Epidemiology

Umbrella reviews: what they are and why we need them

Cystic echinococcosis in unaccompanied minor refugees from Afghanistan and the Middle East to Germany, July 2016 through June 2017 Abstract Cystic echinococcosis (CE) is not covered by current refugee screening protocols. After we had detected CE among several refugees attending our clinic from Afghanistan and the Middle East, serological examinations for CE were performed for apparently healthy unaccompanied minor refugees from these regions.

The long and winding road to causality

Blood–brain barrier transcytosis genes, risk of dementia and stroke: a prospective cohort study of 74,754 individuals Abstract To test whether genetic variants in PICALM, BIN1, CD2AP, and RIN3—suggested to be involved in blood–brain barrier amyloid-β transcytosis pathways—associate with Alzheimer's disease, all dementia, suggested vascular dementia, and stroke, and whether such associations are independent of the strong ε4 APOE risk allele. In a prospective cohort study of 74,754 individuals from the general population we genotyped PICALM(rs10792832), BIN1 (rs6733839), CD2AP (rs10948363), and RIN3 (rs10498633), and generated a weighted and a simple allele score. Multifactorially adjusted hazard ratios for the fourth quartile versus the first quartile of the weighted allele score were 1.42 (95% confidence interval 1.22–1.64) for Alzheimer's disease, and 1.33 (1.19–1.48) for all dementia. For suggested vascular dementia and stroke the corresponding estimates were 1.71 (1.18–2.49) and 1.12 (1.04–1.22), respectively. Hazard ratios were similar after APOE adjustment. Genetic variants in PICALM, BIN1, CD2AP, and RIN3 are associated with increased risk of Alzheimer's disease, all dementia, and suggested vascular dementia independent of the strong APOE ε4 allele. These findings may suggest that clathrin-mediated endocytosis in clearance of amyloid-β across the blood–brain barrier is important for the integrity of both brain tissue and cerebral vessels.

Hospitalisation of people with dementia: evidence from English electronic health records from 2008 to 2016 Abstract Hospitalisation of people with dementia is associated with adverse outcomes and high costs. We aimed to examine general, i.e. non-psychiatric, hospitalisation rates, changes since 2008 and factors associated with admission. We also aimed to compare admission rates of people with dementia with age-matched people without dementia. We conducted a cohort study of adults ≥ 65 years, with dementia diagnosed during the 2008–2016 study window, derived from a large secondary mental healthcare database in South London, UK. We used national general hospital records to identify emergency and elective hospitalisations. We calculated the cumulative incidence and rate of hospitalisation and examined predictors of hospitalisation using negative binomial regression, with multiple imputation for missing covariate data. We calculated age-standardised admission ratio for people with dementia compared to those without. Of 10,137 people, 50.6% were admitted to hospital in the year following dementia diagnosis and 75.9% were admitted during median 2.5 years follow-up. Annual admission rate was 1.26/person-year of which 0.90/person-year were in emergency. Emergency hospitalisation rate increased throughout the study period. Compared to controls without diagnosed dementia in the catchment area, the age-standardised emergency admission ratio for people with dementia was 2.06 (95% CI 1.95, 2.18). Male, older, white and socio-economically deprived people and those with clinically significant comorbid physical illness, depressed mood, activity of daily living or living condition problems had more hospitalisations. Emergency hospitalisations of people with dementia are higher than those without, and increasing. Many factors associated with admission are social and psychological, and may be targets for future interventions that aim to reduce avoidable admissions.

Causal criteria: time has come for a revision Abstract Epidemiologists study associations but they are usually interested in causation that could lead to disease prevention. Experience show, however, that many of the associations we identify are not the causes we take an interest in (correlation is not causation). In order to proper translate association into causes, a set of causal criteria was developed 50–60 years ago and they became important tools guiding this translational process (sometimes correlation is causation). Best known of these are the Bradford Hill 'criteria'. In these last 50 years, epidemiologic theory and infrastructure have advanced rapidly without changes in these causal criteria. We think time has come to revisit the 'old' criteria to see which ones we should keep and which ones should be taken out or be replaced by new measures of association. Robustness of these criteria in attempts to make the association go away should have high priority. A group of renowned internationally recognized researchers should have this task. Since classifying associations as causes is often done in order to reduce or eliminate the exposures of concern results from conditional outcome research should also be used. We therefore suggest to add a 'consequence' criterion. We argue that a consequence criterion that provides a framework for assessing or prescribing action worthy or right in social contexts is needed. A consequence criterion will also influence how strict our causal criteria need to be before leading to action and will help in separating the 'causal discussion' and the discussion on what to do about it. A consequence criterion will be a tool in handling dilemmas over values (as social solidarity, fairness, autonomy). It will have implications for the interpretation and use of the procedural criteria of causality. Establishing interconnected procedural and consequence criteria should be a task for institutions representing and being recognized by experts, civil society and the state.

Asthma and selective migration from farming environments in a three-generation cohort study Abstract Individuals raised on a farm appear to have less asthma than individual raised elsewhere. However, selective migration might contribute to this as may also the suggested protection from farm environment. This study investigated if parents with asthma are less likely to raise their children on a farm. This study involved three generations: 6045 participants in ECRHS/RHINE cohorts (born 1945–1973, denoted G1), their 10,121 parents (denoted G0) and their 8260 offspring participating in RHINESSA (born 1963–1998, denoted G2). G2-offspring provided information on parents not participating in ECRHS/RHINE. Asthma status and place of upbringing for all three generations were reported in questionnaires by G1 in 2010–2012 and by G2 in 2013–2016. Binary regressions with farm upbringing as outcome were performed to explore associations between parental asthma and offspring farm upbringing in G0–G1 and G1–G2. Having at least one parent with asthma was not associated with offspring farm upbringing, either in G1–G2 (RR 1.11, 95% CI 0.81–1.52) or in G0–G1 (RR 0.99, 0.85–1.15). G1 parents with asthma born in a city tended to move and raise their G2 offspring on a farm (RR 2.00, 1.12–3.55), while G1 parents with asthma born on a farm were less likely to raise their G2 offspring on a farm (RR 0.34, 0.11–1.06). This pattern was not observed in analyses of G0–G1. This study suggests that the protective effect from farm upbringing on subsequent asthma development could not be explained by selective migration. Intriguingly, asthmatic parents appeared to change environment when having children.

Identifying dementia outcomes in UK Biobank: a validation study of primary care, hospital admissions and mortality data Abstract Prospective, population-based studies that recruit participants in mid-life are valuable resources for dementia research. Follow-up in these studies is often through linkage to routinely-collected healthcare datasets. We investigated the accuracy of these datasets for dementia case ascertainment in a validation study using data from UK Biobank—an open access, population-based study of > 500,000 adults aged 40–69 years at recruitment in 2006–2010. From 17,198 UK Biobank participants recruited in Edinburgh, we identified those with ≥ 1 dementia code in their linked primary care, hospital admissions or mortality data and compared their coded diagnoses to clinical expert adjudication of their full-text medical record. We calculated the positive predictive value (PPV, the proportion of cases identified that were true positives) for all-cause dementia, Alzheimer's disease and vascular dementia for each dataset alone and in combination, and explored algorithmic code combinations to improve PPV. Among 120 participants, PPVs for all-cause dementia were 86.8%, 87.3% and 80.0% for primary care, hospital admissions and mortality data respectively and 82.5% across all datasets. We identified three algorithms that balanced a high PPV with reasonable case ascertainment. For Alzheimer's disease, PPVs were 74.1% for primary care, 68.2% for hospital admissions, 50.0% for mortality data and 71.4% in combination. PPV for vascular dementia was 43.8% across all sources. UK routinely-collected healthcare data can be used to identify all-cause dementia in prospective studies. PPVs for Alzheimer's disease and vascular dementia are lower. Further research is required to explore the geographic generalisability of these findings.

Blood pressure, hypertension and the risk of abdominal aortic aneurysms: a systematic review and meta-analysis of cohort studies Abstract Abdominal aortic aneurysms (AAA) are fatal in 80% of the cases when ruptured. Hypertension has been considered a potential risk factor for AAA; but the findings from prospective cohort studies have not been entirely consistent, nor have they been summarised in a comprehensive meta-analysis. Our aim was to conduct a systematic review and meta-analysis of cohort studies of the association between blood pressure, hypertension and AAA to clarify the strength and shape of these associations. We searched PubMed and Embase databases for relevant cohort studies up to April 30th, 2018. Random-effects models were used to calculate summary relative risks (RRs) and 95% confidence intervals (CIs). The meta-analysis included 21 cohort studies (20 publications) with data on 28,162 cases and 5,440,588 participants. The findings indicate that the RR of AAA in hypertensive patients is 1.66 times (95% CI: 1.49–1.85, I2 = 79.3%, n = 13) that of non-hypertensive patients. In addition, there was a 14% (95% CI: 6–23%, I2 = 30.5%, n = 6) and a 28% (95% CI: 12–46%, I2 = 80.1%, n = 6) increase in the RR of AAA for every 20 mmHg and 10 mmHg increase in systolic blood pressure (SBP) and diastolic blood pressure (DBP), respectively. The analysis of DBP showed evidence of a strong and highly significant nonlinear dose–response relationship (p < 0.001) with a steeper association from 80 mmHg and above. This meta-analysis suggests that hypertension increases the risk of developing AAA by 66%. Further studies are needed to clarify the underlying mechanism explaining the much stronger association between DBP and AAA than for SBP.

The association between weight at birth and breast cancer risk revisited using Mendelian randomisation Abstract Observational studies suggest that higher birth weight (BW) is associated with increased risk of breast cancer in adult life. We conducted a two-sample Mendelian randomisation (MR) study to assess whether this association is causal. Sixty independent single nucleotide polymorphisms (SNPs) known to be associated at P < 5 × 10−8 with BW were used to construct (1) a 41-SNP instrumental variable (IV) for univariable MR after removing SNPs with pleiotropic associations with other breast cancer risk factors and (2) a 49-SNP IV for multivariable MR after filtering SNPs for data availability. BW predicted by the 41-SNP IV was not associated with overall breast cancer risk in inverse-variance weighted (IVW) univariable MR analysis of genetic association data from 122,977 breast cancer cases and 105,974 controls (odds ratio = 0.86 per 500 g higher BW; 95% confidence interval 0.73–1.01). Sensitivity analyses using four alternative methods and three alternative IVs, including an IV with 59 of the 60 BW-associated SNPs, yielded similar results. Multivariable MR adjusting for the effects of the 49-SNP IV on birth length, adult height, adult body mass index, age at menarche, and age at menopause using IVW and MR-Egger methods provided estimates consistent with univariable analyses. Results were also similar when all analyses were repeated after restricting to estrogen receptor-positive or -negative breast cancer cases. Point estimates of the odds ratios from most analyses performed indicated an inverse relationship between genetically-predicted BW and breast cancer, but we are unable to rule out an association between the non-genetically-determined component of BW and breast cancer. Thus, genetically-predicted higher BW was not associated with an increased risk of breast cancer in adult life in our MR study.