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  • EpiMetal: an open-source graphical web browser tool for easy statistical analyses in epidemiology and metabolomics
    Int. J. Epidemiol. (IF 7.339) Pub Date : 2020-01-16
    Ekholm J, Ohukainen P, Kangas A, et al.

    MotivationAn intuitive graphical interface that allows statistical analyses and visualizations of extensive data without any knowledge of dedicated statistical software or programming. Implementation EpiMetal is a single-page web application written in JavaScript, to be used via a modern desktop web browser. General features Standard epidemiological analyses and self-organizing maps for data-driven metabolic profiling are included. Multiple extensive datasets with an arbitrary number of continuous and category variables can be integrated with the software. Any snapshot of the analyses can be saved and shared with others via a www-link. We demonstrate the usage of EpiMetal using pilot data with over 500 quantitative molecular measures for each sample as well as in two large-scale epidemiological cohorts (N >10 000). AvailabilityThe software usage exemplar and the pilot data are open access online at [http://EpiMetal.computationalmedicine.fi]. MIT licensed source code is available at the Github repository at [https://github.com/amergin/epimetal].

    更新日期:2020-01-16
  • Use of E-values for addressing confounding in observational studies—an empirical assessment of the literature
    Int. J. Epidemiol. (IF 7.339) Pub Date : 2020-01-13
    Blum M, Tan Y, Ioannidis J.

    BackgroundE-values are a recently introduced approach to evaluate confounding in observational studies. We aimed to empirically assess the current use of E-values in published literature. MethodsWe conducted a systematic literature search for all publications, published up till the end of 2018, which cited at least one of two inceptive E-value papers and presented E-values for original data. For these case publications we identified control publications, matched by journal and issue, where the authors had not calculated E-values. ResultsIn total, 87 papers presented 516 E-values. Of the 87 papers, 14 concluded that residual confounding likely threatens at least some of the main conclusions. Seven of these 14 named potential uncontrolled confounders. 19 of 87 papers related E-value magnitudes to expected strengths of field-specific confounders. The median E-value was 1.88, 1.82, and 2.02 for the 43, 348, and 125 E-values where confounding was felt likely to affect the results, unlikely to affect the results, or not commented upon, respectively. The 69 case-control publication pairs dealt with effect sizes of similar magnitude. Of 69 control publications, 52 did not comment on unmeasured confounding and 44/69 case publications concluded that confounding was unlikely to affect study conclusions. ConclusionsFew papers using E-values conclude that confounding threatens their results, and their E-values overlap in magnitude with those of papers acknowledging susceptibility to confounding. Facile automation in calculating E-values may compound the already poor handling of confounding. E-values should not be a substitute for careful consideration of potential sources of unmeasured confounding. If used, they should be interpreted in the context of expected confounding in specific fields.

    更新日期:2020-01-13
  • Is mode of transport to work associated with mortality in the working-age population? Repeated census-cohort studies in New Zealand 1996, 2001 and 2006
    Int. J. Epidemiol. (IF 7.339) Pub Date : 2020-01-13
    Shaw C, Blakely T, Atkinson J, et al.

    BackgroundIncreasing active transport is proposed as a means to address both health and environmental issues. However, the associations between specific modes, such as cycling, walking and public transport, and health outcomes remain unclear. We examined the association between mode of travel to work and mortality. MethodsCohort studies of the entire New Zealand working population were created using 1996, 2001 and 2006 censuses linked to mortality data. Mode of travel to work was that reported on census day, and causes of death examined were ischaemic heart disease and injury. Main analyses were Poisson regression models adjusted for socio-demographics. Sensitivity analyses included: additional adjustment for smoking in the 1996 and 2006 cohorts, and bias analysis about non-differential misclassification of cycling vs car use. ResultsWalking (5%) and cycling (3%) to work were uncommon. Compared with people reporting using motor vehicles to travel to work, those cycling had a reduced all-cause mortality (ACM) in the socio-demographic adjusted models RR 0.87 (0.77–0.98). Those walking (0.97, 0.90–1.04) and taking public transport (0.96, 0.88–1.05) had no substantive difference in ACM. No mode of transport was associated with detectable statistically significant reductions in cause-specific mortality. Sensitivity analyses found weaker associations when adjusting for smoking and stronger associations correcting for likely non-differential misclassification of cycling. ConclusionsThis large cohort study supports an association between cycling to work and reduced ACM, but found no association for walking or public-transport use and imprecise cause-specific mortality patterns.

    更新日期:2020-01-13
  • Determinants of the population health distribution: an illustration examining body mass index
    Int. J. Epidemiol. (IF 7.339) Pub Date : 2020-01-13
    Bann D, Fitzsimons E, Johnson W.

    Most epidemiological studies examine how risk factors relate to average difference in outcomes (linear regression) or odds of a binary outcome (logistic regression); they do not explicitly examine whether risk factors are associated differentially across the distribution of the health outcome investigated. This paper documents a phenomenon found repeatedly in the minority of epidemiological studies which do this (via quantile regression): associations between a range of established risk factors and body mass index (BMI) are progressively stronger in the upper ends of the BMI distribution. In this paper, we document this finding and provide illustrative evidence of it in the 1958 British birth cohort study. Associations of low childhood socio-economic position, high maternal weight, low childhood general cognition and adult physical inactivity with higher BMI are larger at the upper end of the BMI distribution, on both absolute and relative scales. For example, effect estimates for socio-economic position and childhood cognition were around three times larger at the 90th compared with 10th quantile, while effect estimates for physical inactivity were increasingly larger from the 50th to 90th quantiles, yet null at lower quantiles. We provide potential explanations for these findings and discuss implications. Risk factors may have larger causal effects among those in worse health, and these effects may not be discovered when health is only examined in average terms. In such scenarios, population-based approaches to intervention may have larger benefits than anticipated when assuming equivalent benefit across the population. Further research is needed to understand why effect estimates differ across the BMI outcome distribution and to investigate whether differential effects exist for other physical and mental health outcomes.

    更新日期:2020-01-13
  • The state of the HIV epidemic in rural KwaZulu-Natal, South Africa: a novel application of disease metrics to assess trajectories and highlight areas for intervention
    Int. J. Epidemiol. (IF 7.339) Pub Date : 2020-01-13
    Vandormael A, Cuadros D, Kim H, et al.

    BackgroundSouth Africa is at the epicentre of the HIV pandemic, with the world's highest number of new infections and the largest treatment programme. Using metrics proposed by the Joint United Nations Programme on AIDS (UNAIDS), we evaluate progress toward epidemic control and highlight areas for intervention in a hyperendemic South African setting. MethodsThe Africa Health Research Institute (AHRI) maintains a comprehensive population-based surveillance system in the Hlabisa sub-district of KwaZulu-Natal. Between 2005 and 2017, we tested 39 735 participants (aged 15–49 years) for HIV and followed 22 758 HIV-negative and 13 460 HIV-positive participants to identify new infections and all-cause AIDS-related deaths, respectively. Using these data, we estimated the percentage reduction in incidence, the absolute incidence rate, the incidence-mortality ratio and the incidence-prevalence ratio over place and time. ResultsWe observed a 62% reduction in the number of new infections among men between 2012 and 2017 and a 34% reduction among women between 2014 and 2017. Among men, the incidence-mortality ratio peaked at 4.1 in 2013 and declined to 3.1 in 2017, and among women it fell from a high of 6.4 in 2014 to 4.3 in 2017. Between 2012 and 2017, the female-incidence/male-prevalence ratio declined from 0.24 to 0.13 and the male-incidence/female-prevalence ratio from 0.05 to 0.02. ConclusionsUsing data from a population-based cohort study, we report impressive progress toward HIV epidemic control in a severely affected South African setting. However, overall progress is off track for 2020 targets set by the UNAIDS. Spatial estimates of the metrics, which demonstrate remarkable heterogeneity over place and time, indicate areas that could benefit from additional or optimized HIV prevention services.

    更新日期:2020-01-13
  • No multiplicative GXE interactions for breast cancer risk: Have we reached a verdict or is the jury still out?
    Int. J. Epidemiol. (IF 7.339) Pub Date : 2019-12-31
    Terry M.

    In this issue of the IJE, Kapoor et al.1 report findings from the most comprehensive breast cancer (BC) study to date evaluating gene–environment (GXE) interactions, with 205 BC susceptibility genes and 13 established BC risk factors. With both its size and scope, this study provides evidence specific to the evaluation of the potential use of GXE interactions in risk models and for considering potential aetiologic mechanisms. The study used data from the Breast Cancer Association Consortium (BCAC) and assessed genetic variants with two platforms—iCOGS (28 176 cases and 32 209 controls) and OncoArray (44 109 cases and 48 145 controls). The OncoArray platform has ∼2.5 times the coverage of single nucleotide polymorphisms (SNPs), with 533 000 SNPs compared with 211 155 SNPs on iCOGS. The investigators performed analyses separately by platform and then combined data using meta-analytic techniques. Specifically, they examined interactions with age at menarche, parity (ever, number and age at first birth), breastfeeding (ever and overall duration), ever use of oral contraceptives, body mass index (BMI), adult height, lifetime alcohol consumption, cigarette smoking (current and overall pack-years based on duration and intensity) and menopausal hormone therapy (MHT, opposed and unopposed). The key finding was an overall lack of multiplicative GXE interactions with established BC risk factors with few exceptions.

    更新日期:2019-12-31
  • Corrigendum to: Cohort Profile: The Hoorn Studies
    Int. J. Epidemiol. (IF 7.339) Pub Date : 2019-12-26
    Rutters F, Nijpels G, Elders P, et al.

    Nine patients were inadvertently omitted from the 2000-2001 follow-up visit, changing the total from 822 to 831. This affected the text, and values in Figure 1, Table 2 and Table 4.

    更新日期:2019-12-27
  • Difference in difference, controlled interrupted time series and synthetic controls
    Int. J. Epidemiol. (IF 7.339) Pub Date : 2019-03-24
    Lopez Bernal J, Cummins S, Gasparrini A.

    We thank Benmarhnia and Rudolph1 for their critical appraisal of our recent article on the use of controls in interrupted time series (ITS) studies.2 This offers the opportunity to clarify some important issues related to ITS and controlled ITS (CITS) designs and their comparison with other methods applied for public health evaluation. In particular, we argue that Benmarhnia and Rudolph based their assessment on three incorrect premises: that ITS without control is not a valid design for assessing causal relationships; that CITS is just another name for the difference-in-difference (DID) design that they advocate; and that the synthetic control methodology represents an alternative to CITS.

    更新日期:2019-12-25
  • A rose by any other name still needs to be identified (with plausible assumptions)
    Int. J. Epidemiol. (IF 7.339) Pub Date : 2019-03-28
    Benmarhnia T, Rudolph K.

    Evaluating the impact of public health programmes is important to ensure they are accomplishing their desired goals and to inform future decision making. We appreciate Lopez Bernal et al.’s attention to this practical topic.1

    更新日期:2019-12-25
  • The association of urine metals and metal mixtures with cardiovascular incidence in an adult population from Spain: the Hortega Follow-Up Study
    Int. J. Epidemiol. (IF 7.339) Pub Date : 2019-04-09
    Domingo-Relloso A, Grau-Perez M, Briongos-Figuero L, et al.

    BackgroundThe association of low-level exposure to metals and metal mixtures with cardiovascular incidence in the general population has rarely been studied. We flexibly evaluated the association of urinary metals and metal mixtures concentrations with cardiovascular diseases in a representative sample of a general population from Spain. MethodsUrine antimony (Sb), barium (Ba), cadmium (Cd), chromium (Cr), cobalt (Co), copper (Cu), molybdenum (Mo), vanadium (V) and zinc (Zn) were measured in 1171 adults without clinical cardiovascular diseases, who participated in the Hortega Study. Cox proportional hazard models were used for evaluating the association between single metals and cardiovascular incidence. We used a Probit extension of Bayesian Kernel Machine Regression (BKMR-P) to handle metal mixtures in a survival setting. ResultsIn single-metal models, the hazard ratios [confidence intervals (CIs)] of cardiovascular incidence, comparing the 80th to the 20th percentiles of metal distributions, were 1.35 (1.06, 1.72) for Cu, 1.43 (1.07, 1.90) for Zn, 1.51 (1.13, 2.03) for Sb, 1.46 (1.13, 1.88) for Cd, 1.64 (1.05, 2.58) for Cr and 1.31 (1.01, 1.71) for V. BKMR-P analysis was confirmatory of these findings, supporting that Cu, Zn, Sb, Cd, Cr and V are related to cardiovascular incidence in the presence of the other metals. Cd and Sb showed the highest posterior inclusion probabilities. ConclusionsUrine Cu, Zn, Sb, Cd, Cr and V were independently associated with increased cardiovascular risk at levels relevant for the general population of Spain. Urine metals in the mixture were also jointly associated with cardiovascular incidence, with Cd and Sb being the most important components of the mixture.

    更新日期:2019-12-25
  • Measles, mumps and rubella vs diphtheria–tetanus–acellular-pertussis–inactivated-polio–Haemophilus influenzae type b as the most recent vaccine and risk of early ‘childhood asthma’
    Int. J. Epidemiol. (IF 7.339) Pub Date : 2019-04-10
    Rieckmann A, Hærskjold A, Benn C, et al.

    Background and objectiveLive vaccines may have beneficial non-specific effects. We tested whether the live measles, mumps and rubella (MMR) vaccine compared with the non-live diphtheria–tetanus–acellular-pertussis–inactivated-polio–Haemophilus influenzae type b (DTaP-IPV-Hib) vaccine as the most recent vaccine was associated with less childhood asthma and fewer acute hospital contacts for childhood asthma among boys and girls. MethodsThis study is a nationwide register-based cohort study of 338 761 Danish children born between 1999 and 2006. We compared (i) the incidence of first-registered childhood asthma based on hospital contacts and drug prescriptions and (ii) the incidence of severe asthma defined as acute hospital contacts for childhood asthma between the ages of 15 and 48 months among children whose last received vaccine was three doses of DTaP-IPV-Hib and then MMR with children whose last received vaccine was three doses of DTaP-IPV-Hib. ResultsFor boys, following the recommended vaccine schedule of MMR after DTaP-IPV-Hib3 compared with DTaP-IPV-Hib3 as the last received vaccine, MMR was associated with 8.1 (95% confidence interval 3.9–12.3) fewer childhood asthma cases per 1000 boys, corresponding to 10% (5–15%) reduction in the cumulative incidence of childhood asthma. MMR, when given last, was also associated with 16.3 (95% confidence interval 12.7–20.0) fewer acute hospital admissions for childhood asthma per 1000 boys, corresponding to a 27% (22–31%) reduction in the cumulative incidence. No associations were seen for girls. ConclusionMMR may have a protective effect against childhood asthma for boys. This calls for an understanding of whether non-specific effects of vaccines can be used to optimize our vaccine programmes.

    更新日期:2019-12-25
  • Preterm birth and risk of sleep-disordered breathing from childhood into mid-adulthood
    Int. J. Epidemiol. (IF 7.339) Pub Date : 2019-04-21
    Crump C, Friberg D, Li X, et al.

    BackgroundPreterm birth (gestational age <37 weeks) has previously been associated with cardiometabolic and neuropsychiatric disorders into adulthood, but has seldom been examined in relation to sleep disorders. We conducted the first population-based study of preterm birth in relation to sleep-disordered breathing (SDB) from childhood into mid-adulthood. MethodsA national cohort study was conducted of all 4 186 615 singleton live births in Sweden during 1973–2014, who were followed for SDB ascertained from nationwide inpatient and outpatient diagnoses through 2015 (maximum age 43 years). Cox regression was used to examine gestational age at birth in relation to SDB while adjusting for other perinatal and maternal factors, and co-sibling analyses assessed for potential confounding by unmeasured shared familial factors. ResultsThere were 171 100 (4.1%) persons diagnosed with SDB in 86.0 million person-years of follow-up. Preterm birth was associated with increased risk of SDB from childhood into mid-adulthood, relative to full-term birth (39–41 weeks) [adjusted hazard ratio (aHR), ages 0–43 years: 1.43; 95% confidence interval (CI), 1.40, 1.46; P<0.001; ages 30–43 years: 1.40; 95% CI, 1.34, 1.47; P<0.001]. Persons born extremely preterm (<28 weeks) had more than 2-fold risks (aHR, ages 0–43 years: 2.63; 95% CI, 2.41, 2.87; P<0.001; ages 30–43 years: 2.22; 95% CI, 1.64, 3.01; P<0.001). These associations affected both males and females, but accounted for more SDB cases among males (additive interaction, P=0.003). Co-sibling analyses suggested that these findings were only partly due to shared genetic or environmental factors in families. ConclusionsPreterm-born children and adults need long-term follow-up for anticipatory screening and potential treatment of SDB.

    更新日期:2019-12-25
  • Comparative validation of an epigenetic mortality risk score with three aging biomarkers for predicting mortality risks among older adult males
    Int. J. Epidemiol. (IF 7.339) Pub Date : 2019-04-30
    Gao X, Colicino E, Shen J, et al.

    BackgroundA ‘mortality risk score’ (MS) based on ten prominent mortality-related cytosine-phosphate-guanine (CpG) sites was previously associated with all-cause mortality, but has not been verified externally. We aimed to validate the association of MS with mortality and to compare MS with three aging biomarkers: telomere length (TL), DNA methylation age (DNAmAge) and phenotypic age (DNAmPhenoAge) to explore whether MS can serve as a reliable measure of biological aging and mortality. MethodsAmong 534 males aged 55–85 years from the US Normative Aging Study, the MS, DNAmAge and DNAmPhenoAge were derived from blood DNA methylation profiles from the Illumina HumanMethylation450 BeadChip, and TL was measured by quantitative real-time polymerase chain reaction (qRT-PCR). ResultsA total of 147 participants died during a median follow-up of 9.4 years. The MS showed strong associations with all-cause, cardiovascular disease (CVD) and cancer mortality. After controlling for all potential covariates, participants with high MS (>5 CpG sites with aberrant methylation) had almost 4-fold all-cause mortality (hazard ratio: 3.84, 95% confidence interval: 1.92–7.67) compared with participants with a low MS (0–1 CpG site with aberrant methylation). Similar patterns were observed with respect to CVD and cancer mortality. MS was associated with TL and DNAmPhenoAge acceleration but not with DNAmAge acceleration. Although the MS and DNAmPhenoAge acceleration were independently associated with all-cause mortality, the former exhibited a higher predictive accuracy of mortality than the latter. ConclusionsMS has the potential to be a prominent predictor of mortality that could enhance survival prediction in clinical settings.

    更新日期:2019-12-25
  • Polygenic risk scores for Alzheimer’s disease, and academic achievement, cognitive and behavioural measures in children from the general population
    Int. J. Epidemiol. (IF 7.339) Pub Date : 2019-05-05
    Korologou-Linden R, Anderson E, Jones H, et al.

    ObjectiveSeveral studies report a polygenic component of risk for Alzheimer’s disease. Understanding whether this polygenic signal is associated with educational, cognitive and behavioural outcomes in children could provide an earlier window for intervention. MethodsWe examined whether polygenic risk scores (PRS) at varying P-value thresholds in children from the Avon Longitudinal Study of Parents and Children were associated with academic achievement, cognitive and behavioural measures in childhood and adolescence. ResultsWe did not detect any evidence that the genome-wide significant PRS (5x10-8) were associated with these outcomes. PRS at the highest P-value threshold examined (P ≤ 5x10-1) were associated with lower academic achievement in adolescents (Key Stage 3; β: -0.03; 95% confidence interval: -0.05, -0.003) but the effect was attenuated when single nucleotide polymorphisms (SNPs) associated with educational attainment were removed. These PRS were associated with lower IQ (β: -0.04; 95% CI: -0.07, -0.02) at age 8 years with the effect remaining after removing SNPs associated with educational attainment. ConclusionsSNPs mediating the biological effects of Alzheimer’s disease are unlikely to operate early in life. The evidence of association between PRS for Alzheimer’s disease at liberal thresholds and cognitive measures suggest shared genetic pathways between Alzheimer’s disease, academic achievement and cognition.

    更新日期:2019-12-25
  • Exploring the bidirectional associations between loneliness and cognitive functioning over 10 years: the English longitudinal study of ageing
    Int. J. Epidemiol. (IF 7.339) Pub Date : 2019-05-05
    Yin J, Lassale C, Steptoe A, et al.

    BackgroundAs the population ages, cognitive decline and dementia have become major health concerns in the UK. Loneliness has been linked to cognitive decline, but the reverse causality of this association remains unclear. This study aims to examine whether there is a bidirectional relationship between loneliness and cognitive function in older English adults (age 50 years and over) over a 10-year follow-up. MethodsData came from a nationally representative sample of 5885 participants in the English Longitudinal Study of Ageing (ELSA), free of stroke or dementia and followed every 2 years up to wave 7 (2014–15). At each wave, cognitive function was measured with word recall and verbal fluency tests, and loneliness was measured with the abridged version of the revised UCLA Loneliness Scale. Bivariate dual change score models were used to assess the multivariate associations between loneliness and cognitive function, used interchangeably as exposures and outcomes. ResultsGreater loneliness at baseline was associated with poorer memory [β intercept = −0.03, standard error (SE) = 0.01, P = 0.016] and verbal fluency (β intercept = −0.01, SE = 001, P = 0.027) at baseline, and with a stronger linear rate of decline in both memory (β linear slope = −0.07, SE = 001, P ≤ 0.001) and verbal fluency (β linear slope = −0.09, SE = 0.03, P = 0.003) over a 10-year follow-up period, although the performance on verbal fluency did not change substantially on average over this period. We also found that higher baseline memory, but not verbal fluency, predicted a slower change in loneliness (β linear slope = −0.01, SE = 001, P = 0.004) and that a linear decline in memory was associated with an acceleration in loneliness (β quadratic slope = −0.02, SE = 001, P ≤ 0.001) during follow-up. ConclusionsHigher loneliness is associated with poorer cognitive function at baseline and contributes to a worsening in memory and verbal fluency over a decade. These factors seem, however, to be partially intertwined, since baseline memory and its rate of decline also contribute to an increase in loneliness over time.

    更新日期:2019-12-25
  • Adherence to the Dietary Approaches to Stop Hypertension (DASH) diet and risk of total and cause-specific mortality: results from the Golestan Cohort Study
    Int. J. Epidemiol. (IF 7.339) Pub Date : 2019-05-05
    Mokhtari Z, Sharafkhah M, Poustchi H, et al.

    ObjectiveTo evaluate the association between adherence to the Dietary Approaches to Stop Hypertension (DASH) diet and overall and cause-specific mortality in the Golestan Cohort Study (GCS). MethodsA total of 50 045 participants aged 40 years or older were recruited from Golestan Province, Iran, from 2004 to 2008 and followed for a mean of 10.64 years. The DASH diet score was calculated for each individual based on food groups. The primary outcome measure was death from any cause. ResultsDuring 517 326 person-years of follow-up, 6763 deaths were reported. After adjustment for potential confounders, DASH diet score was inversely associated with risk of death from all causes and cancers [hazard ratio (HR): 0.86; 95% confidence interval (CI): 0.75, 0.98; and HR: 0.65; 95% CI: 0.47, 0.90, respectively]. A higher DASH diet score was associated with lower risk of gastrointestinal cancer mortality in men (HR: 0.55; 95% CI: 0.30, 0.99). A greater adherence to DASH diet was also associated with lower other-cancer mortality in women (HR: 0.50; 95% CI: 0.24, 0.99). No association between DASH diet score and cardiovascular disease mortality was observed, except that those dying of cardiovascular disease were younger than 50 years of age and smokers. ConclusionsOur findings suggest that maintaining a diet similar to the DASH diet is independently associated with reducing the risk of total death, cancers, and especially gastrointestinal cancers in men.

    更新日期:2019-12-25
  • Selection bias introduced by informative censoring in studies examining effects of vaccination in infancy
    Int. J. Epidemiol. (IF 7.339) Pub Date : 2019-05-09
    López-López J, Sterne J, Higgins J.

    BackgroundMany studies have examined ‘non-specific’ vaccine effects on infant mortality: attention has been particularly drawn to diphtheria-tetanus-pertussis (DTP) vaccine, which has been proposed to be associated with an increased mortality risk. Both right and left censoring are common in such studies. MethodsWe conducted simulation studies examining right censoring (at measles vaccination) and left censoring (by excluding early follow-up) in a variety of scenarios in which confounding was and was not present. We estimated both unadjusted and adjusted hazard ratios (HRs), averaged across simulations. ResultsWe identified scenarios in which right-censoring at measles vaccination was informative and so introduced bias in the direction of a detrimental effect of DTP vaccine. In some, but not all, situations, adjusting for confounding by health status removed the bias caused by censoring. However, such adjustment will not always remove bias due to informative censoring: inverse probability weighting was required in one scenario. Bias due to left censoring arose when both health status and DTP vaccination were associated with mortality during the censored early follow-up and was in the direction of attenuating a beneficial effect of DTP on mortality. Such bias was more severe when the effect of DTP changed over time. ConclusionsEstimates of non-specific effects of vaccines may be biased by informative right or left censoring. Authors of studies estimating such effects should consider the potential for such bias and use appropriate statistical approaches to control for it. Such approaches require measurement of prognostic factors that predict censoring.

    更新日期:2019-12-25
  • Getting more from heterogeneous HIV-1 surveillance data in a high immigration country: estimation of incidence and undiagnosed population size using multiple biomarkers
    Int. J. Epidemiol. (IF 7.339) Pub Date : 2019-05-10
    Giardina F, Romero-Severson E, Axelsson M, et al.

    BackgroundMost HIV infections originate from individuals who are undiagnosed and unaware of their infection. Estimation of this quantity from surveillance data is hard because there is incomplete knowledge about (i) the time between infection and diagnosis (TI) for the general population, and (ii) the time between immigration and diagnosis for foreign-born persons. MethodsWe developed a new statistical method for estimating the incidence of HIV-1 and the number of undiagnosed people living with HIV (PLHIV), based on dynamic modelling of heterogeneous HIV-1 surveillance data. The methods consist of a Bayesian non-linear mixed effects model using multiple biomarkers to estimate TI of HIV-1-positive individuals, and a novel incidence estimator which distinguishes between endogenous and exogenous infections by modelling explicitly the probability that a foreign-born person was infected either before or after immigration. The incidence estimator allows for direct calculation of the number of undiagnosed persons. The new methodology is illustrated combining heterogeneous surveillance data from Sweden between 2003 and 2015. ResultsA leave-one-out cross-validation study showed that the multiple-biomarker model was more accurate than single biomarkers (mean absolute error 1.01 vs ≥1.95). We estimate that 816 [95% credible interval (CI) 775-865] PLHIV were undiagnosed in 2015, representing a proportion of 10.8% (95% CI 10.3-11.4%) of all PLHIV. ConclusionsThe proposed methodology will enhance the utility of standard surveillance data streams and will be useful to monitor progress towards and compliance with the 90–90-90 UNAIDS target.

    更新日期:2019-12-25
  • Software Application Profile: The Anchored Multiplier calculator—a Bayesian tool to synthesize population size estimates
    Int. J. Epidemiol. (IF 7.339) Pub Date : 2019-05-18
    Wesson P, McFarland W, Qin C, et al.

    Estimating the number of people in hidden populations is needed for public health research, yet available methods produce highly variable and uncertain results. The Anchored Multiplier calculator uses a Bayesian framework to synthesize multiple population size estimates to generate a consensus estimate. Users submit point estimates and lower/upper bounds which are converted to beta probability distributions and combined to form a single posterior probability distribution. The Anchored Multiplier calculator is available as a web browser-based application. The software allows for unlimited empirical population size estimates to be submitted and combined according to Bayes Theorem to form a single estimate. The software returns output as a forest plot (to visually compare data inputs and the final Anchored Multiplier estimate) and a table that displays results as population percentages and counts. The web application ‘Anchored Multiplier Calculator’ is free software and is available at [http://globalhealthsciences.ucsf.edu/resources/tools] or directly at [http://anchoredmultiplier.ucsf.edu/].

    更新日期:2019-12-25
  • Race differences in cardiovascular disease and breast cancer mortality among US women diagnosed with invasive breast cancer
    Int. J. Epidemiol. (IF 7.339) Pub Date : 2019-06-01
    Troeschel A, Liu Y, Collin L, et al.

    BackgroundBreast cancer (BC) survivors are at increased risk of cardiovascular disease (CVD) due to shared risk factors with BC and cardiotoxic treatment effects. We aim to investigate racial differences in mortality due to CVD and BC among women diagnosed with invasive BC. MethodsData from 407 587 non-Hispanic Black (NHB) and White (NHW) women diagnosed with malignant BC (1990–2014) were obtained from the Surveillance, Epidemiology, and End Results database. Cumulative incidence of mortality due to CVD and BC was calculated by race and age (years). Cox models were used to obtain hazard ratios (HR) and 95% confidence intervals (95%CI) for the association of race/ethnicity with cause-specific mortality. ResultsThe 20-year cumulative incidence of CVD-related mortality was higher among younger NHBs than NHWs (e.g. age 55–69: 13.3% vs 8.9%, respectively). NHBs had higher incidence of BC-specific mortality than NHWs, regardless of age. There was a monotonic reduction in CVD-related mortality disparities with increasing age (age <55: HR = 3.71, 95%CI: 3.29, 4.19; age 55–68: HR = 2.31, 95%CI: 2.15, 2.49; age 69+: HR = 1.24, 95%CI: 1.19, 1.30). The hazard of BC-specific mortality among NHBs was approximately twice that of NHWs (e.g. age <55: HR = 1.98, 95%CI: 1.92, 2.04). ConclusionsThere are substantial differences in mortality due to CVD and BC between NHB and NHW women diagnosed with invasive BC. Racial differences were greatest among younger women for CVD-related mortality and similar across age groups for BC-specific mortality. Future studies should identify pathways through which race/ethnicity affects cause-specific mortality, to inform efforts towards reducing disparities.

    更新日期:2019-12-25
  • Bias control in the analysis of case–control studies with incidence density sampling
    Int. J. Epidemiol. (IF 7.339) Pub Date : 2019-06-17
    Cheung Y, Ma X, Lam K, et al.

    BackgroundPrevious simulation studies of the case–control study design using incidence density sampling, which required individual matching for time, showed biased estimates of association from conditional logistic regression (CLR) analysis; however, the reason for this is unknown. Separately, in the analysis of case–control studies using the exclusive sampling design, it has been shown that unconditional logistic regression (ULR) with adjustment for an individually matched binary factor can give unbiased estimates. The validity of this analytic approach in incidence density sampling needs evaluation. MethodsIn extensive simulations using incidence density sampling, we evaluated various analytic methods: CLR with and without a bias-reduction method, ULR with adjustment for time in quintiles (and residual time within quintiles) and ULR with adjustment for matched sets and bias reduction. We re-analysed a case–control study of Haemophilus influenzae type B vaccine using these methods. ResultsWe found that the bias in the CLR analysis from previous studies was due to sparse data bias. It can be controlled by the bias-reduction method for CLR or by increasing the number of cases and/or controls. ULR with adjustment for time in quintiles usually gave results highly comparable to CLR, despite breaking the matches. Further adjustment for residual time trends was needed in the case of time-varying effects. ULR with adjustment for matched sets tended to perform poorly despite bias reduction. ConclusionsStudies using incidence density sampling may be analysed by either ULR with adjustment for time or CLR, possibly with bias reduction.

    更新日期:2019-12-25
  • Are younger cohorts in the USA and England ageing better?
    Int. J. Epidemiol. (IF 7.339) Pub Date : 2019-06-25
    de la Fuente J, Caballero F, Verdes E, et al.

    BackgroundWhether worldwide increases in life expectancy are accompanied by a better health status is still a debate. People age differently, and there is a need to disentangle whether healthy-ageing pathways can be shaped by cohort effects. This study aims to analyse trends in health status in two large nationally representative samples of older adults from England and the USA. MethodsThe sample comprised 55 684 participants from the first seven waves of the English Longitudinal Study of Ageing (ELSA), and the first 11 waves of the Health and Retirement Study (HRS). A common latent health score based on Bayesian multilevel item response theory was used. Two Bayesian mixed-effects multilevel models were used to assess cohort effects on health in ELSA and HRS separately, controlling for the effect of household wealth and educational attainment. ResultsSimilar ageing trends were found in ELSA (β=–0.311; p<0.001) and HRS (β=–0.393; p<0.001). The level of education moderated the life-course effect on health in both ELSA (β=–0.082; p<0.05) and HRS (β=–0.084; p<0.05). A birth-year effect was found for those belonging to the highest quintiles of household wealth in both ELSA (β = 0.125; p<0.001) and HRS (β = 0.170; p<0.001). ConclusionsHealth inequalities have increased in recent cohorts, with the wealthiest participants presenting a better health status in both the USA and English populations. Actions to promote health in the ageing population should consider the increasing inequality scenario, not only by applying highly effective interventions, but also by making them accessible to all members of society.

    更新日期:2019-12-25
  • Folic acid supplementation and risk for congenital limb reduction defects in China
    Int. J. Epidemiol. (IF 7.339) Pub Date : 2019-06-29
    Liu J, Li Z, Ye R, et al.

    BackgroundFolic acid (FA) supplementation prevents neural tube defects, but there are mixed results for its ability to prevent limb reduction defects. We examined whether a preventive effect of FA supplementation exists for congenital limb reduction defects in a large population in China. MethodsData from a large population-based cohort study in China were used to evaluate the effects of FA supplementation on birth defects. All births at 20 complete gestational weeks, including live births, stillbirths and pregnancy terminations, and all structural congenital anomalies, regardless of gestational week, were recorded. A total of 247 831 singleton live births delivered at gestational ages of 20–42 weeks to women from northern and southern China with full information on FA intake were included. Limb reduction defects were classified by subtype and maternal FA supplementation. ResultsThe prevalence of limb reduction defects was 2.7 per 10 000 births among women who took FA compared with 9.7 per 10 000 births among those who did not take FA in northern China; the prevalence was 4.5 and 3.8 per 10 000 births, respectively, in southern China. In both unadjusted and adjusted analyses, the estimated relative risk for upper limb reduction defects [odds ratio (OR) = 0.17, 95% confidence interval (CI): 0.04, 0.63] and total limb reduction defects (OR = 0.24, 95% CI: 0.08, 0.70) in northern China, but not for lower limb reduction defects ,was significantly decreased in association with FA supplementation in northern China. There was no association between FA supplementation and either an increased or decreased risk for limb reduction defects in southern China. ConclusionsFA supplementation successfully reduces the prevalence of limb reduction defects in northern China, whose population has low folate concentrations.

    更新日期:2019-12-25
  • Residential distance from high-voltage overhead power lines and risk of Alzheimer’s dementia and Parkinson’s disease: a population-based case-control study in a metropolitan area of Northern Italy
    Int. J. Epidemiol. (IF 7.339) Pub Date : 2019-07-06
    Gervasi F, Murtas R, Decarli A, et al.

    BackgroundThe association between the extremely low-frequency magnetic field generated by overhead power lines and neurodegenerative disease is still a matter of debate. MethodsA population-based case-control study was carried out on the residents in the Milan metropolitan area between 2011 and 2016 to evaluate the possible association between exposure to extremely low-frequency magnetic fields generated by high-voltage overhead power lines and Alzheimer's dementia and Parkinson's disease. A statistical analysis was performed on cases and controls matched by sex, year of birth and municipality of residence (with a case to controls ratio of 1 : 4) using conditional logistic regression models adjusted for socio-economic deprivation and distance from the major road network as potential confounders. ResultsOdds ratios for residents <50 m from the source of exposure compared with residents at ≥600 m turned out to be 1.11 (95% confidence interval: 0.95–1.30) for Alzheimer's dementia and 1.09 (95% confidence interval: 0.92–1.30) for Parkinson's disease. ConclusionsThe finding of a weak association between exposure to the extremely low-frequency magnetic field and neurodegenerative diseases suggests the continuation of research on this topic. Moreover, the low consistency between the results of the already existing studies emphasises the importance of increasingly refined study designs.

    更新日期:2019-12-25
  • Retirement and decline in episodic memory: analysis from a prospective study of adults in England
    Int. J. Epidemiol. (IF 7.339) Pub Date : 2019-07-06
    Romero Starke K, Seidler A, Hegewald J, et al.

    BackgroundWork has been associated with cognitive health. We examined whether retirement from work is associated with a decrease in episodic memory and whether this effect differs when considering workers’ occupational class. MethodsIn this prospective study using the English Longitudinal Study of Ageing (ELSA), we examined 1629 persons aged 50–75 years who were in paid work at baseline. A two-slope random effects linear regression centred at retirement was used to study the effect of retirement on episodic memory. The potential effect modification by occupational class was examined. ResultsWhile memory trajectories show slightly decreasing memory scores before and afterretirement, the decreasing rates for both periods were similar [episodic memory β2b−β2a= −0.03, 95% confidence interval (CI) −0.08, 0.02]. When stratifying by occupational class, there was also no substantial difference in episodic memory trajectories before and after retirement. However, the lower occupational class showed a clear decline in episodic memory with time (pre-retirement β2a = −0.11, 95% CI −0.19, −0.03; post-retirement β2b = −0.13, 95% CI −0.19, −0.07) which was not evident for the higher occupational classes. ConclusionsOur results show no observable difference in trajectories of change in episodic memory before and after retirement. However, the steeper memory decline in workers belonging to the lower occupational class may limit their prospect of prolonging their working lives. Hence enrichment programmes for the prevention of memory decline for these workers should be considered.

    更新日期:2019-12-25
  • Obesity and risk of infections: results from men and women in the Swedish National March Cohort
    Int. J. Epidemiol. (IF 7.339) Pub Date : 2019-07-10
    Ghilotti F, Bellocco R, Ye W, et al.

    BackgroundPrevious studies have shown an association between body mass index (BMI) and infections, but the literature on type-specific community acquired infections is still limited. MethodsWe included 39 163 Swedish adults who completed a questionnaire in September 1997 and were followed through record-linkages until December 2016. Information on BMI was self-reported and infections were identified from the Swedish National Patient Register using International Classification of Diseases (ICD), Tenth Revision (ICD-10) codes. We fitted multivariable Cox proportional hazards models for time-to-first-event analysis, and we used extensions of the standard Cox model when repeated events were included. ResultsDuring a 19-year follow-up 32% of the subjects had at least one infection requiring health care contact, leading to a total of 27 675 events. We found an increased incidence of any infection in obese women [hazard ratio (HR) = 1.22; 95% confidence interval (CI) = 1.12; 1.33] and obese men (HR = 1.25; 95% CI = 1.09; 1.43) compared with normal weight subjects. For specific infections, higher incidences were observed for skin infections in both genders (HR = 1.76; 95% CI = 1.47; 2.12 for obese females and HR = 1.74; 95% CI = 1.33; 2.28 for obese males) and gastrointestinal tract infections (HR = 1.44; 95% CI = 1.19; 1.75), urinary tract infections (HR = 1.30; 95% CI = 1.08; 1.55) and sepsis (HR = 2.09; 95% CI = 1.46; 2.99) in obese females. When accounting for repeated events, estimates similar to the aforementioned ones were found. ConclusionsObesity was associated with an increased risk of infections in both genders. Results from multiple-failure survival analysis were consistent with those from classic Cox models.

    更新日期:2019-12-25
  • Meat intake and risk of hepatocellular carcinoma in two large US prospective cohorts of women and men
    Int. J. Epidemiol. (IF 7.339) Pub Date : 2019-07-13
    Ma Y, Yang W, Li T, et al.

    BackgroundEpidemiological evidence on the associations between meat intake and risk of hepatocellular carcinoma (HCC) was limited and inconsistent. MethodsWe prospectively examined the association between consumption of meats and meat mutagens with HCC risk using data from the Nurses’ Health Study and the Health Professionals Follow-up Study. Cox proportional-hazards regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) after adjusting for known liver-cancer risk factors. ResultsDuring up to 32 years of follow-up, we documented 163 incident HCC cases. The HRs of HCC for the highest vs the lowest tertile intake levels were 1.84 (95% CI: 1.16–2.92, Ptrend = 0.04) for processed red meats and 0.61 (95% CI: 0.40–0.91, Ptrend = 0.02) for total white meats. There was a null association between unprocessed red meats and HCC risk (HR = 1.06, 95% CI: 0.68–1.63, Ptrend = 0.85). We found both poultry (HR = 0.60, 95% CI: 0.40–0.90, Ptrend = 0.01) and fish (HR = 0.70, 95% CI: 0.47–1.05, Ptrend = 0.10) were inversely associated with HCC risk. The HR for HCC risk was 0.79 (95% CI: 0.61–1.02) when 1 standard deviation of processed red meats was substituted with an equivalent amount of poultry or fish intake. We also found a suggestive positive association of intake of meat-derived mutagenicity or heterocyclic amines with risk of HCC. ConclusionsProcessed red meat intake might be associated with higher, whereas poultry or possibly fish intake might be associated with lower, risk of HCC. Replacing processed red meat with poultry or fish might be associated with reduced HCC risk.

    更新日期:2019-12-25
  • The long-term rapid increase in incidence of adenocarcinoma of the kidney in the USA, especially among younger ages
    Int. J. Epidemiol. (IF 7.339) Pub Date : 2019-07-16
    Zheng T, Zhu C, Bassig B, et al.

    BackgroundWe previously observed a rapid increase in the incidence of renal cell carcinoma (RCC) in men and women between 1935 and 1989 in the USA, using data from the Connecticut Tumor Registry. This increase appeared to be largely explained by a positive cohort effect, but no population-based study has been conducted to comprehensively examine age-period-cohort effects by histologic types for the past decade. MethodsWe calculated age-adjusted and age-specific incidence rates of the two major kidney-cancer subtypes RCC and renal urothelial carcinoma, and conducted an age-period-cohort analysis of 114 138 incident cases of kidney cancer reported between 1992 and 2014 to the Surveillance, Epidemiology, and End Results programme. ResultsThe age-adjusted incidence rates of RCC have been increasing consistently in the USA among both men and women (from 12.18/100 000 in 1992–1994 to 18.35/100 000 in 2010–2014 among men; from 5.77/100 000 in 1992–1994 to 8.63/100 000 in 2010–2014 among women). Incidence rates generally increased in successive birth cohorts, with a continuing increase in rates among the younger age groups (ages 0–54 years) in both men and women and among both Whites and Blacks. These observations were confirmed by age-period-cohort modelling, which suggested an increasing birth-cohort trend for RCC beginning with 1955 birth cohorts, regardless of the assumed value for the period effect for both men and women and for Whites and Blacks. ConclusionsKnown risk factors for kidney cancer may not fully account for the observed increasing rates or the birth-cohort pattern for RCC, prompting the need for additional etiologic hypotheses (such as environmental exposures) to investigate these descriptive patterns.

    更新日期:2019-12-25
  • The current scope of healthcare-associated infection surveillance activities in hospitalized immunocompromised patients: a systematic review
    Int. J. Epidemiol. (IF 7.339) Pub Date : 2019-07-30
    Valentine J, Hall L, Verspoor K, et al.

    BackgroundImmunocompromised patients are at increased risk of acquiring healthcare-associated infections (HAIs) and often require specialized models of care. Surveillance of HAIs is essential for effective infection-prevention programmes. However, little is known regarding standardized or specific surveillance methods currently employed for high-risk hospitalized patients. MethodsA systematic review adopting a narrative synthesis approach of published material between 1 January 2000 and 31 March 2018 was conducted. Publications describing the application of traditional and/or electronic surveillance of HAIs in immunocompromised patient settings were identified from the Ovid MEDLINE®, Ovid Embase® and Elsevier Scopus® search engines [PROSPERO international prospective register of systematic reviews (registration ID: CRD42018093651)]. ResultsIn total, 2708 studies were screened, of whom 17 fulfilled inclusion criteria. Inpatients diagnosed with haematological malignancies were the most-represented immunosuppressed population. The majority of studies described manual HAI surveillance utilizing internationally accepted definitions for infection. Chart review of diagnostic and pathology reports was most commonly employed for case ascertainment. Data linkage of disparate datasets was performed in two studies. The most frequently monitored infections were bloodstream infections and invasive fungal disease. No surveillance programmes applied risk adjustment for reporting surveillance outcomes. ConclusionsTargeted, tailored monitoring of HAIs in high-risk immunocompromised settings is infrequently reported in current hospital surveillance programmes. Standardized surveillance frameworks, including risk adjustment and timely data dissemination, are required to adequately support infection-prevention programmes in these populations.

    更新日期:2019-12-25
  • Assessing longer-term effectiveness of a combined household-level piped water and sanitation intervention on child diarrhoea, acute respiratory infection, soil-transmitted helminth infection and nutritional status: a matched cohort study in rural Odisha, India
    Int. J. Epidemiol. (IF 7.339) Pub Date : 2019-07-30
    Reese H, Routray P, Torondel B, et al.

    BackgroundOpen defecation is widespread in rural India, and few households have piped water connections. While government and other efforts have increased toilet coverage in India, and evaluations found limited immediate impacts on health, longer-term effects have not been rigorously assessed. MethodsWe conducted a matched cohort study to assess the longer-term effectiveness of a combined household-level piped water and sanitation intervention implemented by Gram Vikas (an Indian NGO) in rural Odisha, India. Forty-five intervention villages were randomly selected from a list of those where implementation was previously completed at least 5 years before, and matched to 45 control villages. We conducted surveys and collected stool samples between June 2015 and October 2016 in households with a child <5 years of age (n = 2398). Health surveillance included diarrhoea (primary outcome), acute respiratory infection (ARI), soil-transmitted helminth infection, and anthropometry. ResultsIntervention villages had higher improved toilet coverage (85% vs 18%), and increased toilet use by adults (74% vs 13%) and child faeces disposal (35% vs 6%) compared with control villages. There was no intervention association with diarrhoea [adjusted OR (aOR): 0.94, 95% confidence interval (CI): 0.74–1.20] or ARI. Compared with controls, children in intervention villages had lower helminth infection (aOR: 0.44, 95% CI: 0.18, 1.00) and improved height-for-age z scores (HAZ) (+0.17, 95% CI: 0.03–0.31). ConclusionsThis combined intervention, where household water connections were contingent on community-wide household toilet construction, was associated with improved HAZ, and reduced soil-transmitted helminth (STH) infection, though not reduced diarrhoea or ARI. Further research should explore the mechanism through which these heterogenous effects on health may occur.

    更新日期:2019-12-25
  • Risk factors for subarachnoid haemorrhage: a nationwide cohort of 950 000 adults
    Int. J. Epidemiol. (IF 7.339) Pub Date : 2019-07-30
    Sundström J, Söderholm M, Söderberg S, et al.

    BackgroundSubarachnoid haemorrhage (SAH) is a devastating disease, with high mortality rate and substantial disability among survivors. Its causes are poorly understood. We aimed to investigate risk factors for SAH using a novel nationwide cohort consortium. MethodsWe obtained individual participant data of 949 683 persons (330 334 women) between 25 and 90 years old, with no history of SAH at baseline, from 21 population-based cohorts. Outcomes were obtained from the Swedish Patient and Causes of Death Registries. ResultsDuring 13 704 959 person-years of follow-up, 2659 cases of first-ever fatal or non-fatal SAH occurred, with an age-standardized incidence rate of 9.0 [95% confidence interval (CI) (7.4–10.6)/100 000 person-years] in men and 13.8 [(11.4–16.2)/100 000 person-years] in women. The incidence rate increased exponentially with higher age. In multivariable-adjusted Poisson models, marked sex interactions for current smoking and body mass index (BMI) were observed. Current smoking conferred a rate ratio (RR) of 2.24 (95% CI 1.95–2.57) in women and 1.62 (1.47–1.79) in men. One standard deviation higher BMI was associated with an RR of 0.86 (0.81–0.92) in women and 1.02 (0.96–1.08) in men. Higher blood pressure and lower education level were also associated with higher risk of SAH. ConclusionsThe risk of SAH is 45% higher in women than in men, with substantial sex differences in risk factor strengths. In particular, a markedly stronger adverse effect of smoking in women may motivate targeted public health initiatives.

    更新日期:2019-12-25
  • The CDC Field Epidemiology Manual. Sonja A. Rasmussen and Richard A. Goodman (eds)
    Int. J. Epidemiol. (IF 7.339) Pub Date : 2019-08-03
    Sheppeard V.

    The CDC Field Epidemiology Manual.RasmussenSonja A. and GoodmanRichard A. (eds.) 4th edition. Oxford University Press, 2019, pp. 528, £35.99, ISBN 9780190624248

    更新日期:2019-12-25
  • Integrating a One Health approach into epidemiology to improve public policy
    Int. J. Epidemiol. (IF 7.339) Pub Date : 2019-08-31
    Kahn L.

    Public policies rely on robust epidemiological studies to develop effective disease prevention strategies. One Health, the concept that human, animal, environmental and ecosystem health are linked, provides a useful framework for researching, analysing and addressing complex interactions between multifactorial health challenges such as antimicrobial resistance.

    更新日期:2019-12-25
  • Is the long-term decline in cardiovascular-disease mortality in high-income countries over? Evidence from national vital statistics
    Int. J. Epidemiol. (IF 7.339) Pub Date : 2019-08-05
    Lopez A, Adair T.

    BackgroundThe substantial decline in cardiovascular-disease (CVD) mortality in high-income countries has underpinned their increasing longevity over the past half-century. However, recent evidence suggests this long-term decline may have stagnated, and even reversed in younger populations. We assess recent CVD-mortality trends in high-income populations and discuss the findings in relation to trends in risk factors. MethodsWe used vital statistics since 2000 for 23 high-income countries published in the World Health Organization Mortality Database. Age-standardized CVD death rates by sex for all ages, and at ages 35–74 years, were calculated and smoothed using LOWESS regression. Findings were contrasted with the Global Burden of Disease (GBD) Study. ResultsThe rate of decline in CVD mortality has slowed considerably in most countries in recent years for both males and females, particularly at ages 35–74 years. Based on the latest year of data, the decline in the CVD-mortality rate at ages 35–74 years was <2% (about half the annual average since 2000) for at least one sex in more than half the countries. In North America (US males and females, Canada females), the CVD-mortality rate even increased in the most recent year. The GBD Study estimates, after correcting for misdiagnoses, suggest an even more alarming reversal, with CVD death rates rising in seven countries for at least one sex in 2017. The rate of decline and initial level of CVD mortality appear largely unrelated. ConclusionsA significant slowdown in CVD-mortality decline is now apparent across high-income countries with diverse epidemiological environments. High and increasing obesity levels, limited potential future gains from further reducing already low smoking prevalence, especially in English-speaking countries, and persistent inequalities in mortality risk pose significant challenges for public policy to promote better cardiovascular health.

    更新日期:2019-12-25
  • Dietary n-3 polyunsaturated fatty acids, fish intake and healthy ageing
    Int. J. Epidemiol. (IF 7.339) Pub Date : 2019-09-28
    García-Esquinas E, Ortolá R, Banegas J, et al.

    BackgroundSeafood consumption and dietary intake of n-3 polyunsaturated fatty acids (PUFA) protect from cardiovascular disease, muscle wasting and mortality; however, their role in delaying unhealthy ageing is uncertain. MethodsA prospective cohort study with 1592 community-dwelling individuals aged ≥60 years recruited in 2008–2010, and followed through 2015. Intake of seafood and n-3 PUFA [eicosapentanoic acid (EPA) and docosahexanoic acid (DHA)] was estimated using a validated diet history and food composition tables. Unhealthy ageing was assessed across the domains of physical and cognitive function, mental health, morbidity, self-rated health and vitality. ResultsHigher blue fish consumption was negatively associated with unhealthy ageing in 2015 [multivariate ß (95% confidence interval) per interquartile range (IQR) increase of fish: −0.49 (−0.90; −0.08)] and, specifically, was associated with lower accumulation of functional impairments [−1.00 (−1.71; −0.28)] and morbidities [−0.30 (−0.73; 0.13)]. Individuals with high intakes of EPA (≥0.47 g/day) and DHA (≥0.89 g/day) presented the highest reductions in age-related deficits accumulation: −1.61 (−3.01; −0.22) and −1.34 (−2.76; 0.08), respectively. Intake of EPA and DHA were negatively associated with the accumulation of functional deficits [results per IQR increase: −0.79 (−1.64; −0.06) and −0.84 (−1.67; −0.01), respectively] and morbidities [−0.60 (−1.10; −1.11) and −0.60 (−1.09; −0.11)]. No associations were observed between n-3 PUFA and self-rated or mental health, or between white fish and unhealthy ageing. ConclusionsIn this cohort of Spanish individuals with elevated intake of fish and a high adherence to the Mediterranean diet, consumption of blue fish and n-3 PUFA had a prospective protective association with deficits accumulation.

    更新日期:2019-12-25
  • BMI and weight changes and risk of obesity-related cancers: a pooled European cohort study
    Int. J. Epidemiol. (IF 7.339) Pub Date : 2019-09-30
    Bjørge T, Häggström C, Ghaderi S, et al.

    BackgroundObesity is an established risk factor for several cancers. Adult weight gain has been associated with increased cancer risk, but studies on timing and duration of adult weight gain are relatively scarce. We examined the impact of BMI (body mass index) and weight changes over time, as well as the timing and duration of excess weight, on obesity- and non-obesity-related cancers. MethodsWe pooled health data from six European cohorts and included 221 274 individuals with two or more height and weight measurements during 1972–2014. Several BMI and weight measures were constructed. Cancer cases were identified through linkage with national cancer registries. Hazard ratios (HRs) of cancer with 95% confidence intervals (CIs) were derived from time-dependent Cox-regression models. ResultsDuring follow-up, 27 881 cancer cases were diagnosed; 9761 were obesity-related. The HR of all obesity-related cancers increased with increasing BMI at first and last measurement, maximum BMI and longer duration of overweight (men only) and obesity. Participants who were overweight before age 40 years had an HR of obesity-related cancers of 1.16 (95% CI 1.02, 1.32) and 1.15 (95% CI 1.04, 1.27) in men and women, respectively, compared with those who were not overweight. The risk increase was particularly high for endometrial (70%), male renal-cell (58%) and male colon cancer (29%). No positive associations were seen for cancers not regarded as obesity-related. ConclusionsAdult weight gain was associated with increased risk of several major cancers. The degree, timing and duration of overweight and obesity also seemed to be important. Preventing weight gain may reduce the cancer risk.

    更新日期:2019-12-25
  • Using structural equation modelling to untangle sanitation, water and hygiene pathways for intervention improvements in height-for-age in children <5 years old
    Int. J. Epidemiol. (IF 7.339) Pub Date : 2019-10-09
    Reese H, Sinharoy S, Clasen T.

    BackgroundDespite a strong theoretical rationale for combining water, sanitation and hygiene (WaSH) interventions to improve child health, study findings are heterogeneous with little understanding of the mechanisms for these effects. Our study objective was to demonstrate the utility of structural equation modeling (SEM) to assess intervention effects on height-for-age z score (HAZ) through the complex system of WaSH pathways. MethodsWe used data from a matched cohort effectiveness evaluation of a combined on-premise piped water and improved sanitation intervention in rural Odisha, India. Height/length was measured in children 0–59 months old (n = 1826) from 90 matched villages in February–June 2016. WaSH behaviours and infrastructure were assessed through household surveys and observation, respectively. We used SEM to calculate the standardized path coefficients and the total contributions of WaSH pathways to HAZ. ResultsIntervention improvements on HAZ were through the sanitation pathway (coverage → use β: 0.722; use → HAZ β: 0.116), with piped water coverage indirectly affecting HAZ through improved sanitation use (β: 0.148). Although the intervention had a positive association with handwashing station coverage, there was no evidence of a total hygiene pathway effect on HAZ or further direct effects through the water pathways. ConclusionsThis study demonstrates the utility of SEM to assess the mechanisms through which combined WaSH interventions impact HAZ as a system of pathways, providing a more nuanced assessment than estimation of the total intervention effect. Our finding, that water impacts HAZ through the sanitation pathway, is an important and actionable insight for WaSH programming.

    更新日期:2019-12-25
  • Investigating associations between rural-to-urban migration and cardiometabolic disease in Malawi: a population-level study
    Int. J. Epidemiol. (IF 7.339) Pub Date : 2019-10-11
    Chilunga F, Musicha C, Tafatatha T, et al.

    BackgroundThe extent to which rural-to-urban migration affects risk for cardiometabolic diseases (CMD) in Africa is not well understood. We investigated prevalence and risk for obesity, diabetes, hypertension and precursor conditions by migration status. MethodsIn a cross-sectional survey in Malawi (February 2013–March 2017), 13 903 rural, 9929 rural-to-urban migrant and 6741 urban residents (≥18 years old) participated. We interviewed participants, measured blood pressure and collected anthropometric data and fasting blood samples to estimate population prevalences and odds ratios, using negative binomial regression, for CMD, by migration status. In a sub-cohort of 131 rural–urban siblings-sets, migration-associated CMD risk was explored using conditional Poisson regression. ResultsIn rural, rural-to-urban migrant and urban residents, prevalence estimates were; 8.9, 20.9 and 15.2% in men and 25.4, 43.9 and 39.3% in women for overweight/obesity; 1.4, 2.9 and 1.9% in men and 1.5, 2.8 and 1.7% in women for diabetes; and 13.4, 18.8 and 12.2% in men and 13.7, 15.8 and 10.2% in women for hypertension. Rural-to-urban migrants had the greatest risk for hypertension (adjusted relative risk for men 1.18; 95% confidence interval 1.04–1.34 and women 1.17: 95% confidence interval 1.05–1.29) and were the most screened, diagnosed and treated for CMD, compared with urban residents. Within sibling sets, rural-to-urban migrant siblings had a higher risk for overweight and pre-hypertension, with no evidence for differences by duration of stay. ConclusionsRural-to-urban migration is associated with increased CMD risk in Malawi. In a poor country experiencing rapid urbanization, interventions for the prevention and management of CMD, which reach migrant populations, are needed.

    更新日期:2019-12-25
  • Corrigendum to: Cohort Profile: The Canadian Longitudinal Study on Aging (CLSA)
    Int. J. Epidemiol. (IF 7.339) Pub Date : 2019-10-11
    Raina P, Wolfson C, Kirkland S, et al.

    First published online: 6 September 2019, Int J Epidemiol 2019, doi: https://doi.org/10.1093/ije/dyz173

    更新日期:2019-12-25
  • Reflections on modern methods: linkage error bias
    Int. J. Epidemiol. (IF 7.339) Pub Date : 2019-10-21
    Doidge J, Harron K.

    Linked data are increasingly being used for epidemiological research, to enhance primary research, and in planning, monitoring and evaluating public policy and services. Linkage error (missed links between records that relate to the same person or false links between unrelated records) can manifest in many ways: as missing data, measurement error and misclassification, unrepresentative sampling, or as a special combination of these that is specific to analysis of linked data: the merging and splitting of people that can occur when two hospital admission records are counted as one person admitted twice if linked and two people admitted once if not. Through these mechanisms, linkage error can ultimately lead to information bias and selection bias; so identifying relevant mechanisms is key in quantitative bias analysis. In this article we introduce five key concepts and a study classification system for identifying which mechanisms are relevant to any given analysis. We provide examples and discuss options for estimating parameters for bias analysis. This conceptual framework provides the ‘links’ between linkage error, information bias and selection bias, and lays the groundwork for quantitative bias analysis for linkage error.

    更新日期:2019-12-25
  • Forest loss shapes the landscape suitability of Kyasanur Forest disease in the biodiversity hotspots of the Western Ghats, India
    Int. J. Epidemiol. (IF 7.339) Pub Date : 2019-11-18
    Walsh M, Mor S, Maity H, et al.

    BackgroundAnthropogenic pressure in biodiversity hotspots is increasingly recognized as a major driver of the spillover and expansion of zoonotic disease. In the Western Ghats region of India, a devastating tick-borne zoonosis, Kyasanur Forest disease (KFD), has been expanding rapidly beyond its endemic range in recent decades. It has been suggested that anthropogenic pressure in the form of land use changes that lead to the loss of native forest may be directly contributing to the expanding range of KFD, but clear evidence has not yet established the association between forest loss and KFD risk. MethodsThe current study sought to investigate the relationship between KFD landscape suitability and both forest loss and mammalian species richness, to inform its epidemiology and infection ecology. A total of 47 outbreaks of KFD between 1 January 2012 and 30 June 2019 were modelled as an inhomogeneous Poisson process. ResultsBoth forest loss [relative risk (RR) = 1.83; 95% confidence interval (CI) 1.33–2.51] and mammalian species richness (RR = 1.29; 95% CI 1.16–1.42) were strongly associated with increased risk of KFD and dominated its landscape suitability. ConclusionsThese results provide the first evidence of a clear association between increasing forest loss and risk for KFD. Moreover, the findings also highlight the importance of forest loss in areas of high biodiversity. Therefore, this evidence provides strong support for integrative approaches to public health which incorporate conservation strategies simultaneously protective of humans, animals and the environment.

    更新日期:2019-12-25
  • A Mendelian randomization analysis of circulating lipid traits and breast cancer risk
    Int. J. Epidemiol. (IF 7.339) Pub Date : 2019-12-23
    Beeghly-Fadiel A, , Khankari N, et al.

    BackgroundConventional epidemiologic studies have evaluated associations between circulating lipid levels and breast cancer risk, but results have been inconsistent. As Mendelian randomization analyses may provide evidence for causal inference, we sought to evaluate potentially unbiased associations between breast cancer risk and four genetically predicted lipid traits. MethodsPrevious genome-wide association studies (GWAS) have identified 164 discrete variants associated with high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), triglycerides and total cholesterol. We used 162 of these unique variants to construct weighted genetic scores (wGSs) for a total of 101 424 breast cancer cases and 80 253 controls of European ancestry from the Breast Cancer Association Consortium (BCAC). Unconditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for associations between per standard deviation increase in genetically predicted lipid traits and breast cancer risk. Additional Mendelian randomization analysis approaches and sensitivity analyses were conducted to assess pleiotropy and instrument validity. ResultsCorresponding to approximately 15 mg/dL, one standard deviation increase in genetically predicted HDL-C was associated with a 12% increased breast cancer risk (OR: 1.12, 95% CI: 1.08–1.16). Findings were consistent after adjustment for breast cancer risk factors and were robust in several sensitivity analyses. Associations with genetically predicted triglycerides and total cholesterol were inconsistent, and no association for genetically predicted LDL-C was observed. ConclusionsThis study provides strong evidence that circulating HDL-C may be associated with an increased risk of breast cancer, whereas LDL-C may not be related to breast cancer risk.

    更新日期:2019-12-25
  • Determinants of physical, mental and social well-being: a longitudinal environment-wide association study
    Int. J. Epidemiol. (IF 7.339) Pub Date : 2019-12-23
    Ni M, Yao X, Cheung F, et al.

    BackgroundAlthough the World Health Organization (WHO) has defined health as a state of physical, mental and social well-being, public health strategies have primarily focused on one domain of well-being. We sought to systematically and simultaneously identify and validate associations of behavioural patterns, psychosocial factors, mental and physical health conditions, access to and utilization of health care and anthropometrics with physical, mental and social well-being. MethodsWe conducted a longitudinal environment-wide association study (EWAS) with a training and testing set approach, accounting for multiple testing using a false discovery rate control. We used multivariate multilevel regression to examine the association of each exposure at wave 1 with the three outcomes at wave 2 in the Hong Kong FAMILY Cohort (n = 10 484). ResultsOut of 194 exposures, we identified and validated 14, 5 and 5 exposures that were individually associated with physical, mental and social well-being, respectively. We discovered three factors, namely depressive symptoms, life satisfaction and happiness, that were simultaneously associated with the three domains that define health. ConclusionsThese associations, if verified to be causal, could become intervention targets to holistically improve population health. Our findings provide empirical support for placing mental health at the forefront of the public health agenda, and also support recent calls to use life satisfaction and happiness to guide public policy.

    更新日期:2019-12-25
  • Ondansetron use in the first trimester of pregnancy and the risk of neonatal ventricular septal defect
    Int. J. Epidemiol. (IF 7.339) Pub Date : 2019-12-20
    Lemon L, Bodnar L, Garrard W, et al.

    BackgroundLiterature is divided regarding the risk of neonatal ventricular septal defect (VSD) associated with first trimester ondansetron use in pregnancy. MethodsWe evaluated the risk of VSD associated with first trimester exposure to intravenous or oral ondansetron in 33 677 deliveries at Magee–Womens Hospital in Pittsburgh, PA (2006–2014). Using log-binomial regression, we evaluated the risk: (1) in the full cohort, (2) using propensity score designs with both matching and inverse probability weighting and (3) utilizing clustered trajectory analysis evaluating the role of dose. Sensitivity analyses assessed the association between ondansetron and all recorded birth defects in aggregate. ResultsA total of 3733 (11%) pregnancies were exposed to ondansetron in the first trimester (dose range: 2.4–1008 mg). Ondansetron was associated with increased risk of VSD with risk ratios ranging from 1.7 [95% confidence interval (CI) 1.0–2.9] to 2.1 (95% CI 1.1–4.0) across methods. Risks correspond to one additional VSD for approximately every 330 pregnancies exposed in the first trimester. The association was dose-dependent with increased risk in women receiving highest cumulative doses compared with lowest doses [adjusted risk ratio: 3.2 (95% CI 1.0–9.9)]. The association between ondansetron and congenital malformations was diluted as the outcome included additional birth defects. ConclusionsFirst trimester ondansetron use is associated with an increased risk of neonatal VSD potentially driven by higher doses. This risk should be viewed in the context of risks attributable to severe untreated nausea and vomiting of pregnancy.

    更新日期:2019-12-20
  • Reducing socio-economic inequalities in all-cause mortality: a counterfactual mediation approach
    Int. J. Epidemiol. (IF 7.339) Pub Date : 2019-12-19
    Laine J, Baltar V, Stringini S, et al.

    BackgroundSocio-economic inequalities in mortality are well established, yet the contribution of intermediate risk factors that may underlie these relationships remains unclear. We evaluated the role of multiple modifiable intermediate risk factors underlying socio-economic-associated mortality and quantified the potential impact of reducing early all-cause mortality by hypothetically altering socio-economic risk factors. MethodsData were from seven cohort studies participating in the LIFEPATH Consortium (total n = 179 090). Using both socio-economic position (SEP) (based on occupation) and education, we estimated the natural direct effect on all-cause mortality and the natural indirect effect via the joint mediating role of smoking, alcohol intake, dietary patterns, physical activity, body mass index, hypertension, diabetes and coronary artery disease. Hazard ratios (HRs) were estimated, using counterfactual natural effect models under different hypothetical actions of either lower or higher SEP or education. ResultsLower SEP and education were associated with an increase in all-cause mortality within an average follow-up time of 17.5 years. Mortality was reduced via modelled hypothetical actions of increasing SEP or education. Through higher education, the HR was 0.85 [95% confidence interval (CI) 0.84, 0.86] for women and 0.71 (95% CI 0.70, 0.74) for men, compared with lower education. In addition, 34% and 38% of the effect was jointly mediated for women and men, respectively. The benefits from altering SEP were slightly more modest. ConclusionsThese observational findings support policies to reduce mortality both through improving socio-economic circumstances and increasing education, and by altering intermediaries, such as lifestyle behaviours and morbidities.

    更新日期:2019-12-19
  • Low-dose aspirin use and endometrial cancer mortality—a Danish nationwide cohort study
    Int. J. Epidemiol. (IF 7.339) Pub Date : 2019-12-17
    Sperling C, Verdoodt F, Aalborg G, et al.

    BackgroundAccumulating evidence suggests that aspirin use may improve survival in cancer patients, however, for endometrial cancer, epidemiological evidence is limited and results are equivocal. In a nationwide cohort study, we examined the association between post-diagnostic low-dose aspirin use and endometrial cancer mortality. MethodsFrom the Danish Cancer Registry, we identified all women with a primary diagnosis of endometrial cancer. Women diagnosed between 2000 and 2012, aged 30–84 years, who had no history of cancer (except non-melanoma skin cancer) and were alive 1 year after the cancer diagnosis were eligible. We obtained information on pre- and post-diagnostic use (≥1 prescription) of low-dose aspirin, mortality and potential confounding factors from nationwide registries. Using Cox regression models, we estimated adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between post-diagnostic low-dose aspirin use and endometrial cancer mortality. The exposure was modelled as both time-varying as well as time-fixed within exposure windows of 1 and 5 years. ResultsWe identified 6694 endometrial cancer patients with a maximum follow-up of 13 years. In the time-varying analysis, post-diagnostic low-dose aspirin use was associated with a HR of 1.10 (95% CI 0.90–1.33) for endometrial cancer mortality. We found no indication of a dose–response association according to increasing tablet strength, cumulative amount or duration of use, and the HRs were similar for pre-diagnostic and post-diagnostic low-dose aspirin use compared with non-use. ConclusionsWe found no indication that post-diagnostic low-dose aspirin use was associated with reduced mortality for endometrial cancer; rather our findings suggested a concern for increased mortality.

    更新日期:2019-12-18
  • Proxy gene-by-environment Mendelian randomization study confirms a causal effect of maternal smoking on offspring birthweight, but little evidence of long-term influences on offspring health
    Int. J. Epidemiol. (IF 7.339) Pub Date : 2019-12-13
    Yang Q, Millard L, Davey Smith G.

    BackgroundA lack of genetic data across generations makes transgenerational Mendelian randomization (MR) difficult. We used UK Biobank and a novel proxy gene-by-environment MR to investigate effects of maternal smoking heaviness in pregnancy on offspring health, using participants’ (generation one: G1) genotype (rs16969968 in CHRNA5) as a proxy for their mothers’ (G0) genotype. MethodsWe validated this approach by replicating an established effect of maternal smoking heaviness on offspring birthweight. Then we applied this approach to explore effects of maternal (G0) smoking heaviness on offspring (G1) later life outcomes and on birthweight of G1 women’s children (G2). ResultsEach additional smoking-increasing allele in offspring (G1) was associated with a 0.018 [95% confidence interval (CI): -0.026, -0.009] kg lower G1 birthweight in maternal (G0) smoking stratum, but no meaningful effect (-0.002 kg; 95% CI: -0.008, 0.003) in maternal non-smoking stratum (interaction P-value = 0.004). The differences in associations of rs16969968 with grandchild’s (G2) birthweight between grandmothers (G0) who did, versus did not, smoke were heterogeneous (interaction P-value = 0.042) among mothers (G1) who did (-0.020 kg/allele; 95% CI: -0.044, 0.003), versus did not (0.007 kg/allele; 95% CI: -0.005, 0.020), smoke in pregnancy. ConclusionsOur study demonstrated how offspring genotype can be used to proxy for the mother’s genotype in gene-by-environment MR. We confirmed the causal effect of maternal (G0) smoking on offspring (G1) birthweight, but found little evidence of an effect on G1 longer-term health outcomes. For grandchild’s (G2) birthweight, the effect of grandmother’s (G0) smoking heaviness in pregnancy may be modulated by maternal (G1) smoking status in pregnancy.

    更新日期:2019-12-13
  • Polygenic risk scores and the prediction of common diseases
    Int. J. Epidemiol. (IF 7.339) Pub Date : 2019-12-12
    Ala-Korpela M, Holmes M.

    There is growing interest in the potential translational applications of omics data. This applies to, e.g. metabolomics, an area in which the Journal published a themed issue in 2016 with an accompanying editorial titled ‘Metabolic profiling—multitude of technologies with great research potential, but (when) will translation emerge?’1 Despite two decades of extensive investigations with optimistic statements of potential translational applications, there is no metabolomics-derived biomarker (of either an individual metabolite in isolation or multiple metabolites in combination) that has yet to mature into clinical utility. On appraising the recent activity in polygenic risk scores (PRSs) and disease prediction, we notice parallel themes to the decades-old search for conventional (non-genetic) predictive biomarkers. An overwhelming sense of hype and a rush to translate dominates the field of genetic research of disease prediction using genetic risk scores (GRSs).

    更新日期:2019-12-13
  • Corrigendum to: Educational Note: Paradoxical collider effect in the analysis of non-communicable disease epidemiological data: a reproducible illustration and web application
    Int. J. Epidemiol. (IF 7.339) Pub Date : 2019-12-10
    Luque-Fernandez M, Schomaker M, Redondo-Sanchez D, et al.

    First published online: 14 December 2018, Int J Epidemiol 2019; 48: 640–53. doi: https://doi.org/10.1093/ije/dyy275

    更新日期:2019-12-11
  • Corrigendum to: Data Resource Profile: The Systemic Anti-Cancer Therapy (SACT) Dataset
    Int. J. Epidemiol. (IF 7.339) Pub Date : 2019-12-10
    Bright C, Lawton S, Benson S, et al.

    First published online: 24 July 2019, Int J Epidemiol 2019; doi: https://doi.org/10.1093/ije/dyz137

    更新日期:2019-12-11
  • Reflection on modern methods: five myths about measurement error in epidemiological research
    Int. J. Epidemiol. (IF 7.339) Pub Date : 2019-12-10
    van Smeden M, Lash T, Groenwold R.

    Epidemiologists are often confronted with datasets to analyse which contain measurement error due to, for instance, mistaken data entries, inaccurate recordings and measurement instrument or procedural errors. If the effect of measurement error is misjudged, the data analyses are hampered and the validity of the study’s inferences may be affected. In this paper, we describe five myths that contribute to misjudgments about measurement error, regarding expected structure, impact and solutions to mitigate the problems resulting from mismeasurements. The aim is to clarify these measurement error misconceptions. We show that the influence of measurement error in an epidemiological data analysis can play out in ways that go beyond simple heuristics, such as heuristics about whether or not to expect attenuation of the effect estimates. Whereas we encourage epidemiologists to deliberate about the structure and potential impact of measurement error in their analyses, we also recommend exercising restraint when making claims about the magnitude or even direction of effect of measurement error if not accompanied by statistical measurement error corrections or quantitative bias analysis. Suggestions for alleviating the problems or investigating the structure and magnitude of measurement error are given.

    更新日期:2019-12-11
  • Appraising causal relationships of dietary, nutritional and physical-activity exposures with overall and aggressive prostate cancer: two-sample Mendelian-randomization study based on 79 148 prostate-cancer cases and 61 106 controls
    Int. J. Epidemiol. (IF 7.339) Pub Date : 2019-12-05
    Kazmi N, Haycock P, Tsilidis K, et al.

    BackgroundProstate cancer is the second most common male cancer worldwide, but there is substantial geographical variation, suggesting a potential role for modifiable risk factors in prostate carcinogenesis. MethodsWe identified previously reported prostate cancer risk factors from the World Cancer Research Fund (WCRF)’s systematic appraisal of the global evidence (2018). We assessed whether each identified risk factor was causally associated with risk of overall (79 148 cases and 61 106 controls) or aggressive (15 167 cases and 58 308 controls) prostate cancer using Mendelian randomization (MR) based on genome-wide association-study summary statistics from the PRACTICAL and GAME-ON/ELLIPSE consortia. We assessed evidence for replication in UK Biobank (7844 prostate-cancer cases and 204 001 controls). ResultsWCRF identified 57 potential risk factors, of which 22 could be instrumented for MR analyses using single nucleotide polymorphisms. For overall prostate cancer, we identified evidence compatible with causality for the following risk factors (odds ratio [OR] per standard deviation increase; 95% confidence interval): accelerometer-measured physical activity, OR = 0.49 (0.33–0.72; P = 0.0003); serum iron, OR = 0.92 (0.86–0.98; P = 0.007); body mass index (BMI), OR = 0.90 (0.84–0.97; P = 0.003); and monounsaturated fat, OR = 1.11 (1.02–1.20; P = 0.02). Findings in our replication analyses in UK Biobank were compatible with our main analyses (albeit with wide confidence intervals). In MR analysis, height was positively associated with aggressive-prostate-cancer risk: OR = 1.07 (1.01–1.15; P = 0.03). ConclusionsThe results for physical activity, serum iron, BMI, monounsaturated fat and height are compatible with causality for prostate cancer. The results suggest that interventions aimed at increasing physical activity may reduce prostate-cancer risk, although interventions to change other risk factors may have negative consequences on other diseases.

    更新日期:2019-12-05
  • Effects of body mass index on relationship status, social contact and socio-economic position: Mendelian randomization and within-sibling study in UK Biobank
    Int. J. Epidemiol. (IF 7.339) Pub Date : 2019-12-04
    Howe L, Kanayalal R, Harrison S, et al.

    BackgroundWe assessed whether body mass index (BMI) affects social and socio-economic outcomes. MethodsWe used Mendelian randomization (MR), non-linear MR and non-genetic and MR within-sibling analyses, to estimate relationships of BMI with six socio-economic and four social outcomes in 378 244 people of European ancestry in UK Biobank. ResultsIn MR of minimally related individuals, higher BMI was related to higher deprivation, lower income, fewer years of education, lower odds of degree-level education and skilled employment. Non-linear MR suggested both low (bottom decile, <22 kg/m2) and high (top seven deciles, >24.6 kg/m2) BMI, increased deprivation and reduced income. Non-genetic within-sibling analysis supported an effect of BMI on socio-economic position (SEP); precision in within-sibling MR was too low to draw inference about effects of BMI on SEP. There was some evidence of pleiotropy, with MR Egger suggesting limited effects of BMI on deprivation, although precision of these estimates is also low. Non-linear MR suggested that low BMI (bottom three deciles, <23.5 kg/m2) reduces the odds of cohabiting with a partner or spouse in men, whereas high BMI (top two deciles, >30.7 kg/m2) reduces the odds of cohabitation in women. Both non-genetic and MR within-sibling analyses supported this sex-specific effect of BMI on cohabitation. In men only, higher BMI was related to lower participation in leisure and social activities. There was little evidence that BMI affects visits from friends and family or having someone to confide in. ConclusionsBMI may affect social and socio-economic outcomes, with both high and low BMI being detrimental for SEP, although larger within-family MR studies may help to test the robustness of MR results in unrelated individuals. Triangulation of evidence across MR and within-family analyses supports evidence of a sex-specific effect of BMI on cohabitation.

    更新日期:2019-12-04
  • Associations of exposure to green space with problem behaviours in preschool-aged children
    Int. J. Epidemiol. (IF 7.339) Pub Date : 2019-11-28
    Liao J, Yang S, Xia W, et al.

    BackgroundLimited evidence is available regarding the association of green-space exposure with childhood behavioural development. This study aimed to investigate the associations of exposure to green space with multiple syndromes of behavioural development in preschool children. MethodsThis cross-sectional study was conducted in Wuhan, China from April 2016 to June 2018. We recruited a sample of 6039 children aged 5–6 years from 17 kindergartens located in five urban districts of the city. We measured the greenness using average Normalized Difference Vegetation Index (NDVI) within a circular buffer area of 100 metres surrounding the central point of residences and kindergartens. We calculated the residence–kindergarten-weighted greenness by assuming that children spent 16 hours per day at home and 8 hours at kindergarten. The problem behaviours of children were evaluated at kindergarten using the Childhood Behavioral Checklist (CBCL) and standardized into problem behavioural T scores. Linear mixed-effect models and linear-regression models were used to estimate the associations. ResultsWe observed decreases in problem behaviours associated with kindergarten and residence–kindergarten-weighted surrounding greenness in preschool children. For example, a one-interquartile range increase in kindergarten and residence–kindergarten-weighted NDVI was associated with decreased T scores for total behaviour by −0.61 [95% confidence interval (CI): −1.09, −0.13) and −0.49 (95% CI −0.85, −0.12), anxiety and depression by −0.65 (95% CI: −1.13, −0.17) and −0.46 (95% CI: −0.82, −0.10), aggressive behaviour by −0.53 (95% CI: −1.01, −0.05) and −0.38 (95% CI: −0.75, −0.02) and hyperactivity and attention deficit by −0.54 (95% CI: −1.01, −0.07) and −0.48 (95% CI: −0.83, −0.12), respectively. Stratified analyses indicated that the associations of green-space exposure with problem behaviours were stronger in boys than in girls. ConclusionsChildren attending kindergartens with higher levels of surrounding green space exhibited better behavioural development. The mechanisms underlying these associations should be explored further.

    更新日期:2019-11-30
  • Most recommended medical interventions reach P<0.005 for their primary outcomes in meta-analyses
    Int. J. Epidemiol. (IF 7.339) Pub Date : 2019-11-25
    Koletsi D, Solmi M, Pandis N, et al.

    BackgroundIt has been proposed that the threshold of statistical significance should shift from P-value < 0.05 to P-value < 0.005, but there is concern that this move may dismiss effective, useful interventions. We aimed to assess how often medical interventions are recommended although their evidence in meta-analyses of randomized trials lies between P-value = 0.05 and P-value = 0.005. MethodsWe included Cochrane systematic reviews (SRs) published from 1 January 2013 to 30 June 2014 that had at least one meta-analysis with GRADE (Grading of Recommendations Assessment, Development and Evaluation) assessment and at least one primary outcome having favourable results for efficacy at P-value < 0.05. Only comparisons of randomized trials between active versus no treatment/placebo were included. We then assessed the respective UpToDate recommendations for clinical practice from 22 May 2018 to 5 October 2018 and recorded how many treatments were recommended and what were the P-values in their meta-analysis evidence. The primary analysis was based on the first-listed outcomes. ResultsOf 608 screened SRs with GRADE assessment, 113 SRs were eligible, including 143 comparisons of which 128 comparisons had first-listed primary outcomes with UpToDate coverage. Altogether, 60% (58/97) of interventions with P-values < 0.005 for their evidence were recommended versus 32% (10/31) of those with P-value 0.005–0.05. Therefore, most (58/68, 85.2%) of the recommended interventions had P-values < 0.005 for the first-listed primary outcome. Of the 10 exceptions, 4 had other primary outcomes with P-values < 0.005 and another 4 had additional extensive evidence for similar indications that would allow extrapolation for practice recommendations. ConclusionsFew interventions are recommended without their evidence from meta-analyses of randomized trials reaching P-value < 0.005.

    更新日期:2019-11-26
  • Comparison with randomized controlled trials as a strategy for evaluating instruments in Mendelian randomization
    Int. J. Epidemiol. (IF 7.339) Pub Date : 2019-11-25
    Gill D, Walker V, Martin R, et al.

    The Mendelian randomization (MR) approach uses genetic variants as instrumental variables to study the effect of an exposure on an outcome.1 In this way, by selecting genetic variants that serve as instrumental variables for drug effects, it can also be possible to study corresponding drug side-effects and repurposing potential.2 Such an approach has recently been applied to antihypertensive drugs by two separate research groups independently of each other.3,4 Here, the authors of these two papers collaboratively discuss a strategy that can be used for validating instruments for such study.

    更新日期:2019-11-26
  • Food insecurity and the extremes of childhood weight: defining windows of vulnerability
    Int. J. Epidemiol. (IF 7.339) Pub Date : 2019-11-21
    Zhu Y, Mangini L, Hayward M, et al.

    BackgroundWeight extremes and food insecurity (FIS) represent public-health challenges, yet their associations in childhood remain unclear. We aimed to investigate the longitudinal time-specific relationship between FIS and risk of overweight/obesity and underweight in kindergarten through 8th grade. MethodsIn the prospective Early Childhood Longitudinal Study–Kindergarten Cohort (1998–2007) of 6368 children, household FIS was assessed by the validated US Household Food Security Survey Module in kindergarten, 3rd, 5th and 8th grades. Multivariable linear-regression and Poisson-regression models were computed. ResultsCompared with children experiencing food security (FS), children exposed to FIS in 5th grade had 0.19 [95% confidence interval (CI): 0.07–0.30] and 0.17 (0.06–0.27) higher body mass index z-score (BMIZ) in the 5th and 8th grades, respectively, whereas FIS in the 8th grade was associated with a 0.29 (0.19–0.40) higher BMIZ at the same wave, after adjusting for covariates and FIS at earlier waves. Children with FIS vs FS had 27% (relative risk: 1.27, 95% CI: 1.07–1.51), 21% (1.21, 1.08–1.35) and 28% (1.28, 1.07–1.53) higher risk of overweight/obesity in the 3rd, 5th and 8th grades, respectively, adjusting for covariates and FIS at prior wave(s). Children with FIS vs FS in kindergarten had a 2.76-fold (1.22–6.25) higher risk of underweight in the 8th grade. ConclusionsProximal exposure to household FIS was associated with a higher risk of overweight/obesity in the 3rd, 5th and 8th grades. FIS in kindergarten was associated with a risk of underweight in the 8th grade. Thus, FIS coexists in weight extremes during vulnerable early-life windows in the USA, similarly to the global burden of FIS.

    更新日期:2019-11-21
  • Circulating vitamin D concentrations and risk of breast and prostate cancer: a Mendelian randomization study
    Int. J. Epidemiol. (IF 7.339) Pub Date : 2018-12-28
    Jiang X, Dimou N, Al-Dabhani K, et al.

    BackgroundObservational studies have suggested an association between circulating vitamin D concentrations [25(OH)D] and risk of breast and prostate cancer, which was not supported by a recent Mendelian randomization (MR) analysis comprising 15 748 breast and 22 898 prostate-cancer cases. Demonstrating causality has proven challenging and one common limitation of MR studies is insufficient power. MethodsWe aimed to determine whether circulating concentrations of vitamin D are causally associated with the risk of breast and prostate cancer, by using summary-level data from the largest ever genome-wide association studies conducted on vitamin D (N = 73 699), breast cancer (Ncase = 122 977) and prostate cancer (Ncase = 79 148). We constructed a stronger instrument using six common genetic variants (compared with the previous four variants) and applied several two-sample MR methods. ResultsWe found no evidence to support a causal association between 25(OH)D and risk of breast cancer [OR per 25 nmol/L increase, 1.02 (95% confidence interval: 0.97–1.08), P = 0.47], oestrogen receptor (ER)+ [1.00 (0.94–1.07), P = 0.99] or ER− [1.02 (0.90–1.16), P = 0.75] subsets, prostate cancer [1.00 (0.93–1.07), P = 0.99] or the advanced subtype [1.02 (0.90–1.16), P = 0.72] using the inverse-variance-weighted method. Sensitivity analyses did not reveal any sign of directional pleiotropy. ConclusionsDespite its almost five-fold augmented sample size and substantially improved statistical power, our MR analysis does not support a causal effect of circulating 25(OH)D concentrations on breast- or prostate-cancer risk. However, we can still not exclude a modest or non-linear effect of vitamin D. Future studies may be designed to understand the effect of vitamin D in subpopulations with a profound deficiency.

    更新日期:2019-11-17
  • Shift work, DNA methylation and epigenetic age
    Int. J. Epidemiol. (IF 7.339) Pub Date : 2019-03-15
    White A, Kresovich J, Xu Z, et al.

    BackgroundShift work has been associated with increased risk of age-related morbidity and mortality. Biological age, estimated using DNA methylation (DNAm), may quantify the biological consequences of shift work on the risk of age-related disease. We examined whether prior employment in shift-working occupations was associated with epigenetic age acceleration. MethodsIn a sample of non-Hispanic White women aged 35–74 (n = 2574), we measured DNAm using the Illumina Infinium Human450 BeadChip and calculated DNAm age using three established epigenetic clocks. Age-acceleration metrics were derived by regressing DNAm age on chronological age and predicting the residuals. Using linear regression, we estimated associations between shift work history and age acceleration. We also conducted an epigenome-wide association study using robust linear-regression models corrected with false discovery rate (FDR) q-values. ResultsApproximately 7% of women reported any shift work. Higher age acceleration was observed for a 1-year increase in overall [β = 0.11, 95% confidence interval (CI): 0.02–0.21] and night-specific shift work (β = 0.12, 95% CI: 0.03–0.21). The association was strongest for ≥10 years of night shift work (β = 3.16, 95% CI: 1.17–5.15). From the epigenome-wide association study, years of overall and night shift work were associated with DNAm at 66 and 85 CpG sites (FDR < 0.05), respectively. Years of night shift work was associated with lower methylation of a CpG in the gene body of ZFHX3(cg04994202, q = 0.04), a gene related to circadian rhythm. ConclusionsShift work was associated with differential CpG site methylation and with differential DNAm patterns, measured by epigenetic age acceleration, consistent with long-term negative health effects.

    更新日期:2019-11-17
  • Association between maternal shift work and infant neurodevelopmental outcomes: results from the Taiwan Birth Cohort Study with propensity-score-matching analysis
    Int. J. Epidemiol. (IF 7.339) Pub Date : 2019-03-29
    Wei C, Chen M, Lin C, et al.

    BackgroundMaternal shift work is associated with preterm delivery, small-for-gestational-age new-borns, childhood obesity and future behavioural problems. However, the adverse effects on and interactions of maternal shift work with infant neurodevelopment remain uncertain. Therefore, we examined the associations between maternal-shift-work status and infant neurodevelopmental parameters. MethodsThe Taiwan Birth Cohort Study is a nationwide birth cohort study following representatively sampled mother–infant pairs in 2005. The participants’ development and exposure conditions were assessed by home interviews with structured questionnaires at 6 and 18 months of age. Propensity scores were calculated with predefined covariates for 1:1 matching. Multivariate conditional logistic regression and the Cox proportional-hazards model were used to examine the association between maternal-shift-work status and infant neurodevelopmental-milestone-achievement status. ResultsIn this study, 5637 term singletons were included, with 2098 cases selected in the propensity-score-matched subpopulation. Persistent maternal shift work was associated with increased risks of delays in gross-motor neurodevelopmental milestones [aOR = 1.36, 95% confidence interval (CI) = 1.06–1.76 for walking steadily], fine-motor neurodevelopmental milestones (aOR = 1.39, 95% CI = 1.07–1.80 for scribbling) and social neurodevelopmental milestones (aOR = 1.35, 95% CI = 1.03–1.76 for coming when called upon). Moreover, delayed gross-motor and social development were identified in the propensity-score-matched sub-cohort. ConclusionsThis study shows negative associations between maternal shift work and delayed neurodevelopmental-milestone achievement in the gross-motor, fine-motor and social domains at 18 months. Future research is necessary to elucidate the possible underlying mechanisms and long-term health effects.

    更新日期:2019-11-17
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