American Journal of Epidemiology - recent issues

Fri, 30 Oct 2009 15:14:56 PDT

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Fri, 30 Oct 2009 15:14:56 PDT

Editorial Board

Fri, 30 Oct 2009 15:14:56 PDT

Cover

Fri, 30 Oct 2009 15:14:56 PDT

Towards Reducing Disparities in Disparities Research

Rowland Hogue, C. J. — Fri, 30 Oct 2009 15:14:57 PDT

Discovery Properties of Genome-wide Association Signals From Cumulatively Combined Data Sets

Pereira, T. V., Patsopoulos, N. A., Salanti, G., Ioannidis, J. P. A. — Fri, 30 Oct 2009 15:14:57 PDT

Genetic effects for common variants affecting complex disease risk are subtle. Single genome-wide association (GWA) studies are typically underpowered to detect these effects, and combination of several GWA data sets is needed to enhance discovery. The authors investigated the properties of the discovery process in simulated cumulative meta-analyses of GWA study-derived signals allowing for potential genetic model misspecification and between-study heterogeneity. Variants with null effects on average (but also between-data set heterogeneity) could yield false-positive associations with seemingly homogeneous effects. Random effects had higher than appropriate false-positive rates when there were few data sets. The log-additive model had the lowest false-positive rate. Under heterogeneity, random-effects meta-analyses of 2–10 data sets averaging 1,000 cases/1,000 controls each did not increase power, or the meta-analysis was even less powerful than a single study (power desert). Upward bias in effect estimates and underestimation of between-study heterogeneity were common. Fixed-effects calculations avoided power deserts and maximized discovery of association signals at the expense of much higher false-positive rates. Therefore, random- and fixed-effects models are preferable for different purposes (fixed effects for initial screenings, random effects for generalizability applications). These results may have broader implications for the design and interpretation of large-scale multiteam collaborative studies discovering common gene variants.

Meta- and Pooled Analyses of the Methylenetetrahydrofolate Reductase (MTHFR) C677T Polymorphism and Colorectal Cancer: A HuGE-GSEC Review

Fri, 30 Oct 2009 15:14:57 PDT

Worldwide, over 1 million cases of colorectal cancer (CRC) were reported in 2002, with a 50% mortality rate, making CRC the second most common cancer in adults. Certain racial/ethnic populations continue to experience a disproportionate burden of CRC. A common polymorphism in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene has been associated with a lower risk of CRC. The authors performed both a meta-analysis (29 studies; 11,936 cases, 18,714 controls) and a pooled analysis (14 studies; 5,068 cases, 7,876 controls) of the C677T MTHFR polymorphism and CRC, with stratification by racial/ethnic population and behavioral risk factors. There were few studies on different racial/ethnic populations. The overall meta-analysis odds ratio for CRC for persons with the TT genotype was 0.83 (95% confidence interval (CI): 0.77, 0.90). An inverse association was observed in whites (odds ratio = 0.83, 95% CI: 0.74, 0.94) and Asians (odds ratio = 0.80, 95% CI: 0.67, 0.96) but not in Latinos or blacks. Similar results were observed for Asians, Latinos, and blacks in the pooled analysis. The inverse association between the MTHFR 677TT polymorphism and CRC was not significantly modified by smoking status or body mass index; however, it was present in regular alcohol users only. The MTHFR 677TT polymorphism seems to be associated with a reduced risk of CRC, but this may not hold true for all populations.

Genetic Variations in Xenobiotic Metabolic Pathway Genes, Personal Hair Dye Use, and Risk of Non-Hodgkin Lymphoma

Fri, 30 Oct 2009 15:14:57 PDT

From 1996 to 2000, the authors conducted a population-based case-control study among Connecticut women to test the hypothesis that genetic variation in xenobiotic metabolic pathway genes modifies the relation between hair dye use and risk of non-Hodgkin lymphoma. No effect modifications were found for women who started using hair dyes in 1980 or afterward. For women who started using hair dye before 1980 as compared with never users, a statistically significantly increased risk of non-Hodgkin lymphoma was found for carriers of CYP2C9 Ex3-52C>T TT/CT genotypes (odds ratio (OR) = 2.9, 95% confidence interval (CI): 1.4, 6.1), CYP2E1 -332T>A AT/AA genotypes (OR = 2.0, 95% CI: 1.2, 3.4), a homozygous or heterozygous 3-base-pair deletion in intron 6 of GSTM3 (OR = 2.3, 95% CI: 1.3, 4.1), GSTP1 Ex5-24A>G AA genotypes (OR = 1.8, 95% CI: 1.1, 2.9), or NAT2 genotypes conferring intermediate/rapid acetylator status (OR = 1.6, 95% CI: 1.0, 2.7). The observed associations were mainly seen for follicular lymphoma. In contrast, no significantly increased risk was observed for starting hair dye use before 1980 (relative to never use) among women who were homozygous wild-type for the CYP2C9, CYP2E1, or GSTM3 polymorphisms, women carrying 1 or 2 copies of the variant GSTP1 allele, or women who were slow NAT2 acetylators. A possible role of genetic variation in xenobiotic metabolism in the carcinogenicity of hair dye use needs to be confirmed in larger studies.

Body Size, Recreational Physical Activity, and B-Cell Non-Hodgkin Lymphoma Risk Among Women in the California Teachers Study

Fri, 30 Oct 2009 15:14:57 PDT

Nutritional status and physical activity are known to alter immune function, which may be relevant to lymphomagenesis. The authors examined body size measurements and recreational physical activity in relation to risk of B-cell non-Hodgkin lymphoma (NHL) in the prospective California Teachers Study. Between 1995 and 2007, 574 women were diagnosed with incident B-cell NHL among 121,216 eligible women aged 22–84 years at cohort entry. Multivariable-adjusted relative risks and 95% confidence intervals were estimated by fitting Cox proportional hazards models for all B-cell NHL combined and for the 3 most common subtypes: diffuse large B-cell lymphoma, follicular lymphoma, and B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma. Height was positively associated with risk of all B-cell NHLs (for >1.70 vs. 1.61–1.65 m, relative risk = 1.50, 95% confidence interval: 1.16, 1.96) and chronic lymphocytic leukemia/small lymphocytic lymphoma (relative risk = 1.93, 95% confidence interval: 1.09, 3.41). Weight and body mass index at age 18 years were positive predictors of B-cell NHL risk overall. These findings indicate that greater height, which may reflect genetics, early life immune function, infectious exposures, nutrition, or growth hormone levels, may play a role in NHL etiology. Adiposity at age 18 years may be more relevant to NHL etiology than that in later life.

Genetic Variation in the Progesterone Receptor and Metabolism Pathways and Hormone Therapy in Relation to Breast Cancer Risk

Fri, 30 Oct 2009 15:14:57 PDT

The relevance of progesterone to breast carcinogenesis is highlighted by evidence indicating that use of combined estrogen-progesterone therapy (EPT) is more strongly related to breast cancer risk than is use of unopposed estrogen therapy. However, few investigators have assessed how genetic variation in progesterone-related genes modifies the effect of EPT on risk. In an analysis combining data from 2 population-based case-control studies of postmenopausal breast cancer (1,296 cases and 1,055 controls) conducted in Washington State in 1997–1999 and 2000–2004, the authors evaluated how 51 single nucleotide polymorphisms in 7 progesterone-related genes (AKR1C1, AKR1C2, AKR1C3, CYP3A4, SRD5A1, SRD5A2, and PGR) influenced breast cancer risk. There was no appreciable association with breast cancer risk overall for any single nucleotide polymorphism. For rs2854482 in AKR1C2, carrying 1 or 2 A alleles was associated with a 2.0-fold increased breast cancer risk in EPT users (95% confidence interval: 1.0, 4.0) but not in never users (P_{heterogeneity} = 0.03). For rs12387 in AKR1C3, the presence of 1 or 2 G alleles was associated with a 1.5-fold increased risk among EPT users (95% confidence interval: 1.1, 2.2) but not in never users (P_{heterogeneity} = 0.02). Interpretation of these subgroup associations must await the results of similar studies conducted in other populations.

Physical Activity's Impact on the Association of Fat and Fiber Intake With Survival After Breast Cancer

Holmes, M. D., Chen, W. Y., Hankinson, S. E., Willett, W. C. — Fri, 30 Oct 2009 15:14:57 PDT

This study examined whether, after a breast cancer diagnosis, high intake of animal fat was associated with increased breast cancer mortality and high intake of fiber was associated with decreased breast cancer mortality. Participants were 3,846 US female nurses diagnosed with stages I–III breast cancer between 1976 and 2001 and followed until death or May 2006. Breast cancer mortality was calculated according to dietary intake quintiles first assessed at least 12 months after diagnosis and was cumulatively averaged and updated. There were 446 breast cancer deaths. In simple models adjusted for time since diagnosis, age, and energy intake, animal fat intake was associated with increased breast cancer death, and cereal fiber intake was associated with reduced breast cancer death. However, no associations were found in fully adjusted models: for animal fat, the relative risks for increasing quintiles were 1.00, 0.89, 0.86, 0.85, and 0.89 (95% confidence interval: 0.61, 1.28), P = 0.68; for cereal fiber, they were 1.00, 0.95, 0.76, 0.81, and 1.00 (95% confidence interval: 0.71, 1.40), P = 0.59. Results of simple models adjusted additionally for physical activity were similar to those for full multivariate models. Results show that physical activity strongly confounds the association between diet and survival.

Postmenopausal Breast Cancer Risk and Dietary Patterns in the E3N-EPIC Prospective Cohort Study

Fri, 30 Oct 2009 15:14:57 PDT

Since evidence relating diet to breast cancer risk is not sufficiently consistent to elaborate preventive proposals, the authors examined the association between dietary patterns and breast cancer risk in a large French cohort study. The analyses included 2,381 postmenopausal invasive breast cancer cases diagnosed during a median 9.7-year follow-up period (1993–2005) among 65,374 women from the E3N-EPIC cohort. Scores for dietary patterns were obtained by factor analysis, and breast cancer hazard ratios were estimated by Cox proportional hazards regression for the highest quartile of dietary pattern score versus the lowest. Two dietary patterns were identified: "alcohol/Western" (essentially meat products, French fries, appetizers, rice/pasta, potatoes, pulses, pizza/pies, canned fish, eggs, alcoholic beverages, cakes, mayonnaise, and butter/cream) and "healthy/Mediterranean" (essentially vegetables, fruits, seafood, olive oil, and sunflower oil). The first pattern was positively associated with breast cancer risk (hazard ratio = 1.20, 95% confidence interval (CI): 1.03, 1.38; P = 0.007 for linear trend), especially when tumors were estrogen receptor-positive/progesterone receptor-positive. The "healthy/Mediterranean" pattern was negatively associated with breast cancer risk (hazard ratio = 0.85, 95% CI: 0.75, 0.95; P = 0.003 for linear trend), especially when tumors were estrogen receptor-positive/progesterone receptor-negative. Adherence to a diet comprising mostly fruits, vegetables, fish, and olive/sunflower oil, along with avoidance of Western-type foods, may contribute to a substantial reduction in postmenopausal breast cancer risk.

Association of Perfluorooctanoic Acid and Perfluorooctane Sulfonate With Serum Lipids Among Adults Living Near a Chemical Plant

Steenland, K., Tinker, S., Frisbee, S., Ducatman, A., Vaccarino, V. — Fri, 30 Oct 2009 15:14:57 PDT

Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are compounds that do not occur in nature but have been widely used since World War II and persist indefinitely in the environment. They are present in the serum of Americans with median levels of 4 ng/mL and 21 ng/mL, respectively. PFOA has been positively associated with cholesterol in several studies of workers. A cross-sectional study of lipids and PFOA and PFOS was conducted among 46,294 community residents aged 18 years or above, who drank water contaminated with PFOA from a chemical plant in West Virginia. The mean levels of serum PFOA and PFOS in 2005–2006 were 80 ng/mL (median, 27 ng/mL) and 22 ng/mL (median, 20 ng/mL), respectively. All lipid outcomes except high density lipoprotein cholesterol showed significant increasing trends by increasing decile of either compound; high density lipoprotein cholesterol showed no association. The predicted increase in cholesterol from lowest to highest decile for either compound was 11–12 mg/dL. The odds ratios for high cholesterol (≥240 mg/dL), by increasing quartile of PFOA, were 1.00, 1.21 (95% confidence interval (CI): 1.12, 1.31), 1.33 (95% CI: 1.23, 1.43), and 1.40 (95% CI: 1.29, 1.51) and were similar for PFOS quartiles. Because these data are cross-sectional, causal inference is limited. Nonetheless, the associations between these compounds and lipids raise concerns, given their common presence in the general population.

Correlates of Multiple Chronic Disease Behavioral Risk Factors in Canadian Children and Adolescents

Alamian, A., Paradis, G. — Fri, 30 Oct 2009 15:14:57 PDT

The authors assessed individual, social, and school correlates of multiple chronic disease behavioral risk factors (physical inactivity, sedentary behavior, tobacco smoking, alcohol drinking, and high body mass index) in a representative sample of Canadian youth aged 10–15 years (mean = 12.5 years) attending public schools. Cross-sectional data (n = 1,747) from cycle 4 (2000–2001) of the National Longitudinal Survey of Children and Youth were used. Ordinal regression models were constructed to investigate associations between selected covariates and multiple behavioral risk-factor levels (0/1, 2, 3, or 4/5 risk factors). Older age (odds ratio (OR) = 1.95, 95% confidence interval (CI): 1.21, 3.13), caregiver smoking (OR = 1.49, 95% CI: 1.09, 2.03), reporting that most/all of one's peers smoked (OR = 7.31, 95% CI: 4.00, 13.35) or drank alcohol (OR = 3.77, 95% CI: 2.18, 6.53), and living in a lone-parent family (OR = 1.94, 95% CI: 1.31, 2.88) increased the likelihood of having multiple behavioral risk factors. Youth with high self-esteem (OR = 0.92, 95% CI: 0.85, 0.99) and youth from families with postsecondary education (OR = 0.58, 95% CI: 0.41, 0.82) were less likely to have a higher number of risk factors. Although several individual and social characteristics were associated with multiple behavioral risk factors, no school-related correlates emerged. These variables should be considered when planning prevention programs.

The Aftermath of Hip Fracture: Discharge Placement, Functional Status Change, and Mortality

Fri, 30 Oct 2009 15:14:57 PDT

The authors prospectively explored the consequences of hip fracture with regard to discharge placement, functional status, and mortality using the Survey on Assets and Health Dynamics Among the Oldest Old (AHEAD). Data from baseline (1993) AHEAD interviews and biennial follow-up interviews were linked to Medicare claims data from 1993–2005. There were 495 postbaseline hip fractures among 5,511 respondents aged ≥69 years. Mean age at hip fracture was 85 years; 73% of fracture patients were white women, 45% had pertrochanteric fractures, and 55% underwent surgical pinning. Most patients (58%) were discharged to a nursing facility, with 14% being discharged to their homes. In-hospital, 6-month, and 1-year mortality were 2.7%, 19%, and 26%, respectively. Declines in functional-status-scale scores ranged from 29% on the fine motor skills scale to 56% on the mobility index. Mean scale score declines were 1.9 for activities of daily living, 1.7 for instrumental activities of daily living, and 2.2 for depressive symptoms; scores on mobility, large muscle, gross motor, and cognitive status scales worsened by 2.3, 1.6, 2.2, and 2.5 points, respectively. Hip fracture characteristics, socioeconomic status, and year of fracture were significantly associated with discharge placement. Sex, age, dementia, and frailty were significantly associated with mortality. This is one of the few studies to prospectively capture these declines in functional status after hip fracture.

Optimizing Influenza Sentinel Surveillance at the State Level

Fri, 30 Oct 2009 15:14:57 PDT

Influenza-like illness data are collected via an Influenza Sentinel Provider Surveillance Network at the state level. Because participation is voluntary, locations of the sentinel providers may not reflect optimal geographic placement. The purpose of this study was to determine the "best" locations for sentinel providers in Iowa by using a maximal coverage model (MCM) and to compare the population coverage obtained with that of the current sentinel network. The authors used an MCM to maximize the Iowa population located within 20 miles (32.2 km) of 1–143 candidate sites and calculated the coverage provided by each additional site. The first MCM location covered 15% of the population; adding a second increased coverage to 25%. Additional locations provided more coverage but with diminishing marginal returns. In contrast, the existing 22 Iowa sentinel locations covered 56% of the population, the same coverage achieved with just 10 MCM sites. Using 22 MCM sites covered more than 75% of the population, an improvement over the current site placement, adding nearly 600,000 Iowa residents. Given scarce public health resources, MCMs can help surveillance efforts by prioritizing recruitment of sentinel locations.

Analyses of Injury Count Data: Some Do's and Don'ts

Shrier, I., Steele, R. J., Hanley, J., Rich, B. — Fri, 30 Oct 2009 15:14:57 PDT

The analysis of injury data requires different considerations from the analysis of other types of outcomes because an individual can experience the outcome many times. When describing injury patterns using numerator-only data (e.g., proportion of upper-extremity injuries vs. lower-extremity injuries), simple comparisons of proportions are inappropriate because 1) individuals are compared with themselves and 2) multiple testing increases the potential for incorrect inference. Bootstrapping (resampling) techniques can be used to determine confidence intervals and whether the frequencies significantly differ across categories. When describing injury rates, the authors suggest plotting the observed injury rate against the number of exposures to obtain a visual representation of the heterogeneity of risk across individuals. Because the distribution of injury rates is often skewed, some research questions may be best addressed by comparing the weighted median injury rates instead of the weighted mean injury rates (which are given by standard formulae). Again, resampling techniques can be used to obtain a null distribution for injury rates in order to determine whether there are subjects who have unexpectedly high injury rates. More advanced analyses are required to account for multiplicity.

Applying Quantitative Bias Analysis to Epidemiologic Data: By Timothy L. Lash, Matthew P. Fox, and Aliza K. Fink

Howe, C. J., Cole, S. R. — Fri, 30 Oct 2009 15:14:57 PDT

Statistical Modeling for Biomedical Researchers: A Simple Introduction to the Analysis of Complex Data, 2nd Edition: By William D. Dupont

Azen, S. P. — Fri, 30 Oct 2009 15:14:57 PDT

Re: "Determinants of Quality of Interview and Impact on Risk Estimates in a Case-Control Study of Bladder Cancer"

Eluf-Neto, J. — Fri, 30 Oct 2009 15:14:57 PDT

Three Authors Reply

Villanueva, C. M., Silverman, D. T., Kogevinas, M. — Fri, 30 Oct 2009 15:14:57 PDT

Re: "Methods of Covariate Selection: Directed Acyclic Graphs and the Change-in-Estimate Procedure"

Nie, L. — Fri, 30 Oct 2009 15:14:57 PDT

Three of the Authors Reply

Weng, H.-Y., Messam, L. L. McV., Hertz-Picciotto, I. — Fri, 30 Oct 2009 15:14:57 PDT

Cover

Thu, 15 Oct 2009 04:46:59 PDT

Editorial Board

Thu, 15 Oct 2009 04:46:59 PDT

Subscriptions

Thu, 15 Oct 2009 04:46:59 PDT

Editorial: Breathing New Life Into Pneumonia Epidemiology

Levine, O. S., Klugman, K. P. — Thu, 15 Oct 2009 04:46:59 PDT

Socioeconomic Position and the Tracking of Physical Activity and Cardiorespiratory Fitness From Childhood to Adulthood

Cleland, V. J., Ball, K., Magnussen, C., Dwyer, T., Venn, A. — Thu, 15 Oct 2009 04:46:59 PDT

This study examined the influence of childhood socioeconomic position (SEP) and social mobility on activity and fitness tracking from childhood into adulthood. In a prospective cohort of 2,185 Australian adults (aged 26–36 years), first examined in 1985 (at ages 7–15 years), self-reported physical activity and cardiorespiratory fitness (subsample only) were measured. SEP measures included retrospectively reported parental education (baseline) and own education (follow-up). There was little evidence of a relation between childhood SEP and activity tracking, but high childhood SEP (maternal education) was associated with a 59% increased likelihood of persistent fitness, and medium childhood SEP (paternal and parental education) was associated with a 33%–36% decreased likelihood of persistent fitness. Upward social mobility was associated with a greater likelihood of increasing activity (38%–49%) and fitness (90%), and persistently high SEP was associated with a greater likelihood of increasing activity (males: 58%) and fitness (males and females combined: 89%). In conclusion, persistently high SEP and upward social mobility were associated with increases in activity and fitness from childhood to adulthood. Findings highlight socioeconomic differentials in activity and fitness patterns and suggest that improvements in education may represent a pathway through which physical activity levels can be increased and health benefits achieved.

Invited Commentary: Physical Activity Over the Life Course--Whose Behavior Changes, When, and Why?

Corder, K., Ogilvie, D., van Sluijs, E. M. F. — Thu, 15 Oct 2009 04:46:59 PDT

Physical activity tends to decline from childhood into adulthood. Maintaining high levels of physical activity throughout life is therefore an important public health objective. Relatively little is known about changes in physical activity behavior over the life course, the domains of physical activity in which they occur, the characteristics of those whose physical activity declines, and the factors associated with such changes. In the future, incorporating more accurate measures of physical activity in large population studies would help to establish more accurate estimates of associations in this area. Determinants of behavior change, including the effects of socioeconomic position and social mobility on physical activity and fitness, are likely to change constantly throughout life, but it is largely unknown which determinants are most important at each life stage, let alone whether and at what times those determinants change. Better evidence on determinants of behavior change throughout the life course would contribute greatly to understanding when and how to intervene to help create and sustain lifelong healthy behavior patterns in those who have the most to gain from adopting them.

Cleland et al. Respond to "Physical Activity Over the Life Course"

Cleland, V. J., Ball, K., Magnussen, C., Dwyer, T., Venn, A. — Thu, 15 Oct 2009 04:47:00 PDT

Declines in Physical Activity and Higher Systolic Blood Pressure in Adolescence

Maximova, K., O'Loughlin, J., Paradis, G., Hanley, J. A., Lynch, J. — Thu, 15 Oct 2009 04:47:00 PDT

The authors examined the potential association between changes in the number of moderate-to-vigorous physical activity (MVPA) sessions per week, adiposity, and systolic blood pressure (SBP) during adolescence. SBP and anthropometric factors were assessed biannually (1999/2000, 2002, and 2004) in a cohort of 1,293 Canadian adolescents aged 12–13 years in 1999. Self-reported 7-day recall data on MVPA sessions ≥5 minutes in duration were collected every 3 months over the 5-year period. Estimates of initial level and rate of decline in number of MVPA sessions per week from individual growth models were used as predictors of SBP in linear regression models. A decline of 1 MVPA session per week with each year of age was associated with 0.29-mm Hg and 0.19-mm Hg higher SBPs in girls and boys, respectively, in early adolescence (ages 12.8–15.1 years) and 0.40-mm Hg and 0.18-mm Hg higher SBPs, respectively, in late adolescence (ages 15.2–17.0 years). The associations were not attenuated by changes in body mass index, waist circumference, or skinfold thickness in girls during late adolescence. Although weaker, associations were evident in boys during late adolescence, as well as in both girls and boys during early adolescence. These results support prevention of declines in MVPA during adolescence to prevent higher blood pressure in youth.

Recreational Physical Activity and Steroid Hormone Levels in Postmenopausal Women

Bertone-Johnson, E. R., Tworoger, S. S., Hankinson, S. E. — Thu, 15 Oct 2009 04:47:00 PDT

Recreational physical activity has been both positively and inversely associated with cancer risk for postmenopausal women, acting presumably through hormonal mechanisms. Relatively little is known about the effects of exercise on postmenopausal steroid hormone levels. The authors evaluated the association between recreational activity and plasma steroid hormones among 623 US healthy, postmenopausal women in the Nurses’ Health Study not using exogenous hormones at the time of blood draw (1989–1990). Participants self-reported recreational physical activity by questionnaire in 1986, 1988, and 1992. Plasma samples were assayed for estrogens, androgens, and sex hormone-binding globulin. Geometric mean hormone levels adjusted and not adjusted for body mass index were calculated. In general, estrogen and androgen levels were lower in the most- and the least-active women compared with those reporting moderate activity, suggesting a U-shaped relation. For example, estrone sulfate levels in quintiles 1–5 of metabolic equivalent task-hours were 197, 209, 222, 214, and 195 pg/mL, respectively. Tests for nonlinearity using polynomial regression were significant for several estrogens, androgens, and sex hormone-binding globulin (2-sided P ≤ 0.01). These results suggest the possibility of a nonlinear relation between recreational physical activity and hormone levels in postmenopausal women.

Prospective Study of Urban Form and Physical Activity in the Black Women's Health Study

Thu, 15 Oct 2009 04:47:00 PDT

The authors used data from the Black Women's Health Study to assess the association between neighborhood urban form and physical activity. Women reported hours/week of utilitarian and exercise walking and of vigorous activity in 1995 and on biennial follow-up questionnaires through 2001. Housing density, road networks, availability of public transit, sidewalks, and parks were characterized for the residential neighborhoods of 20,354 Black Women's Health Study participants living in New York, New York; Chicago, Illinois; and Los Angeles, California. The authors quantified the associations between features of the environment and physical activity using odds ratios for ≥5 relative to <5 hours/week of physical activity. For all women, housing density had the strongest association with utilitarian walking (odds ratio for the most- compared with the least-dense quintile = 2.72, 95% confidence interval: 2.22, 3.31), followed by availability of public transit. Women who moved during follow-up to neighborhoods of lower density were 36% more likely to decrease their levels of utilitarian walking, and those who moved to neighborhoods of higher density were 23% more likely to increase their levels of utilitarian walking, relative to women who moved to neighborhoods of similar density. These data suggest that increases in housing density may lead to increases in utilitarian walking among African-American women.

Risk of Autism and Increasing Maternal and Paternal Age in a Large North American Population

Grether, J. K., Anderson, M. C., Croen, L. A., Smith, D., Windham, G. C. — Thu, 15 Oct 2009 04:47:00 PDT

Previous studies are inconsistent regarding whether there are independent effects of maternal and paternal age on the risk of autism. Different biologic mechanisms are suggested by maternal and paternal age effects. The study population included all California singletons born in 1989–2002 (n = 7,550,026). Children with autism (n = 23,311) were identified through the California Department of Developmental Services and compared with the remainder of the study population, with parental ages and covariates obtained from birth certificates. Adjusted odds ratios and 95% confidence intervals were used to evaluate the risk of autism associated with increasing maternal and paternal age. In adjusted models that included age of the other parent and demographic covariates, a 10-year increase in maternal age was associated with a 38% increase in the odds ratio for autism (odds ratio = 1.38, 95% confidence interval: 1.32, 1.44), and a 10-year increase in paternal age was associated with a 22% increase (odds ratio = 1.22, 95% confidence interval: 1.18, 1.26). Maternal and paternal age effects were seen in subgroups defined by race/ethnicity and other covariates and were of greater magnitude among first-born compared with later-born children. Further studies are needed to help clarify the biologic mechanisms involved in the independent association of autism risk with increasing maternal and paternal age.

Antenatal and Postnatal Iron Supplementation and Childhood Mortality in Rural Nepal: A Prospective Follow-up in a Randomized, Controlled Community Trial

Thu, 15 Oct 2009 04:47:01 PDT

The long-term benefits of antenatal iron supplementation in child survival are not known. In 1999–2001, 4,926 pregnant women in rural Nepal participated in a cluster-randomized, double-masked, controlled trial involving 4 alternative combinations of micronutrient supplements, each containing vitamin A. The authors examined the impact on birth weight and early infant mortality in comparison with controls, who received vitamin A only. They followed the surviving offspring of these women at approximately age 7 years to study effects of in utero supplementation on survival. Of 4,130 livebirths, 209 infants died in the first 3 months and 8 were lost to follow-up. Of those remaining, 3,761 were followed, 150 died between ages 3 months and 7 years, and 152 were lost to follow-up. Mortality rates per 1,000 child-years from birth to age 7 years differed by maternal supplementation group, as follows: folic acid, 13.4; folic acid-iron, 10.3; folic acid-iron-zinc, 12.0; multiple micronutrients; 14.0; and controls, 15.2. Hazard ratios were 0.90 (95% confidence interval (CI): 0.65, 1.22), 0.69 (95% CI: 0.49, 0.99), 0.80 (95% CI: 0.58, 1.11), and 0.93 (95% CI: 0.66, 1.31), respectively, in the 4 supplementation groups. Maternal iron-folic acid supplementation reduced mortality among these children by 31% between birth and age 7 years. These results provide additional motivation for strengthening antenatal iron-folic acid programs.

Maternal Licorice Consumption and Detrimental Cognitive and Psychiatric Outcomes in Children

Thu, 15 Oct 2009 04:47:01 PDT

Overexposure to glucocorticoids may link prenatal adversity with detrimental outcomes in later life. Glycyrrhiza, a natural constituent of licorice, inhibits placental 11-beta-hydroxysteroid dehydrogenase type 2, the feto-placental "barrier" to higher maternal levels of cortisol. The authors studied whether prenatal exposure to glycyrrhiza in licorice exerts detrimental effects on cognitive performance (subtests of the Wechsler Intelligence Scale for Children III as well as the Children's Developmental Neuropsychological Assessment and the Beery Developmental Test of Visual-Motor Integration) and psychiatric symptoms (Child Behavior Checklist) in 321 Finnish children 8.1 years of age born in 1998 as healthy singletons at 35–42 weeks of gestation. In comparison to the group with zero–low glycyrrhiza exposure (0–249 mg/week), those with high exposure (≥500 mg/week) had significant decrements in verbal and visuospatial abilities and in narrative memory (range of mean differences in standard deviation units, –0.31 to –0.41; P < 0.05) and significant increases in externalizing symptoms and in attention, rule-breaking, and aggression problems (range of odds ratios, 2.15 to 3.43; P < 0.05). The effects on cognitive performance appeared dose related. Data are compatible with adverse fetal "programming" by overexposure to glucocorticoids and caution against excessive intake of licorice-containing foodstuffs during pregnancy.

Association of White Matter Lesions and Lacunar Infarcts With Executive Functioning: The SMART-MR Study

Thu, 15 Oct 2009 04:47:01 PDT

The authors investigated the association of white matter lesions and lacunar infarcts with cognitive performance and whether brain atrophy mediates these associations. Within the Second Manifestations of Arterial Disease-Magnetic Resonance study (2001–2005, the Netherlands), cross-sectional analyses of 522 patients were performed (mean age, 57 years (standard deviation, 10); 76% male). Brain segmentation was used to quantify volumes of brain tissue, cerebrospinal fluid, and white matter lesions. Infarcts were rated visually. Brain volume, ventricular volume, and gray matter volume were divided by intracranial volume to obtain indicators of brain atrophy. Neuropsychological tests assessing executive functioning and memory were performed, and scores were transformed into z scores. The authors used linear regression analyses, adjusted for age, sex, education, intelligence, and vascular risk factors, to investigate the association of white matter lesions and number of lacunar infarcts with cognitive performance. A 1-standard-deviation higher volume of white matter lesions (β = –0.12, 95% confidence interval: –0.20, –0.04) and the presence of ≥2 lacunar infarcts (β = –0.48, 95% confidence interval: –0.87, –0.09) were associated with worse executive functioning. These associations remained after adjusting for brain atrophy. Both were not associated with worse memory. Results suggest that subcortical ischemic vascular lesions are associated with decreased executive functioning, but not with memory functioning, independent of brain atrophy.

Blood Cadmium and Lead and Chronic Kidney Disease in US Adults: A Joint Analysis

Thu, 15 Oct 2009 04:47:01 PDT

Environmental cadmium and lead exposures are widespread, and both metals are nephrotoxic at high exposure levels. Few studies have evaluated the associations between low-level cadmium and clinical renal outcomes, particularly with respect to joint cadmium and lead exposure. The geometric mean levels of blood cadmium and lead were 0.41 µg/L (3.65 nmol/L) and 1.58 µg/dL (0.076 µmol/L), respectively, in 14,778 adults aged ≥20 years who participated in the National Health and Nutrition Examination Survey (1999–2006). After adjustment for survey year, sociodemographic factors, chronic kidney disease risk factors, and blood lead, the odds ratios for albuminuria (≥30 mg/g creatinine), reduced estimated glomerular filtration rate (eGFR) (<60 mL/minute/1.73 m²), and both albuminuria and reduced eGFR were 1.92 (95% confidence interval (CI): 1.53, 2.43), 1.32 (95% CI: 1.04, 1.68), and 2.91 (95% CI: 1.76, 4.81), respectively, comparing the highest with the lowest blood cadmium quartiles. The odds ratios comparing participants in the highest with the lowest quartiles of both cadmium and lead were 2.34 (95% CI: 1.72, 3.18) for albuminuria, 1.98 (95% CI: 1.27, 3.10) for reduced eGFR, and 4.10 (95% CI: 1.58, 10.65) for both outcomes. These findings support consideration of cadmium and lead as chronic kidney disease risk factors in the general population and provide novel evidence of risk with environmental exposure to both metals.

Meat and Meat-related Compounds and Risk of Prostate Cancer in a Large Prospective Cohort Study in the United States

Thu, 15 Oct 2009 04:47:01 PDT

The authors examined associations between meat consumption (type, cooking method, and related mutagens), heme iron, nitrite/nitrate, and prostate cancer in a cohort of 175,343 US men aged 50–71 years. During 9 years of follow-up (1995–2003), they ascertained 10,313 prostate cancer cases (1,102 advanced) and 419 fatal cases. Hazard ratios comparing the fifth intake quintile with the first revealed elevated risks associated with red and processed meat for total (red meat: hazard ratio (HR) = 1.12, 95% confidence interval (CI): 1.04, 1.21; processed meat: HR = 1.07, 95% CI: 1.00, 1.14) and advanced (red meat: HR = 1.31, 95% CI: 1.05, 1.65; processed meat: HR = 1.32, 95% CI: 1.08, 1.61) prostate cancer. Heme iron, barbecued/grilled meat, and benzo[a]pyrene were all positively associated with total (HR = 1.09 (95% CI: 1.02, 1.17), HR = 1.11 (95% CI: 1.03, 1.19), and HR = 1.09 (95% CI: 1.00, 1.18), respectively) and advanced (HR = 1.28 (95% CI: 1.03, 1.58), HR = 1.36 (95% CI: 1.10, 1.69), and HR = 1.28 (95% CI: 1.00, 1.65), respectively) disease. Nitrite (HR = 1.24, 95% CI: 1.02, 1.51) and nitrate (HR = 1.31, 95% CI: 1.07, 1.61) intakes were associated with advanced prostate cancer. There were no clear associations for fatal prostate cancer. Red and processed meat may be positively associated with prostate cancer via mechanisms involving heme iron, nitrite/nitrate, grilling/barbecuing, and benzo[a]pyrene.

Using Time-dependent Covariate Analysis to Elucidate the Relation of Smoking History to Warthin's Tumor Risk

Freedman, L. S., Oberman, B., Sadetzki, S. — Thu, 15 Oct 2009 04:47:01 PDT

The authors aimed to elucidate the relation of the time-dependent smoking history parameters—age at smoking initiation and smoking intensity, duration, and latency—to the risk of Warthin's tumor, a benign tumor of the salivary gland for which cigarette smoking is a strong risk factor. They studied 117 cases of Warthin's tumor and 336 matched controls included in an Israeli nationwide case-control study of parotid gland tumors conducted from 2002 to 2003 by using the Cox regression model with time-dependent covariates, with age as the time axis. When current age and smoking duration were included in the statistical model, the authors show that the coefficient of a latency variable does not represent latency as such, but a balancing of the effects of age at initiation and time since cessation. They found a strong positive linear effect of duration of smoking, together with a positive nonlinear effect of intensity that levels off at higher intensities, and a negative effect of latency from 25 years onward. The latter finding implies that the effect of time since cessation dominates the effect of age at initiation, with risk decreasing sharply after smoking cessation. The relation of smoking variables to Warthin's tumor agrees with the patterns reported for lung cancer.

Using a Longitudinal Model to Estimate the Effect of Methicillin-resistant Staphylococcus aureus Infection on Length of Stay in an Intensive Care Unit

Barnett, A. G., Batra, R., Graves, N., Edgeworth, J., Robotham, J., Cooper, B. — Thu, 15 Oct 2009 04:47:01 PDT

Health-care-associated methicillin-resistant Staphylococcus aureus (MRSA) infection may cause increased hospital stay, or sometimes death. Quantifying this effect is complicated because the exposure is time dependent: infection may prolong hospital stay, while longer stays increase infection risk. In this paper, the authors overcome these problems by using a multinomial longitudinal model to estimate the daily probability of death and discharge. They then extend the basic model to estimate how the effect of MRSA infection varies over time and to quantify number of excess days in the intensive care unit due to infection. They found that infection decreased the relative risk of discharge (relative risk ratio = 0.68, 95% credible interval: 0.54, 0.82). Infection on the first day of admission resulted in a mean extra stay of 0.3 days (95% credible interval: 0.1, 0.5) for a patient with an Acute Physiology and Chronic Health Evaluation II score of 10 and 1.2 days (95% credible interval: 0.5, 2.0) for a patient with a score of 30. The decrease in the relative risk of discharge remained fairly constant with day of MRSA infection but was slightly stronger closer to the start of infection. Results confirm the importance of MRSA infection in increasing stay in an intensive care unit but suggest that previous work may have systematically overestimated the effect size.

Editorial Board

Thu, 01 Oct 2009 05:00:43 PDT

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Thu, 01 Oct 2009 05:00:43 PDT

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Thu, 01 Oct 2009 05:00:43 PDT

Total Exposure and Exposure Rate Effects for Alcohol and Smoking and Risk of Head and Neck Cancer: A Pooled Analysis of Case-Control Studies

Thu, 01 Oct 2009 05:00:43 PDT

Although cigarette smoking and alcohol consumption increase risk for head and neck cancers, there have been few attempts to model risks quantitatively and to formally evaluate cancer site-specific risks. The authors pooled data from 15 case-control studies and modeled the excess odds ratio (EOR) to assess risk by total exposure (pack-years and drink-years) and its modification by exposure rate (cigarettes/day and drinks/day). The smoking analysis included 1,761 laryngeal, 2,453 pharyngeal, and 1,990 oral cavity cancers, and the alcohol analysis included 2,551 laryngeal, 3,693 pharyngeal, and 3,116 oval cavity cancers, with over 8,000 controls. Above 15 cigarettes/day, the EOR/pack-year decreased with increasing cigarettes/day, suggesting that greater cigarettes/day for a shorter duration was less deleterious than fewer cigarettes/day for a longer duration. Estimates of EOR/pack-year were homogeneous across sites, while the effects of cigarettes/day varied, indicating that the greater laryngeal cancer risk derived from differential cigarettes/day effects and not pack-years. EOR/drink-year estimates increased through 10 drinks/day, suggesting that greater drinks/day for a shorter duration was more deleterious than fewer drinks/day for a longer duration. Above 10 drinks/day, data were limited. EOR/drink-year estimates varied by site, while drinks/day effects were homogeneous, indicating that the greater pharyngeal/oral cavity cancer risk with alcohol consumption derived from the differential effects of drink-years and not drinks/day.

Tumor Necrosis Factor Polymorphisms and Alcoholic Liver Disease: A HuGE Review and Meta-Analysis

Marcos, M., Gomez-Munuera, M., Pastor, I., Gonzalez-Sarmiento, R., Laso, F.-J. — Thu, 01 Oct 2009 05:00:43 PDT

The association between alcoholic liver disease (ALD) and tumor necrosis factor- gene (TNFA) polymorphisms has been analyzed in several studies, but results have been conflicting. The main purpose of this study was to integrate previous findings and explore whether these polymorphisms are associated with susceptibility to ALD. The authors surveyed studies on the relation between TNFA gene polymorphisms and ALD by means of an electronic database search. A meta-analysis was conducted in a random-effects model. The association between ALD and the –238G>A or –308G>A polymorphism of the TNFA gene has been analyzed in 11 studies. Concerning the –238G>A polymorphism, the authors found a significant association between possession of the A allele and risk of alcoholic liver cirrhosis (odds ratio = 1.47, 95% confidence interval: 1.05, 2.07). Meta-analysis of the relation between the –308G>A polymorphism and ALD did not show any significant association. Given the limited number of studies and the potential biases, more data are needed to confirm the association described for the –238A allele.

The Association of Body Mass Index With Health Outcomes: Causal, Inconsistent, or Confounded?

Shahar, E. — Thu, 01 Oct 2009 05:00:43 PDT

According to the definition of confounding in a causal diagram, the association of body mass index (weight (kg)/height (m)²) with health-related outcomes is almost always noncausal, attributable to confounding by weight and perhaps height. The same conclusion holds for any other deterministic derivation from weight and height. No causal knowledge is gained by estimating a nonexistent effect of body mass index.

Invited Commentary: Causal Diagrams and Measurement Bias

Hernan, M. A., Cole, S. R. — Thu, 01 Oct 2009 05:00:43 PDT

Causal inferences about the effect of an exposure on an outcome may be biased by errors in the measurement of either the exposure or the outcome. Measurement errors of exposure and outcome can be classified into 4 types: independent nondifferential, dependent nondifferential, independent differential, and dependent differential. Here the authors describe how causal diagrams can be used to represent these 4 types of measurement bias and discuss some problems that arise when using measured exposure variables (e.g., body mass index) to make inferences about the causal effects of unmeasured constructs (e.g., "adiposity"). The authors conclude that causal diagrams need to be used to represent biases arising not only from confounding and selection but also from measurement.

Shahar Responds to "Causal Diagrams and Measurement Bias"

Shahar, E. — Thu, 01 Oct 2009 05:00:43 PDT

Test-Retest Reliability of a Sexual Behavior Interview for Men Residing in Brazil, Mexico, and the United States: The HPV in Men (HIM) Study

Thu, 01 Oct 2009 05:00:43 PDT

Understanding the natural history of sexually transmitted infections requires the collection of data on sexual behavior. However, there is concern that self-reported information on sexual behavior may not be valid, especially if study participants are culturally and linguistically distinct. The authors completed a test-retest reliability study of 1,069 men recruited in Brazil, Mexico, and the United States in 2005 and 2006. All of the men completed the same computer-assisted self-interview approximately 3 weeks apart. Refusal rates, kappa coefficients, and intraclass correlation coefficients were calculated for the full sample and by country, age, and lifetime number of female sex partners. Reliability coefficients for each study site and the combined population were high for almost all questions. With few exceptions, the authors found high test-retest reliability with a computer-assisted self-interview on sexual behavior used in 3 culturally and linguistically distinct countries.

Control Selection and Participation in an Ongoing, Population-based, Case-Control Study of Birth Defects: The National Birth Defects Prevention Study

Thu, 01 Oct 2009 05:00:43 PDT

To evaluate the representativeness of controls in an ongoing, population-based, case-control study of birth defects in 10 centers across the United States, researchers compared 1997–2003 birth certificate data linked to selected controls (n = 6,681) and control participants (n = 4,395) with those from their base populations (n = 2,468,697). Researchers analyzed differences in population characteristics (e.g., percentage of births at ≥2,500 g) for each group. Compared with their base populations, control participants did not differ in distributions of maternal or paternal age, previous livebirths, maternal smoking, or diabetes, but they did differ in other maternal (i.e., race/ethnicity, education, entry into prenatal care) and infant (i.e., birth weight, gestational age, and plurality) characteristics. Differences in distributions of maternal, but not infant, characteristics were associated with participation by selected controls. Absolute differences in infant characteristics for the base population versus control participants were ≤1.3 percentage points. Differences in infant characteristics were greater at centers that selected controls from hospitals compared with centers that selected controls from electronic birth certificates. These findings suggest that control participants in the National Birth Defects Prevention Study generally are representative of their base populations. Hospital-based control selection may slightly underascertain infants affected by certain adverse birth outcomes.

Hypothesis-Driven Candidate Gene Association Studies: Practical Design and Analytical Considerations

Thu, 01 Oct 2009 05:00:43 PDT

Candidate gene association studies (CGAS) are a useful epidemiologic approach to drawing inferences about relations between genes and disease, especially when experimental data support the involvement of specific biochemical pathways. The value of CGAS is apparent when allele frequencies are low, effect sizes are small, or the study population is limited or unique. CGAS is also valuable for validating previous reports of genetic associations with disease in different populations. Despite the many advantages, the information generated from CGAS is sometimes compromised because of either inefficient study design or suboptimal analytical approaches. Here the authors discuss issues related to the study design and statistical analyses of CGAS that can help to optimize their usefulness and information content. These issues include judicious hypothesis-driven selection of biochemical pathways, genes, and single nucleotide polymorphisms, as well as appropriate quality control and analytical procedures for measuring main effects and for evaluating environmental exposure modifications and interactions. A study design algorithm using the example of DNA repair genes and cancer is presented for purposes of illustration.

Impact of Genotype Misclassification on Genetic Association Estimates and the Bayesian Adjustment

Hossain, S., Le, N. D., Brooks-Wilson, A. R., Spinelli, J. J. — Thu, 01 Oct 2009 05:00:43 PDT

Genotypes of single nucleotide polymorphisms are subject to misclassification. If ignored, such misclassification can seriously distort the estimated genotype effects on the disease or outcome of interest. Validation data (gold standard or replicated surrogates) are required to assess the degree of misclassification and make adjustments. In practice, gold standard measurements may be unavailable or impractical. Collecting replicated surrogates is a reasonable option for validation data. In most practical applications, collecting replicated surrogates on all study subjects is not feasible; however, obtaining replicated surrogates on a subsample of the study population may be quite feasible. Generating duplicate data for a subsample of the study population is now common practice among genotyping laboratories. The authors propose a Bayesian method that can adjust for genotype misclassification using partial validation data. Simulation results show that the proposed method substantially reduces misclassification bias from the estimated genotype-disease association and provides appropriate uncertainty assessment, as well as improves other desirable properties of the estimated effects. The authors also provide an example showing the application of the proposed method to study data relating non-Hodgkin lymphoma to a single nucleotide polymorphism in the aryl hydrocarbon receptor gene.

Development of Predictive Models for Airflow Obstruction in Alpha-1-Antitrypsin Deficiency

Thu, 01 Oct 2009 05:00:44 PDT

Alpha-1-antitrypsin deficiency is a genetic condition associated with severe, early-onset chronic obstructive pulmonary disease (COPD). However, there is significant variability in lung function impairment among persons with the protease inhibitor ZZ genotype. Early identification of persons at highest risk of developing lung disease could be beneficial in guiding monitoring and treatment decisions. Using a multicenter, family-based study sample (2002–2005) of 372 persons with the protease inhibitor ZZ genotype, the authors developed prediction models for forced expiratory volume in 1 second (FEV₁) and the presence of severe COPD using demographic, clinical, and genetic variables. Half of the data sample was used for model development, and the other half was used for model validation. In the training sample, variables found to be predictive of both FEV₁ and severe COPD were age, sex, pack-years of smoking, bronchodilator responsiveness, chronic bronchitis symptoms, and index case status. In the validation sample, the predictive model for FEV₁ explained 50% of the variance in FEV₁, and the model for severe COPD exhibited excellent discrimination (c statistic = 0.88).

Maternal Catecholamine Levels in Midpregnancy and Risk of Preterm Delivery

Thu, 01 Oct 2009 05:00:44 PDT

Associations between stress hormones and preterm delivery have not been fully explored. In this study, pregnant women enrolled from 52 clinics in 5 Michigan communities (1998–2004) provided urine samples for 3 days (waking and bedtime) during midpregnancy. Urinary catecholamine levels (epinephrine, norepinephrine, and dopamine) were measured in a subcohort (247 preterm and 760 term deliveries), and a 3-day median value was calculated. Polytomous logistic regression models assessed relations between catecholamine quartiles (of the median) and a 4-level outcome variable (i.e., term (referent) and 3 preterm delivery subtypes: spontaneous; premature rupture of membranes; and medically indicated). Final models incorporated other relevant covariates (e.g., creatinine, demographic, behavior). The risk of spontaneous preterm delivery was increased in the highest versus lowest quartile of norepinephrine and dopamine: norepinephrine, waking (adjusted odds ratio (AOR) = 3.7, 95% confidence interval (CI): 1.8, 7.9) and bedtime (AOR = 2.5, 95% CI: 1.3, 4.9); dopamine, waking (AOR = 2.6, 95% CI: 1.4, 5.1) and bedtime (AOR = 2.3, 95% CI: 1.2, 4.6). Adjusted odds ratios were further strengthened after removing women whose placentas showed evidence of acute infection or vascular pathology. High catecholamine levels in maternal urine may be indicative of excess stressors and/or predisposition to elevated sympathetic activation that contributes to increased risk of spontaneous preterm delivery.

Pregnancy-associated Hypertensive Disorders and Adult Cognitive Function Among Danish Conscripts

Ehrenstein, V., Rothman, K. J., Pedersen, L., Hatch, E. E., Sorensen, H. T. — Thu, 01 Oct 2009 05:00:44 PDT

The authors examined the association of gestational hypertensive disorders (hypertension, preeclampsia, eclampsia) with adult cognitive function among men born in 1978–1983 in a well-defined geographic area of northern Denmark. Data from the Danish Medical Birth Registry, the Danish National Registry of Patients, and draft board records were linked. Cognitive function was measured at conscription by using the Boerge Prien group intelligence test. Test scores were converted to the conventional IQ scale (mean = 100 (standard deviation, 15)). Low cognitive function was defined as IQ <85. Of the 17,457 men who underwent intelligence testing, 891 (5.1%) were born after a pregnancy involving hospitalization for a gestational hypertensive disorder. Compared with conscripts born after normotensive pregnancy, conscripts exposed to maternal gestational hypertension had an adjusted prevalence ratio for low cognitive function of 1.34 (95% confidence interval (CI): 1.01, 1.77). For those exposed to mild preeclampsia and severe preeclampsia/eclampsia, adjusted prevalence ratios were 1.34 (95% CI: 1.09, 1.65) and 1.10 (95% CI: 0.48, 2.51), respectively. The corresponding adjusted mean differences in IQ scores were –2.0 (95% CI: –4.0, 0.0), –3.2 (95% CI: –4.7, –1.8), and –2.0 (95% CI: –7.2, 3.2). In this study, prenatal exposure to gestational hypertensive disorders was associated with slightly reduced adult cognitive performance among male conscripts.

Vitamin D Status and the Risk of Cardiovascular Disease Death

Thu, 01 Oct 2009 05:00:44 PDT

Accumulating evidence suggests that inadequate vitamin D levels may predispose people to chronic diseases. The authors aimed to investigate whether serum 25-hydroxyvitamin D (25(OH)D) level predicts mortality from cardiovascular disease (CVD). The study was based on the Mini-Finland Health Survey and included 6,219 men and women aged ≥30 years who were free from CVD at baseline (1978–1980). During follow-up through 2006, 640 coronary disease deaths and 293 cerebrovascular disease deaths were identified. Levels of 25(OH)D were determined from serum collected at baseline. Cox's proportional hazards model was used to assess the association between 25(OH)D and risk of CVD death. After adjustment for potential confounders, the hazard ratio for total CVD death was 0.76 (95% confidence interval (95% CI): 0.60, 0.95) for the highest quintile of 25(OH)D level versus the lowest. The association was evident for cerebrovascular death (hazard ratio = 0.48, 95% CI: 0.31, 0.75) but not coronary death (hazard ratio = 0.91, 95% CI: 0.70, 1.18). A low vitamin D level may be associated with higher risk of a fatal CVD event, particularly cerebrovascular death. These findings need to be replicated in other populations. To demonstrate a causal link between vitamin D and CVD, randomized controlled trials are required.

Physical Activity Levels and Cognition in Women With Type 2 Diabetes

Devore, E. E., Kang, J. H., Okereke, O., Grodstein, F. — Thu, 01 Oct 2009 05:00:44 PDT

Persons with type 2 diabetes have a high risk of late-life cognitive impairment, and physical activity might be a potential target for modifying this risk. Therefore, the authors evaluated the association between physical activity level and cognition in women with type 2 diabetes. Beginning in 1995–2000, cognitive function was assessed in 1,550 Nurses’ Health Study participants aged ≥70 years with type 2 diabetes. Follow-up assessments were completed twice thereafter, at 2-year intervals. Multivariate-adjusted linear regression models were used to obtain mean differences in baseline cognitive scores and cognitive decline across tertiles of long-term physical activity. Initial results from age- and education-adjusted models indicated that greater physical activity levels were associated with better baseline cognition (for a global score averaging scores from 6 cognitive tests, P-trend = 0.02). However, results were substantially attenuated after adjustment for multiple potential confounders, largely because of physical disability indicators (global score: P-trend = 0.06); for example, the mean difference for the global score was 0.07 standard units (95% confidence interval: –0.01, 0.15) when comparing extreme tertiles. Results were similar for cognitive decline. These findings indicate little overall association between physical activity and cognition after adjustment for disability factors in older women with type 2 diabetes.

Physical, Psychological, and Functional Comorbidities of Multisymptom Illness in Australian Male Veterans of the 1991 Gulf War

Kelsall, H. L., McKenzie, D. P., Sim, M. R., Leder, K., Forbes, A. B., Dwyer, T. — Thu, 01 Oct 2009 05:00:44 PDT

Multisymptom illness is more prevalent in 1991 Gulf War veterans than in military comparison groups; less is known about comorbidities. The authors compared physical, psychological, and functional comorbidities in Australian male Gulf War I veterans with those in actively (non-Gulf) deployed and nondeployed military personnel by using a questionnaire and medical assessment in 2000–2002. Multisymptom illness was more common in male Gulf War veterans than in the comparison group (odds ratio (OR) = 1.80, 95% confidence interval (CI): 1.48, 2.19). Stratifying by deployment status in the comparison group made little difference in this association. Gulf War veterans with multisymptom illness had increased psychiatric disorders, including major depression (OR = 6.31, 95% CI: 4.19, 9.52) and posttraumatic stress disorder (OR = 9.77, 95% CI: 5.39, 18.59); increased unexplained chronic fatigue (OR = 13.32, 95% CI: 7.70, 23.05); and more reported functional impairment and poorer quality of life, but objective physical and laboratory outcomes were similar to those for veterans without multisymptom illness. Similar patterns were found in the comparison groups; differences across the 3 groups were statistically significant for only hospitalization, obstructive liver disease, and Epstein-Barr virus exposure. Multisymptom illness is more prevalent in Gulf War I veterans, but the pattern of comorbidities is similar for actively deployed and nondeployed military personnel.

Air Pollution and Hospitalization for Headache in Chile

Dales, R. E., Cakmak, S., Vidal, C. B. — Thu, 01 Oct 2009 05:00:44 PDT

The authors performed a time-series analysis to test the association between air pollution and daily numbers of hospitalizations for headache in 7 Chilean urban centers during the period 2001–2005. Results were adjusted for day of the week and humidex. Three categories of headache—migraine, headache with cause specified, and headache not otherwise specified—were all associated with air pollution. Relative risks for migraine associated with interquartile-range increases in specific air pollutants were as follows: 1.11 (95% confidence interval (CI): 1.06, 1.17) for a 1.15-ppm increase in carbon monoxide; 1.11 (95% CI: 1.06, 1.17) for a 28.97-µg/m³ increase in nitrogen dioxide; 1.10 (95% CI: 1.04, 1.17) for a 6.20-ppb increase in sulfur dioxide; 1.17 (95% CI: 1.08, 1.26) for a 69.51-ppb increase in ozone; 1.11 (95% CI: 1.00, 1.19) for a 21.51-µg/m³ increase in particulate matter less than 2.5 µm in aerodynamic diameter (PM_2.5); and 1.10 (95% CI: 1.04, 1.15) for a 37.79-µg/m³ increase in particulate matter less than 10 µm in aerodynamic diameter (PM₁₀). There was no significant effect modification by age, sex, or season. The authors conclude that air pollution appears to increase the risk of headache in Santiago Province. If the relation is causal, the morbidity associated with headache should be considered when estimating the burden of illness and costs associated with poor air quality.

American Journal of Epidemiology - recent issues

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Cover

Towards Reducing Disparities in Disparities Research

Discovery Properties of Genome-wide Association Signals From Cumulatively Combined Data Sets

Meta- and Pooled Analyses of the Methylenetetrahydrofolate Reductase (MTHFR) C677T Polymorphism and Colorectal Cancer: A HuGE-GSEC Review

Genetic Variations in Xenobiotic Metabolic Pathway Genes, Personal Hair Dye Use, and Risk of Non-Hodgkin Lymphoma

Body Size, Recreational Physical Activity, and B-Cell Non-Hodgkin Lymphoma Risk Among Women in the California Teachers Study

Genetic Variation in the Progesterone Receptor and Metabolism Pathways and Hormone Therapy in Relation to Breast Cancer Risk

Physical Activity's Impact on the Association of Fat and Fiber Intake With Survival After Breast Cancer

Postmenopausal Breast Cancer Risk and Dietary Patterns in the E3N-EPIC Prospective Cohort Study

Association of Perfluorooctanoic Acid and Perfluorooctane Sulfonate With Serum Lipids Among Adults Living Near a Chemical Plant

Correlates of Multiple Chronic Disease Behavioral Risk Factors in Canadian Children and Adolescents

The Aftermath of Hip Fracture: Discharge Placement, Functional Status Change, and Mortality

Optimizing Influenza Sentinel Surveillance at the State Level

Analyses of Injury Count Data: Some Do's and Don'ts

Applying Quantitative Bias Analysis to Epidemiologic Data: By Timothy L. Lash, Matthew P. Fox, and Aliza K. Fink

Statistical Modeling for Biomedical Researchers: A Simple Introduction to the Analysis of Complex Data, 2nd Edition: By William D. Dupont

Re: "Determinants of Quality of Interview and Impact on Risk Estimates in a Case-Control Study of Bladder Cancer"

Three Authors Reply

Re: "Methods of Covariate Selection: Directed Acyclic Graphs and the Change-in-Estimate Procedure"

Three of the Authors Reply

Cover

Table of contents

Editorial Board

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Editorial: Breathing New Life Into Pneumonia Epidemiology

Socioeconomic Position and the Tracking of Physical Activity and Cardiorespiratory Fitness From Childhood to Adulthood

Invited Commentary: Physical Activity Over the Life Course--Whose Behavior Changes, When, and Why?

Cleland et al. Respond to "Physical Activity Over the Life Course"

Declines in Physical Activity and Higher Systolic Blood Pressure in Adolescence

Recreational Physical Activity and Steroid Hormone Levels in Postmenopausal Women

Prospective Study of Urban Form and Physical Activity in the Black Women's Health Study

Risk of Autism and Increasing Maternal and Paternal Age in a Large North American Population

Antenatal and Postnatal Iron Supplementation and Childhood Mortality in Rural Nepal: A Prospective Follow-up in a Randomized, Controlled Community Trial

Maternal Licorice Consumption and Detrimental Cognitive and Psychiatric Outcomes in Children

Association of White Matter Lesions and Lacunar Infarcts With Executive Functioning: The SMART-MR Study

Blood Cadmium and Lead and Chronic Kidney Disease in US Adults: A Joint Analysis

Meat and Meat-related Compounds and Risk of Prostate Cancer in a Large Prospective Cohort Study in the United States

Using Time-dependent Covariate Analysis to Elucidate the Relation of Smoking History to Warthin's Tumor Risk

Using a Longitudinal Model to Estimate the Effect of Methicillin-resistant Staphylococcus aureus Infection on Length of Stay in an Intensive Care Unit

Editorial Board

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Cover

Total Exposure and Exposure Rate Effects for Alcohol and Smoking and Risk of Head and Neck Cancer: A Pooled Analysis of Case-Control Studies

Tumor Necrosis Factor Polymorphisms and Alcoholic Liver Disease: A HuGE Review and Meta-Analysis

The Association of Body Mass Index With Health Outcomes: Causal, Inconsistent, or Confounded?

Invited Commentary: Causal Diagrams and Measurement Bias

Shahar Responds to "Causal Diagrams and Measurement Bias"

Test-Retest Reliability of a Sexual Behavior Interview for Men Residing in Brazil, Mexico, and the United States: The HPV in Men (HIM) Study

Control Selection and Participation in an Ongoing, Population-based, Case-Control Study of Birth Defects: The National Birth Defects Prevention Study

Hypothesis-Driven Candidate Gene Association Studies: Practical Design and Analytical Considerations

Impact of Genotype Misclassification on Genetic Association Estimates and the Bayesian Adjustment

Development of Predictive Models for Airflow Obstruction in Alpha-1-Antitrypsin Deficiency

Maternal Catecholamine Levels in Midpregnancy and Risk of Preterm Delivery

Pregnancy-associated Hypertensive Disorders and Adult Cognitive Function Among Danish Conscripts

Vitamin D Status and the Risk of Cardiovascular Disease Death

Physical Activity Levels and Cognition in Women With Type 2 Diabetes

Physical, Psychological, and Functional Comorbidities of Multisymptom Illness in Australian Male Veterans of the 1991 Gulf War

Air Pollution and Hospitalization for Headache in Chile