Ethnic disparities in progression rates for sight-threatening diabetic retinopathy in diabetic eye screening: a population-based retrospective cohort study.

INTRODUCTION: The English Diabetic Eye Screening Programme (DESP) offers people living with diabetes (PLD) annual eye screening. We examined incidence and determinants of sight-threatening diabetic retinopathy (STDR) in a sociodemographically diverse multi-ethnic population. RESEARCH DESIGN AND METHODS: North East London DESP cohort data (January 2012 to December 2021) with 137 591 PLD with no retinopathy, or non-STDR at baseline in one/both eyes, were used to calculate STDR incidence rates by sociodemographic factors, diabetes type, and duration. HR from Cox models examined associations with STDR. RESULTS: There were 16 388 incident STDR cases over a median of 5.4 years (IQR 2.8-8.2; STDR rate 2.214, 95% CI 2.214 to 2.215 per 100 person-years). People with no retinopathy at baseline had a lower risk of sight-threatening diabetic retinopathy (STDR) compared with those with non-STDR in one eye (HR 3.03, 95% CI 2.91 to 3.15, p<0.001) and both eyes (HR 7.88, 95% CI 7.59 to 8.18, p<0.001). Black and South Asian individuals had higher STDR hazards than white individuals (HR 1.57, 95% CI 1.50 to 1.64 and HR 1.36, 95% CI 1.31 to 1.42, respectively). Additionally, every 5-year increase in age at inclusion was associated with an 8% reduction in STDR hazards (p<0.001). CONCLUSIONS: Ethnic disparities exist in a health system limited by capacity rather than patient economic circumstances. Diabetic retinopathy at first screen is a strong determinant of STDR development. By using basic demographic characteristics, screening programmes or clinical practices can stratify risk for sight-threatening diabetic retinopathy development.

Two-year recall for people with no diabetic retinopathy: a multi-ethnic population-based retrospective cohort study using real-world data to quantify the effect.

BACKGROUND/AIMS: The English Diabetic Eye Screening Programme (DESP) offers people living with diabetes (PLD) annual screening. Less frequent screening has been advocated among PLD without diabetic retinopathy (DR), but evidence for each ethnic group is limited. We examined the potential effect of biennial versus annual screening on the detection of sight-threatening diabetic retinopathy (STDR) and proliferative diabetic retinopathy (PDR) among PLD without DR from a large urban multi-ethnic English DESP. METHODS: PLD in North-East London DESP (January 2012 to December 2021) with no DR on two prior consecutive screening visits with up to 8 years of follow-up were examined. Annual STDR and PDR incidence rates, overall and by ethnicity, were quantified. Delays in identification of STDR and PDR events had 2-year screening intervals been used were determined. FINDINGS: Among 82 782 PLD (37% white, 36% South Asian, and 16% black people), there were 1788 incident STDR cases over mean (SD) 4.3 (2.4) years (STDR rate 0.51, 95% CI 0.47 to 0.55 per 100-person-years). STDR incidence rates per 100-person-years by ethnicity were 0.55 (95% CI 0.48 to 0.62) for South Asian, 0.34 (95% CI 0.29 to 0.40) for white, and 0.77 (95% CI 0.65 to 0.90) for black people. Biennial screening would have delayed diagnosis by 1 year for 56.3% (1007/1788) with STDR and 43.6% (45/103) with PDR. Standardised cumulative rates of delayed STDR per 100 000 persons for each ethnic group were 1904 (95% CI 1683 to 2154) for black people, 1276 (95% CI 1153 to 1412) for South Asian people, and 844 (95% CI 745 to 955) for white people. INTERPRETATION: Biennial screening would have delayed detection of some STDR and PDR by 1 year, especially among those of black ethnic origin, leading to healthcare inequalities.

Automated analysis of vessel morphometry in retinal images from a Danish high street optician setting.

PURPOSE: To evaluate the test performance of the QUARTZ (QUantitative Analysis of Retinal vessel Topology and siZe) software in detecting retinal features from retinal images captured by health care professionals in a Danish high street optician chain, compared with test performance from other large population studies (i.e., UK Biobank) where retinal images were captured by non-experts. METHOD: The dataset FOREVERP (Finding Ophthalmic Risk and Evaluating the Value of Eye exams and their predictive Reliability, Pilot) contains retinal images obtained from a Danish high street optician chain. The QUARTZ algorithm utilizes both image processing and machine learning methods to determine retinal image quality, vessel segmentation, vessel width, vessel classification (arterioles or venules), and optic disc localization. Outcomes were evaluated by metrics including sensitivity, specificity, and accuracy and compared to human expert ground truths. RESULTS: QUARTZ's performance was evaluated on a subset of 3,682 images from the FOREVERP database. 80.55% of the FOREVERP images were labelled as being of adequate quality compared to 71.53% of UK Biobank images, with a vessel segmentation sensitivity of 74.64% and specificity of 98.41% (FOREVERP) compared with a sensitivity of 69.12% and specificity of 98.88% (UK Biobank). The mean (± standard deviation) vessel width of the ground truth was 16.21 (4.73) pixels compared to that predicted by QUARTZ of 17.01 (4.49) pixels, resulting in a difference of -0.8 (1.96) pixels. The differences were stable across a range of vessels. The detection rate for optic disc localisation was similar for the two datasets. CONCLUSION: QUARTZ showed high performance when evaluated on the FOREVERP dataset, and demonstrated robustness across datasets, providing validity to direct comparisons and pooling of retinal feature measures across data sources.

GWAS on retinal vasculometry phenotypes.

The eye is the window through which light is transmitted and visual sensory signalling originates. It is also a window through which elements of the cardiovascular and nervous systems can be directly inspected, using ophthalmoscopy or retinal imaging. Measurements of ocular parameters may therefore offer important information on the physiology and homeostasis of these two important systems. Here we report the results of a genetic characterisation of retinal vasculature. Four genome-wide association studies performed on different aspects of retinal vasculometry phenotypes, such as arteriolar and venular tortuosity and width, found significant similarities between retinal vascular characteristics and cardiometabolic health. Our analyses identified 119 different regions of association with traits of retinal vasculature, including 89 loci associated arteriolar tortuosity, the strongest of which was rs35131825 (p = 2.00×10-108), 2 loci with arteriolar width (rs12969347, p = 3.30×10-09 and rs5442, p = 1.9E-15), 17 other loci associated with venular tortuosity and 11 novel associations with venular width. Our causal inference analyses also found that factors linked to arteriolar tortuosity cause elevated diastolic blood pressure and not vice versa.

Formal registration of visual impairment in people with diabetic retinopathy significantly underestimates the scale of the problem: a retrospective cohort study at a tertiary care eye hospital service in the UK.

AIMS: To analyse the prevalence of visual impairment (VI), compare it to certification of visual impairment (CVI) and analyse VI associations in patients with diabetic retinopathy (DR). METHODS: Retrospective cohort study, which included 8007 patients with DR referred from the English diabetic eye screening programme to a tertiary referral eye hospital. Main outcome measure was VI, defined as vision in the best eye of <6/24. We conducted a multivariable logistic regression for VI as primary outcome of interest, controlling for age, sex, type of diabetes, baseline DR grade, ethnicity and index of multiple deprivation (IMD). RESULTS: Mean age was 64.5 (SD 13.6) years; 61% of patients were men; and 31% of South Asian ethnicity. There were 68 patients with CVI during the study period, and 84% (272/325) of patients with VI did not have CVI after a mean follow-up of 1.87 (SD ±0.86) years. Older age showed a positive association with VI (OR per decade rise 1.88, 95% CI 1.70 to 2.08; p=1.8×10-34). Men had a lower risk of VI (OR 0.62, 95% CI 0.50 to 0.79, p=6.0×10-5), and less deprivation had a graded inverse association with VI (OR per IMD category increase 0.83, 95% CI 0.74 to 0.93, p value for linear trend 0.002). CONCLUSION: The majority of people with vision impairment are not registered at the point of care, which could translate to underestimation of diabetes-related VI and all-cause VI at a national level if replicated at other centres. Further work is needed to explore rates of VI and uptake of registration.

Nonpharmacological Interventions to Lengthen Sleep Duration in Healthy Children: A Systematic Review and Meta-analysis.

Importance: Adequate sleep duration is necessary for many aspects of child health, development, and well-being, yet sleep durations for children are declining, and effective strategies to increase sleep in healthy children remain to be elucidated. Objective: To determine whether nonpharmaceutical interventions to improve sleep duration in healthy children are effective and to identify the key components of these interventions. Data Sources: CENTRAL, MEDLINE, Embase, PsycINFO, Web of Science Core collection, ClinicalTrials.gov, and WHO trials databases were searched from inception to November 15, 2021. Study Selection: Randomized clinical trials of interventions to improve sleep duration in healthy children were independently screened by 2 researchers. A total of 28 478 studies were identified. Data Extraction and Synthesis: Data were processed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) reporting guideline. Random-effects meta-analytic models were used to estimate pooled effect sizes. Main Outcomes and Measures: Difference in sleep duration, measured in minutes. Results: A total of 13 539 child participants from 45 randomized clinical trials were included. Of these, 6897 (50.9%) were in the intervention group and 6642 (49.1%) in the control group, and the mean age ranged from 18 months to 19 years. Pooled results indicate that sleep interventions were associated with 10.5 minutes (95% CI, 5.6-15.4) longer nocturnal sleep duration. There was substantial variation between trials. Sources of variation that were not associated with the study effect size included age group, whether the population was identified as having a sleep problem or being at a socioeconomic disadvantage (eg, coming from a low-income family or area), method of assessment of sleep duration (objective vs subjective), location of intervention delivery (home vs school), whether interventions were delivered in person or used parental involvement, whether behavioral theory was used, environmental change, or had greater or lower intensity. Interventions that included earlier bedtimes were associated with a 47-minute sleep extension (95% CI, 18.9-75.0; 3 trials) compared with remaining studies (7.4 minutes; 95% CI, 2.9-11.8; 42 trials) (P = .006 for group difference). Trials of shorter duration (6 months or less) had larger effects. Conclusions and Relevance: Interventions focused on earlier bedtimes may offer a simple, pragmatic, effective way to meaningfully increase sleep duration that could have important benefits for child health.

Retinal microvascular associations with cardiometabolic risk factors differ by diabetes status: results from the UK Biobank.

AIMS/HYPOTHESIS: The aim of the study was to examine the association of retinal vessel morphometry with BP, body composition and biochemistry, and to determine whether these associations differ by diabetes status. METHODS: The UK Biobank ocular assessment included 68,550 participants aged 40-70 years who underwent non-mydriatic retinal photography, BP and body composition measurements, and haematological analysis. A fully automated image analysis program provided measurements of retinal vessel diameter and tortuosity. The associations between retinal vessel morphology and cardiometabolic risk factors by diabetes status were examined using multilevel linear regression, to provide absolute differences in vessel diameter and percentage differences in tortuosity (allowing for within-person clustering). RESULTS: A total of 50,233 participants (a reduction from 68,550) were included in these analyses. Overall, those with diabetes had significantly more tortuous venules and wider arteriolar diameters compared with those without. Associations between venular tortuosity and cardiometabolic risk factors differed according to diabetes status (p interaction <0.01) for total fat mass index, HbA1c, C-reactive protein, white cell count and granulocyte count. For example, a unit rise in white cell count was associated with a 0.18% increase (95% CI 0.05, 0.32%) in venular tortuosity for those without diabetes and a 1.48% increase (95% CI 0.90, 2.07%) among those with diabetes. For arteriolar diameter, significant interactions were evident for systolic BP, diastolic BP, mean arterial pressure (MAP) and LDL-cholesterol. For example, a 10 mmHg rise in systolic BP was associated with a -0.92 µm difference (95% CI -0.96 to -0.88 µm) in arteriolar diameter for those without diabetes, and a -0.58 µm difference (95% CI -0.76 to -0.41 µm) among those with diabetes. No interactions were observed for arteriolar tortuosity or venular diameters. CONCLUSIONS/INTERPRETATION: We provide clear evidence of the modifying effect of diabetes on cardiometabolic risk factor associations with retinal microvascular architecture. These observations suggest the occurrence of preclinical disease processes, and may be a sign of impaired autoregulation due to hyperglycaemia, which has been suggested to play a pivotal role in the development of diabetes-related microvascular complications. DATA AVAILABILITY: The data supporting the results reported here are available through the UK Biobank ( https://www.ukbiobank.ac.uk/enable-your-research/apply-for-access ).

Foveal Curvature and Its Associations in UK Biobank Participants.

Purpose: To examine whether sociodemographic, and ocular factors relate to optical coherence tomography (OCT)-derived foveal curvature (FC) in healthy individuals. Methods: We developed a deep learning model to quantify OCT-derived FC from 63,939 participants (age range, 39-70 years). Associations of FC with sociodemographic, and ocular factors were obtained using multilevel regression analysis (to allow for right and left eyes) adjusting for age, sex, ethnicity, height (model 1), visual acuity, spherical equivalent, corneal astigmatism, center point retinal thickness (CPRT), intraocular pressure (model 2), deprivation (Townsend index), higher education, annual income, and birth order (model 3). Fovea curvature was modeled as a z-score. Results: Males had on average steeper FC (0.077; 95% confidence interval [CI] 0.077-0.078) than females (0.068; 95% CI 0.068-0.069). Compared with whites, non-white individuals showed flatter FC, particularly those of black ethnicity. In black males, -0.80 standard deviation (SD) change when compared with whites (95% CI -0.89, -0.71; P 5.2e10-68). In black females, -0.70 SD change when compared with whites (95% CI -0.77, -0.63; p 2.3e10-93). Ocular factors (visual acuity, refractive status, and CPRT) showed a graded inverse association with FC that persisted after adjustment. Macular curvature showed a positive association with FC. Income showed a linear trend increase in males (P for linear trend = 0.005). Conclusions: We demonstrate marked differences in FC with ethnicity on the largest cohort studied for this purpose to date. Ocular factors showed a graded association with FC. Implementation of FC quantification in research and on the clinical setting can enhance the understanding of clinical macular phenotypes in health and disease.

Effect of ethnicity and other sociodemographic factors on attendance at diabetic eye screening: a 12-month retrospective cohort study.

OBJECTIVES: To examine the association of sociodemographic characteristics with attendance at diabetic eye screening in a large ethnically diverse urban population. DESIGN: Retrospective cohort study. SETTING: Screening visits in the North East London Diabetic Eye Screening Programme (NELDESP). PARTICIPANTS: 84 449 people with diabetes aged 12 years or older registered in the NELDESP and scheduled for screening between 1 April 2017 and 31 March 2018. MAIN OUTCOME MEASURE: Attendance at diabetic eye screening appointments. RESULTS: The mean age of people with diabetes was 60 years (SD 14.2 years), 53.4% were men, 41% South Asian, 29% White British and 17% Black; 83.4% attended screening. Black people with diabetes had similar levels of attendance compared with White British people. However, South Asian, Chinese and 'Any other Asian' background ethnicities showed greater odds of attendance compared with White British. When compared with their respective reference group, high levels of deprivation, younger age, longer duration of diabetes and worse visual acuity, were all associated with non-attendance. There was a higher likelihood of attendance per quintile improvement in deprivation (OR, 1.06; 95% CI, 1.03 to 1.08), with increasing age (OR per decade, 1.17; 95% CI, 1.15 to 1.19), with better visual acuity (OR per Bailey-Lovie chart line 1.12; 95% CI, 1.11 to 1.14) and with longer time of NELDESP registration (OR per year, 1.02; 95% CI, 1.01 to 1.03). CONCLUSION: Ethnic differences in diabetic eye screening uptake, though small, are evident. Despite preconceptions, a higher likelihood of screening attendance was observed among Asian ethnic groups when compared with the White ethnic group. Poorer socioeconomic profile was associated with higher likelihood of non-attendance for screening. Further work is needed to understand how to target individuals at risk of non-attendance and reduce inequalities.

Association of Childhood Fat Mass and Weight With Adult-Onset Type 2 Diabetes in Denmark.

Importance: Childhood obesity, defined by cutoffs based on the weight-based marker of body mass index, is associated with adult type 2 diabetes (T2D) risk. Whether childhood fat mass (FM) is the driver of these associations is currently unknown. Objective: To quantify and compare height-independent associations between childhood FM and weight with adult T2D risk in a historic Danish cohort. Design, Setting, and Participants: This population-based retrospective cohort study included schoolchildren from The Copenhagen School Health Records Register born between January 1930 and December 1985 with follow-up to adulthood through December 31, 2015. Analyses were based on 269 913 schoolchildren aged 10 years with 21 896 established adult T2D cases and 261 192 children aged 13 years with 21 530 established adult T2D cases for whom childhood height and weight measurements, as well as predicted FM, were available. Statistical analyses were performed between April 2019 to August 2020. Exposures: Childhood FM and weight at ages 10 and 13 years. Main Outcomes and Measures: Diagnoses of T2D were established by linkage to national disease registers for adults aged at least 30 years. Sex-specific Cox regression quantified associations, adjusted for childhood height, which were evaluated within 5 birth-cohort groups. Group-specific results were pooled using random-effects meta-analyses accounting for heterogeneity across group-specific associations. Results: This cohort study analyzed data from 269 913 children aged 10 years (135 940 boys [50.4%]) with 21 896 established adult T2D cases and 261 192 children aged 13 years (131 025 boys [50.2%]) with 21 530 established adult T2D cases. After adjusting for childhood height, increases in FM and weight (per kilogram) among boys aged 10 years were associated with elevated T2D risks at age 50 years of 12% (hazard ratio [HR], 1.12; 95% CI, 1.10-1.14) and 7% (HR, 1.07; 95% CI, 1.05-1.09), respectively, and among girls aged 10 years of 15% (HR, 1.15; 95% CI, 1.13-1.17) and 10% (HR, 1.10; 95% CI, 1.08-1.11), respectively. Among children aged 13 years, increases in FM and weight (per kilogram) were associated with increased T2D risks at age 50 years of 10% (HR, 1.10; 95% CI, 1.09-1.10) and 6% (HR, 1.06; 95% CI, 1.05-1.07) for boys, respectively, and of 10% (HR, 1.10; 95% CI, 1.10-1.11) and 7% (HR, 1.07; 95% CI, 1.06-1.08), respectively, for girls. Conclusions and Relevance: This cohort study found that a 1-kg increase in childhood FM was more strongly associated with increased adult T2D risk than a 1-kg increase in weight, independent of childhood height. Information on FM, rather than weight-based measures, focuses on a modifiable component of weight that may be associated with adult T2D risk. These findings support the assessment of childhood FM in adiposity surveillance initiatives in an effort to reduce long-term T2D risk.

Quantifying childhood fat mass: comparison of a novel height-and-weight-based prediction approach with DXA and bioelectrical impedance.

Accurate assessment of childhood adiposity is important both for individuals and populations. We compared fat mass (FM) predictions from a novel prediction model based on height, weight and demographic factors (height-weight equation) with FM from bioelectrical impedance (BIA) and dual-energy X-ray absorptiometry (DXA), using the deuterium dilution method as a reference standard. FM data from all four methods were available for 174 ALSPAC Study participants, seen 2002-2003, aged 11-12-years. FM predictions from the three approaches were compared to the reference standard using; R2, calibration (slope and intercept) and root mean square error (RMSE). R2 values were high from 'height-weight equation' (90%) but lower than from DXA (95%) and BIA (91%). Whilst calibration intercepts from all three approaches were close to the ideal of 0, the calibration slope from the 'height-weight equation' (slope = 1.02) was closer to the ideal of 1 than DXA (slope = 0.88) and BIA (slope = 0.87) assessments. The 'height-weight equation' provided more accurate individual predictions with a smaller RMSE value (2.6 kg) than BIA (3.1 kg) or DXA (3.4 kg). Predictions from the 'height-weight equation' were at least as accurate as DXA and BIA and were based on simpler measurements and open-source equation, emphasising its potential for both individual and population-level FM assessments.

Evaluating an Intervention to Increase Cereal Fiber Intake in Children: A Randomized Controlled Feasibility Trial.

BACKGROUND: Observational studies have shown that higher cereal fiber intake is associated with reduced type 2 diabetes risk. However, it remains uncertain whether this association is causal. OBJECTIVE: This study evaluated the feasibility of an intervention to increase cereal fiber intake in children using breakfast cereals. METHODS: The study was a 2-arm parallel group randomized controlled trial in 9-10-y-old children, who received free supplies of high-fiber breakfast cereals (>3.5 g/portion) or low-fiber breakfast cereals (<1.0 g/portion) to eat daily for 1 mo with behavioral support to promote adherence. Children provided baseline and 1-mo fasting blood samples, physical measurements, and 24-h dietary recalls. The primary outcome was the group difference in change in plasma total alkylresorcinol (AR) concentration; secondary outcomes were group differences in nutrient intakes and adiposity indices. Analyses (complete case and multiple imputation) were conducted by regressing the final AR concentration on baseline AR in models adjusted for sex, ethnicity, age, and school (random effect). RESULTS: Two-hundred seventy-two children were randomly assigned (137 receiving a low-fiber and 135 a high-fiber diet) and 193 (71%) provided fasting blood samples at baseline and follow-up. Among randomized participants, median (IQR) of baseline AR was 43.1 (24.6-85.5) nmol/L and of cereal fiber intake was 4.5 (2.7-6.4) g; 87% of participants reported consuming the cereal on most or all days. Compared with changes in the low-fiber group, the high-fiber group had greater increases in AR (40.7 nmol/L; 95% CI: 21.7, 59.8 nmol/L, P < 0.0001) and in reported cereal fiber intake (2.9g/d; 95% CI: 2.0, 3.7 g; P < 0.0001). There were no appreciable differences in other secondary outcomes. CONCLUSIONS: We have developed a simple and acceptable nutritional intervention that increases markers of daily cereal fiber intake in children. This intervention could be used to test whether increases in cereal fiber intake in children might reduce insulin resistance. This trial was registered at www.isrctn.com as ISRCTN33260236.

Weekend and weekday associations between the residential built environment and physical activity: Findings from the ENABLE London study.

BACKGROUND: We assessed whether the residential built environment was associated with physical activity (PA) differently on weekdays and weekends, and contributed to socio-economic differences in PA. METHODS: Measures of PA and walkability, park proximity and public transport accessibility were derived for baseline participants (n = 1,064) of the Examining Neighbourhood Activities in Built Living Environments in London (ENABLE London) Study. Multilevel-linear-regressions examined associations between weekend and weekday steps and Moderate to Vigorous PA (MVPA), residential built environment factors, and housing tenure status as a proxy for socio-economic position. RESULTS: A one-unit decrease in walkability was associated with 135 (95% CI [28; 242]) fewer steps and 1.2 (95% CI [0.3; 2.1]) fewer minutes of MVPA on weekend days, compared with little difference in steps and minutes of MVPA observed on weekdays. A 1km-increase in distance to the nearest local park was associated with 597 (95% CI [161; 1032]) more steps and 4.7 (95% CI [1.2; 8.2]) more minutes of MVPA on weekend days; 84 fewer steps (95% CI [-253;420]) and 0.3 fewer minutes of MVPA (95%CI [-2.3, 3.0]) on weekdays. Lower public transport accessibility was associated with increased steps on a weekday (767 steps, 95%CI [-13,1546]) compared with fewer steps on weekend days (608 fewer steps, 95% CI [-44, 1658]). None of the associations between built environment factors and PA on either weekend or weekdays were modified by socio-economic status. However, socio-economic differences in PA related moderately to socio-economic disparities in PA-promoting features of the residential neighbourhood. CONCLUSIONS: The residential built environment is associated with PA differently at weekends and on weekdays, and contributes moderately to socio-economic differences in PA.

Longitudinal impact of changes in the residential built environment on physical activity: findings from the ENABLE London cohort study.

BACKGROUND: Previous research has reported associations between features of the residential built environment and physical activity but these studies have mainly been cross-sectional, limiting inference. This paper examines whether changes in a range of residential built environment features are associated with changes in measures of physical activity in adults. It also explores whether observed effects are moderated by socio-economic status. METHODS: Data from the Examining Neighbourhood Activity in Built Living Environments in London (ENABLE London) study were used. A cohort of 1278 adults seeking to move into social, intermediate, and market-rent East Village accommodation was recruited in 2013-2015, and followed up after 2 years. Accelerometer-derived steps (primary outcome), and GIS-derived measures of residential walkability, park proximity and public transport accessibility were obtained both at baseline and follow-up. Daily steps at follow-up were regressed on daily steps at baseline, change in built environment exposures and confounding variables using multilevel linear regression to assess if changes in neighbourhood walkability, park proximity and public transport accessibility were associated with changes in daily steps. We also explored whether observed effects were moderated by housing tenure as a marker of socio-economic status. RESULTS: Between baseline and follow-up, participants experienced a 1.4 unit (95%CI 1.2,1.6) increase in neighbourhood walkability; a 270 m (95%CI 232,307) decrease in distance to their nearest park; and a 0.7 point (95% CI 0.6,0.9) increase in accessibility to public transport. A 1 s.d. increase in neighbourhood walkability was associated with an increase of 302 (95%CI 110,494) daily steps. A 1 s.d. increase in accessibility to public transport was not associated with any change in steps overall, but was associated with a decrease in daily steps amongst social housing seekers (- 295 steps (95%CI - 595, 3), and an increase in daily steps for market-rent housing seekers (410 95%CI -191, 1010) (P-value for effect modification = 0.03). CONCLUSION: Targeted changes in the residential built environment may result in increases in physical activity levels. However, the effect of improved accessibility to public transport may not be equitable, showing greater benefit to the more advantaged.

Retinal Vasculometry Associations With Glaucoma: Findings From the European Prospective Investigation of Cancer-Norfolk Eye Study.

PURPOSE: To examine retinal vasculometry associations with different glaucomas in older British people. DESIGN: Cross-sectional study. METHODS: A total of 8,623 European Prospective Investigation into Cancer-Norfolk Eye study participants were examined, who underwent retinal imaging, ocular biometry assessment, and clinical ascertainment of ocular hypertensive or glaucoma status (including glaucoma suspect [GS], high-tension open-angle glaucoma [HTG], and normal-tension glaucoma [NTG]). Automated measures of arteriolar and venular tortuosity, area, and width from retinal images were obtained. MainOutcomeMeasures: Associations between glaucoma and retinal vasculometry outcomes were analyzed using multilevel linear regression, adjusted for age, sex, height, axial length, intraocular and systemic blood pressure, and within-person clustering, to provide absolute differences in width and area, and percentage differences in vessel tortuosity. Presence or absence of within-person-between-eye differences in retinal vasculometry by diagnoses were examined. RESULTS: A total of 565,593 vessel segments from 5,947 participants (mean age 67.6 years, SD 7.6 years, 57% women) were included; numbers with HTG, NTG, and GS in at least 1 eye were 87, 82, and 439, respectively. Thinner arterioles (-3.2 µm; 95% confidence interval [CI] -4.4 µm, -1.9 µm) and venules (-2.7 µm; 95% CI -4.9 µm, -0.5 µm) were associated with HTG. Reduced venular area was associated with HTG (-0.2 mm2; 95% CI -0.3 mm2, -0.1 mm2) and NTG (-0.2 mm2; 95% CI -0.3 mm2, -0.0 mm2). Less tortuous retinal arterioles and venules were associated with all glaucomas, but only significantly for GS (-3.9%; 95% CI -7.7%, -0.1% and -4.8%; 95% CI -7.4%, -2.1%, respectively). There was no evidence of within-person-between-eye differences in retinal vasculometry associations by diagnoses. CONCLUSIONS: Retinal vessel width associations with glaucoma and novel associations with vessel area and tortuosity, together with no evidence of within-person-between-eye differences in retinal vasculometry, suggest a vascular cause of glaucoma.

Retinal Vascular Tortuosity and Diameter Associations with Adiposity and Components of Body Composition.

OBJECTIVE: The aim of this study was to assess whether adiposity or body composition relates to microvascular characteristics of the retina, indicative of cardiometabolic function. METHODS: A fully automated QUARTZ software processed retinal images from 68,550 UK Biobank participants (aged 40-69 years). Differences in retinal vessel diameter and tortuosity with body composition measures from the Tanita analyzer were obtained by using multilevel regression analyses adjusted for age, sex, ethnicity, clinic, smoking, and Townsend deprivation index. RESULTS: Venular tortuosity and diameter increased by approximately 2% (P < 10-300 ) and 0.6 µm (P < 10-6 ), respectively, per SD increase in BMI, waist circumference index, waist-hip ratio, total body fat mass index, and fat-free mass index (FFMI). Venular associations with adiposity persisted after adjustment for FFMI, whereas associations with FFMI were weakened by FMI adjustment. Arteriolar diameter (not tortuosity) narrowing with FFMI was independent of adiposity (-0.6 µm; -0.7 to -0.4 µm per SD increment of FFMI), while adiposity associations with arteriolar diameter were largely nonsignificant after adjustment for FFMI. CONCLUSIONS: This demonstrates, on an unprecedented scale, that venular tortuosity and diameter are more strongly associated with adiposity, whereas arteriolar diameter relates more strongly to fat-free mass. Different attributes of the retinal microvasculature may reflect distinct roles of body composition and fatness on the cardiometabolic system.

Evaluating the effect of change in the built environment on mental health and subjective well-being: a natural experiment.

BACKGROUND: Neighbourhood characteristics may affect mental health and well-being, but longitudinal evidence is limited. We examined the effect of relocating to East Village (the former London 2012 Olympic Athletes' Village), repurposed to encourage healthy active living, on mental health and well-being. METHODS: 1278 adults seeking different housing tenures in East village were recruited and examined during 2013-2015. 877 (69%) were followed-up after 2  years; 50% had moved to East Village. Analysis examined change in objective measures of the built environment, neighbourhood perceptions (scored from low to high; quality -12 to 12, safety -10 to 10 units), self-reported mental health (depression and anxiety) and well-being (life satisfaction, life being worthwhile and happiness) among East Village participants compared with controls who did not move to East Village. Follow-up measures were regressed on baseline for each outcome with group status as a binary variable, adjusted for age, sex, ethnicity, housing tenure and household clustering (random effect). RESULTS: Participants who moved to East Village lived closer to their nearest park (528 m, 95% CI 482 to 575 m), in more walkable areas, and had better access to public transport, compared with controls. Living in East Village was associated with marked improvements in neighbourhood perceptions (quality 5.0, 95% CI 4.5 to 5.4 units; safety 3.4, 95% CI 2.9 to 3.9 units), but there was no overall effect on mental health and well-being outcomes. CONCLUSION: Despite large improvements in the built environment, there was no evidence that moving to East Village improved mental health and well-being. Changes in the built environment alone are insufficient to improve mental health and well-being.

The effect of moving to East Village, the former London 2012 Olympic and Paralympic Games Athletes' Village, on mode of travel (ENABLE London study, a natural experiment).

BACKGROUND: Interventions to encourage active modes of travel (walking, cycling) may improve physical activity levels, but longitudinal evidence is limited and major change in the built environment / travel infrastructure may be needed. East Village (the former London 2012 Olympic Games Athletes Village) has been repurposed on active design principles with improved walkability, open space and public transport and restrictions on residential car parking. We examined the effect of moving to East Village on adult travel patterns. METHODS: One thousand two hundred seventy-eight adults (16+ years) seeking to move into social, intermediate, and market-rent East Village accommodation were recruited in 2013-2015, and followed up after 2 years. Individual objective measures of physical activity using accelerometry (ActiGraph GT3X+) and geographic location using GPS travel recorders (QStarz) were time-matched and a validated algorithm assigned four travel modes (walking, cycling, motorised vehicle, train). We examined change in time spent in different travel modes, using multilevel linear regresssion models adjusting for sex, age group, ethnicity, housing group (fixed effects) and household (random effect), comparing those who had moved to East Village at follow-up with those who did not. RESULTS: Of 877 adults (69%) followed-up, 578 (66%) provided valid accelerometry and GPS data for at least 1 day (≥540 min) at both time points; half had moved to East Village. Despite no overall effects on physical activity levels, sizeable improvements in walkability and access to public transport in East Village resulted in decreased daily vehicle travel (8.3 mins, 95%CI 2.5,14.0), particularly in the intermediate housing group (9.6 mins, 95%CI 2.2,16.9), and increased underground travel (3.9 mins, 95%CI 1.2,6.5), more so in the market-rent group (11.5 mins, 95%CI 4.4,18.6). However, there were no effects on time spent walking or cycling. CONCLUSION: Designing walkable neighbourhoods near high quality public transport and restrictions on car usage, may offer a community-wide strategy shift to sustainable transport modes by increasing public transport use, and reducing motor vehicle travel.

Associations of Retinal Microvascular Diameters and Tortuosity With Blood Pressure and Arterial Stiffness: United Kingdom Biobank.

To examine the baseline associations of retinal vessel morphometry with blood pressure (BP) and arterial stiffness in United Kingdom Biobank. The United Kingdom Biobank included 68 550 participants aged 40 to 69 years who underwent nonmydriatic retinal imaging, BP, and arterial stiffness index assessment. A fully automated image analysis program (QUARTZ [Quantitative Analysis of Retinal Vessel Topology and Size]) provided measures of retinal vessel diameter and tortuosity. The associations between retinal vessel morphology and cardiovascular disease risk factors/outcomes were examined using multilevel linear regression to provide absolute differences in vessel diameter and percentage differences in tortuosity (allowing within person clustering), adjusted for age, sex, ethnicity, clinic, body mass index, smoking, and deprivation index. Greater arteriolar tortuosity was associated with higher systolic BP (relative increase, 1.2%; 95% CI, 0.9; 1.4% per 10 mmHg), higher mean arterial pressure, 1.3%; 0.9, 1.7% per 10 mmHg, and higher pulse pressure (PP, 1.8%; 1.4; 2.2% per 10 mmHg). Narrower arterioles were associated with higher systolic BP (-0.9 µm; -0.94, -0.87 µm per 10 mmHg), mean arterial pressure (-1.5 µm; -1.5, -1.5 µm per 10 mmHg), PP (-0.7 µm; -0.8, -0.7 µm per 10 mmHg), and arterial stiffness index (-0.12 µm; -0.14, -0.09 µm per ms/m2). Associations were in the same direction but marginally weaker for venular tortuosity and diameter. This study assessing the retinal microvasculature at scale has shown clear associations between retinal vessel morphometry, BP, and arterial stiffness index. These observations further our understanding of the preclinical disease processes and interplay between microvascular and macrovascular disease.

Development and validation of a prediction model for fat mass in children and adolescents: meta-analysis using individual participant data.

OBJECTIVES: To develop and validate a prediction model for fat mass in children aged 4-15 years using routinely available risk factors of height, weight, and demographic information without the need for more complex forms of assessment. DESIGN: Individual participant data meta-analysis. SETTING: Four population based cross sectional studies and a fifth study for external validation, United Kingdom. PARTICIPANTS: A pooled derivation dataset (four studies) of 2375 children and an external validation dataset of 176 children with complete data on anthropometric measurements and deuterium dilution assessments of fat mass. MAIN OUTCOME MEASURE: Multivariable linear regression analysis, using backwards selection for inclusion of predictor variables and allowing non-linear relations, was used to develop a prediction model for fat-free mass (and subsequently fat mass by subtracting resulting estimates from weight) based on the four studies. Internal validation and then internal-external cross validation were used to examine overfitting and generalisability of the model's predictive performance within the four development studies; external validation followed using the fifth dataset. RESULTS: Model derivation was based on a multi-ethnic population of 2375 children (47.8% boys, n=1136) aged 4-15 years. The final model containing predictor variables of height, weight, age, sex, and ethnicity had extremely high predictive ability (optimism adjusted R2: 94.8%, 95% confidence interval 94.4% to 95.2%) with excellent calibration of observed and predicted values. The internal validation showed minimal overfitting and good model generalisability, with excellent calibration and predictive performance. External validation in 176 children aged 11-12 years showed promising generalisability of the model (R2: 90.0%, 95% confidence interval 87.2% to 92.8%) with good calibration of observed and predicted fat mass (slope: 1.02, 95% confidence interval 0.97 to 1.07). The mean difference between observed and predicted fat mass was -1.29 kg (95% confidence interval -1.62 to -0.96 kg). CONCLUSION: The developed model accurately predicted levels of fat mass in children aged 4-15 years. The prediction model is based on simple anthropometric measures without the need for more complex forms of assessment and could improve the accuracy of assessments for body fatness in children (compared with those provided by body mass index) for effective surveillance, prevention, and management of clinical and public health obesity.