults. Rare variants should only be investigated in users with a family history of early-onset dementia in a first degree relative. Advanced imaging with 18-fluorodeoxyglucose positron emission tomography (FDG-PET) or amyloid PET may be informative in high risk users to clarify the nature and burden of their underlying pathologies. Cerebrospinal fluid biomarkers are not recommended for this setting, and blood-based biomarkers need further validation before clinical use. As new technologies become available, advances in artificial intelligence are likely to improve our ability to combine diverse data to further enhance risk profiling. Ultimately, Brain Health Services have the potential to reduce the future burden of dementia through risk profiling, risk communication, personalized risk reduction, and cognitive enhancement interventions. [ABSTRACT FROM AUTHOR]

To examine the association of alcohol consumption and type of alcoholic beverage with incident cataract surgery in 2 large cohorts. Longitudinal, observational study. We included 469 387 participants of UK Biobank with a mean age of 56 years and 23 162 participants of European Prospective Investigation of Cancer (EPIC)-Norfolk with a mean age of 59 years. Self-reported alcohol consumption at baseline was ascertained by a touchscreen questionnaire in UK Biobank and a food-frequency questionnaire in EPIC-Norfolk. Cases were defined as participants undergoing cataract surgery in either eye as ascertained via data linkage to National Health Service procedure statistics. We excluded participants with cataract surgery up to 1 year after the baseline assessment visit or those with self-reported cataract at baseline. Cox proportional hazards models were used to examine the associations of alcohol consumption with incident cataract surgery, adjusted for age, sex, ethnicity, Townsend deprivation index, body mass index (BMI), smoking, and diabetes status. Incident cataract surgery. There were 19 011 (mean cohort follow-up of 95 months) and 4573 (mean cohort follow-up of 193 months) incident cases of cataract surgery in UK Biobank and EPIC-Norfolk, respectively. Compared with nondrinkers, drinkers were less likely to undergo cataract surgery in UK Biobank (hazard ratio [HR], 0.89; 95% confidence interval [CI], 0.85–0.93) and EPIC-Norfolk (HR, 0.90; 95% CI, 0.84–0.97) after adjusting for covariables. Among alcohol consumers, greater alcohol consumption was associated with a reduced risk of undergoing cataract surgery in EPIC-Norfolk (P < 0.001), whereas a U-shaped association was observed in the UK Biobank. Compared with nondrinkers, subgroup analysis by type of alcohol beverage showed the strongest protective association with wine consumption; the risk of incident cataract surgery was 23% and 14% lower among those in the highest category of wine consumption in EPIC-Norfolk and UK Biobank, respectively. Our findings suggest a lower risk of undergoing cataract surgery with low to moderate alcohol consumption. The association was particularly apparent with wine consumption. We cannot exclude the possibility of residual confounding, and further studies are required to determine whether this association is causal in nature. [ABSTRACT FROM AUTHOR]

Introduction Musical instrument playing provides intellectual stimulation, which is hypothesised to generate cognitive reserve that protects against cognitive impairment. Studies to date have classified musicianship as a binary entity. This investigation draws on the dataset of the European Prospective Investigation of Cancer Norfolk study to examine the effect of frequency of playing on later-life cognition. Methods We compared three categorisations of self-reported musical playing frequency in late mid-life (12-month period) against cognitive performance measured after a 4–11 year delay, adjusted for relevant health and social confounders. Logistic regression models estimated the adjusted association between frequency of musical playing and the likelihood of being in the top and bottom cognitive deciles. Results A total of 5,693 participants (745 musicians) provided data on music playing, cognition and all co-variables. Classification of musicianship by frequency of playing demonstrated key differences in socio-demographic factors. Musicians outperformed non-musicians in cognition generally. Compared with non-musicians, frequent musicians had 80% higher odds of being in the top cognitive decile (OR 1.80 [95% CI 1.19–2.73]), whereas musicians playing at any frequency had 29% higher odds (95% CI 1.03–1.62). There was evidence of a threshold effect, rather than a linear dose–response relationship. Discussion This study supports a positive association between late mid-life musical instrument playing and later-life cognition, although causation cannot be assumed. Musicians playing frequently demonstrated the best cognition. 'Musicians' are a heterogeneous group and frequency of music playing seems a more informative measure than binary classification. Ideally, this more nuanced measure would be collected for different life course phases. [ABSTRACT FROM AUTHOR]

Objectives PMR and GCA are associated with increased risk of vascular disease. However, it remains unclear whether this relationship is causal or reflects a common underlying propensity. The aim of this study was to identify whether known cardiovascular risk factors increase the risk of PMR and GCA. Methods Clinical records were examined using key word searches to identify cases of PMR and GCA, applying current classification criteria in a population-based cohort. Associations between cardiovascular risk factors and incident PMR and GCA were analysed using Cox proportional hazards. Results In 315 022 person years of follow-up, there were 395 incident diagnoses of PMR and 118 incident diagnoses of GCA that met the clinical definition. Raised diastolic blood pressure (>90 mmHg) at baseline/recruitment was associated with subsequent incident PMR [hazard ratio=1.35 (95% CI 1.01, 1.80) P =0.045], and ever-smoking was associated with incident GCA [hazard ratio=2.01 (95% CI 1.26, 3.20) P =0.003]. Estimates were similar when the analysis was restricted to individuals whose diagnoses satisfied the current classification criteria sets. Conclusion PMR and GCA shares common risk factors with vascular disease onset, suggesting a common underlying propensity. This may indicate a potential for disease prevention strategies through modifying cardiovascular risk. [ABSTRACT FROM AUTHOR]

Background: Retinal nerve fiber layer (RNFL) thickness may reflect cerebral status. Objective: This study assessed the relationship between RNFL thickness and incident all-cause dementia in the European Prospective Investigation into Cancer in Norfolk (EPIC-Norfolk) Eye Study. Methods: Glaucoma detection with variable corneal compensation (GDx-VCC) and Heidelberg Retinal Tomograph II (HRT II) derived global mean RNFL thickness from dementia-free participants at baseline within the EPIC-Norfolk Eye Study were analyzed. Incident dementia was identified through linkage to electronic medical records. Cox proportional hazard mixed-effects regression models adjusted for key confounders were used to examine the associations between RNFL thickness and incident dementia in four separate models. Results: 6,239 participants were included with 322 cases of incident dementia and mean age of 67.5-years old, with 49.7% women (median follow-up 13.2-years, interquartile range (11.7 to 14.6 years). Greater RNFL thickness (GDx-VCC) was not significantly associated with a lower risk of incident dementia in the full adjusted model [HR per quartile increase 0.95; 95% CI 0.82–1.10]. Similarly, RNFL thickness assessed with HRT II was also not associated with incident dementia in any model (full adjusted model; HR per quartile increase: 1.06; [95% CI 0.93–1.19]. Gender did not modify any associations under study. Conclusion: GDx-VCC and HRT II derived RNFL thickness are unlikely to be useful predictors of incident dementia. Higher resolution optical imaging technologies may clarify whether there are useful relationships between neuro-retinal morphology and brain measures. [ABSTRACT FROM AUTHOR]

Introduction Low physical capability predicts mortality, perhaps by association with co-morbidity. However, few studies include participants <70 years old with lower co-morbidity burdens compared to older adults. We examined relationships between usual walking speed (UWS), timed chair stands speed, grip strength, standing balance and all-cause mortality in 8477 participants aged 48–92 years enrolled in the European Prospective Investigation of Cancer-Norfolk study. Methods Participants (55.1% female) were followed up for 6.0 years (inter-quartile range 4.6, 7.5). Associations were examined using Cox proportional hazards regression by age-group (<70 years versus ≥70 years) and then in the whole cohort adjusted for age, sex, anthropometry, history of diabetes/stroke/myocardial infarction/cancer, smoking, alcohol intake, socioeconomic status, television viewing time and physical activity. Results Age and sex adjusted associations were similar in younger and older participants (P interaction all >0.05) and those with lower physical capability had higher mortality risk. For example, in those <70 years old hazard ratios (95% confidence interval) for mortality in the third, second and lowest sex-specific quartiles of UWS compared to the highest were 1.21 (0.75, 1.96), 2.11 (1.35, 3.28) and 2.91 (1.84, 4.62) and in participants ≥70 years old were 1.19 (0.73, 1.95), 2.09 (1.35, 3.24) and 2.64 (1.73, 4.02) respectively. In the whole cohort, strong associations between all physical capability tests and mortality persisted after multivariable adjustment and after excluding participants with co-morbidity. Conclusions Physical capability was independently predictive of future mortality risk with similar associations in late mid-life, when co-morbidity burden is lower, as at older age. [ABSTRACT FROM AUTHOR]

Aim: Crowdsourcing is the process of simplifying and outsourcing numerous tasks to many untrained individuals. Our aim was to assess the performance and repeatability of crowdsourcing in the classification of normal and glaucomatous discs from optic disc images. Methods: Optic disc images (N = 127) with pre-determined disease status were selected by consensus agreement from grading experts from a large cohort study. After reading brief illustrative instructions, we requested that knowledge workers (KWs) from a crowdsourcing platform (Amazon MTurk) classified each image as normal or abnormal. Each image was classified 20 times by different KWs. Two study designs were examined to assess the effect of varying KW experience and both study designs were conducted twice for consistency. Performance was assessed by comparing the sensitivity, specificity and area under the receiver operating characteristic curve (AUC). Results: Overall, 2,540 classifications were received in under 24 hours at minimal cost. The sensitivity ranged between 83–88% across both trials and study designs, however the specificity was poor, ranging between 35–43%. In trial 1, the highest AUC (95%CI) was 0.64(0.62–0.66) and in trial 2 it was 0.63(0.61–0.65). There were no significant differences between study design or trials conducted. Conclusions: Crowdsourcing represents a cost-effective method of image analysis which demonstrates good repeatability and a high sensitivity. Optimisation of variables such as reward schemes, mode of image presentation, expanded response options and incorporation of training modules should be examined to determine their effect on the accuracy and reliability of this technique in retinal image analysis. [ABSTRACT FROM AUTHOR]

Background Poor vision is associated with lower socioeconomic status, but less is known about its relationship to area deprivation. Methods The European Prospective Investigation into Cancer and Nutrition study Norfolk Eye Study was a cross-sectional study of 8563 participants with completed eye examinations. Logarithm of the minimum angle of resolution (logMAR) visual acuity (VA) was measured using standard protocols and low vision (LV) was defined as Snellen equivalent (VA) ?6/12 in the better eye. Uncorrected refractive error (URE) was defined as improvement of VA by 2 logarithm of the minimum angle of resolution lines with pinhole. The lowest 5% of index of multiple deprivation rank was used to define the most deprived areas. The index of multiple deprivation is a composite measure using routine data from seven domains of deprivation to identify the most disadvantaged areas in England. Logistic regression was used to examine univariable and multivariable associations with LV. Results Ninety-six participants with missing data were excluded, leaving 8467 for analysis (98.9%). The mean age of the study group was 68.7 years (SD=8.1, range=48-92), with 55.1% women. LV was present in 263 participants (3.1%, 95% CI 2.7 to 3.5%). LV was associated with deprivation after adjusting for age, sex, education, social class and cataract surgery (OR=1.7, 95% CI 1.1 to 2.6, p=0.03), but this effect was mitigated by additionally adjusting for URE (OR=1.5, 95% CI 1.0 to 2.4, p=0.09). Conclusions People with LV are more likely to live in the most deprived areas; this association was independent of socioeconomic status and partly mediated by URE. Targeting URE in deprived areas may reduce health inequalities associated with LV. [ABSTRACT FROM AUTHOR]

Aim: Crowdsourcing is the process of outsourcing numerous tasks to many untrained individuals. Our aim was to assess the performance and repeatability of crowdsourcing for the classification of retinal fundus photography. Methods: One hundred retinal fundus photograph images with pre-determined disease criteria were selected by experts from a large cohort study. After reading brief instructions and an example classification, we requested that knowledge workers (KWs) from a crowdsourcing platform classified each image as normal or abnormal with grades of severity. Each image was classified 20 times by different KWs. Four study designs were examined to assess the effect of varying incentive and KW experience in classification accuracy. All study designs were conducted twice to examine repeatability. Performance was assessed by comparing the sensitivity, specificity and area under the receiver operating characteristic curve (AUC). Results: Without restriction on eligible participants, two thousand classifications of 100 images were received in under 24 hours at minimal cost. In trial 1 all study designs had an AUC (95%CI) of 0.701(0.680–0.721) or greater for classification of normal/abnormal. In trial 1, the highest AUC (95%CI) for normal/abnormal classification was 0.757 (0.738–0.776) for KWs with moderate experience. Comparable results were observed in trial 2. In trial 1, between 64–86% of any abnormal image was correctly classified by over half of all KWs. In trial 2, this ranged between 74–97%. Sensitivity was ≥96% for normal versus severely abnormal detections across all trials. Sensitivity for normal versus mildly abnormal varied between 61–79% across trials. Conclusions: With minimal training, crowdsourcing represents an accurate, rapid and cost-effective method of retinal image analysis which demonstrates good repeatability. Larger studies with more comprehensive participant training are needed to explore the utility of this compelling technique in large scale medical image analysis. [ABSTRACT FROM AUTHOR]

Purpose To examine associations between retinal vessel morphometry and cardiometabolic risk factors in older British men and women. Design Retinal imaging examination as part of the European Prospective Investigation into Cancer—Norfolk Eye Study. Participants Retinal imaging and clinical assessments were carried out in 7411 participants. Retinal images were analyzed using a fully automated validated computerized system that provides novel measures of vessel morphometry. Methods Associations between cardiometabolic risk factors, chronic disease, and retinal markers were analyzed using multilevel linear regression, adjusted for age, gender, and within-person clustering, to provide percentage differences in tortuosity and absolute differences in width. Main Outcomes Measures Retinal arteriolar and venular tortuosity and width. Results In all, 279 802 arterioles and 285 791 venules from 5947 participants (mean age, 67.6 years; standard deviation [SD], 7.6 years; 57% female) were analyzed. Increased venular tortuosity was associated with higher body mass index (BMI; 2.5%; 95% confidence interval [CI], 1.7%–3.3% per 5 kg/m2), hemoglobin A1c (HbA1c) level (2.2%; 95% CI, 1.0%–3.5% per 1%), and prevalent type 2 diabetes (6.5%; 95% CI, 2.8%–10.4%); wider venules were associated with older age (2.6 μm; 95% CI, 2.2–2.9 μm per decade), higher triglyceride levels (0.6 μm; 95% CI, 0.3–0.9 μm per 1 mmol/l), BMI (0.7 μm; 95% CI, 0.4–1.0 per 5 kg/m2), HbA1c level (0.4 μm; 95% CI, –0.1 to 0.9 per 1%), and being a current smoker (3.0 μm; 95% CI, 1.7–4.3 μm); smoking also was associated with wider arterioles (2.1 μm; 95% CI, 1.3–2.9 μm). Thinner venules were associated with high-density lipoprotein (HDL) (1.4 μm; 95% CI, 0.7–2.2 per 1 mmol/l). Arteriolar tortuosity increased with age (5.4%; 95% CI, 3.8%–7.1% per decade), higher systolic blood pressure (1.2%; 95% CI, 0.5%–1.9% per 10 mmHg), in females (3.8%; 95% CI, 1.4%–6.4%), and in those with prevalent stroke (8.3%; 95% CI, –0.6% to 18%); no association was observed with prevalent myocardial infarction. Narrower arterioles were associated with age (0.8 μm; 95% CI, 0.6–1.0 μm per decade), higher systolic blood pressure (0.5 μm; 95% CI, 0.4–0.6 μm per 10 mmHg), total cholesterol level (0.2 μm; 95% CI, 0.0–0.3 μm per 1 mmol/l), and HDL (1.2 μm; 95% CI, 0.7–1.6 μm per 1 mmol/l). Conclusions Metabolic risk factors showed a graded association with both tortuosity and width of retinal venules, even among people without clinical diabetes, whereas atherosclerotic risk factors correlated more closely with arteriolar width, even excluding those with hypertension and cardiovascular disease. These noninvasive microvasculature measures should be evaluated further as predictors of future cardiometabolic disease. [ABSTRACT FROM AUTHOR]

Purpose: To determine if topical beta-blocker use is associated with increased cardiovascular mortality, particularly among people with self-reported glaucoma. Methods: All participants who participated in the first health check (N= 25,639) of the European Prospective Investigation into Cancer (EPIC) Norfolk cohort (1993–2013) were included in this prospective cohort study, with a median follow-up of 17.0 years. We determined use of topical beta-blockers at baseline through a self-reported questionnaire and prescription check at the first clinical visit. Cardiovascular mortality was ascertained through data linkage with the Office for National Statistics mortality database. Hazard ratios (HRs) were estimated using multivariable Cox regression models. Meta-analysis of the present study’s results together with other identified literature was performed using a random effects model. Results: We did not find an association between the use of topical beta-blockers and cardiovascular mortality (HR 0.93, 95% confidence interval, CI, 0.67–1.30). In the 514 participants with self-reported glaucoma, no association was found between the use of topical beta-blockers and cardiovascular mortality (HR 0.89, 95% CI 0.56–1.40). In the primary meta-analysis of four publications, there was no evidence of an association between the use of topical beta-blockers and cardiovascular mortality (pooled HR estimate 1.10, 95% CI 0.84–1.36). Conclusion: Topical beta-blockers do not appear to be associated with excess cardiovascular mortality. This evidence does not indicate that a change in current practice is warranted, although clinicians should continue to assess individual patients and their cardiovascular risk prior to commencing topical beta-blockers. [ABSTRACT FROM PUBLISHER]

Background: We have identified a strong association between daytime napping and increased mortality risk from respiratory diseases, but little is known about the relationship between daytime napping and respiratory morbidity.Methods: Data were drawn from the European Prospective Investigation into Cancer and Nutrition-Norfolk cohort. Participants reported napping habits during 1998-2000 and were followed up for respiratory disease hospital admissions until March 2009. Cox proportional hazards regression was used to examine the association between daytime napping and respiratory disease incidence risk.Results: The study sample included 10,978 men and women with a mean age of 61.9 years, and a total of 946 incident respiratory disease cases were recorded. After adjustment for age, sex, social class, education, marital status, employment status, nightshift work, body mass index, physical activity, smoking, alcohol intake, self-reported general health, hypnotic drug use, habitual sleep duration, and preexisting health conditions, daytime napping was associated with an increase in the overall respiratory disease incidence risk (hazard ratio (HR) = 1.32, 95% confidence interval (CI) 1.15, 1.52 for napping <1 h; HR = 1.54, 95% CI 1.14, 2.09 for napping ≥1 h). This association was more pronounced for lower respiratory diseases, especially for the risk of chronic lower respiratory diseases (HR = 1.52, 95% CI: 1.18, 1.96 for napping <1 h; HR = 1.72, 95% CI: 1.01, 2.92 for napping ≥1 h, overall p = 0.003).Conclusions: Excessive daytime napping might be a useful marker of future respiratory disease incidence risk. Further studies are required to confirm these findings and help understand potential mechanisms. [ABSTRACT FROM AUTHOR]

Purpose: To examine the cross sectional and longitudinal relationship between cardiovascular risk factors and age-related macular degeneration (AMD) in a large British cohort study. Methods: The EPIC Norfolk Eye study is nested in a larger prospective cohort study. Data on cardiovascular risk factors were collected at baseline (1993-1997) and follow up (2006-2011) via clinical examination, validated lifestyle questionnaires and serum blood samples. AMD was ascertained using standardised grading of fundus photographs at the follow up. Logistic regression was used to examine associations between baseline and follow up risk factors with AMD. Results: 5,344 pairs (62.0% of total 8623) of fundus photographs were of sufficient quality for grading of AMD in participants with mean age of 67.4 years old (range 44-91) at diagnosis. There were 28 cases of late AMD (0.5%, 95% confidence interval (CI)=0.3-0.8%) and 645 cases of early AMD (12.1%, 95%CI=11.2-13.0.%). In multivariable analysis, older people with higher levels of baseline high density lipoprotein- cholesterol (HDL-C ) and C-reactive protein (CRP) were more likely to have any signs of AMD, after adjusting for sex, education, smoking, and systolic blood pressure. In cross sectional analysis, only older age and higher HDL were significantly associated with AMD. Conclusions: We have found that older age and higher levels of CRP and HDL-C were associated with increased odds of AMD in this population in the longitudinal analysis, but older age and HDL-C, not CRP was significantly associated with AMD in the cross sectional analysis. The prevalence of AMD in this cohort was low compared to other cohorts in Europe, the US and Australia, and probably reflects the some selection biases in follow up participation as well as the low rate of smoking among our healthy participants. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the relationship between area deprivation, individual socioeconomic status (SES) and age related macular degeneration (AMD). Study design: Cross sectional study nested within a longitudinal cohort study. Methods: Data were collected in the EPIC-Norfolk Eye Study by trained nurses, using standardized protocols and lifestyle questionnaires. The English Index of multiple deprivation 2010 (IMD) was derived from participants' postcodes. AMD was identified from standardized grading of fundus photographs. Logistic regression was used to examine associations between IMD, SES and AMD. Results: 5344 pairs (62.0% of total 8623) of fundus photographs were of sufficient quality for grading of AMD. Of 5182 participants with complete data, AMD was identified in 653 participants (12.60%, 95%CI = 11.7--13.5%). Multivariable logistic regression showed that people living in the most affluent 5% of areas had nearly half the odds of AMD compared to those living in comparatively more deprived areas (OR = 0.56, 95% Cl = 0.36-0.89, P = 0.02), after adjusting for age, sex, education, social class and smoking. Conclusions: The authors found that living in the most affluent areas exerted a protective effect on AMD, independently of education and social class. Further investigation into underlying mechanisms will inform potential interventions to reduce health inequalities relating to AMD. [ABSTRACT FROM AUTHOR]

Objective: To determine the association between systemic medication use and intraocular pressure (IOP) in a population of older British men and women. Design: Population-based, cross-sectional study. Participants: We included 7093 participants from the European Prospective Investigation into Cancer-Norfolk Eye Study. Exclusion criteria were a history of glaucoma therapy (medical, laser, or surgical), IOP asymmetry between eyes of >5 mmHg, and missing data for any covariables. The mean age of participants was 68 years (range, 48-92) and 56% were women. Methods: We measured IOP using the Ocular Response Analyzer. Three readings were taken per eye and the best signal value of the Goldmann-correlated IOP value considered. Participants were asked to bring all their medications and related documentation to the health examination, and these were recorded by the research nurse using an electronic case record form. The medication classes examined were angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, α-blockers, β-blockers, calcium channel blockers, diuretics, nitrates, statins, insulin, biguanides, sulfonylureas, aspirin, and other nonsteroidal anti-inflammatory drugs. We examined associations between medication use and IOP using multivariable linear regression models adjusted for age, sex, and body mass index. Models containing diabetic medication were further adjusted for glycosylated hemoglobin levels. Main Outcome Measures: Mean IOP of the right and left eyes. Results: Use of systemic β-blockers (-0.92 mmHg; 95% CI, -1.19, -0.65; P<0.001) and nitrates (-0.63 mmHg; 95% CI, -1.12, -0.14; P = 0.011) were independently associated with lower IOP. The observed associations between statin or aspirin use with IOP were no longer significant after adjustment for β-blocker use. Conclusions: This is the first population-based study to demonstrate and quantify clinically significant differences in IOP among participants using systemic β-blockers or nitrates. Lower IOP observed in participants using statins or aspirin was explained by concurrent systemic β-blocker use. The study findings may have implications for the management of glaucoma patients with comorbidity, and may provide insight into the pathophysiologic processes underlying IOP. [ABSTRACT FROM AUTHOR]

Epidemiologic studies have reported conflicting results on the relationship between daytime napping and mortality risk, and there are few data on the potential association in the British population. We investigated the associations between daytime napping and all-cause or cause-specific mortality in the European Prospective Investigation Into Cancer-Norfolk study, a British population-based cohort study. Among the 16,374 men and women who answered questions on napping habits between 1998 and 2000, a total of 3,251 died during the 13-year follow-up. Daytime napping was associated with an increased risk of all-cause mortality (for napping less than 1 hour per day on average, hazard ratio = 1.14, 95% confidence interval: 1.02, 1.27; for napping 1 hour or longer per day on average, hazard ratio = 1.32, 95% confidence interval: 1.04, 1.68), independent of age, sex, social class, educational level, marital status, employment status, body mass index, physical activity level, smoking status, alcohol intake, depression, self-reported general health, use of hypnotic drugs or other medications, time spent in bed at night, and presence of preexisting health conditions. This association was more pronounced for death from respiratory diseases (for napping less than 1 hour, hazard ratio = 1.40, 95% confidence interval: 0.95, 2.05; for napping 1 hour or more, hazard ratio = 2.56, 95% confidence interval: 1.34, 4.86) and in individuals 65 years of age or younger. Excessive daytime napping might be a useful marker of underlying health risk, particularly of respiratory problems, especially among those 65 years of age or younger. Further research is required to clarify the nature of the observed association. [ABSTRACT FROM PUBLISHER]

Purpose To examine the relationship between visual acuity (VA) and self-reported vision (SRV) in relation to falls in 8317 participants of the European Prospective Investigation into Cancer-Norfolk Eye study. Methods All participants completed a health questionnaire that included a question regarding SRV and questions regarding the number of falls in the past year. Distance VA was measured using a logMAR chart for each eye. Poor SRV was defined as those reporting fair or poor distance vision. The relationship between VA and SRV and self-rated falls was analysed by logistic regression, adjusting for age, sex, physical activity, body mass index, chronic disease, medication use and grip strength. Results Of 8317 participants, 26.7% (95% CI 25.7% to 27.7%) had fallen in the past 12 months. Worse VA and poorer SRV were associated with one or more falls in multivariable analysis (OR for falls=1.31, 95% CI 1.04 to 1.66 and OR=1.32, 95% CI 1.09 to 1.61, respectively). Poorer SRV was significantly associated with falls even after adjusting for VA (OR=1.28, 95% CI 1.05 to 1.57). Conclusions SRV was associated with falls independently of VA and could be used as a simple proxy measure for other aspects of visual function to detect people requiring vision-related falls interventions. [ABSTRACT FROM AUTHOR]

Aims To investigate if the single nucleotide polymorphisms rs3753841, rs1015213 and rs11024102, recently implicated in the development of acute primary angle closure or primary angle closure glaucoma, are associated with ocular biometric characteristics of British adults in the European Prospective Investigation of Cancer-Norfolk eye study. Methods Genotyping data on rs1015213 (between PCMTD1 and ST18), rs11024102 (at PLEKHA7) and rs3753841 (at COL11A1) were available on 3268 participants. Direct genotypic data was available for rs1015213 and rs3753841. Data was imputed for rs11024102. Ocular biometric data was available on 1137 participants who attended the third European Prospective Investigation of Cancer health examination and 988 (87%) of these participants had no previous cataract surgery either eye. Axial length (AL), anterior chamber depth (ACD) and corneal keratometry were measured by using the Zeiss IOLMaster. Results Presence of at least one A allele (AG or AA genotype) for rs1015213 was associated with a shallower ACD (-0.07 mm, 95% CI -0.01 to -0.14 mm, p=0.028) after adjusting for age and sex (both p⩽0.001). There was no association with AL or corneal keratometry for rs1015213 genotypes. AL, ACD and keratometry were not associated with rs3753841 or rs11024102 genotypes including after adjusting for age and sex. Conclusions This study suggests that primary angle closure glaucoma susceptibility at the PCMTD1-ST18 locus may be partly explained by an association between rs1015213 and ACD in European populations. This effect is equivalent to almost 20% of the SD of the mean ACD of phakic individuals in this cohort. We were not able to identify any association between rs3753841 or rs11024102 and ocular biometry. [ABSTRACT FROM AUTHOR]

Purpose To measure the dimensions of aqueous outflow structures and to investigate associations with intraocular pressure (IOP) and ocular biometry parameters in an older British population. Method Fifty-two participants from the European Prospective Investigation of Cancer-Norfolk eye study underwent imaging using the Heidelberg Spectralis optical coherence tomographer with an anterior segment module. Pseudophakic participants and those known or suspected to have glaucoma were excluded, leaving 46 participants for analysis. Schwalbe's line (SL), scleral spur (SS), Schlemm's canal (SC) diameter and the trabecular meshwork cross-sectional area (TM cross-sectional area (CSA)) were identified and traced using ImageJ software. IOP was measured using the Ocular Response Analyser. Ocular biometry was measured by partial coherence interferometry. Results The mean (SD) subject age was 65.7 years (5.6). The SL and SS were identifiable in all nasal and temporal scans. The mean SL-SS distance was 800 μm (104) nasally and 808 μm (102) temporally. Repeatability of SS-SL, SS-SC, SC and TM CSA was good to excellent, and reproducibility fair to good. Nasal SL-SS distance was inversely associated with anterior chamber depth (ACD) (p=0.007, -116 μm per mm ACD, R²=0.18). Multiple linear regression showed nasal TM CSA was significantly associated with age and IOP (age: p=0.025, 0.007 mm² per decade of age; IOP: p=0.029, -0.0012 mm² per mm Hg, R²=0.23). Conclusions Aqueous outflow structures can be measured by optical coherence tomography, and their dimensions vary significantly with ocular biometric characteristics and IOP. Further investigation is required to determine associations between outflow structure sizes in different populations and pathologies, including ocular hypertension and glaucoma. [ABSTRACT FROM AUTHOR]

Aim To investigate the prevalence of, and demographic associations with, uncorrected refractive error (URE) in an older British population. Methods Data from 4428 participants, aged 48e89 years, who attended an eye examination in the third health check of the European Prospective Investigation into Cancer-Norfolk study and had also undergone an ophthalmic examination were assessed. URE was defined as ≤1 line improvement of visual acuity with pinhole-correction in the better eye in participants with LogMar presenting visual acuity (PVA) <0.3 (PVA <6/12). Refractive error was measured using an autorefractor without cycloplegia. Myopia was defined as spherical equivalent ≤-0.5 dioptre, and hypermetropia ≥0.5 dioptre. Results Adjusted to the 2010 midyear British population, the prevalence of URE in this Norfolk population was 1.9% (95% CI 0.6% to 3.1%). Lower selfrated distance vision was correlated with higher prevalence of URE (ptrend<0.001). In a multivariate logistic regression model adjusting for age, gender, retirement status, educational level and social class, independent significant associations with URE were increasing age (ptrend<0.001) and having hypermetropic or myopic refractive error. Wearing distance spectacles was inversely associated with URE (OR 0.34, 95% CI 0.21 to 0.55, p<0.001). There were 3063 people (69.2%) who wore spectacles/contact lenses for distance vision. Spectacle wear differed according to type of refractive error (p<0.001), and use rose with increasing severity of refractive error (ptrend<0.001). Conclusion Although refractive error is common, the prevalence of URE was found to be low in this population reflecting a low prevalence of PVA<0.3. [ABSTRACT FROM AUTHOR]

Objective: To determine whether the full Mini Mental State Examination (MMSE) scale range can be derived from an abbreviated 11-item version that was designed for testing general cognitive function in a cohort where only a small proportion were expected to be severely impaired or demented.Study Design and Setting: Using simple computation and multiple imputation, the properties of the abbreviated MMSE were compared with the full MMSE score using data from the Medical Research Council Cognitive Function and Ageing Study.Results: Full MMSE scores can be generated for the abbreviated version by assuming high functioning on excluded items. Of the imputed scores, 88.8% were within 1 point of their true value. When the sample was restricted to individuals with normal cognitive functioning (MMSE total score ≥ 24/30), 96.7% of individuals were classified within 1 point of their true total score. The model worked best at predicting cognitive level when cutoff scores were used to classify individuals into impaired vs. not nonimpaired.Conclusion: Full-scale MMSE scores can be reasonably accurately derived from an 11-item abbreviated version. This reduced version can be applied within other frameworks that require reduced test length but need results that are comparable to studies where the full version has been administered. [ABSTRACT FROM AUTHOR]