The Dementias Platform UK (DPUK) Data Portal Bauermeister, Sarah; Orton, Christopher; Thompson, Simon ...
European journal of epidemiology,
06/2020, Letnik:
35, Številka:
6
Journal Article
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The Dementias Platform UK Data Portal is a data repository facilitating access to data for 3 370 929 individuals in 42 cohorts. The Data Portal is an end-to-end data management solution providing a ...secure, fully auditable, remote access environment for the analysis of cohort data. All projects utilising the data are by default collaborations with the cohort research teams generating the data. The Data Portal uses UK Secure eResearch Platform infrastructure to provide three core utilities: data discovery, access, and analysis. These are delivered using a 7 layered architecture comprising: data ingestion, data curation, platform interoperability, data discovery, access brokerage, data analysis and knowledge preservation. Automated, streamlined, and standardised procedures reduce the administrative burden for all stakeholders, particularly for requests involving multiple independent datasets, where a single request may be forwarded to multiple data controllers. Researchers are provided with their own secure ‘lab’ using VMware which is accessed using two factor authentication. Over the last 2 years, 160 project proposals involving 579 individual cohort data access requests were received. These were received from 268 applicants spanning 72 institutions (56 academic, 13 commercial, 3 government) in 16 countries with 84 requests involving multiple cohorts. Projects are varied including multi-modal, machine learning, and Mendelian randomisation analyses. Data access is usually free at point of use although a small number of cohorts require a data access fee.
Summary
Meta‐analyses have found hepatitis C virus (HCV) infection to be associated with an increased risk of type 2 diabetes mellitus (T2DM). Here, we examine this association within a large ...population‐based study, according to HCV RNA status. A data‐linkage approach was used to examine the excess risk of diagnosed T2DM in people diagnosed with antibodies to HCV (anti‐HCV) in Scotland (21 929 anti‐HCV+ves; involving 15 827 HCV RNA+ves, 3927 HCV RNA−ves and 2175 with unknown RNA‐status) compared to that of a threefold larger general population sample matched for gender, age and postcode (65 074 anti‐HCV−ves). To investigate effects of ascertainment bias the following periods were studied: up to 1 year before (pre‐HCV)/within 1 year of (peri‐HCV)/more than 1 year post (post‐HCV) the date of HCV‐diagnosis. T2DM had been diagnosed in 2.9% of anti‐HCV+ves (including 3.2% of HCV RNA+ves and 2.3% of HCV RNA−ves) and 2.7% of anti‐HCV−ves. A higher proportion of T2DM was diagnosed in the peri‐HCV period (i.e. around the time of HCV‐diagnosis) for the anti‐HCV+ves (22%) compared to anti‐HCV−ves (10%). In both the pre‐HCV and post‐HCV periods, only those anti‐HCV+ves living in less deprived areas (13% of the cohort) were found to have a significant excess risk of T2DM compared to anti‐HCV−ves (adjusted odds ratio in the pre‐HCV period: 4.0 for females and 2.3 for males; adjusted hazard ratio in the post‐HCV period: 1.5). These findings were similarly observed for both HCV RNA+ves (chronic) and HCV RNA−ves (resolved). In the largest study of T2DM among chronic HCV‐infected individuals to date, there was no evidence to indicate that infection conveyed an appreciable excess risk of T2DM at the population level.
The rising burden of dementia is a global concern, and there is a need to study its causes, natural history and outcomes. The Secure Anonymised Information Linkage (SAIL) Databank contains ...anonymised, routinely-collected healthcare data for the population of Wales, UK. It has potential to be a valuable resource for dementia research owing to its size, long follow-up time and prospective collection of data during clinical care.
We aimed to apply reproducible methods to create the SAIL dementia e-cohort (SAIL-DeC). We created SAIL-DeC with a view to maximising its utility for a broad range of research questions whilst minimising duplication of effort for researchers.
SAIL contains individual-level, linked primary care, hospital admission, mortality and demographic data. Data are currently available until 2018 and future updates will extend participant follow-up time. We included participants who were born between 1st January 1900 and 1st January 1958 and for whom primary care data were available. We applied algorithms consisting of International Classification of Diseases (versions 9 and 10) and Read (version 2) codes to identify participants with and without all-cause dementia and dementia subtypes. We also created derived variables for comorbidities and risk factors.
From 4.4 million unique participants in SAIL, 1.2 million met the cohort inclusion criteria, resulting in 18.8 million person-years of follow-up. Of these, 129,650 (10%) developed all-cause dementia, with 77,978 (60%) having dementia subtype codes. Alzheimer's disease was the most common subtype diagnosis (62%). Among the dementia cases, the median duration of observation time was 14 years.
We have created a generalisable, national dementia e-cohort, aimed at facilitating epidemiological dementia research.
In countries maintaining national hepatitis C virus (HCV) surveillance systems, a substantial proportion of individuals report no risk factors for infection. Our goal was to estimate the proportion ...of diagnosed HCV antibody-positive persons in Scotland (1991–2010) who probably acquired infection through injecting drug use (IDU), by combining data on IDU risk from four linked data sources using log-linear capture–recapture methods. Of 25 521 HCV-diagnosed individuals, 14 836 (58%) reported IDU risk with their HCV diagnosis. Log-linear modelling estimated a further 2484 HCV-diagnosed individuals with IDU risk, giving an estimated prevalence of 83. Stratified analyses indicated variation across birth cohort, with estimated prevalence as low as 49% in persons born before 1960 and greater than 90% for those born since 1960. These findings provide public-health professionals with a more complete profile of Scotland's HCV-infected population in terms of transmission route, which is essential for targeting educational, prevention and treatment interventions.
It is paramount to understand the epidemiology of chronic hepatitis B to inform national policies on vaccination and screening/testing as well as cost-effectiveness studies. However, information on ...the national (Scottish) prevalence of chronic hepatitis B by ethnic group is lacking. To estimate the number of people with chronic hepatitis B in Scotland in 2009 by ethnicity, gender and age, the test data from virology laboratories in the four largest cities in Scotland were combined with estimates of the ethnic distribution of the Scottish population. Ethnicity in both the test data and the Scottish population was derived using a name-based ethnicity classification software (OnoMAP; Publicprofiler Ltd, UK). For 2009, we estimated 8720 95% confidence interval (CI) 7490–10 230 people aged ⩾15 years were living with chronic hepatitis B infection in Scotland. This corresponds to 0·2% (95% CI 0·17–0·24) of the Scottish population aged ⩾15 years. Although East and South Asians make up a small proportion of the Scottish population, they make up 44% of the infected population. In addition, 75% of those infected were aged 15–44 years with almost 60% male. This study quantifies for the first time on a national level the burden of chronic hepatitis B infection by ethnicity, gender and age. It confirms the importance of promoting and targeting ethnic minority groups for hepatitis B testing.
BackgroundRecent studies have reported conflicting associations between drug prescriptions and incident dementia. Any association between drug and dementia could be due to the drugs directly causing ...or preventing dementia; the drugs being associated with a risk factor for dementia; or the drugs being prescribed as a consequence of prodromal dementia. Based on methodology developed for genome-wide association studies, we systematically analyzed the effect of 733 drugs on incident dementia in a population-wide linkage study and clinically reviewed the associations.MethodsUsing linked, routinely-collected electronic health records from hospital admissions, mortality records and primary care consultations, we followed-up 574,237 Welsh residents from their 60th birthday onwards to classify exposure (drug prescriptions) and dementia incidence. During follow-up, 13,786 (2.4%) of the study population developed dementia. We used time-dependent Cox proportional hazard models to study the effect of exposure on dementia incidence, controlling for the effects of age, sex, year, deprivation and smoking status. To account for multiple testing, we first analyzed a 50% household-area stratified random sample of the study population (discovery cohort), selected results with a Bonferroni-corrected p-value, re-run the analysis of ‘significantly’ associated drugs in the remaining 50% (validation cohort) and once again selected results with a Bonferroni-corrected p-value. We displayed the results (hazard ratio and p-value) from the complete cohort in several stratified volcano-plots and clinically reviewed the findings to identify potential pathways of effect.Results177/733 (24%) of the analysed drugs were significantly associated with dementia incidence. Of those, 7 were for neurodegenerative conditions that can cause dementia, 14 were for vascular diseases, 13 for diabetes, 16 for depression and 39 for symptoms or complications of dementia. Only four, all travel-related vaccines, were associated with a lower dementia incidence. Some drugs associated with an increased hazard of dementia clustered around several unexpected indications, including: gastro-oesophageal reflux disease, altered bowel habit, lower urinary tract symptoms and infections, anxiety, sleep disturbance, pain and nausea/vertigo.DiscussionBy grouping drugs by indication, we identified several drugs with a potential of having a direct association with increased risk of dementia. We also identified drugs which are related to (known) risk factors for dementia, including those prescribed for cardiovascular disease and diabetes. The effect of travel-related vaccines is puzzling and might be more related to a preventative association of travelling with dementia incidence. Most interestingly, we identified several drugs which might have been prescribed as a consequence of a preclinical, non-cognitive syndrome in dementia.
BackgroundPeople with epilepsy (PWE) are reported to have higher risk of dementia. However, the magnitude of this association, whether it varies according to dementia subtypes and whether there are ...factors that modify the association is uncertain. We investigated the apparent association in a large population-based retrospective cohort study using routinely-collected linked health data from hospitalisation, mortality records and primary care consultations.MethodsWe used linked health data from the Secure Anonymised Information Linkage (SAIL) databank to follow-up Welsh residents for whom linked primary care data were available from their 60th birthday to estimate dementia rate and associated risk factors. Disease (dementia), exposure (epilepsy) and covariates (medication, smoking, stroke and diabetes) were classified using previously validated code lists. We studied rate of dementia and dementia subtypes in people with and without epilepsy using (stratified) Kaplan-Meier plots and flexible parametric proportional hazard analyses.The study population comprised 563,808 people of whom 19,807 (4%) had indications of epilepsy in the linked health data. 13,454 (68%) of PWE and 49,439 (9%) of people without epilepsy had at least one record for a prescription of an antiepileptic drug (AED). Compared to people without epilepsy, PWE had lower survival (median survival to age 79 years compared to 84), higher smoking risks (74% compared to 66%) and higher stroke risks (20% compared to 7%) before or during follow-up.ResultsBetween ages 60 and 70 years, 6% of PWE and 1% of people without epilepsy had a diagnosis of dementia; corresponding figures between ages 60 and 80 years were 23% and 8%. The difference in dementia rate between those with and without epilepsy was larger for vascular dementia than for Alzheimer’s disease. The increased rate for PWE was modified by a history of stroke, smoking and, to a lesser effect, diabetes. PWE who were first diagnosed before age 25 years had a lower dementia rate than those diagnosed later in life. Compared to PWE not exposed, those exposed to sodium valproate were at higher risk of dementia (crude HR: 1.7; 95% CI: 1.5–1.9) while those exposed to a group of enzyme-inducing AED were at similar risk (crude HR: 1.1, 95% CI: 1.0–1.3).ConclusionAt least some of the increased risk of dementia in PWE can be attributed to increased vascular risk factors in PWE causing vascular dementia. Given the widespread use of sodium valproate in PWE, the association of the drug with higher dementia risk is concerning.
We report on the construction of a light pulser monitoring system for the electromagnetic lead tungstate (PbWO4) calorimeter of the future P¯ANDA experiment at FAIR. The system consists of a high ...intensity LED source, an optical fibre distribution system, and a novel and compact continuous light attenuation mechanism based on LCDs allowing operation inside the magnetic field of the P¯ANDA detector. The physics objectives of the P¯ANDA experiment require a highly sophisticated electromagnetic calorimeter covering an energy range spanning more than three orders of magnitude. In order to perform precision measurements with this electromagnetic calorimeter based on lead tungstate crystals in the high-luminosity environment of the P¯ANDA experiment, a frequent monitoring of radiation induced transmittance losses in the crystals on a level of 0.5% is required. This precision can be achieved on a day-by-day basis between regular π0/η invariant mass calibrations, performed at least once a day.
Abstract
Background
The risk of morbidity and mortality related to paediatric-onset inflammatory bowel disease (PIBD) and its treatment is a major concern to both patients and clinicians, especially ...when this may affect early adult life. We aimed to determine whether PIBD patients are at increased risk of ischaemic heart disease (IHD), stroke, cancer and death in a nationwide population-based study using administrative health data research methodology.
Methods
All children diagnosed with PIBD in Scotland 1981–2017 were identified within the Scottish Morbidity Record inpatient and day-case dataset (SMR01). PIBD cases were defined as any inpatient International Classification of Diseases (ICD) coding for Crohn’s disease (CD; 555/K50) or ulcerative colitis (UC; 556/K51) until age 16; 10% of cases were individually validated. A nested case-control study (1:3 ratio) matched for sex, age, postcode sector and deprivation quintile within the Scottish population was performed. Data-linkage was applied to SMR01, SMR06 (Scottish Cancer Registry) and NRS deaths datasets to identify any diagnosis of IHD, acute stroke, cancer or mortality. Cancer diagnoses were classified into potential disease related (small bowel, colonic, rectal, anal, hepatobiliary) or treatment related (lymphoma, leukaemia, myeloma, PTLD) cancers. Hazard ratios (HR) were calculated for each outcome using mixed effects Cox regression and the potential effect of sex, year of diagnosis and age at diagnosis were explored.
Results
The study population comprised 2484 children with PIBD and 7451 matched controls. Median age of PIBD diagnosis was 12 years (IQR 10–14) and age at end of follow-up 24 years (IQR 17–33) with 141,605 total person-years follow-up. Validation identified 242/261 true positive cases (positive predictive value 93%). 2 cases (0.08%) and 7 controls (0.09%) had an admission for IHD during follow-up (p = 0.845); 6 cases (0.24%) and 5 controls (0.07%) were admitted for stroke (p = 0.024). PIBD cases had a significantly higher risk of any cancer diagnosis (62 cases: 97 controls) HR 1.97 (p < 0.001), including a 31.9 times higher risk of disease-related cancers (p < 0.001) and a 6 times higher risk of treatment-related cancers (p = 0.011). The effect of PIBD on cancer risk was higher in males, but not related to year or age. PIBD cases had a greater risk of mortality (60 cases: 51 controls) HR 3.61 (p < 0.001). The specific mortality risk from infection was 21.4 times higher in PIBD cases (p = 0.004); the risk of suicide was 2.4 times higher but not statistically significant (p = 0.085). The effect of PIBD on mortality risk was not modified by sex, year or age.
Conclusion
Cancer and mortality are meaningful, serious early adult life adverse sequelae of PIBD however IHD and stroke occur infrequently.
Abstract
Background
The incidence of paediatric-onset inflammatory bowel disease (PIBD) continues to rise, with genetic-environmental interactions expected to play a vital role. Given gestation and ...infancy are sensitive periods for environmental change, we aimed to determine whether a mode of delivery, gestational age or type of infant feeding contribute to the development of PIBD in a nationwide cohort of high-risk Scottish children using administrative health data research methodology.
Methods
All children born in Scotland 1981–2017 were identified within the Scottish Morbidity Record maternity inpatient dataset (SMR02). Data linkage was applied to determine mode of delivery, gestational age and type of infant feeding, with PIBD cases defined as any inpatient International Classification of Diseases (ICD) coding for Crohn’s disease (CD; 555/K50), ulcerative colitis (UC; 556/K51) or inflammatory bowel disease unclassified (IBDU; 558.9/K52.3) until age 16. Validation was performed within an entire Scottish health board (16% of the total population) via individual case-note verification. Hazard ratios (HRs) were calculated for each exposure using Cox proportional hazards models with the following potential confounding factors included as covariates: sex, maternal age, year of birth, postcode area and deprivation quintile. Dependent interactions were also explored between the three main exposures.
Results
A study population of 2 013 851 children were identified including 1721 PIBD cases. Individual validation was performed on all 298 (17%) PIBD-coded patients within NHS Lothian; 242/261 CD and UC cases were validated as true positive (positive predictive value 93%); all 37 IBDU cases were false positive with this ICD code excluded from all further analysis. Children delivered vaginally did not have an altered risk of developing PIBD compared with Caesarean section; adjusted HR 0.95 95% CI 0.84–1.08 (p = 0.424). Children born prematurely did not have an altered risk of developing PIBD; 24–31 weeks gestation HR 0.97 95% CI 0.56–1.68 (p = 0.922); 32–36 weeks gestation HR 0.96 (95% CI 0.76–1.20 (p = 0.699). Children not exclusively breast feeding at 6 weeks of age did not have an altered risk of developing PIBD; formula feeding HR 0.97 95% CI 0.81–1.15 (p = 0.705); other/unknown feeding type HR 0.90 95% CI 0.74–1.08 (p = 0.259). No two-way interactions were significant and none of the three exposures was significantly related to CD or UC in PIBD subtype analysis.
Conclusion
This robust, validated population-based study of over 2 million Scottish births utilising administrative health data confidently demonstrates no association between mode of delivery, gestational age, type of feeding and the development of PIBD.
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