Showing papers in "American Journal of Epidemiology in 2012"
TL;DR: Methods for point and interval estimation of relative risk for log-linear exposure-response relations in meta-analyses of published ordinal categorical exposure- response data have been proposed and the use of 2 publicly available user-friendly programs (Stata and SAS) to implement meta-analysis for dose-response data is illustrated.
Abstract: Two methods for point and interval estimation of relative risk for log-linear exposure-response relations in meta-analyses of published ordinal categorical exposure-response data have been proposed. The authors compared the results of a meta-analysis of published data using each of the 2 methods with the results that would be obtained if the primary data were available and investigated the circumstances under which the approximations required for valid use of each meta-analytic method break down. They then extended the methods to handle nonlinear exposure-response relations. In the present article, methods are illustrated using studies of the relation between alcohol consumption and colorectal and lung cancer risks from the ongoing Pooling Project of Prospective Studies of Diet and Cancer. In these examples, the differences between the results of a meta-analysis of summarized published data and the pooled analysis of the individual original data were small. However, incorrectly assuming no correlation between relative risk estimates for exposure categories from the same study gave biased confidence intervals for the trend and biased P values for the tests for nonlinearity and between-study heterogeneity when there was strong confounding by other model covariates. The authors illustrate the use of 2 publicly available user-friendly programs (Stata and SAS) to implement meta-analysis for dose-response data.
1,041 citations
TL;DR: The authors delineate the study's objectives, principal methodological features, and timeline, and confirm that long-term biologic sample storage will allow investigation of biomarkers that may predict cardiovascular diseases and diabetes.
Abstract: Although low- and middle-income countries still bear the burden of major infectious diseases, chronic noncommunicable diseases are becoming increasingly common due to rapid demographic, epidemiologic, and nutritional transitions. However, information is generally scant in these countries regarding chronic disease incidence, social determinants, and risk factors. The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) aims to contribute relevant information with respect to the development and progression of clinical and subclinical chronic diseases, particularly cardiovascular diseases and diabetes. In this report, the authors delineate the study's objectives, principal methodological features, and timeline. At baseline, ELSA-Brasil enrolled 15,105 civil servants from 5 universities and 1 research institute. The baseline examination (2008-2010) included detailed interviews, clinical and anthropometric examinations, an oral glucose tolerance test, overnight urine collection, a 12-lead resting electrocardiogram, measurement of carotid intima-media thickness, echocardiography, measurement of pulse wave velocity, hepatic ultrasonography, retinal fundus photography, and an analysis of heart rate variability. Long-term biologic sample storage will allow investigation of biomarkers that may predict cardiovascular diseases and diabetes. Annual telephone surveillance, initiated in 2009, will continue for the duration of the study. A follow-up examination is scheduled for 2012-2013.
603 citations
TL;DR: The authors conclude that the increase in the AUC, integrated discrimination improvement, and net reclassification improvement offer complementary information and thus recommend reporting all 3 alongside measures characterizing the performance of the final model.
Abstract: The discrimination of a risk prediction model measures that model's ability to distinguish between subjects with and without events. The area under the receiver operating characteristic curve (AUC) is a popular measure of discrimination. However, the AUC has recently been criticized for its insensitivity in model comparisons in which the baseline model has performed well. Thus, 2 other measures have been proposed to capture improvement in discrimination for nested models: the integrated discrimination improvement and the continuous net reclassification improvement. In the present study, the authors use mathematical relations and numerical simulations to quantify the improvement in discrimination offered by candidate markers of different strengths as measured by their effect sizes. They demonstrate that the increase in the AUC depends on the strength of the baseline model, which is true to a lesser degree for the integrated discrimination improvement. On the other hand, the continuous net reclassification improvement depends only on the effect size of the candidate variable and its correlation with other predictors. These measures are illustrated using the Framingham model for incident atrial fibrillation. The authors conclude that the increase in the AUC, integrated discrimination improvement, and net reclassification improvement offer complementary information and thus recommend reporting all 3 alongside measures characterizing the performance of the final model.
421 citations
TL;DR: This largest epidemiologic study of particulate air pollution in China suggests that short-term exposure to PM(10) is associated with increased mortality risk.
Abstract: China is one of the few countries with some of the highest particulate matter levels in the world. However, only a small number of particulate matter health studies have been conducted in China. The study objective was to examine the association of particulate matter with an aerodynamic diameter of less than 10 μm (PM(10)) with daily mortality in 16 Chinese cities between 1996 and 2008. Two-stage Bayesian hierarchical models were applied to obtain city-specific and national average estimates. Poisson regression models incorporating natural spline smoothing functions were used to adjust for long-term and seasonal trends of mortality, as well as other time-varying covariates. The averaged daily concentrations of PM(10) in the 16 Chinese cities ranged from 52 μg/m(3) to 156 μg/m(3). The 16-city combined analysis showed significant associations of PM(10) with mortality: A 10-μg/m(3) increase in 2-day moving-average PM(10) was associated with a 0.35% (95% posterior interval (PI): 0.18, 0.52) increase of total mortality, 0.44% (95% PI: 0.23, 0.64) increase of cardiovascular mortality, and 0.56% (95% PI: 0.31, 0.81) increase of respiratory mortality. Females, older people, and residents with low educational attainment appeared to be more vulnerable to PM(10) exposure. Conclusively, this largest epidemiologic study of particulate air pollution in China suggests that short-term exposure to PM(10) is associated with increased mortality risk.
356 citations
TL;DR: It is suggested that low-carbohydrate diets are at least as effective as low-fat diets at reducing weight and improving metabolic risk factors and could be recommended to obese persons with abnormal metabolicrisk factors for the purpose of weight loss.
Abstract: The effects of low-carbohydrate diets (≤45% of energy from carbohydrates) versus low-fat diets (≤30% of energy from fat) on metabolic risk factors were compared in a meta-analysis of randomized controlled trials Twenty-three trials from multiple countries with a total of 2,788 participants met the predetermined eligibility criteria (from January 1, 1966 to June 20, 2011) and were included in the analyses Data abstraction was conducted in duplicate by independent investigators Both low-carbohydrate and low-fat diets lowered weight and improved metabolic risk factors Compared with participants on low-fat diets, persons on low-carbohydrate diets experienced a slightly but statistically significantly lower reduction in total cholesterol (27 mg/dL; 95% confidence interval: 08, 46), and low density lipoprotein cholesterol (37 mg/dL; 95% confidence interval: 10, 64), but a greater increase in high density lipoprotein cholesterol (33 mg/dL; 95% confidence interval: 19, 47) and a greater decrease in triglycerides (−140 mg/dL; 95% confidence interval: −194, −87) Reductions in body weight, waist circumference and other metabolic risk factors were not significantly different between the 2 diets These findings suggest that low-carbohydrate diets are at least as effective as low-fat diets at reducing weight and improving metabolic risk factors Low-carbohydrate diets could be recommended to obese persons with abnormal metabolic risk factors for the purpose of weight loss Studies demonstrating long-term effects of low-carbohydrate diets on cardiovascular events were warranted
335 citations
TL;DR: Complete case analysis with covariate adjustment and multiple imputation yield similar estimates in the event of missing outcome data, as long as the same predictors of missingness are included, and can and should be used as the analysis of choice more often.
Abstract: Although missing outcome data are an important problem in randomized trials and observational studies, methods to address this issue can be difficult to apply. Using simulated data, the authors compared 3 methods to handle missing outcome data: 1) complete case analysis; 2) single imputation; and 3) multiple imputation (all 3 with and without covariate adjustment). Simulated scenarios focused on continuous or dichotomous missing outcome data from randomized trials or observational studies. When outcomes were missing at random, single and multiple imputations yielded unbiased estimates after covariate adjustment. Estimates obtained by complete case analysis with covariate adjustment were unbiased as well, with coverage close to 95%. When outcome data were missing not at random, all methods gave biased estimates, but handling missing outcome data by means of 1 of the 3 methods reduced bias compared with a complete case analysis without covariate adjustment. Complete case analysis with covariate adjustment and multiple imputation yield similar estimates in the event of missing outcome data, as long as the same predictors of missingness are included. Hence, complete case analysis with covariate adjustment can and should be used as the analysis of choice more often. Multiple imputation, in addition, can accommodate the missing-not-at-random scenario more flexibly, making it especially suited for sensitivity analyses.
325 citations
TL;DR: A simple procedure based on marginal structural models that directly parameterize the natural direct and indirect effects of interest is introduced and has the advantage that it can be conducted in standard software.
Abstract: An important problem within both epidemiology and many social sciences is to break down the effect of a given treatment into different causal pathways and to quantify the importance of each pathway. Formal mediation analysis based on counterfactuals is a key tool when addressing this problem. During the last decade, the theoretical framework for mediation analysis has been greatly extended to enable the use of arbitrary statistical models for outcome and mediator. However, the researcher attempting to use these techniques in practice will often find implementation a daunting task, as it tends to require special statistical programming. In this paper, the authors introduce a simple procedure based on marginal structural models that directly parameterize the natural direct and indirect effects of interest. It tends to produce more parsimonious results than current techniques, greatly simplifies testing for the presence of a direct or an indirect effect, and has the advantage that it can be conducted in standard software. However, its simplicity comes at the price of relying on correct specification of models for the distribution of mediator (and exposure) and accepting some loss of precision compared with more complex methods. Web Appendixes 1 and 2, which are posted on the Journal's Web site (http://aje.oupjournals.org/), contain implementation examples in SAS software (SAS Institute, Inc., Cary, North Carolina) and R language (R Foundation for Statistical Computing, Vienna, Austria).
323 citations
TL;DR: This article presents several methods that are useful for evaluating the validity of an MR study and applies these methods to a recent MR study that used fat mass and obesity-associated genotype as an IV to estimate the effect of obesity on mental disorder.
Abstract: As with other instrumental variable (IV) analyses, Mendelian randomization (MR) studies rest on strong assumptions. These assumptions are not routinely systematically evaluated in MR applications, although such evaluation could add to the credibility of MR analyses. In this article, the authors present several methods that are useful for evaluating the validity of an MR study. They apply these methods to a recent MR study that used fat mass and obesity-associated (FTO) genotype as an IV to estimate the effect of obesity on mental disorder. These approaches to evaluating assumptions for valid IV analyses are not fail-safe, in that there are situations where the approaches might either fail to identify a biased IV or inappropriately suggest that a valid IV is biased. Therefore, the authors describe the assumptions upon which the IV assessments rely. The methods they describe are relevant to any IV analysis, regardless of whether it is based on a genetic IV or other possible sources of exogenous variation. Methods that assess the IV assumptions are generally not conclusive, but routinely applying such methods is nonetheless likely to improve the scientific contributions of MR studies.
242 citations
TL;DR: There are independent effects of traffic-related noise and air pollution on CHD mortality, and subjects in the highest noise decile had a 22% increase inCHD mortality compared with persons in the lowest decile.
Abstract: In metropolitan areas, road traffic is a major contributor to ambient air pollution and the dominant source of community noise. The authors investigated the independent and joint influences of community noise and traffic-related air pollution on risk of coronary heart disease (CHD) mortality in a population-based cohort study with a 5-year exposure period (January 1994-December 1998) and a 4-year follow-up period (January 1999-December 2002). Individuals who were 45-85 years of age and resided in metropolitan Vancouver, Canada, during the exposure period and did not have known CHD at baseline were included (n = 445,868). Individual exposures to community noise and traffic-related air pollutants, including black carbon, particulate matter less than or equal to 2.5 μm in aerodynamic diameter, nitrogen dioxide, and nitric oxide, were estimated at each person's residence using a noise prediction model and land-use regression models, respectively. CHD deaths were identified from the provincial death registration database. After adjustment for potential confounders, including traffic-related air pollutants or noise, elevations in noise and black carbon equal to the interquartile ranges were associated with 6% (95% confidence interval: 1, 11) and 4% (95% confidence interval: 1, 8) increases, respectively, in CHD mortality. Subjects in the highest noise decile had a 22% (95% confidence interval: 4, 43) increase in CHD mortality compared with persons in the lowest decile. These findings suggest that there are independent effects of traffic-related noise and air pollution on CHD mortality.
240 citations
TL;DR: Results from prospective observational studies suggest an approximately 40% excess risk of CHD in employees working long hours in employees with a history of coronary heart disease.
Abstract: The authors aggregated the results of observational studies examining the association between long working hours and coronary heart disease (CHD). Data sources used were MEDLINE (through January 19, 2011) and Web of Science (through March 14, 2011). Two investigators independently extracted results from eligible studies. Heterogeneity between the studies was assessed using the I(2) statistic, and the possibility of publication bias was assessed using the funnel plot and Egger's test for small-study effects. Twelve studies were identified (7 case-control, 4 prospective, and 1 cross-sectional). For a total of 22,518 participants (2,313 CHD cases), the minimally adjusted relative risk of CHD for long working hours was 1.80 (95% confidence interval (CI): 1.42, 2.29), and in the maximally (multivariate-) adjusted analysis the relative risk was 1.59 (95% CI: 1.23, 2.07). The 4 prospective studies produced a relative risk of 1.39 (95% CI: 1.12, 1.72), while the corresponding relative risk in the 7 case-control studies was 2.43 (95% CI: 1.81, 3.26). Little evidence of publication bias but relatively large heterogeneity was observed. Studies varied in size, design, measurement of exposure and outcome, and adjustments. In conclusion, results from prospective observational studies suggest an approximately 40% excess risk of CHD in employees working long hours.
234 citations
TL;DR: Current use of corticosteroids was associated with an increased risk of cardiovascular events in patients with systemic lupus erythematosus, consistent with findings in several recent publications among cohorts with other diseases.
Abstract: Patients with systemic lupus erythematosus (SLE) are at excess risk of cardiovascular events (CVEs). There is uncertainty regarding the relative importance of SLE disease activity, medications, or traditional risk factors in this increased risk. To gain insight into this, the authors analyzed data from a cohort of 1,874 patients with SLE who were seen quarterly at a single clinical center (April 1987–June 2010) using pooled logistic regression analysis. In 9,485 person-years of follow-up, the authors observed 134 CVEs (rate = 14.1/1,000 person-years). This was 2.66 times what would be expected in the general population based on Framingham risk scores (95% confidence interval: 2.16, 3.16). After adjustment for age, CVE rates were not associated with duration of SLE. However, they were associated with average past levels of SLE disease activity and recent levels of circulating anti-double-stranded DNA. Past use of corticosteroids (in the absence of current use) was not associated with CVE rates. However, persons currently using 20 mg/day or more of corticosteroids had a substantial increase in risk even after adjustment for disease activity. Thus, consistent with findings in several recent publications among cohorts with other diseases, current use of corticosteroids was associated with an increased risk of CVEs. These results suggest a short-term impact of corticosteroids on CVE risk.
TL;DR: It appears that the greater the proportion of prevalent statin users in observational studies, the larger the discrepancy between observational and randomized estimates.
Abstract: Randomized clinical trials (RCTs) are usually the preferred strategy with which to generate evidence of comparative effectiveness, but conducting an RCT is not always feasible. Though observational studies and RCTs often provide comparable estimates, the questioning of observational analyses has recently intensified because of randomized-observational discrepancies regarding the effect of postmenopausal hormone replacement therapy on coronary heart disease. Reanalyses of observational data that excluded prevalent users of hormone replacement therapy led to attenuated discrepancies, which begs the question of whether exclusion of prevalent users should be generally recommended. In the current study, the authors evaluated the effect of excluding prevalent users of statins in a meta-analysis of observational studies of persons with cardiovascular disease. The pooled, multivariate-adjusted mortality hazard ratio for statin use was 0.77 (95% confidence interval (CI): 0.65, 0.91) in 4 studies that compared incident users with nonusers, 0.70 (95% CI: 0.64, 0.78) in 13 studies that compared a combination of prevalent and incident users with nonusers, and 0.54 (95% CI: 0.45, 0.66) in 13 studies that compared prevalent users with nonusers. The corresponding hazard ratio from 18 RCTs was 0.84 (95% CI: 0.77, 0.91). It appears that the greater the proportion of prevalent statin users in observational studies, the larger the discrepancy between observational and randomized estimates.
TL;DR: Analysis of longitudinal weather and influenza mortality data, observed every month between January 1973 and December 2002, for each of 359 urban US counties, indicated that absolute humidity was an especially critical determinant of observed human influenza mortality, even after controlling for temperature.
Abstract: Recent research exploring associations between environmental factors and influenza outcomes has devoted substantial attention to the role of absolute humidity. However, the existing literature provides very little quantitative epidemiologic evidence on the relations between absolute humidity and other weather variables and influenza outcomes in human populations. In the present study, the authors helped fill this gap by analyzing longitudinal weather and influenza mortality data, observed every month between January 1973 and December 2002, for each of 359 urban US counties. A flexible regression model was used to simultaneously explore fully nonlinear relations between absolute humidity and influenza outcomes and temperature and influenza outcomes. Results indicated that absolute humidity was an especially critical determinant of observed human influenza mortality, even after controlling for temperature. There were important nonlinear relations; humidity levels below approximately 6 g of water vapor per kilogram of air were associated with increases in influenza mortality. Model predictions suggested that approximately half of the average seasonal differences in US influenza mortality can be explained by seasonal differences in absolute humidity alone. Temperature modestly influenced influenza mortality as well, although results were less robust.
TL;DR: It is suggested that night work may increase cancer risk at several sites among men, with risks generally being increased across all duration categories.
Abstract: Night work might influence cancer risk, possibly via suppression of melatonin release. In a population-based case-control study conducted in Montreal, Quebec, Canada, between 1979 and 1985, job histories, including work hours, were elicited from 3,137 males with incident cancer at one of 11 anatomic sites and from 512 controls. Compared with men who never worked at night, the adjusted odds ratios among men who ever worked at night were 1.76 (95% confidence interval (CI): 1.25, 2.47) for lung cancer, 2.03 (95% CI: 1.43, 2.89) for colon cancer, 1.74 (95% CI: 1.22, 2.49) for bladder cancer, 2.77 (95% CI: 1.96, 3.92) for prostate cancer, 2.09 (95% CI: 1.40, 3.14) for rectal cancer, 2.27 (95% CI: 1.24, 4.15) for pancreatic cancer, and 2.31 (95% CI: 1.48, 3.61) for non-Hodgkin's lymphoma. Equivocal evidence or no evidence was observed for cancers of the stomach (odds ratio (OR) = 1.34, 95% CI: 0.85, 2.10), kidney (OR = 1.42, 95% CI: 0.86, 2.35), and esophagus (OR = 1.51, 95% CI: 0.80, 2.84) and for melanoma (OR = 1.04, 95% CI: 0.49, 2.22). There was no evidence of increasing risk with increasing duration of night work, with risks generally being increased across all duration categories. Results suggest that night work may increase cancer risk at several sites among men.
TL;DR: The authors combined individual-level data from 14 European cohort studies to examine the association between favorable work characteristics and leisure-time physical inactivity in a total of 170,162 employees, and suggest that unfavorable work characteristics may have a spillover effect on leisure- time physical activity.
Abstract: Unfavorable work characteristics, such as low job control and too high or too low job demands, have been suggested to increase the likelihood of physical inactivity during leisure time, but this has not been verified in large-scale studies. The authors combined individual-level data from 14 European cohort studies (baseline years from 1985-1988 to 2006-2008) to examine the association between unfavorable work characteristics and leisure-time physical inactivity in a total of 170,162 employees (50% women; mean age, 43.5 years). Of these employees, 56,735 were reexamined after 2-9 years. In cross-sectional analyses, the odds for physical inactivity were 26% higher (odds ratio = 1.26, 95% confidence interval: 1.15, 1.38) for employees with high-strain jobs (low control/high demands) and 21% higher (odds ratio = 1.21, 95% confidence interval: 1.11, 1.31) for those with passive jobs (low control/low demands) compared with employees in low-strain jobs (high control/low demands). In prospective analyses restricted to physically active participants, the odds of becoming physically inactive during follow-up were 21% and 20% higher for those with high-strain (odds ratio = 1.21, 95% confidence interval: 1.11, 1.32) and passive (odds ratio = 1.20, 95% confidence interval: 1.11, 1.30) jobs at baseline. These data suggest that unfavorable work characteristics may have a spillover effect on leisure-time physical activity.
TL;DR: It is concluded that hyperuricemia in the midtwenties is an independent marker for predicting diabetes and prediabetes among young adults in the subsequent 15 years.
Abstract: The objective of this study was to assess the utility of hyperuricemia as a marker for diabetes and prediabetes (impaired fasting glucose) and insulin resistance in young adults. Using Cox proportional hazards regression models, the authors analyzed 15-year follow-up data on 5,012 persons in 4 US cities who were aged 18-30 years and diabetes-free at the time of enrollment. At baseline (1986), 88% of participants had a body mass index (weight (kg)/height (m)(2)) less than 30. During the follow-up period (through 2001), the incidence rates of diabetes and prediabetes (insulin resistance and impaired fasting glucose) were higher among persons with greater serum urate concentrations. In multivariable Cox regression analyses that adjusted for age, gender, race, body mass index, family history of diabetes, diastolic blood pressure, total cholesterol, smoking, and alcohol use, the hazard ratios for diabetes, insulin resistance, and prediabetes among persons with hyperuricemia (serum urate level >7 mg/dL vs. ≤7.0 mg/dL) were 1.87 (95% confidence interval (CI): 1.33, 2.62), 1.36 (95% CI: 1.23, 1.51), and 1.25 (95% CI: 1.04, 1.52), respectively. This observation was generally consistent across subgroups. The authors conclude that hyperuricemia in the midtwenties is an independent marker for predicting diabetes and prediabetes among young adults in the subsequent 15 years.
TL;DR: In this article, a time-series analysis was conducted to examine seasonal variation of mortality risk in association with particulate matter less than 2.5 μm in aerodynamic diameter (PM(2.5)) and chemical species.
Abstract: The authors conducted a time-series analysis to examine seasonal variation of mortality risk in association with particulate matter less than 2.5 μm in aerodynamic diameter (PM(2.5)) and chemical species in Xi'an, China, using daily air pollution and all-cause and cause-specific mortality data (2004-2008). Poisson regression incorporating natural splines was used to estimate mortality risks of PM(2.5) and its chemical components, adjusting for day of the week, time trend, and meteorologic effects. Increases of 2.29% (95% confidence interval: 0.83, 3.76) for all-cause mortality and 3.08% (95% confidence interval: 0.94, 5.26) for cardiovascular mortality were associated with an interquartile range increase of 103.0 μg/m(3) in lagged 1-2 day PM(2.5) exposure. Stronger effects were observed for the elderly (≥65 years), males, and cardiovascular diseases groups. Secondary components (sulfate and ammonium), combustion species (elemental carbon, sulfur, chlorine), and transition metals (chromium, lead, nickel, and zinc) appeared most responsible for increased risk, particularly in the cold months. The authors concluded that differential association patterns observed across species and seasons indicated that PM(2.5)-related effects might not be sufficiently explained by PM(2.5) mass alone. Future research is needed to examine spatial and temporal varying factors that might play important roles in modifying the PM(2.5)-mortality association.
TL;DR: Higher prenatal PAH exposures were significantly associated with higher childhood body size and the data indicate that prenatal exposure to PAHs is associated with obesity in childhood.
Abstract: There are concerns that prenatal exposure to endocrine-disrupting chemicals increases children’s risk of obesity. African-American and Hispanic children born in the Bronx or Northern Manhattan, New York (1998–2006), whose mothers underwent personal air monitoring for polycyclic aromatic hydrocarbon (PAH) exposure during pregnancy, were followed up to ages 5 (n = 422) and 7 (n = 341) years. At age 5 years, 21% of the children were obese, as were 25% of those followed to age 7 years. After adjustment for child’s sex, age at measurement, ethnicity, and birth weight and maternal receipt of public assistance and prepregnancy obesity, higher prenatal PAH exposures were significantly associated with higher childhood body size. In adjusted analyses, compared with children of mothers in the lowest tertile of PAH exposure, children of mothers in the highest exposure tertile had a 0.39-unit higher body mass index z score (95% confidence interval (CI): 0.08, 0.70) and a relative risk of 1.79 (95% CI: 1.09, 2.96) for obesity at age 5 years, and they had a 0.30-unit higher body mass index z score (95% CI: 0.01, 0.59), a 1.93-unit higher percentage of body fat (95% CI: 0.33, 3.54), and a relative risk of 2.26 (95% CI: 1.28, 4.00) for obesity at age 7 years. The data indicate that prenatal exposure to PAHs is associated with obesity in childhood.
TL;DR: It is shown that WHtR has a modestly but statistically greater importance than BMI and WHR in prediction of diabetes, and measuring height in addition to WC appeared to have no additional benefit.
Abstract: The aim of this meta-analysis was to compare the association of waist-to-height ratio (WHtR) with risk of incident diabetes with the associations of 3 other conventional obesity indicators (body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR)) with risk of incident diabetes. Literature searches in MEDLINE (January 1950 to April 27, 2011) and EMBASE (January 1974 to April 27, 2011) were conducted for prospective studies that made it possible to estimate the relative risk of diabetes per 1-standard deviation increase in WHtR, in addition to the RR of BMI, WC, or WHR. Strength of the estimated pooled relative risk for a 1-standard deviation increase of each indicator (expressed as RR(WHtR), RR(BMI), RR(WC), and RR(WHR)) was compared with a bivariate random-effects model. Pooled relative risks of the 15 eligible studies with 6,472 diabetes cases were 1.62 (95% CI: 1.48, 1.78) for RR(WHtR), 1.55 (95% CI: 1.43, 1.69) for RR(BMI), 1.63 (95% CI: 1.49, 1.79) for RR(WC), and 1.52 (95% CI: 1.40, 1.66) for RR(WHR). WHtR had an association stronger than that of BMI (P<0.001) or WHR (P<0.001). The present meta-analysis showed that WHtR has a modestly but statistically greater importance than BMI and WHR in prediction of diabetes. Nevertheless, measuring height in addition to WC appeared to have no additional benefit.
TL;DR: Both prevalent and incident self-reported diabetes were 84%-97% specific and 55%-80% sensitive as compared with reference definitions using glucose and medication criteria as well as self- reported diabetes was >92% reliable over time.
Abstract: The objective of this study was to assess the validity of prevalent and incident self-reported diabetes compared with multiple reference definitions and to assess the reliability (repeatability) of a self-reported diagnosis of diabetes. Data from 10,321 participants in the Atherosclerosis Risk in Communities (ARIC) Study who attended visit 4 (1996-1998) were analyzed. Prevalent self-reported diabetes was compared with reference definitions defined by fasting glucose and medication use obtained at visit 4. Incident self-reported diabetes was assessed during annual follow-up telephone calls and was compared with reference definitions defined by fasting glucose, hemoglobin A1c, and medication use obtained during an in-person visit attended by a subsample of participants (n = 1,738) in 2004-2005. The sensitivity of prevalent self-reported diabetes ranged from 58.5% to 70.8%, and specificity ranged from 95.6% to 96.8%, depending on the reference definition. Similarly, the sensitivity of incident self-reported diabetes ranged from 55.9% to 80.4%, and specificity ranged from 84.5% to 90.6%. Percent positive agreement of self-reported diabetes during 9 years of repeat assessments ranged from 92.7% to 95.4%. Both prevalent self-reported diabetes and incident self-reported diabetes were 84%-97% specific and 55%-80% sensitive as compared with reference definitions using glucose and medication criteria. Self-reported diabetes was >92% reliable over time.
TL;DR: The authors found that 4-6 administrations of the 24HR is optimal for most nutrients and food groups and that combined use of multiple 24HR and FFQ data sometimes provides data superior to use of either method alone, especially for foods that are not regularly consumed.
Abstract: With the advent of Internet-based 24-hour recall (24HR) instruments, it is now possible to envision their use in cohort studies investigating the relation between nutrition and disease. Understanding that all dietary assessment instruments are subject to measurement errors and correcting for them under the assumption that the 24HR is unbiased for usual intake, here the authors simultaneously address precision, power, and sample size under the following 3 conditions: 1) 1-12 24HRs; 2) a single calibrated food frequency questionnaire (FFQ); and 3) a combination of 24HR and FFQ data. Using data from the Eating at America's Table Study (1997-1998), the authors found that 4-6 administrations of the 24HR is optimal for most nutrients and food groups and that combined use of multiple 24HR and FFQ data sometimes provides data superior to use of either method alone, especially for foods that are not regularly consumed. For all food groups but the most rarely consumed, use of 2-4 recalls alone, with or without additional FFQ data, was superior to use of FFQ data alone. Thus, if self-administered automated 24HRs are to be used in cohort studies, 4-6 administrations of the 24HR should be considered along with administration of an FFQ.
TL;DR: In men, social isolation is not only an important risk factor for mortality but is also likely to contribute to differences in mortality by SES, according to analysis of data from the British Whitehall II Study cohort.
Abstract: The authors examined the associations of social support with socioeconomic status (SES) and with mortality, as well as how SES differences in social support might account for SES differences in mortality. Analyses were based on 9,333 participants from the British Whitehall II Study cohort, a longitudinal cohort established in 1985 among London-based civil servants who were 35-55 years of age at baseline. SES was assessed using participant's employment grades at baseline. Social support was assessed 3 times in the 24.4-year period during which participants were monitored for death. In men, marital status, and to a lesser extent network score (but not low perceived support or high negative aspects of close relationships), predicted both all-cause and cardiovascular mortality. Measures of social support were not associated with cancer mortality. Men in the lowest SES category had an increased risk of death compared with those in the highest category (for all-cause mortality, hazard ratio = 1.59, 95% confidence interval: 1.21, 2.08; for cardiovascular mortality, hazard ratio = 2.48, 95% confidence interval: 1.55, 3.92). Network score and marital status combined explained 27% (95% confidence interval: 14, 43) and 29% (95% confidence interval: 17, 52) of the associations between SES and all-cause and cardiovascular mortality, respectively. In women, there was no consistent association between social support indicators and mortality. The present study suggests that in men, social isolation is not only an important risk factor for mortality but is also likely to contribute to differences in mortality by SES.
TL;DR: Using data on 18 constituents and data from 1,060 patients admitted to a Boston medical center with ischemic stroke in 2003-2008, the authors illustrate several options for modeling the association between constituents and health outcomes that account for the impact of PM2.5.
Abstract: There is increasing interest in evaluating the association between specific fine-particle (particles with aerodynamic diameters less than 2.5 µm; PM2.5) constituents and adverse health outcomes rather than focusing solely on the impact of total PM2.5. Because PM2.5 may be related to both constituent concentration and health outcomes, constituents that are more strongly correlated with PM2.5 may appear more closely related to adverse health outcomes than other constituents even if they are not inherently more toxic. Therefore, it is important to properly account for potential confounding by PM2.5 in these analyses. Usually, confounding is due to a factor that is distinct from the exposure and outcome. However, because constituents are a component of PM2.5, standard covariate adjustment is not appropriate. Similar considerations apply to source-apportioned concentrations and studies assessing either short-term or long-term impacts of constituents. Using data on 18 constituents and data from 1,060 patients admitted to a Boston medical center with ischemic stroke in 2003–2008, the authors illustrate several options for modeling the association between constituents and health outcomes that account for the impact of PM2.5. Although the different methods yield results with different interpretations, the relative rankings of the association between constituents and ischemic stroke were fairly consistent across models.
University of Toronto1, University of Göttingen2, International Agency for Research on Cancer3, Pennsylvania State University4, Mayo Clinic5, Wayne State University6, University of Hawaii at Manoa7, University of California, Los Angeles8, University of Michigan9, Nofer Institute of Occupational Medicine10, Russian Academy11, Palacký University, Olomouc12, Charles University in Prague13, Carol Davila University of Medicine and Pharmacy14, University of Liverpool15, Princess Margaret Cancer Centre16, University of California, San Francisco17, University of Genoa18, Dartmouth College19, National Institutes of Health20, Memorial Sloan Kettering Cancer Center21
TL;DR: It is suggested that previous lung diseases influence lung cancer risk independently of tobacco use and that these diseases are important for assessing individual risk.
Abstract: To clarify the role of previous lung diseases (chronic bronchitis, emphysema, pneumonia, and tuberculosis) in the development of lung cancer, the authors conducted a pooled analysis of studies in the International Lung Cancer Consortium. Seventeen studies including 24,607 cases and 81,829 controls (noncases), mainly conducted in Europe and North America, were included (1984–2011). Using self-reported data on previous diagnoses of lung diseases, the authors derived study-specific effect estimates by means of logistic regression models or Cox proportional hazards models adjusted for age, sex, and cumulative tobacco smoking. Estimates were pooled using random-effects models. Analyses stratified by smoking status and histology were also conducted. A history of emphysema conferred a 2.44-fold increased risk of lung cancer (95% confidence interval (CI): 1.64, 3.62 (16 studies)). A history of chronic bronchitis conferred a relative risk of 1.47 (95% CI: 1.29, 1.68 (13 studies)). Tuberculosis (relative risk = 1.48, 95% CI: 1.17, 1.87 (16 studies)) and pneumonia (relative risk = 1.57, 95% CI: 1.22, 2.01 (12 studies)) were also associated with lung cancer risk. Among never smokers, elevated risks were observed for emphysema, pneumonia, and tuberculosis. These results suggest that previous lung diseases influence lung cancer risk independently of tobacco use and that these diseases are important for assessing individual risk.
TL;DR: Repeated use of antibiotics may reflect shared susceptibility to childhood infections and pediatric Crohn's disease or alternatively may trigger disease development.
Abstract: To determine whether childhood exposure to antibiotics is associated with the risk of developing inflammatory bowel disease (IBD), the authors conducted a national, register-based study comprising all children born in 1994-2008 in Finland and diagnosed with IBD by October 2010. The authors identified 595 children with IBD (233 with Crohn's disease and 362 with ulcerative colitis) and 2,380 controls matched for age, gender, and place of residence. The risk of pediatric Crohn's disease increased with the number of antibiotic purchases from birth to the index date and persisted when the 6 months preceding the case's diagnosis were excluded (for 7-10 purchases vs. none, odds ratio = 3.48, 95% confidence interval: 1.57, 7.34; conditional logistic regression). The association between Crohn's disease and antibiotic use was stronger in boys than in girls (P = 0.01). Cephalosporins showed the strongest association with Crohn's disease (for 3 purchases vs. nonuse, odds ratio = 2.82, 95% confidence interval: 1.65, 4.81). Antibiotic exposure was not associated with the development of pediatric ulcerative colitis. Repeated use of antibiotics may reflect shared susceptibility to childhood infections and pediatric Crohn's disease or alternatively may trigger disease development.
TL;DR: In conclusion, asthma was prospectively associated with increased risk of major CVD and modifying effects were noted for sex and asthma medication use but not for comorbid allergy.
Abstract: Asthma has been associated with increased cardiovascular disease (CVD) risk. The authors ascertained the association of asthma with CVD and the roles that sex, concurrent allergy, and asthma medications may play in this association. They assembled a cohort of 203,595 Northern California adults with asthma and a parallel asthma-free referent cohort (matched 1:1 on age, sex, and race/ethnicity); both cohorts were followed for incident nonfatal or fatal CVD and all-cause mortality from January 1, 1996, through December 31, 2008. Each cohort was 66% female and 47% white. After adjustment for age, sex, race/ethnicity, cardiac risk factors, and comorbid allergy, asthma was associated with a 1.40-fold (95% confidence interval (CI): 1.35, 1.45) increased hazard of coronary heart disease, a 1.20-fold (95% CI: 1.15, 1.25) hazard of cerebrovascular disease, a 2.14-fold (95% CI: 2.06, 2.22) hazard of heart failure, and a 3.28-fold (95% CI: 3.15, 3.41) hazard of all-cause mortality. Stronger associations were noted among women. Comorbid allergy predicted CVD but did not synergistically increase the CVD risk associated with asthma. Only asthma patients using asthma medications (particularly those on oral corticosteroids alone or in combination) were at enhanced risk of CVD. In conclusion, asthma was prospectively associated with increased risk of major CVD. Modifying effects were noted for sex and asthma medication use but not for comorbid allergy.
TL;DR: Findings suggest that associations between maternal smoking during pregnancy and child ADHD may be due to genetic or household-level confounding rather than to causal intrauterine effects.
Abstract: Maternal smoking during pregnancy is associated with attention deficit hyperactivity disorder (ADHD) in offspring. It is assumed by many that this association is causal. Others suggest that observed associations are due to unmeasured genetic factors or other confounding factors. The authors compared risks of maternal smoking during pregnancy with those of paternal smoking during pregnancy. With a causal intrauterine effect, no independent association should be observed between paternal smoking and offspring ADHD. If the association is due to confounding factors, risks of offspring ADHD should be of similar magnitudes regardless of which parent smokes. This hypothesis was tested in 8,324 children from a well-characterized United Kingdom prospective cohort study, the Avon Longitudinal Study of Parents and Children (data from 1991–2000). Associations between offspring ADHD and maternal and paternal smoking during pregnancy were compared using regression analyses. Offspring ADHD symptoms were associated with exposure to both maternal and paternal smoking during pregnancy (mothers: β = 0.25, 95% confidence interval: 0.18, 0.32; fathers: β = 0.21, 95% confidence interval: 0.15, 0.27). When paternal smoking was examined in the absence of maternal smoking, associations remained and did not appear to be due to passive smoking exposure in utero. These findings suggest that associations between maternal smoking during pregnancy and child ADHD may be due to genetic or household-level confounding rather than to causal intrauterine effects.
TL;DR: Investigation of the association of the traditional Mediterranean diet and major food groups with incidence of and mortality from cerebrovascular disease in a Mediterranean population provided support for an inverse association of adherence to the Mediterranean diet with CBVD incidence and mortality.
Abstract: The authors aimed to evaluate the association of the traditional Mediterranean diet and major food groups with incidence of and mortality from cerebrovascular disease (CBVD) in a Mediterranean population. The study population was a cohort of 23,601 participants from the Greek segment of the EPIC Study (European Prospective Investigation into Cancer and Nutrition) who were free of cardiovascular diseases and cancer at baseline (1994-1999). Diet was assessed by means of a validated food frequency questionnaire. A 10-point scale integrating key Mediterranean diet characteristics was used to assess the participants' degree of adherence to this diet. During a median follow-up period of 10.6 years (1994-2009), 395 confirmed incident cases and 196 deaths from CBVD were recorded. Using Cox proportional hazards regression and adjusting for potential confounders, increased adherence to the Mediterranean diet, as measured by 2-point increments in score, was inversely associated with CBVD incidence (adjusted hazard ratio = 0.85, 95% confidence interval: 0.74, 0.96) and mortality (adjusted hazard ratio = 0.88, 95% CI: 0.73, 1.06). These inverse trends were mostly evident among women and with respect to ischemic rather than hemorrhagic CBVD and were largely driven by consumption of vegetables, legumes, and olive oil. These data provide support for an inverse association of adherence to the Mediterranean diet with CBVD incidence and mortality.
TL;DR: It is suggested that even moderate amounts of activity may be associated with longer telomeres, warranting further investigation in large prospective studies.
Abstract: Leukocyte telomere length (LTL) is a potential indicator of cellular aging; however, its relation to physical activity and sedentary behavior is unclear. The authors examined cross-sectionally associations among activity, sedentary behavior, and LTL among 7,813 women aged 43-70 years in the Nurses' Health Study. Participants self-reported activity by questionnaire in 1988 and 1992 and sedentary behavior in 1992. Telomere length in peripheral blood leukocytes, collected in 1989-1990, was measured by quantitative polymerase chain reaction. The least-squares mean telomere length (z-score) was calculated after adjustment for age and other potential confounders. For total activity, moderately or highly active women had a 0.07-standard deviation (SD) increase in LTL (2-sided P(trend) = 0.02) compared with those least active. Greater moderate- or vigorous-intensity activity was also associated with increased LTL (SD = 0.11 for 2-4 vs. <1 hour/week and 0.04 for ≥7 vs. <1 hour/week; 2-sided P(trend) = 0.02). Specifically, calisthenics or aerobics was associated with increased LTL (SD = 0.10 for ≥2.5 vs. 0 hours/week; 2-sided P(trend) = 0.04). Associations remained after adjustment for body mass index. Other specific activities and sitting were unassociated with LTL. Although associations were modest, these findings suggest that even moderate amounts of activity may be associated with longer telomeres, warranting further investigation in large prospective studies.
TL;DR: Risk of hospitalization for influenza or pneumonia was 25% lower for ATIV relative to TIV, and ATIV is likely to be even more protective than this result suggests.
Abstract: Although vaccination against influenza is recommended for elderly and high-risk patients in many countries, efficacy in the elderly has been suboptimal. The MF59 adjuvanted trivalent inactivated vaccine (ATIV) was developed to increase the immune response of elderly subjects to influenza vaccination, but its effectiveness has not yet been well documented. This prospective, observational study evaluated the relative effectiveness of ATIV versus nonadjuvanted trivalent inactivated vaccine (TIV) in individuals at least 65 years of age in Lombardy, northern Italy. Hospitalizations for influenza or pneumonia (International Classification of Diseases, Ninth Revision, Clinical Modification, codes 480-487) during the 2006-2007, 2007-2008, and 2008-2009 influenza seasons were identified from administrative databases. Stratified and regression analyses, including the propensity score to adjust for confounding, as well as generalized estimating equations to account for repeated vaccination, were used. Overall, 107,661 records were evaluated, contributing 170,988 person-seasons of observation. Since ATIV is preferentially recommended for more frail individuals, subjects vaccinated with ATIV were older and had more functional impairment and comorbidities. In the primary analysis, risk of hospitalization for influenza or pneumonia was 25% lower for ATIV relative to TIV (relative risk = 0.75, 95% confidence interval: 0.57, 0.98). To the extent that there is residual bias, ATIV is likely to be even more protective than this result suggests.