Epidemiology

Extending inferences from a randomized trial to a target population

New methods for generalizability and transportability: the new norm

Coffee consumption and all-cause and cause-specific mortality: a meta-analysis by potential modifiers Abstract Coffee consumption has been associated with decreased mortality in previous studies. As aging, obesity, and lifestyle factors affect the risk of mortality, the association between coffee and mortality needs to be examined in various subpopulations by characteristics of subjects. To quantitatively assess this association, we conducted an updated meta-analysis including stratified analyses by potential modifiers. We searched in the PubMed and Web of Science databases through March 8, 2019, and conducted meta-analysis including linear and non-linear dose–response analyses. We identified 40 studies including 3,852,651 subjects and 450,256 all-cause and cause-specific deaths. Non-linear inverse associations between coffee consumption and mortality from all-causes, cardiovascular disease (CVD), and cancers were found. The lowest relative risk (RR) was at intakes of 3.5 cups/day for all-cause mortality (RR = 0.85, 95% CI 0.82–0.89), 2.5 cups/day for CVD mortality (RR = 0.83, 95% CI 0.80–0.87), and 2 cups/day for cancer mortality (RR = 0.96, 95% CI 0.94–0.99), while additional intakes were not associated with further lower mortality. An inverse association between coffee consumption and all-cause mortality was maintained irrespective of age, overweight status, alcohol drinking, smoking status, and caffeine content of coffee. By region, Europe and Asia showed stronger inverse associations than US. A non-linear inverse association was found for mortality from respiratory disease and diabetes, while linear inverse association was found for mortality from non-CVD, non-cancer causes. Moderate coffee consumption (e.g. 2–4 cups/day) was associated with reduced all-cause and cause-specific mortality, compared to no coffee consumption. The inverse association between coffee and all-cause mortality was consistent by potential modifiers except region.

A descriptive review of variable selection methods in four epidemiologic journals: there is still room for improvement Abstract A review of epidemiological papers conducted in 2009 concluded that several studies employed variable selection methods susceptible to introduce bias and yield inadequate inferences. Many new confounder selection methods have been developed since then. The goal of the study was to provide an updated descriptive portrait of which variable selection methods are used by epidemiologists for analyzing observational data. Studies published in four major epidemiological journals in 2015 were reviewed. Only articles concerned with a predictive or explicative objective and reporting on the analysis of individual data were included. Method(s) employed for selecting variables were extracted from retained articles. A total of 975 articles were retrieved and 299 met eligibility criteria, 292 of which pursued an explicative objective. Among those, 146 studies (50%) reported using prior knowledge or causal graphs for selecting variables, 34 (12%) used change in effect estimate methods, 26 (9%) used stepwise approaches, 16 (5%) employed univariate analyses, 5 (2%) used various other methods and 107 (37%) did not provide sufficient details to allow classification (more than one method could be employed in a single article). Despite being less frequent than in the previous review, stepwise and univariable analyses, which are susceptible to introduce bias and produce inadequate inferences, were still prevalent. Moreover, 37% studies did not provide sufficient details to assess how variables were selected. We thus believe there is still room for improvement in variable selection methods used by epidemiologists and in their reporting.

Interaction between lifestyle and genetic susceptibility in myopia: the Generation R study Abstract Myopia is a refractive error of the eye caused by a complex interplay between nature and nurture. The aim of this study was to investigate whether environmental risk factors can influence the genetic effect in children developing myopia. A total of 3422 children participating in the birth-cohort study Generation R underwent an extensive eye examination at 9 years with measurements of refractive error and axial length corneal radius ratio (AL/CR). Environmental risk factors were evaluated using a questionnaire, and environmental risk scores (ERS) were calculated using backward regression analyses. Genetic risk scores (GRS) were calculated based on all currently known risk variants for myopia. Gene-environment interaction (G×E) was investigated using linear and logistic regression analyses. The predictive value of G×E and parental myopia was estimated using receiver operating characteristic curves. Myopia prevalence was 12%. Both GRS (P < 0.01) and ERS (P < 0.01) were significantly associated with myopia and AL/CR, as was G×E interaction (P < 0.01 for myopia; P = 0.07 for AL/CR). The predictive value of parental myopia was 0.67 (95% CI 0.65–0.70), similar to the values of GRS (0.67; 95% CI 0.64–0.70; P = 0.98) and ERS (0.69; 95% CI 0.66–0.72; P = 0.98). Adding G×E interaction significantly improved the predictive value to 0.73 (95% CI 0.70–0.75; P < 0.01). This study provides evidence that nature and nurture are equally important for myopia and AL/CR; however, the combination has the strongest influence. Since myopia genes are common in the population, adjustment of lifestyle should be a major focus in the prevention of myopia.

Birth seasonality and risk of autism spectrum disorder Abstract Season of birth has been hypothesized to be a risk factor for autism spectrum disorder (ASD). However, the evidence has been mixed and limited due to methodological challenges. We examine ASD birth trends for 5,464,628 births across 5 countries. ASD birth prevalence data were obtained from the International Collaboration for Autism Registry Epidemiology database, including children born in Denmark, Finland, Norway, Sweden, and Western Australia. Empirical mode decomposition and cosinor modeling were used to assess seasonality. We show seasonal variation in ASD births for the countries of Finland and Sweden. There was a modest increase in risk for children born in the fall and a modest decrease in risk for children born in the spring. Solar radiation levels around conception and the postnatal period were inversely correlated with seasonal trends in ASD risk. In the first multinational study of birth seasonality of ASD, there was evidence supporting the presence of seasonal trends in Finland and Sweden. The observations that risk was highest for fall births (i.e., conceived in the winter) and lowest for spring births (i.e., conceived in the summer), and sunlight levels during critical neurodevelopmental periods explained much of the seasonal trends, are consistent with the hypothesis that a seasonally fluctuating risk factor may influence risk of ASD.

Quantification of biological age as a determinant of age-related diseases in the Rotterdam Study: a structural equation modeling approach Abstract Chronological age alone is not a sufficient measure of the true physiological state of the body. The aims of the present study were to: (1) quantify biological age based on a physiological biomarker composite model; (2) and evaluate its association with death and age-related disease onset in the setting of an elderly population. Using structural equation modeling we computed biological age for 1699 individuals recruited from the first and second waves of the Rotterdam study. The algorithm included nine physiological parameters (c-reactive protein, creatinine, albumin, total cholesterol, cytomegalovirus optical density, urea nitrogen, alkaline phosphatase, forced expiratory volume and systolic blood pressure). We assessed the association between biological age, all-cause mortality, all-cause morbidity and specific age-related diseases over a median follow-up of 11 years. Biological age, compared to chronological age or the traditional biomarkers of age-related diseases, showed a stronger association with all-cause mortality (HR 1.15 vs. 1.13 and 1.10), all-cause morbidity (HR 1.06 vs. 1.05 and 1.03), stroke (HR 1.17 vs. 1.08 and 1.04), cancer (HR 1.07 vs. 1.04 and 1.02) and diabetes mellitus (HR 1.12 vs. 1.01 and 0.98). Individuals who were biologically younger exhibited a healthier life-style as reflected in their lower BMI (P < 0.001) and lower incidence of stroke (P < 0.001), cancer (P < 0.01) and diabetes mellitus (P = 0.02). Collectively, our findings suggest that biological age based on the biomarker composite model of nine physiological parameters is a useful construct to assess individuals 65 years and older at increased risk for specific age-related diseases.

Generalizing from the results of randomized studies of treatment: Can non-randomized studies be of help?

Intake of 12 food groups and disability-adjusted life years from coronary heart disease, stroke, type 2 diabetes, and colorectal cancer in 16 European countries Abstract Our aim was to estimate and rank 12 food groups according to disability-adjusted life years (DALYs) from coronary heart disease (CHD), stroke, type 2 diabetes (T2D), and colorectal cancer (CRC) in 16 European countries. De novo published non-linear dose–response meta-analyses of prospective studies (based on 297 primary reports), and food consumption data from the European Food Safety Authority Comprehensive European Food Consumption Database in Exposure Assessment, and DALY estimates from the Institute for Health Metrics and Evaluation were used. By implementing disease-specific counterfactual scenarios of theoretical minimum risk exposure level (TMRELs), the proportion of DALYs attributed to 12 food groups was estimated. In addition, a novel modelling approach was developed to obtain a single (optimized) TMREL across diseases. Four scenarios were analysed (A: disease-specific TMRELs/all food-disease associations; B: disease-specific TMRELs/only significant food-disease associations; C: single TMREL/all food-disease associations; D: single TMREL/only significant food-disease associations). Suboptimal food intake was associated with the following proportions of DALYs; Scenario A (highest-estimate) and D (lowest-estimate): CHD (A: 67%, D: 52%), stroke (A: 49%, D: 30%), T2D (A: 57%, D: 51%), and CRC (A: 54%, D: 40%). Whole grains (10%) had the highest impact on DALYs, followed by nuts (7.1%), processed meat (6.4%), fruit (4.4%) and fish and legumes (4.2%) when combining all scenarios. The contribution to total DALYs of all food groups combined in the different scenarios ranged from 41–52% in Austria to 51–69% in the Czech-Republic. These findings could have important implications for planning future food-based dietary guidelines as a public health nutrition strategy.

Association between tea consumption and risk of cancer: a prospective cohort study of 0.5 million Chinese adults Abstract Current experimental and epidemiological studies provide inconsistent evidence toward the association between tea consumption and cancer incidence. We investigated whether tea consumption was associated with the incidence of all cancers and six leading types of cancer (lung cancer, stomach cancer, colorectal cancer, liver cancer, female breast cancer and cervix uteri cancer) among 455,981 participants aged 30–79 years in the prospective cohort China Kadoorie Biobank. Tea consumption was assessed at baseline (2004–2008) with an interviewer-administered questionnaire. Cancer cases were identified by linkage to the national health insurance system. Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). In the present population, daily tea consumers were more likely to be current smokers and daily alcohol consumers. 22,652 incident cancers occurred during 10.1 years follow-up (5.04 cases/1000 person-years). When we restricted analyses to non-smokers and non-excessive alcohol consumers to minimize confounding, tea consumption was not associated with all cancers (daily consumers who added tea leaves > 4.0 g/day vs. less-than-weekly consumers: HR, 1.03; 95%CI, 0.93–1.13), lung cancer (HR, 1.08; CI, 0.84–1.40), colorectal cancer (HR, 1.08; CI, 0.81–1.45) and liver cancer (HR, 1.08; CI, 0.75–1.55), yet might be associated with increased risk of stomach cancer (HR, 1.46; CI, 1.07–1.99). In both less-than-daily and daily tea consumers, all cancer risk increased with the amount of tobacco smoked or alcohol consumed. Our findings suggest tea consumption may not provide preventive effect against cancer incidence.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com