648 results found
Ward H, Atchison C, Whitaker M, et al., 2021, SARS-CoV-2 antibody prevalence in England following the first peak of the pandemic., Nature Communications, ISSN: 2041-1723
Gill D, 2020, Urate, blood pressure and cardiovascular disease: evidence from Mendelian randomization and meta-analysis of clinical trials, Hypertension, ISSN: 0194-911X
Riley S, Walters C, Wang H, et al., 2020, REACT-1 round 7 updated report: regional heterogeneity in changes in prevalence of SARS-CoV-2 infection during the second national COVID-19 lockdown in England, REACT-1 round 7 updated report: regional heterogeneity in changes in prevalence of SARS-CoV-2 infection during the second national COVID-19 lockdown in England, London, Publisher: Imperial College London
BackgroundEngland exited a four-week second national lockdown on 2nd December 2020 initiated in response to the COVID-19 pandemic. Prior results showed that prevalence dropped during the first half of lockdown, with greater reductions in higher-prevalence northern regions.MethodsREACT-1 is a series of community surveys of SARS-CoV-2 RT-PCR swab-positivity in England, designed to monitor the spread of the epidemic and thus increase situational awareness. Round 7 of REACT-1 commenced swab-collection on 13th November 2020. A prior interim report included data from 13th to 24th November 2020 for 105,122 participants. Here, we report data for the entire round with swab results obtained up to 3rd December 2020.ResultsBetween 13th November and 3rd December (round 7) there were 1,299 positive swabs out of 168,181 giving a weighted prevalence of 0.94% (95% CI 0.87%, 1.01%) or 94 per 10,000 people infected in the community in England. This compares with a prevalence of 1.30% (1.21%, 1.39%) from 16th October to 2nd November 2020 (round 6), a decline of 28%. Prevalence during the latter half of round 7 was 0.91% (95% CI, 0.81%, 1.03%) compared with 0.96% (0.87%, 1.05%) in the first half. The national R number in round 7 was estimated at 0.96 (0.88, 1.03) with a decline in prevalence observed during the first half of this period no longer apparent during the second half at the end of lockdown. During round 7 there was a marked fall in prevalence in West Midlands, a levelling off in some regions and a rise in London. R numbers at regional level ranged from 0.60 (0.41, 0.80) in West Midlands up to 1.27 (1.04, 1.54) in London, where prevalence was highest in the east and south-east of the city. Nationally, between 13th November and 3rd December, the highest prevalence was in school-aged children especially at ages 13-17 years at 2.04% (1.69%, 2.46%), or approximately 1 in 50.ConclusionBetween the previous round and round 7 (during lockdown), there was a fall in prevalence of SARS-C
Ware J, Tadros R, Francis C, et al., 2020, Shared genetic pathways contribute to risk of hypertrophic and dilated cardiomyopathies with opposite directions of effect, Nature Genetics, ISSN: 1061-4036
The heart muscle diseases hypertrophic (HCM) and dilated (DCM) cardiomyopathies are leading causes of sudden death and heart failure in young otherwise healthy individuals. We conducted genome-wide association studies (GWAS) and multi-trait analyses in HCM (1,733 cases), DCM (5,521 cases), and nine left ventricular (LV) traits in 19,260 UK Biobank participants with structurally-normal hearts. We identified 16 loci associated with HCM, 13 with DCM, and 23 with LV traits. We show strong genetic correlations between LV traits and cardiomyopathies, with opposing effects in HCM and DCM. Two-sample Mendelian randomization supports a causal association linking increased contractility with HCM risk. A polygenic risk score (PRS) explains a significant portion of phenotypic variability in carriers of HCM-causing rare variants. Our findings thus provide evidence that PRS may account for variability in Mendelian diseases. More broadly, we provide insights into how genetic pathways may lead to distinct disorders through opposing genetic effects.
Yang JJ, Tzoulaki I, Karaman I, et al., 2020, Circulating Trimethylamine N-oxide (TMAO) in Association with Diet and Cardiometabolic Biomarkers: An International Pooled Analysis, American Journal of Clinical Nutrition, ISSN: 0002-9165
Lee M, Carter E, Yan L, et al., 2020, Determinants of personal exposure to PM2.5 and black carbon in Chinese adults: a 1 repeated-measures study in villages using solid fuel energy, Environment International, ISSN: 0160-4120
Riley S, Eales O, Walters CE, et al., 2020, REACT-1 round 7 interim report: fall in prevalence of swab-positivity in England during national lockdown
<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>The second wave of the 2020 COVID-19 pandemic in England has been characterized by high growth and prevalence in the North with lower prevalence in the South. High prevalence was first observed at younger adult ages before spreading out to school-aged children and older adults. Local tiered interventions were in place up to 5th November 2020 at which time a second national lockdown was implemented.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>REACT-1 is a repeated cross-sectional survey of SARS-CoV-2 swab-positivity in random samples of the population of England. The current period of data collection (round 7) commenced on 13th November 2020 and we report interim results here for swabs collected up to and including 24th November 2020. Because there were two distinct periods of growth during the previous round 6, here we compare results from round 7 (mainly) with the second half of round 6, which obtained swabs between 26th October and 2nd November 2020. We report prevalence both unweighted and reweighted to be representative of the population of England. We describe trends in unweighted prevalence with daily growth rates, doubling times, reproduction numbers (R) and splines. We estimated odds ratios for swab-positivity using mutually-adjusted multivariable logistic regression models.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>We found 821 positives from 105,123 swabs giving an unweighted prevalence of 0.78% (95% CI, 0.73%, 0.84%) and a weighted prevalence of 0.96% (0.87%, 1.05%). The weighted prevalence estimate was ∼30% lower than that of 1.32% (1.20%, 1.45%) obtained in the second half of round 6. This decrease corresponds to a halving time of 37 (30, 47) days and an R number of 0.88 (0.86, 0.91). Using only data from th
Chadeau M, Bodinier B, Vermeulen R, et al., 2020, Education, biological ageing, all-cause and cause-specific mortality and morbidity: UK Biobank Cohort Study, EClinicalMedicine, Vol: 29-30, ISSN: 2589-5370
BackgroundSocioeconomic position as measured by education may be embodied and affect the functioning of key physiological systems. Links between social disadvantage, its biological imprint, and cause-specific mortality and morbidity have not been investigated in large populations, and yet may point towards areas for public health interventions beyond targeting individual behaviours.MethodsUsing data from 366,748 UK Biobank participants with 13 biomarker measurements, we calculated a Biological Health Score (BHS, ranging from 0 to 1) capturing the level of functioning of five physiological systems. Associations between BHS and incidence of cardiovascular disease (CVD) and cancer, and mortality from all, CVD, cancer, and external causes were examined. We explored the role of education in these associations. Mendelian randomisation using genetic evidence was used to triangulate these findings.FindingsAn increase in BHS of 0.1 was associated with all-cause (HR = 1.14 [1.12–1.16] and 1.09 [1.07–1.12] in men and women respectively), cancer (HR = 1.11 [1.09–1.14] and 1.07 [1.04–1.10]) and CVD (HR = 1.25 [1.20–1.31] and 1.21 [1.11–1.31]) mortality, CVD incidence (HR = 1.15 [1.13–1.16] and 1.17 [1.15–1.19]). These associations survived adjustment for education, lifestyle-behaviours, body mass index (BMI), co-morbidities and medical treatments. Mendelian randomisation further supported the link between the BHS and CVD incidence (HR = 1.31 [1.21–1.42]). The BHS contributed to CVD incidence prediction (age-adjusted C-statistic = 0.58), other than through education and health behaviours.InterpretationThe BHS captures features of the embodiment of education, health behaviours, and more proximal unknown factors which all complementarily contribute to all-cause, cancer and CVD morbidity and premature death.
Surendran P, Gao H, Zhang W, et al., 2020, Discovery of rare variants associated with blood pressure regulation trhough meta-analaysis of 1.3 million individuals, Nature Genetics, ISSN: 1061-4036
Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency, MAF > 0.05). In a meta-analysis of up to >1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (MAF≤ 0.01) variant BP associations (P < 5 × 10-8), of which 32 were in new BP-associated loci and 55 were independent BP-associated SNVs within known BP-associated regions. Average effects of rare variants (44% coding) were ~8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (e.g.GATA5, PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.
Davies B, Parkes BL, Bennett J, et al., 2020, Community factors and excess mortality in first wave of the COVID-19 pandemic
<jats:p>Risk factors for increased risk of death from Coronavirus Disease 19 (COVID-19) have been identified<jats:sup>1,2</jats:sup> but less is known on characteristics that make communities resilient or vulnerable to the mortality impacts of the pandemic. We applied a two-stage Bayesian spatial model to quantify inequalities in excess mortality at the community level during the first wave of the pandemic in England. We used geocoded data on all deaths in people aged 40 years and older during March-May 2020 compared with 2015-2019 in 6,791 local communities. Here we show that communities with an increased risk of excess mortality had a high density of care homes, and/or high proportion of residents on income support, living in overcrowded homes and/or high percent of people with a non-White ethnicity (including Black, Asian and other minority ethnic groups). Conversely, after accounting for other community characteristics, we found no association between population density or air pollution and excess mortality. Overall, the social and environmental variables accounted for around 15% of the variation in mortality at community level. Effective and timely public health and healthcare measures that target the communities at greatest risk are urgently needed if England and other industrialised countries are to avoid further widening of inequalities in mortality patterns during the second wave.</jats:p>
Kolbeinsson A, Filippi S, Panagakis I, et al., 2020, Accelerated MRI-predicted brain ageing and its associations with cardiometabolic and brain disorders, Scientific Reports, Vol: 10, ISSN: 2045-2322
Brain structure in later life reflects both influences of intrinsic aging and those of lifestyle, environment and disease. We developed a deep neural network model trained on brain MRI scans of healthy people to predict “healthy” brain age. Brain regions most informative for the prediction included the cerebellum, hippocampus, amygdala and insular cortex. We then applied this model to data from an independent group of people not stratified for health. A phenome-wide association analysis of over 1,410 traits in the UK Biobank with differences between the predicted and chronological ages for the second group identified significant associations with over 40 traits including diseases (e.g., type I and type II diabetes), disease risk factors (e.g., increased diastolic blood pressure and body mass index), and poorer cognitive function. These observations highlight relationships between brain and systemic health and have implications for understanding contributions of the latter to late life dementia risk.
Stevelink SAM, Opie E, Pernet D, et al., 2020, Probable PTSD, depression and anxiety in 40,299 UK police officers and staff: Prevalence, risk factors and associations with blood pressure, PLoS One, Vol: 15, ISSN: 1932-6203
INTRODUCTION: Police employees undertake challenging duties which may adversely impact their health. This study explored the prevalence of and risk factors for probable mental disorders amongst a representative sample of UK police employees. The association between mental illness and alterations in blood pressure was also explored. METHODS: Data were used from the Airwave Health Monitoring Study which was established to monitor the possible physical health impacts of a new communication system on police employees. Data included sociodemographic characteristics, lifestyle habits, depression, anxiety, and post-traumatic stress disorder (PTSD) symptoms and blood pressure. Descriptive statistics were used to explore the prevalence of probable mental disorders and associated factors. Stepwise linear regression was conducted, controlling for confounding variables, to examine associations between mental disorders and blood pressure. RESULTS: The sample included 40,299 police staff, police constable/sergeants and inspectors or above. Probable depression was most frequently reported (9.8%), followed by anxiety (8.5%) and PTSD (3.9%). Groups at risk for probable mental disorders included police staff, and police employees who reported drinking heavily. Police employees exposed to traumatic incidents in the past six months had a doubling in rates of anxiety or depression and a six-fold increase in PTSD compared to those with no recent trauma exposure. Adjusted logistic regression models did not reveal any significant association between probable mental disorders and systolic blood pressure but significantly elevated diastolic blood pressure (≈1mmHg) was found across mental disorders. CONCLUSIONS: These results show lower rates of probable mental disorders, especially PTSD, than reported in other studies focusing on police employees. Although mental ill health was associated with increased diastolic blood pressure, this was unlikely to be clinically significant. These fin
Riley S, Ainslie K, Eales O, et al., 2020, REACT-1 round 6 updated report: high prevalence of SARS-CoV-2 swab positivity with reduced rate of growth in England at the start of November 2020
BackgroundEngland is now in the midst of its second wave of the COVID-19 pandemic. Multiple regions of the country are at high infection prevalence and all areas experienced rapid recent growth of the epidemic during October 2020.MethodsREACT-1 is a series of community surveys of SARS-CoV-2 RT-PCR swab-positivity in England designed to monitor the spread of the epidemic and thus increase situational awareness. Round 6 of REACT-1 commenced swab-collection on 16th October. A prior interim report included data from 16th to 25th October for 85,971 participants. Here, we report data for the entire round on 160,175 participants with swab results obtained up to 2nd November 2020.ResultsOverall weighted prevalence of infection in the community in England was 1.3% or 130 people per 10,000 infected, up from 60 people per 10,000 in the round 5 report (18th September to 5th October 2020), doubling every 24 days on average since the prior round. The corresponding R number was estimated to be 1.2. Prevalence of infection was highest in North West (2.4%, up from 1.2% ), followed by Yorkshire and The Humber (2.3% up from 0.84%), West Midlands (1.6% up from 0.60%), North East (1.5% up from 1.1%), East Midlands (1.3% up from 0.56%), London (0.97%, up from 0.54%), South West (0.80% up from 0.33%), South East (0.69% up from 0.29%), and East of England (0.69% up from 0.30%). Rapid growth in the South observed in the first half of round 6 was no longer apparent in the second half of round 6. We also observed a decline in prevalence in Yorkshire and The Humber during this period. Comparing the first and second halves of round 6, there was a suggestion of decline in weighted prevalence in participants aged 5 to 12 years and in those aged 25 to 44 years. While prevalence remained high, in the second half of round 6 there was suggestion of a slight fall then rise that was seen nationally and also separately in both the North and the South.ConclusionThe impact of the second national lockdown
Rodriguez-Martinez A, Zhou B, Sophiea MK, et al., 2020, Height and body-mass index trajectories of school-aged children and adolescents from 1985 to 2019 in 200 countries and territories: a pooled analysis of 2181 population-based studies with 65 million participants, The Lancet, Vol: 396, Pages: 1511-1524, ISSN: 0140-6736
SummaryBackgroundComparable global data on health and nutrition of school-aged children and adolescents are scarce. We aimed to estimate age trajectories and time trends in mean height and mean body-mass index (BMI), which measures weight gain beyond what is expected from height gain, for school-aged children and adolescents.MethodsFor this pooled analysis, we used a database of cardiometabolic risk factors collated by the Non-Communicable Disease Risk Factor Collaboration. We applied a Bayesian hierarchical model to estimate trends from 1985 to 2019 in mean height and mean BMI in 1-year age groups for ages 5–19 years. The model allowed for non-linear changes over time in mean height and mean BMI and for non-linear changes with age of children and adolescents, including periods of rapid growth during adolescence.FindingsWe pooled data from 2181 population-based studies, with measurements of height and weight in 65 million participants in 200 countries and territories. In 2019, we estimated a difference of 20 cm or higher in mean height of 19-year-old adolescents between countries with the tallest populations (the Netherlands, Montenegro, Estonia, and Bosnia and Herzegovina for boys; and the Netherlands, Montenegro, Denmark, and Iceland for girls) and those with the shortest populations (Timor-Leste, Laos, Solomon Islands, and Papua New Guinea for boys; and Guatemala, Bangladesh, Nepal, and Timor-Leste for girls). In the same year, the difference between the highest mean BMI (in Pacific island countries, Kuwait, Bahrain, The Bahamas, Chile, the USA, and New Zealand for both boys and girls and in South Africa for girls) and lowest mean BMI (in India, Bangladesh, Timor-Leste, Ethiopia, and Chad for boys and girls; and in Japan and Romania for girls) was approximately 9–10 kg/m2. In some countries, children aged 5 years started with healthier height or BMI than the global median and, in some cases, as healthy as the best performing countries, but they became
Riley S, Ainslie KEC, Eales O, et al., 2020, High prevalence of SARS-CoV-2 swab positivity and increasing R number in England during October 2020: REACT-1 round 6 interim report, Publisher: medRxiv
Background REACT-1 measures prevalence of SARS-CoV-2 infection in representative samples of the population in England using PCR testing from self-administered nose and throat swabs. Here we report interim results for round 6 of observations for swabs collected from the 16th to 25th October 2020 inclusive. Methods REACT-1 round 6 aims to collect data and swab results from 160,000 people aged 5 and above. Here we report results from the first 86,000 individuals. We estimate prevalence of PCR-confirmed SARS-CoV-2 infection, reproduction numbers (R) and temporal trends using exponential growth or decay models. Prevalence estimates are presented both unweighted and weighted to be representative of the population of England, accounting for response rate, region, deprivation and ethnicity. We compare these interim results with data from round 5, based on swabs collected from 18th September to 5th October 2020 inclusive. Results Overall prevalence of infection in the community in England was 1.28% or 128 people per 10,000, up from 60 per 10,000 in the previous round. Infections were doubling every 9.0 (6.1, 18) days with a national reproduction number (R) estimated at 1.56 (1.27, 1.88) compared to 1.16 (1.05, 1.27) in the previous round. Prevalence of infection was highest in Yorkshire and The Humber at 2.72% (2.12%, 3.50%), up from 0.84% (0.60%, 1.17%), and the North West at 2.27% (1.90%, 2.72%), up from 1.21% (1.01%, 1.46%), and lowest in South East at 0.55% (0.45%, 0.68%), up from 0.29% (0.23%, 0.37%). Clustering of cases was more prevalent in Lancashire, Manchester, Liverpool and West Yorkshire, West Midlands and East Midlands. Interim estimates of R were above 2 in the South East, East of England, London and South West, but with wide confidence intervals. Nationally, prevalence increased across all age groups with the greatest increase in those aged 55-64 at 1.20% (0.99%, 1.46%), up 3-fold from 0.37% (0.30%, 0.46%). In those aged over 65, prevalence was 0.81% (0.58%, 0
Riley S, Ainslie KEC, Eales O, et al., 2020, High and increasing prevalence of SARS-CoV-2 swab positivity in England during end September beginning October 2020: REACT-1 round 5 updated report, Publisher: Cold Spring Harbor Laboratory
<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>REACT-1 is quantifying prevalence of SARS-CoV-2 infection among random samples of the population in England based on PCR testing of self-administered nose and throat swabs. Here we report results from the fifth round of observations for swabs collected from the 18th September to 5th October 2020. This report updates and should be read alongside our round 5 interim report.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Representative samples of the population aged 5 years and over in England with sample size ranging from 120,000 to 175,000 people at each round. Prevalence of PCR-confirmed SARS-CoV-2 infection, estimation of reproduction number (R) and time trends between and within rounds using exponential growth or decay models.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>175,000 volunteers tested across England between 18th September and 5th October. Findings show a national prevalence of 0.60% (95% confidence interval 0.55%, 0.71%) and doubling of the virus every 29 (17, 84) days in England corresponding to an estimated national R of 1.16 (1.05, 1.27). These results correspond to 1 in 170 people currently swab-positive for the virus and approximately 45,000 new infections each day. At regional level, the highest prevalence is in the North West, Yorkshire and The Humber and the North East with strongest regional growth in North West, Yorkshire and The Humber and West Midlands.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Rapid growth has led to high prevalence of SARS-CoV-2 virus in England, with highest rates in the North of England. Prevalence has increased in all age groups, including those at highest risk. Improved compliance with existing policy and, as necessar
Huang J, Zuber V, Matthews P, et al., 2020, Sleep, major depressive disorder and Alzheimer’s disease: a Mendelian randomisation study, Neurology, Vol: 95, ISSN: 0028-3878
ObjectiveTo explore the causal relationships between sleep, major depressive disorder (MDD), and Alzheimer’s disease (AD).MethodsWe conducted bi-directional two-sample Mendelian randomisation analyses. Genetic associations were obtained from the largest genome-wide association studies currently available in UK Biobank (N=446,118), the Psychiatric Genomics Consortium (N=18,759), and the International Genomics of Alzheimer’s Project (N=63,926). We used the inverse variance weighted Mendelian randomisation method to estimate causal effects, and weighted median and MR-Egger for sensitivity analyses to test for pleiotropic effects. ResultsWe found that higher risk of AD was significantly associated with being a “morning person” (odds ratio (OR)=1.01, P=0.001), shorter sleep duration (self-reported: β=-0.006, P=1.9×10-4; accelerometer-based: β=-0.015, P=6.9×10-5), less likely to report long sleep (β=-0.003, P=7.3×10-7), earlier timing of the least active 5 hours (β=-0.024, P=1.7×10-13), and a smaller number of sleep episodes (β=-0.025, P=5.7×10-14) after adjusting for multiple comparisons. We also found that higher risk of AD was associated with lower risk of insomnia (OR=0.99, P=7×10-13). However, we did not find evidence either that these abnormal sleep patterns were causally related to AD or for a significant causal relationship between MDD and risk of AD. ConclusionWe found that AD may causally influence sleep patterns. However, we did not find evidence supporting a causal role of disturbed sleep patterns for AD or evidence for a causal relationship between MDD and AD.
Riley S, Ainslie KEC, Eales O, et al., 2020, High prevalence of SARS-CoV-2 swab positivity in England during September 2020: interim report of round 5 of REACT-1 study, Publisher: Cold Spring Harbor Laboratory Press
Background REACT-1 is a community survey of PCR confirmed swab-positivity for SARS-CoV-2 among random samples of the population in England. This interim report includes data from the fifth round of data collection currently underway for swabs sampled from the 18th to 26th September 2020.Methods Repeated cross-sectional surveys of random samples of the population aged 5 years and over in England with sample size ranging from 120,000 to 160,000 people in each round of data collection. Collection of self-administered nose and throat swab for PCR and questionnaire data. Prevalence of swab-positivity by round and by demographic variables including age, sex, region, ethnicity. Estimation of reproduction number (R) between and within rounds, and time trends using exponential growth or decay model. Assessment of geographical clustering based on boundary-free spatial model.Results Over the 9 days for which data are available, we find 363 positives from 84,610 samples giving a weighted prevalence to date of 0.55% (0.47%, 0.64%) in round 5. This implies that 411,000 (351,000, 478,000) people in England are virus-positive under the assumption that the swab assay is 75% sensitive. Using data from the most recent two rounds, we estimate a doubling time of 10.6 (9.4, 12.0) days covering the period 20th August to 26th September, corresponding to a reproduction number R of 1.47 (1.40, 1.53). Using data only from round 5 we estimate a reproduction number of 1.06 (0.74, 1.46) with probability of 63% that R is greater than 1. Between rounds 4 and 5 there was a marked increase in unweighted prevalence at all ages. In the most recent data, prevalence was highest in the 18 to 24 yrs age group at 0.96% (0.68%, 1.36%). At 65+ yrs prevalence increased 7-fold between rounds 4 and 5 from 0.04% (0.03%, 0.07%) to 0.29% (0.23%, 0.37%). Prevalence increased in all regions between rounds 4 and 5, giving the highest unweighted prevalence in round 5 in the North West at 0.86% (0.69%, 1.06%). In Lond
Aljuraiban GS, Pertiwi K, Stamler J, et al., 2020, Potato consumption, by preparation method and meal quality, with blood pressure and body mass index: The INTERMAP study, Clinical Nutrition, Vol: 39, Pages: 3042-3048, ISSN: 0261-5614
BACKGROUND AND AIMS: Previous studies have reported associations between higher potato intake and higher blood pressure (BP) and/or risk of hypertension and obesity. These studies rarely considered preparation methods of potatoes, overall dietary pattern or the nutrient quality of the meals. These factors may affect the association of potato intake with BP and body mass index (BMI). This study investigated potato consumption by amount, type of processing, overall dietary pattern, and nutrient quality of the meals in relation to BP and BMI. METHODS: Cross-sectional analyses were conducted among 2696 participants aged 40-59 y in the US and UK samples of the International Study of Macro- and Micro-Nutrients and Blood Pressure (INTERMAP). Nutrient quality of individual food items and the overall diet was assessed with the Nutrient-Rich Foods (NRF) index. RESULTS: No associations with BP or BMI were found for total potato intake nor for boiled, mashed, or baked potatoes or potato-based mixed dishes. In US women, higher intake of fried potato was associated with 2.29 mmHg (95% CI: 0.55, 3.83) higher systolic BP and with 1.14 mmHg (95% CI: 0.10, 2.17) higher diastolic BP, independent of BMI. Higher fried potato consumption was directly associated with a +0.86 kg/m2 difference in BMI (95% CI: 0.24, 1.58) in US women. These associations were not found in men. Higher intakes of fried potato meals with a lower nutritional quality (NRF index≤ 2) were positively associated with systolic (3.88 mmHg; 95% CI: 2.63, 5.53) and diastolic BP (1.62 mmHg; 95% CI: 0.48, 2.95) in US women. No associations with BP were observed for fried potato meals with a higher nutritional quality (NRF index> 2). CONCLUSIONS: Fried potato was directly related to BP and BMI in women, but non-fried potato was not. Poor-nutrient quality meals were associated with intake of fried potatoes and higher BP, suggesting that accompanied dietary choices are key mediators of
Allen N, Arnold M, Parish S, et al., 2020, Approaches to minimising the epidemiological impact of sources of systematic and random variation that may affect biochemistry assay data in UK Biobank, Wellcome Open Research, Vol: 5, Pages: 1-18, ISSN: 2398-502X
Background : UK Biobank is a large prospective study that recruited 500,000 participants aged 40 to 69 years, between 2006-2010.The study has collected (and continues to collect) extensive phenotypic and genomic data about its participants. In order to enhance further the value of the UK Biobank resource, a wide range of biochemistry markers were measured in all participants with an available biological sample. Here, we describe the approaches UK Biobank has taken to minimise error related to sample collection, processing, retrieval and assay measurement. Methods : During routine quality control checks, the laboratory team observed that some assay results were lower than expected for samples acquired during certain time periods. Analyses were undertaken to identify and correct for the unexpected dilution identified during sample processing, and for expected error caused by laboratory drift of assay results. Results : The vast majority (92%) of biochemistry serum assay results were assessed to be not materially affected by dilution, with an estimated difference in concentration of less than 1% (i.e. either lower or higher) than that expected if the sample were unaffected; 8.3% were estimated to be diluted by up to 10%; very few samples appeared to be diluted more than this. Biomarkers measured in urine (creatinine, microalbumin, sodium, potassium) and red blood cells (HbA1c) were not affected. In order to correct for laboratory variation over the assay period, all assay results were adjusted for date of assay, with the exception of those that had a high biological coefficient of variation or evident seasonal variability: vitamin D, lipoprotein (a), gamma glutamyltransferase, C-reactive protein and rheumatoid factor. Conclusions : Rigorous approaches related to sample collection, processing, retrieval, assay measurement and data analysis have been taken to mitigate the impact of both systematic and random variation in epidemiological analyses that use the biochemistry
Riley S, Ainslie KEC, Eales O, et al., 2020, Resurgence of SARS-CoV-2 in England: detection by community antigen surveillance, Publisher: Cold Spring Harbor Laboratory
<jats:p>BackgroundBased on cases and deaths, transmission of SARS-CoV-2 in England peaked in late March and early April 2020 and then declined until the end of June. Since the start of July, cases have increased, while deaths have continued to decrease.MethodsWe report results from 594,000 swabs tested for SARS-CoV-2 virus obtained from a representative sample of people in England over four rounds collected regardless of symptoms, starting in May 2020 and finishing at the beginning of September 2020. Swabs for the most recent two rounds were taken between 24th July and 11th August and for round 4 between 22nd August and 7th September. We estimate weighted overall prevalence, doubling times between and within rounds and associated reproduction numbers. We obtained unweighted prevalence estimates by sub-groups: age, sex, region, ethnicity, key worker status, household size, for which we also estimated odds of infection. We identified clusters of swab-positive participants who were closer, on average, to other swab-positiveparticipants than would be expected.FindingsOver all four rounds of the study, we found that 72% (67%, 76%) of swab-positive individuals were asymptomatic at the time of swab and in the week prior. The epidemic declined between rounds 1 and 2, and rounds 2 and 3. However, the epidemic was increasing between rounds 3 and 4, with a doubling time of 17 (13, 23) days corresponding to an R value of 1.3 (1.2, 1.4). When analysing round 3 alone, we found that the epidemic had started to grow again with 93% probability. Using only the most recent round 4 data, we estimated a doubling time of 7.7 (5.5, 12.7) days, corresponding to an R value of 1.7 (1.4, 2.0). Cycle threshold values were lower (viral loads were higher) for rounds 1 and 4 than they were for rounds 2 and 3. In round 4, we observed the highest prevalence in participants aged 18 to 24 years at 0.25% (0.16%, 0.41%), increasing from 0.08% (0.04%, 0.18%) in round 3. We observed the lowest prev
Vuckovic D, Bao EL, Akbari P, et al., 2020, The polygenic and monogenic basis of blood traits and diseases, Cell, Vol: 182, Pages: 1214-1231.e11, ISSN: 0092-8674
Blood cells play essential roles in human health, underpinning physiological processes such as immunity, oxygen transport, and clotting, which when perturbed cause a significant global health burden. Here we integrate data from UK Biobank and a large-scale international collaborative effort, including data for 563,085 European ancestry participants, and discover 5,106 new genetic variants independently associated with 29 blood cell phenotypes covering a range of variation impacting hematopoiesis. We holistically characterize the genetic architecture of hematopoiesis, assess the relevance of the omnigenic model to blood cell phenotypes, delineate relevant hematopoietic cell states influenced by regulatory genetic variants and gene networks, identify novel splice-altering variants mediating the associations, and assess the polygenic prediction potential for blood traits and clinical disorders at the interface of complex and Mendelian genetics. These results show the power of large-scale blood cell trait GWAS to interrogate clinically meaningful variants across a wide allelic spectrum of human variation.
Chen M-H, Raffield LM, Mousas A, et al., 2020, Trans-ethnic and Ancestry-Specific Blood-Cell Genetics in 746,667 Individuals from 5 Global Populations, CELL, Vol: 182, Pages: 1198-+, ISSN: 0092-8674
Graham N, Junghans C, Downes R, et al., 2020, SARS-CoV-2 infection, clinical features and outcome of COVID-19 in United Kingdom nursing homes, Journal of Infection, Vol: 81, Pages: 411-419, ISSN: 0163-4453
OBJECTIVES: To understand SARS-Co-V-2 infection and transmission in UK nursing homes in order to develop preventive strategies for protecting the frail elderly residents. METHODS: An outbreak investigation involving 394 residents and 70 staff, was carried out in 4 nursing homes affected by COVID-19 outbreaks in central London. Two point-prevalence surveys were performed one week apart where residents underwent SARS-CoV-2 testing and had relevant symptoms documented. Asymptomatic staff from three of the four homes were also offered SARS-CoV-2 testing. RESULTS: Overall, 26% (95% CI 22 to 31) of residents died over the two-month period. All-cause mortality increased by 203% (95% CI 70 to 336) compared with previous years. Systematic testing identified 40% (95% CI 35 to 46) of residents as positive for SARS-CoV-2, and of these 43% (95% CI 34 to 52) were asymptomatic and 18% (95% CI 11 to 24) had only atypical symptoms; 4% (95% CI -1 to 9) of asymptomatic staff also tested positive. CONCLUSIONS: The SARS-CoV-2 outbreak in four UK nursing homes was associated with very high infection and mortality rates. Many residents developed either atypical or no discernible symptoms. A number of asymptomatic staff members also tested positive, suggesting a role for regular screening of both residents and staff in mitigating future outbreaks.
Kaura A, Sterne J, Trickey A, et al., 2020, Invasive versus non-invasive management of elderly patients with non-ST elevation myocardial infarction: cohort study based on routine clinical data, The Lancet, Vol: 396, Pages: 623-634, ISSN: 0140-6736
BackgroundPrevious trials suggest lower long-term mortality after invasive rather than non-invasive management among patients with non-ST elevation myocardial infarction (NSTEMI), but these excluded very elderly patients.MethodsWe estimated the effect of invasive versus non-invasive management within 3 days of peak troponin on survival in NSTEMI patients aged ≥80 years, using routine clinical data collected during 2010–2017 (NIHR Health Informatics Collaborative). Propensity scores based on pre-treatment variables were derived using logistic regression; patients with high probabilities of non-invasive or invasive management were excluded. Patients who died within 3 days without receiving invasive management were assigned to the invasive or non-invasive management groups based on their propensity scores, to mitigate immortal time bias. We estimated mortality hazard ratios comparing invasive with non-invasive management, and also compared rates of hospital admission for heart failure.FindingsOf 1976 patients with NSTEMI, 101 died within 3 days of their peak troponin, whilst 375 were excluded because of extreme propensity scores. The remaining 1500 patients (56% non-invasive management) had a median age 86 (IQR 82-89) years. During median follow-up of 3.0 (IQR 1.2-4.8) years, there were 613 (41%) deaths. Using inverse probability weighting, adjusted cumulative 5-year mortality was 36% and 55% in the invasive and non-invasive management groups, respectively. The mortality hazard ratio comparing invasive with non-invasive management was 0.64 (95% CI 0.52-0.79) after multivariable adjustment for clinical characteristics and propensity score and inclusion of patients who died within three days. Invasive management was associated with lower incidence of hospital admissions for heart failure (adjusted rate ratio compared with non-invasive management 0.67, 95% CI 0.48–0.93).
Riley S, Atchison C, Ashby D, et al., 2020, REal-time Assessment of Community Transmission (REACT) of SARS-CoV-2 virus: Study protocol, Wellcome Open Research, Vol: 5, Pages: 200-200
<ns3:p><ns3:bold>Background:</ns3:bold> England, UK has one of the highest rates of confirmed COVID-19 mortality globally. Until recently, testing for the SARS-CoV-2 virus focused mainly on healthcare and care home settings. As such, there is far less understanding of community transmission.</ns3:p><ns3:p> <ns3:bold>Protocol:</ns3:bold> The REal-time Assessment of Community Transmission (REACT) programme is a major programme of home testing for COVID-19 to track progress of the infection in the community.</ns3:p><ns3:p> REACT-1 involves cross-sectional surveys of viral detection (virological swab for RT-PCR) tests in repeated samples of 100,000 to 150,000 randomly selected individuals across England. This examines how widely the virus has spread and how many people are currently infected. The age range is 5 years and above. Individuals are sampled from the England NHS patient list.</ns3:p><ns3:p> REACT-2 is a series of five sub-studies towards establishing the seroprevalence of antibodies to SARS-CoV-2 in England as an indicator of historical infection. The main study (study 5) uses the same design and sampling approach as REACT-1 using a self-administered lateral flow immunoassay (LFIA) test for IgG antibodies in repeated samples of 100,000 to 200,000 adults aged 18 years and above. To inform study 5, studies 1-4 evaluate performance characteristics of SARS-CoV-2 LFIAs (study 1) and different aspects of feasibility, usability and application of LFIAs for home-based testing in different populations (studies 2-4).</ns3:p><ns3:p> <ns3:bold>Ethics and dissemination: </ns3:bold>The study has ethical approval. Results are reported using STROBE guidelines and disseminated through reports to public health bodies, presentations at scientific meetings and open access publications.</ns3:p><ns3:p> <ns3:bold>Conclusions: </ns3:bold>This study provides robust estimat
Chadeau M, Bodinier B, Elliott J, et al., 2020, Risk factors for positive and negative COVID-19 tests: a cautious and in-depth analysis of UK Biobank data, International Journal of Epidemiology, ISSN: 0300-5771
BackgroundThe recent COVID-19 outbreak has generated an unprecedented public health crisis, with millions of infections and hundreds of thousands of deaths worldwide. Using hospital-based or mortality data, several COVID-19 risk factors have been identified, but these may be confounded or biased.MethodsUsing SARS-CoV-2 infection test data (N=4,509 tests; 1,325 positive) from Public Health England, linked to the UK Biobank study, we explored the contribution of demographic, social, health risk, medical, and environmental factors to COVID-19 risk. We used multivariable and penalised logistic regression models for the risk of (i) being tested, (ii) testing positive/negative in the study population and, adopting a test negative design, (iv) the risk of testing positive within the tested population.ResultsIn the fully adjusted model, variables independently associated with the risk of being tested for COVID-19 with OR >1.05 were: male sex; Black ethnicity; social disadvantage (as measured by education, housing and income); occupation (healthcare worker, retired, unemployed); ever smoker; severely obese; comorbidities; and greater exposure to PM2.5-absorbance. Of these, only male sex, non-White ethnicity, lower educational attainment, and none of the comorbidities or health risk factors, were associated with testing positive among tested individuals.ConclusionsWe adopted a careful and exhaustive approach within a large population-based cohort, which enabled us to triangulate evidence linking, male sex, lower educational attainment, non-White ethnicity with the risk of COVID-19. The elucidation of the joint and independent effects of these factors is a high-priority area for further research to inform on COVID-19 natural history.
Atchison C, Pristerà P, Cooper E, et al., 2020, Usability and acceptability of home-based self-testing for SARS-CoV-2 antibodies for population surveillance., Clinical Infectious Diseases, ISSN: 1058-4838
BACKGROUND: This study assesses acceptability and usability of home-based self-testing for SARS-CoV-2 antibodies using lateral flow immunoassays (LFIA). METHODS: We carried out public involvement and pilot testing in 315 volunteers to improve usability. Feedback was obtained through online discussions, questionnaires, observations and interviews of people who tried the test at home. This informed the design of a nationally representative survey of adults in England using two LFIAs (LFIA1 and LFIA2) which were sent to 10,600 and 3,800 participants, respectively, who provided further feedback. RESULTS: Public involvement and pilot testing showed high levels of acceptability, but limitations with the usability of kits. Most people reported completing the test; however, they identified difficulties with practical aspects of the kit, particularly the lancet and pipette, a need for clearer instructions and more guidance on interpretation of results. In the national study, 99.3% (8,693/8,754) of LFIA1 and 98.4% (2,911/2,957) of LFIA2 respondents attempted the test and 97.5% and 97.8% of respondents completed it, respectively. Most found the instructions easy to understand, but some reported difficulties using the pipette (LFIA1: 17.7%) and applying the blood drop to the cassette (LFIA2: 31.3%). Most respondents obtained a valid result (LFIA1: 91.5%; LFIA2: 94.4%). Overall there was substantial concordance between participant and clinician interpreted results (kappa: LFIA1 0.72; LFIA2 0.89). CONCLUSION: Impactful public involvement is feasible in a rapid response setting. Home self-testing with LFIAs can be used with a high degree of acceptability and usability by adults, making them a good option for use in seroprevalence surveys.
Chatzidiakou L, Krause A, Han Y, et al., 2020, Using low-cost sensor technologies and advanced computational methods to improve dose estimations in health panel studies: results of the AIRLESS project, Journal of Exposure Science and Environmental Epidemiology, Vol: 30, Pages: 981-989, ISSN: 1559-0631
BackgroundAir pollution epidemiology has primarily relied on fixed outdoor air quality monitoring networks and static populations.MethodsTaking advantage of recent advancements in sensor technologies and computational techniques, this paper presents a novel methodological approach that improves dose estimations of multiple air pollutants in large-scale health studies. We show the results of an intensive field campaign that measured personal exposures to gaseous pollutants and particulate matter of a health panel of 251 participants residing in urban and peri-urban Beijing with 60 personal air quality monitors (PAMs). Outdoor air pollution measurements were collected in monitoring stations close to the participants’ residential addresses. Based on parameters collected with the PAMs, we developed an advanced computational model that automatically classified time-activity-location patterns of each individual during daily life at high spatial and temporal resolution.ResultsApplying this methodological approach in two established cohorts, we found substantial differences between doses estimated from outdoor and personal air quality measurements. The PAM measurements also significantly reduced the correlation between pollutant species often observed in static outdoor measurements, reducing confounding effects.ConclusionsFuture work will utilise these improved dose estimations to investigate the underlying mechanisms of air pollution on cardio-pulmonary health outcomes using detailed medical biomarkers in a way that has not been possible before.
Flower B, Brown JC, Simmons B, et al., 2020, Clinical and laboratory evaluation of SARS-CoV-2 lateral flow assays for use in a national COVID-19 sero-prevalence survey, Thorax, Vol: 75, Pages: 1082-1088, ISSN: 0040-6376
BackgroundAccurate antibody tests are essential to monitor the SARS-CoV-2 pandemic. Lateral flow immunoassays (LFIAs) can deliver testing at scale. However, reported performance varies, and sensitivity analyses have generally been conducted on serum from hospitalised patients. For use in community testing, evaluation of finger-prick self-tests, in non-hospitalised individuals, is required.MethodsSensitivity analysis was conducted on 276 non-hospitalised participants. All had tested positive for SARS-CoV-2 by RT-PCR and were ≥21d from symptom-onset. In phase I we evaluated five LFIAs in clinic (with finger-prick) and laboratory (with blood and sera) in comparison to a) PCR-confirmed infection and b) presence of SARS-CoV-2 antibodies on two “in-house” ELISAs. Specificity analysis was performed on 500 pre-pandemic sera. In phase II, six additional LFIAs were assessed with serum.Findings95% (95%CI [92.2, 97.3]) of the infected cohort had detectable antibodies on at least one ELISA. LFIA sensitivity was variable, but significantly inferior to ELISA in 8/11 assessed. Of LFIAs assessed in both clinic and laboratory, finger-prick self-test sensitivity varied from 21%-92% vs PCR-confirmed cases and 22%-96% vs composite ELISA positives. Concordance between finger-prick and serum testing was at best moderate (kappa 0.56) and, at worst, slight (kappa 0.13). All LFIAs had high specificity (97.2% - 99.8%).InterpretationLFIA sensitivity and sample concordance is variable, highlighting the importance of evaluations in setting of intended use. This rigorous approach to LFIA evaluation identified a test with high specificity (98.6% (95%CI [97.1, 99.4])), moderate sensitivity (84.4% with fingerprick (95%CI [70.5, 93.5])), and moderate concordance, suitable for seroprevalence surveys.
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