Completeness, agreement, and representativeness of ethnicity recording in the United Kingdom's Clinical Practice Research Datalink (CPRD) and linked Hospital Episode Statistics (HES).

BACKGROUND: This descriptive study assessed the completeness, agreement, and representativeness of ethnicity recording in the United Kingdom (UK) Clinical Practice Research Datalink (CPRD) primary care databases alone and, for those patients registered with a GP in England, when linked to secondary care data from Hospital Episode Statistics (HES). METHODS: Ethnicity records were assessed for all patients in the May 2021 builds of the CPRD GOLD and CPRD Aurum databases for all UK patients. In analyses of the UK, English data was from combined CPRD-HES, whereas data from Northern Ireland, Scotland, and Wales drew from CPRD only. The agreement of ethnicity records per patient was assessed within each dataset (CPRD GOLD, CPRD Aurum, and HES datasets) and between datasets at the highest level ethnicity categorisation ('Asian', 'black', 'mixed', 'white', 'other'). Representativeness was assessed by comparing the ethnic distributions at the highest-level categorisation of CPRD-HES to those from the Census 2011 across the UK's devolved administrations. Additionally, CPRD-HES was compared to the experimental ethnic distributions for England and Wales from the Office for National Statistics in 2019 (ONS2019) and the English ethnic distribution from May 2021 from NHS Digital's General Practice Extraction Service Data for Pandemic Planning and Research with HES data linkage (GDPPR-HES). RESULTS: In CPRD-HES, 81.7% of currently registered patients in the UK had ethnicity recorded in primary care. For patients with multiple ethnicity records, mismatched ethnicity within individual primary and secondary care datasets was < 10%. Of English patients with ethnicity recorded in both CPRD and HES, 93.3% of records matched at the highest-level categorisation; however, the level of agreement was markedly lower in the 'mixed' and 'other' ethnic groups. CPRD-HES was less proportionately 'white' compared to the UK Census 2011 (80.3% vs. 87.2%) and experimental ONS2019 data (80.4% vs. 84.3%). CPRD-HES was aligned with the ethnic distribution from GDPPR-HES ('white' 80.4% vs. 80.7%); however, with a smaller proportion classified as 'other' (1.1% vs. 2.8%). CONCLUSIONS: CPRD-HES has suitable representation of all ethnic categories with some overrepresentation of minority ethnic groups and a smaller proportion classified as 'other' compared to the UK general population from other data sources. CPRD-HES data is useful for studying health risks and outcomes in typically underrepresented groups.

Herpes simplex virus and rates of cognitive decline or whole brain atrophy in the Dominantly Inherited Alzheimer Network.

OBJECTIVE: To investigate whether herpes simplex virus type 1 (HSV-1) infection was associated with rates of cognitive decline or whole brain atrophy among individuals from the Dominantly Inherited Alzheimer Network (DIAN). METHODS: Among two subsets of the DIAN cohort (age range 19.6-66.6 years; median follow-up 3.0 years) we examined (i) rate of cognitive decline (N = 164) using change in mini-mental state examination (MMSE) score, (ii) rate of whole brain atrophy (N = 149), derived from serial MR imaging, calculated using the boundary shift integral (BSI) method. HSV-1 antibodies were assayed in baseline sera collected from 2009-2015. Linear mixed-effects models were used to compare outcomes by HSV-1 seropositivity and high HSV-1 IgG titres/IgM status. RESULTS: There was no association between baseline HSV-1 seropositivity and rates of cognitive decline or whole brain atrophy. Having high HSV-1 IgG titres/IgM was associated with a slightly greater decline in MMSE points per year (difference in slope - 0.365, 95% CI: -0.958 to -0.072), but not with rate of whole brain atrophy. Symptomatic mutation carriers declined fastest on both MMSE and BSI measures, however, this was not influenced by HSV-1. Among asymptomatic mutation carriers, rates of decline on MMSE and BSI were slightly greater among those who were HSV-1 seronegative. Among mutation-negative individuals, no differences were seen by HSV-1. Stratifying by APOE4 status yielded inconsistent results. INTERPRETATION: We found no evidence for a major role of HSV-1, measured by serum antibodies, in cognitive decline or whole brain atrophy among individuals at high risk of early-onset AD.

No evidence that herpes zoster is associated with increased risk of dementia diagnosis.

OBJECTIVE: To investigate whether herpes zoster (HZ) was associated with subsequent increased risk of dementia diagnosis. METHODS: We conducted a historical cohort study using primary care electronic health records from the Clinical Practice Research Datalink in the United Kingdom. Individuals with incident HZ aged ≥40 years from 2000 to 2017 were matched with up to four individuals without HZ by age, sex, primary care practise and calendar time. The primary outcome was a new diagnosis of all-cause dementia. We used the Cox proportional hazards regression adjusting for demographic, lifestyle and clinical confounders to assess any association between HZ and dementia. We investigated interactions with sex, frailty index and antiviral treatment and conducted various sensitivity analyses. RESULTS: The cohort comprised 177,144 individuals with HZ and 706,901 matched unexposed individuals (median age 65 years (IQR 55.1-75.0), 40% male) followed for a median duration of 4.6 years (IQR 2.0-8.1). In total, 26,585 (3%) patients had an incident dementia diagnosis recorded and 113,056 patients died (12.8%). HZ was associated with a small reduction in dementia diagnosis (adjusted HR 0.92 (95% CI 0.89-0.95)), occurring predominantly in frail individuals and females. For patients who were fit (578,115, 65%), no association was seen (adjusted HR 0.97, 95% CI 0.92-1.02). There was no association between HZ and a composite outcome of dementia or death (adjusted HR 1.00, 95% CI 0.99-1.02). Dementia risk did not vary by prescription of antiviral agents. Sensitivity analyses showed consistent results. INTERPRETATION: HZ was not associated with increased dementia diagnosis in a UK primary care-based cohort.

Ethnic Differences in Dementia Risk: A Systematic Review and Meta-Analysis.

BACKGROUND: Globally around 50 million people have dementia. Risk factors for dementia such as hypertension and diabetes are more common in Black, Asian, and other ethnic minorities. There are also marked ethnic inequalities in care seeking, likelihood of diagnosis, and uptake of treatments for dementia. Nevertheless, ethnic differences in dementia incidence and prevalence remain under-explored. OBJECTIVE: To examine published peer-reviewed observational studies comparing age-specific or age-adjusted incidence or prevalence rates of dementia between at least two ethnic groups. METHODS: We searched seven databases on 1 September 2019 using search terms for ethnicity, dementia, and incidence or prevalence. We included population-based studies comparing incidence or prevalence of dementia after accounting for age of at least two ethnic groups in adults aged 18 or more. Meta-analysis was conducted for eligible ethnic comparisons. RESULTS: We included 12 cohort studies and seven cross-sectional studies. Thirteen were from the US, and two studies each from the UK, Singapore, and Xinjiang Uyghur Autonomous Region in China. The pooled risk ratio for dementia incidence obtained from four studies comparing Black and White ethnic groups was 1.33 (95% CI 1.07-1.65; I-squared = 58.0%). The pooled risk ratio for dementia incidence comparing the Asian and White ethnic groups was 0.86 (95% CI 0.728-1.01; I-squared = 43.9%). There was no difference in the incidence of dementia for Latino ethnic group compared to the White ethnic group. CONCLUSION: Evidence to date suggest there are ethnic differences in risk of dementia. Better understanding of the drivers of these differences may inform efforts to prevent or treat dementia.

Ethnicity and risk of diagnosed dementia after stroke: a cohort study using the Clinical Practice Research Datalink.

INTRODUCTION: The UK has over 1.2 million stroke survivors. Stroke is a major risk factor for dementia, and along with other risk factors such as hypertension and diabetes, is more common among Black, Asian and other ethnic minorities (BAME). We aimed to explore whether diagnosed dementia differed by ethnicity among adult stroke survivors. METHODOLOGY: Using the UK Clinical Practice Research Datalink and linked hospital data, we conducted a cohort study among patients aged ≥40 years who had an incident stroke between 2005 and 2016. We fitted multivariable Cox proportional hazard models to estimate ethnic differences in the risk of poststroke dementia, adjusting for major clinical and social confounders. RESULTS: Our cohort comprised 45 474 stroke survivors (mean age 72.6 years, 49% female), of whom 95.7% were White, 2.0% South Asian, 1.2% Black and 1.1% of Mixed/Other ethnicity. Of these, 4624 (10.2%) were diagnosed with poststroke dementia over a median follow-up of 3.26 years. Compared with the White ethnic group, those of Black ethnicity were 42% more likely to be diagnosed with dementia (adjusted HR 1.42, 95% CI 1.05 to 1.93). There was no association between any other ethnic group and poststroke dementia diagnosis. DISCUSSION: There was good evidence that those of Black ethnicity had higher risk of diagnosed dementia poststroke. Further understanding of the mechanisms of this relationship could help target interventions at communities most at risk of dementia poststroke.

National, regional, and worldwide estimates of low birthweight in 2015, with trends from 2000: a systematic analysis.

BACKGROUND: Low birthweight (LBW) of less than 2500 g is an important marker of maternal and fetal health, predicting mortality, stunting, and adult-onset chronic conditions. Global nutrition targets set at the World Health Assembly in 2012 include an ambitious 30% reduction in LBW prevalence between 2012 and 2025. Estimates to track progress towards this target are lacking; with this analysis, we aim to assist in setting a baseline against which to assess progress towards the achievement of the World Health Assembly targets. METHODS: We sought to identify all available LBW input data for livebirths for the years 2000-16. We considered population-based national or nationally representative datasets for inclusion if they contained information on birthweight or LBW prevalence for livebirths. A new method for survey adjustment was developed and used. For 57 countries with higher quality time-series data, we smoothed country-reported trends in birthweight data by use of B-spline regression. For all other countries, we estimated LBW prevalence and trends by use of a restricted maximum likelihood approach with country-level random effects. Uncertainty ranges were obtained through bootstrapping. Results were summed at the regional and worldwide level. FINDINGS: We collated 1447 country-years of birthweight data (281 million births) for 148 countries of 195 UN member states (47 countries had no data meeting inclusion criteria). The estimated worldwide LBW prevalence in 2015 was 14·6% (uncertainty range [UR] 12·4-17·1) compared with 17·5% (14·1-21·3) in 2000 (average annual reduction rate [AARR] 1·23%). In 2015, an estimated 20·5 million (UR 17·4-24·0 million) livebirths were LBW, 91% from low-and-middle income countries, mainly southern Asia (48%) and sub-Saharan Africa (24%). INTERPRETATION: Although these estimates suggest some progress in reducing LBW between 2000 and 2015, achieving the 2·74% AARR required between 2012 and 2025 to meet the global nutrition target will require more than doubling progress, involving both improved measurement and programme investments to address the causes of LBW throughout the lifecycle. FUNDING: Bill & Melinda Gates Foundation, The Children's Investment Fund Foundation, United Nations Children's Fund (UNICEF), and WHO.

Know Your Heart: Rationale, design and conduct of a cross-sectional study of cardiovascular structure, function and risk factors in 4500 men and women aged 35-69 years from two Russian cities, 2015-18.

Russia has one of the highest rates of cardiovascular disease in the world. The International Project on Cardiovascular Disease in Russia (IPCDR) was set up to understand the reasons for this. A substantial component of this study was the Know Your Heart Study devoted to characterising the nature and causes of cardiovascular disease in Russia by conducting large cross-sectional surveys in two Russian cities Novosibirsk and Arkhangelsk. The study population was 4542 men and women aged 35-69 years recruited from the general population. Fieldwork took place between 2015-18. There were two study components: 1) a baseline interview to collect information on socio-demographic characteristics and cardiovascular risk factors, usually conducted at home, and 2) a comprehensive health check at a primary care clinic which included detailed examination of the cardiovascular system. In this paper we describe in detail the rationale for, design and conduct of these studies.

Stillbirths: rates, risk factors, and acceleration towards 2030.

An estimated 2.6 million third trimester stillbirths occurred in 2015 (uncertainty range 2.4-3.0 million). The number of stillbirths has reduced more slowly than has maternal mortality or mortality in children younger than 5 years, which were explicitly targeted in the Millennium Development Goals. The Every Newborn Action Plan has the target of 12 or fewer stillbirths per 1000 births in every country by 2030. 94 mainly high-income countries and upper middle-income countries have already met this target, although with noticeable disparities. At least 56 countries, particularly in Africa and in areas affected by conflict, will have to more than double present progress to reach this target. Most (98%) stillbirths are in low-income and middle-income countries. Improved care at birth is essential to prevent 1.3 million (uncertainty range 1.2-1.6 million) intrapartum stillbirths, end preventable maternal and neonatal deaths, and improve child development. Estimates for stillbirth causation are impeded by various classification systems, but for 18 countries with reliable data, congenital abnormalities account for a median of only 7.4% of stillbirths. Many disorders associated with stillbirths are potentially modifiable and often coexist, such as maternal infections (population attributable fraction: malaria 8.0% and syphilis 7.7%), non-communicable diseases, nutrition and lifestyle factors (each about 10%), and maternal age older than 35 years (6.7%). Prolonged pregnancies contribute to 14.0% of stillbirths. Causal pathways for stillbirth frequently involve impaired placental function, either with fetal growth restriction or preterm labour, or both. Two-thirds of newborns have their births registered. However, less than 5% of neonatal deaths and even fewer stillbirths have death registration. Records and registrations of all births, stillbirths, neonatal, and maternal deaths in a health facility would substantially increase data availability. Improved data alone will not save lives but provide a way to target interventions to reach more than 7000 women every day worldwide who experience the reality of stillbirth.

National, regional, and worldwide estimates of stillbirth rates in 2015, with trends from 2000: a systematic analysis.

BACKGROUND: Previous estimates have highlighted a large global burden of stillbirths, with an absence of reliable data from regions where most stillbirths occur. The Every Newborn Action Plan (ENAP) targets national stillbirth rates (SBRs) of 12 or fewer stillbirths per 1000 births by 2030. We estimate SBRs and numbers for 195 countries, including trends from 2000 to 2015. METHODS: We collated SBR data meeting prespecified inclusion criteria from national routine or registration systems, nationally representative surveys, and other data sources identified through a systematic review, web-based searches, and consultation with stillbirth experts. We modelled SBR (≥28 weeks' gestation) for 195 countries with restricted maximum likelihood estimation with country-level random effects. Uncertainty ranges were obtained through a bootstrap approach. FINDINGS: Data from 157 countries (2207 datapoints) met the inclusion criteria, a 90% increase from 2009 estimates. The estimated average global SBR in 2015 was 18·4 per 1000 births, down from 24·7 in 2000 (25·5% reduction). In 2015, an estimated 2·6 million (uncertainty range 2·4-3·0 million) babies were stillborn, giving a 19% decline in numbers since 2000 with the slowest progress in sub-Saharan Africa. 98% of all stillbirths occur in low-income and middle-income countries; 77% in south Asia and sub-Saharan Africa. INTERPRETATION: Progress in reducing the large worldwide stillbirth burden remains slow and insufficient to meet national targets such as for ENAP. Stillbirths are increasingly being counted at a local level, but countries and the global community must further improve the quality and comparability of data, and ensure that this is more clearly linked to accountability processes including the Sustainable Development Goals. FUNDING: Save the Children's Saving Newborn Lives programme to The London School of Hygiene & Tropical Medicine.