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Neighborhood Poverty and Injection Cessation in a Sample of Injection Drug Users

Neighborhood socioeconomic environment may be a determinant of injection drug use cessation. The authors used data from a prospective cohort study of Baltimore City, Maryland, injection drug users assessed between 1990 and 2006. The study examined the relation between living in a poorer neighborhood and the probability of injection cessation among active injectors, independent of individual characteristics and while respecting the temporality of potential confounders, exposure, and outcome. Participants’ residences were geocoded, and the crude, adjusted, and inverse probability of exposure weighted associations between neighborhood poverty and injection drug use cessation were estimated. Weighted models showed a strong association between neighborhood poverty and injection drug use cessation; living in a neighborhood with fewer than 10%, compared with more than 30%, of residents in poverty was associated with a 44% increased odds of not injecting in the prior 6 months (odds ratio = 1.44, 95% confidence interval: 1.14, 1.82). Results show that neighborhood environment may be an important determinant of drug injection behavior independent of individual-level characteristics.

Variation in Child Cognitive Ability by Week of Gestation Among Healthy Term Births

The authors investigated variations in cognitive ability by gestational age among 13,824 children at age 6.5 years who were born at term with normal weight, using data from a prospective cohort recruited in 1996–1997 in Belarus. The mean differences in the Wechsler Abbreviated Scales of Intelligence were examined by gestational age in completed weeks and by fetal growth after controlling for maternal and family characteristics. Compared with the score for those born at 39–41 weeks, the full-scale intelligence quotient (IQ) score was 1.7 points (95% confidence interval (CI): –2.7, –0.7) lower in children born at 37 weeks and 0.4 points (95% CI: –1.1, 0.02) lower at 38 weeks after controlling for confounders. There was also a graded relation in postterm children: a 0.5-points (95% CI: –2.6, 1.6) lower score at 42 weeks and 6.0 points (95% CI: –15.1, 3.1) lower at 43 weeks. Compared with children born large for gestational age (>90th percentile), children born small for gestational age (<10th percentile) had the lowest IQ, followed by those at the 10th–50th percentile and those at the >50th–90th percentile. These findings suggest that, even among healthy children born at term, cognitive ability at age 6.5 years is lower in those born at 37 or 38 weeks and those with suboptimal fetal growth.

Maternal Dietary Glycemic Intake and the Risk of Neural Tube Defects

Both maternal diabetes and obesity have been associated with an increased risk of neural tube defects (NTD), possibly due to a sustained state of hyperglycemia and/or hyperinsulinemia. Data were collected in the Boston University Slone Birth Defects Study (a case-control study) from 1988 to 1998. The authors examined whether high dietary glycemic index (DGI) and high dietary glycemic load (DGL) increased the risk of NTDs in nondiabetic women. Mothers of NTD cases and nonmalformed controls were interviewed in person within 6 months after delivery about diet and other exposures. Odds ratios and 95% confidence intervals were estimated from logistic regression for high DGI (≥60) and high DGL (≥205), with cutpoints determined by cubic spline. Of 698 case mothers, 25% had high DGI and 4% had high DGL. Of 696 control mothers, 15% had high DGI and 2% had high DGL. After adjustment for sociodemographic factors and other dietary factors, the odds ratio for high DGI was 1.5 (95% confidence interval: 1.1, 2.0); for high DGL, it was 1.8 (95% confidence interval: 0.8, 4.0). Diets with proportionally high DGI or DGL may put the developing fetus at risk of an NTD, adding further evidence that hyperglycemia lies within the pathogenic pathway.

Menopausal Hormone Therapy Use and Risk of Invasive Colon Cancer: The California Teachers Study

Results from epidemiologic studies of hormone therapy use and colon cancer risk are inconsistent. This question was investigated in the California Teachers Study (1995–2006) among 56,864 perimenopausal or postmenopausal participants under 80 years of age with no prior colorectal cancer by using Cox proportional hazards regression. Incident invasive colon cancer was diagnosed among 442 participants. Baseline-recent hormone therapy users were at 36% lower risk for colon cancer versus baseline-never users (baseline-recent users: relative risk (RR) = 0.64, 95% confidence interval (CI): 0.51, 0.80). Results did not differ by formulation. Estimated risk was lower among baseline-recent hormone therapy users with increasing duration between 5 and 15 years of use (RR = 0.49, 95% CI: 0.35, 0.68), but the trend did not persist in the longest duration group, more than 15 years of use (RR = 0.69, 95% CI: 0.52, 0.92; Ptrend = 0.60). Long-term recreational physical activity, obesity, regular use of nonsteroidal antiinflammatory medications, and daily alcohol intake did not modify these effects; baseline-recent use was more strongly associated with colon cancer risk among women with a family history of colorectal cancer (Pheterogeneity = 0.04). Baseline-recent hormone therapy use was inversely associated with invasive colon cancer risk among perimenopausal and postmenopausal women in the California Teachers Study.

Cardiorespiratory Fitness Levels Among US Adults 20-49 Years of Age: Findings From the 1999-2004 National Health and Nutrition Examination Survey

Data from the 1999–2004 National Health and Nutrition Examination Survey were used to describe the distribution of cardiorespiratory fitness and its association with obesity and leisure-time physical activity (LTPA) for adults 20–49 years of age without physical limitations or indications of cardiovascular disease. A sample of 7,437 adults aged 20–49 years were examined at a mobile examination center. Of 4,860 eligible for a submaximal treadmill test, 3,250 completed the test and were included in the analysis. The mean maximal oxygen uptake ( max) was estimated as 44.5, 42.8, and 42.2 mL/kg/minute for men 20–29, 30–39, and 40–49 years of age, respectively. For women, it was 36.5, 35.4, and 34.4 mL/kg/minute for the corresponding age groups. Non-Hispanic black women had lower fitness levels than did non-Hispanic white and Mexican-American women. Regardless of gender or race/ethnicity, people who were obese had a significantly lower estimated maximal oxygen uptake than did nonobese adults. Furthermore, a positive association between fitness level and LTPA participation was observed for both men and women. These results can be used to track future population assessments and to evaluate interventions. The differences in fitness status among population subgroups and by obesity status or LTPA can also be used to develop health policies and targeted educational campaigns.

Dairy Intake and the Risk of Bladder Cancer in the Netherlands Cohort Study on Diet and Cancer

The authors examined the association between the intake of different dairy products and the risk of bladder cancer in 120,852 men and women aged 55–69 years participating in the Netherlands Cohort Study on Diet and Cancer. Dairy product intake was assessed in 1986 by using a 150-item food frequency questionnaire. The cohort was followed for 16.3 years, and 1,549 incident cases of bladder cancer were analyzed. Cox proportional hazards analysis was applied with a case-cohort approach by using the follow-up data of a random subcohort (n = 5,000). Multivariate hazard ratio estimates comparing the highest with the lowest quintile of total dairy intake were 1.01 (95% confidence interval (CI): 0.81, 1.27; Ptrend = 0.68). A statistically significant association for fermented milk products was found only for the second quintile (median, 12 g/day) (hazard ratio = 0.71, 95% CI: 0.56, 0.91). Compared with nonconsumers, women with 25–75 g/day of butter consumption had a hazard ratio of 1.61 (95% CI: 1.03, 2.50; Ptrend < 0.01). No association was found with cheese, calcium, lactose, or nonfermented dairy intake. These results provide weak evidence that bladder cancer risk is inversely associated with low intake of fermented dairy products and suggest a positive association with butter intake in women.

Presence of Gallstones or Kidney Stones and Risk of Type 2 Diabetes

Recent evidence suggests that gallstones and kidney stones are associated with insulin resistance, but the relation between stone diseases and the risk of developing type 2 diabetes mellitus is not clear. Participants in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study (Potsdam, Germany) provided information about the presence of gallstones and kidney stones at recruitment between 1994 and 1998. On biennial questionnaires, participants reported newly diagnosed type 2 diabetes mellitus, and confirmation was obtained from treating physicians. During a mean follow-up period of 7.0 years between 1994 and 2005, 849 incident cases of type 2 diabetes were identified among 25,166 participants. After adjustment for sex, age, waist circumference, and lifestyle risk factors, persons with reported gallstones (n = 3,293) had an increased risk of type 2 diabetes (relative risk = 1.42, 95% confidence interval: 1.21, 1.68). Among the 23,817 participants with information on reported kidney stones (784 cases of incident diabetes), those who developed kidney stones (n = 2,468) were not at increased risk of diabetes in multivariable-adjusted models (relative risk = 1.05, 95% confidence interval: 0.86, 1.27). These findings suggest that gallstones, but not kidney stones, may predict the risk of developing type 2 diabetes, providing physicians with an interventional opportunity to implement adequate prevention measures.

Pesticide Use and Thyroid Disease Among Women in the Agricultural Health Study

Thyroid disease is common, and evidence of an association between organochlorine exposure and thyroid disease is increasing. The authors examined the cross-sectional association between ever use of organochlorines and risk of hypothyroidism and hyperthyroidism among female spouses (n = 16,529) in Iowa and North Carolina enrolled in the Agricultural Health Study in 1993–1997. They also assessed risk of thyroid disease in relation to ever use of herbicides, insecticides, fungicides, and fumigants. Prevalence of self-reported clinically diagnosed thyroid disease was 12.5%, and prevalence of hypothyroidism and hyperthyroidism was 6.9% and 2.1%, respectively. There was an increased odds of hypothyroidism with ever use of organochlorine insecticides (adjusted odds ratio (ORadj) = 1.2 (95% confidence interval (CI): 1.0, 1.6) and fungicides (ORadj = 1.4 (95% CI: 1.1, 1.8) but no association with ever use of herbicides, fumigants, organophosphates, pyrethroids, or carbamates. Specifically, ever use of the organochlorine chlordane (ORadj = 1.3 (95% CI: 0.99, 1.7), the fungicides benomyl (ORadj = 3.1 (95% CI: 1.9, 5.1) and maneb/mancozeb (ORadj = 2.2 (95% CI: 1.5, 3.3), and the herbicide paraquat (ORadj = 1.8 (95% CI: 1.1, 2.8) was significantly associated with hypothyroidism. Maneb/mancozeb was the only pesticide associated with both hyperthyroidism (ORadj = 2.3 (95% CI: 1.2, 4.4) and hypothyroidism. These data support a role of organochlorines, in addition to fungicides, in the etiology of thyroid disease among female spouses enrolled in the Agricultural Health Study.

Estimates of the Transmissibility of the 1968 (Hong Kong) Influenza Pandemic: Evidence of Increased Transmissibility Between Successive Waves

The transmissibility of the strain of influenza virus which caused the 1968 influenza pandemic is poorly understood. Increases in outbreak size between the first and second waves suggest that it may even have increased between successive waves. The authors estimated basic and effective reproduction numbers for both waves of the 1968 influenza pandemic. Epidemic curves and overall attack rates for the 1968 pandemic, based on clinical and serologic data, were retrieved from published literature. The basic and effective reproduction numbers were estimated from 46 and 17 data sets for the first and second waves, respectively, based on the growth rate and/or final size of the epidemic. Estimates of the basic reproduction number (R0) were in the range of 1.06–2.06 for the first wave and, assuming cross-protection, 1.21–3.58 in the second. Within each wave, there was little geographic variation in transmissibility. In the 10 settings for which data were available for both waves, R0 was estimated to be higher during the second wave than during the first. This might partly explain the larger outbreaks in the second wave as compared with the first. This potential for change in viral behavior may have consequences for future pandemic mitigation strategies.

Comparing 3 Dietary Pattern Methods--Cluster Analysis, Factor Analysis, and Index Analysis--With Colorectal Cancer Risk: The NIH-AARP Diet and Health Study

The authors compared dietary pattern methods—cluster analysis, factor analysis, and index analysis—with colorectal cancer risk in the National Institutes of Health (NIH)–AARP Diet and Health Study (n = 492,306). Data from a 124-item food frequency questionnaire (1995–1996) were used to identify 4 clusters for men (3 clusters for women), 3 factors, and 4 indexes. Comparisons were made with adjusted relative risks and 95% confidence intervals, distributions of individuals in clusters by quintile of factor and index scores, and health behavior characteristics. During 5 years of follow-up through 2000, 3,110 colorectal cancer cases were ascertained. In men, the vegetables and fruits cluster, the fruits and vegetables factor, the fat-reduced/diet foods factor, and all indexes were associated with reduced risk; the meat and potatoes factor was associated with increased risk. In women, reduced risk was found with the Healthy Eating Index-2005 and increased risk with the meat and potatoes factor. For men, beneficial health characteristics were seen with all fruit/vegetable patterns, diet foods patterns, and indexes, while poorer health characteristics were found with meat patterns. For women, findings were similar except that poorer health characteristics were seen with diet foods patterns. Similarities were found across methods, suggesting basic qualities of healthy diets. Nonetheless, findings vary because each method answers a different question.

Biochemical Validation of Food Frequency Questionnaire-Estimated Carotenoid, {alpha}-Tocopherol, and Folate Intakes Among African Americans and Non-Hispanic Whites in the Southern Community Cohort Study

Few food frequency questionnaires (FFQs) have been developed specifically for use among African Americans, and reports of FFQ performance among African Americans or low-income groups assessed using biochemical indicators are scarce. The authors conducted a validation study within the Southern Community Cohort Study to evaluate FFQ-estimated intakes of -carotene, β-carotene, β-cryptoxanthin, lutein/zeaxanthin, lycopene, folate, and -tocopherol in relation to blood levels of these nutrients. Included were 255 nonsmoking participants (125 African Americans, 130 non-Hispanic whites) who provided a blood sample at the time of study enrollment and FFQ administration in 2002–2004. Levels of biochemical indicators of each micronutrient (-tocopherol among women only) significantly increased with increasing FFQ-estimated intake (adjusted correlation coefficients: -carotene, 0.35; β-carotene, 0.28; β-cryptoxanthin, 0.35; lutein/zeaxanthin, 0.28; lycopene, 0.15; folate, 0.26; -tocopherol, 0.26 among women; all P's < 0.05). Subjects in the top decile of FFQ intake had blood levels that were 27% (lycopene) to 178% (β-cryptoxanthin) higher than those of subjects in the lowest decile. Satisfactory FFQ performance was noted even for participants with less than a high school education. Some variation was noted in the FFQ's ability to predict blood levels for subgroups defined by race, sex, and other characteristics, but overall the Southern Community Cohort Study FFQ appears to generate useful dietary exposure rankings in the cohort.

A Comparison of Sample Size and Power in Case-Only Association Studies of Gene-Environment Interaction

Assuming continuous, normally distributed environmental and categorical genotype variables, the authors compare 6 case-only designs for tests of association in gene-environment interaction. Novel tests modeling the environmental variable as either the response or the predictor and allowing a genetic variable with multiallelic variants are included. The authors show that tests imposing the same genotypic pattern of inheritance perform similarly regardless of whether genotype is the response variable or the predictor variable. The novel tests using the genetic variable as the response variable are advantageous because they are robust to non-normally distributed environmental exposures. Dominance deviance—deviation from additivity in the main or interaction effects—is key to test performance: When it is zero or modest, tests searching for a trend with increasing risk alleles are optimal; when it is large, tests for genotypic effects are optimal. However, the authors show that dominance deviance is attenuated when it is observed at a proxy locus, which is common in genome-wide association studies, so large dominance deviance is likely to be rare. The authors conclude that the trend test is the appropriate tool for large-scale association scans where the true gene-environment interaction model is unknown. The common practice of assuming a dominant pattern of inheritance can cause serious losses of power in the presence of any recessive, or modest dominant, effects.

Marginal Structural Models for Sufficient Cause Interactions

Sufficient cause interactions concern cases in which there is a particular causal mechanism for some outcome that requires the presence of 2 or more specific causes to operate. Empirical conditions have been derived to test for sufficient cause interactions. However, when regression outcome models are used to control for confounding variables in tests for sufficient cause interactions, the outcome models impose restrictions on the relation between the confounding variables and certain unidentified background causes within the sufficient cause framework; often, these assumptions are implausible. By using marginal structural models, rather than outcome regression models, to test for sufficient cause interactions, modeling assumptions are instead made on the relation between the causes of interest and the confounding variables; these assumptions will often be more plausible. The use of marginal structural models also allows for testing for sufficient cause interactions in the presence of time-dependent confounding. Such time-dependent confounding may arise in cases in which one factor of interest affects both the second factor of interest and the outcome. It is furthermore shown that marginal structural models can be used not only to test for sufficient cause interactions but also to give lower bounds on the prevalence of such sufficient cause interactions.

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Neighborhood Poverty and Injection Cessation in a Sample of Injection Drug Users

Variation in Child Cognitive Ability by Week of Gestation Among Healthy Term Births

Maternal Dietary Glycemic Intake and the Risk of Neural Tube Defects

Menopausal Hormone Therapy Use and Risk of Invasive Colon Cancer: The California Teachers Study

Cardiorespiratory Fitness Levels Among US Adults 20-49 Years of Age: Findings From the 1999-2004 National Health and Nutrition Examination Survey

Dairy Intake and the Risk of Bladder Cancer in the Netherlands Cohort Study on Diet and Cancer

Presence of Gallstones or Kidney Stones and Risk of Type 2 Diabetes

Pesticide Use and Thyroid Disease Among Women in the Agricultural Health Study

Estimates of the Transmissibility of the 1968 (Hong Kong) Influenza Pandemic: Evidence of Increased Transmissibility Between Successive Waves

Comparing 3 Dietary Pattern Methods--Cluster Analysis, Factor Analysis, and Index Analysis--With Colorectal Cancer Risk: The NIH-AARP Diet and Health Study

Biochemical Validation of Food Frequency Questionnaire-Estimated Carotenoid, {alpha}-Tocopherol, and Folate Intakes Among African Americans and Non-Hispanic Whites in the Southern Community Cohort Study

A Comparison of Sample Size and Power in Case-Only Association Studies of Gene-Environment Interaction

Marginal Structural Models for Sufficient Cause Interactions

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Tumor Necrosis Factor (TNF) and Lymphotoxin-{alpha} (LTA) Polymorphisms and Risk of Non-Hodgkin Lymphoma in the InterLymph Consortium

In an International Lymphoma Epidemiology Consortium pooled analysis, polymorphisms in 2 immune-system-related genes, tumor necrosis factor (TNF) and interleukin-10 (IL10), were associated with non-Hodgkin lymphoma (NHL) risk. Here, 8,847 participants were added to previous data (patients diagnosed from 1989 to 2005 in 14 case-control studies; 7,999 cases, 8,452 controls) for testing of polymorphisms in the TNF –308G>A (rs1800629), lymphotoxin- (LTA) 252A>G (rs909253), IL10 –3575T>A (rs1800890, rs1800896), and nucleotide-binding oligomerization domain containing 2 (NOD2) 3020insC (rs2066847) genes. Odds ratios were estimated for non-Hispanic whites and several ethnic subgroups using 2-sided tests. Consistent with previous findings, odds ratios were increased for "new" participant TNF –308A carriers (NHL: per-allele odds ratio (ORallelic) = 1.10, Ptrend = 0.001; diffuse large B-cell lymphoma (DLBCL): ORallelic = 1.23, Ptrend = 0.004). In the combined population, odds ratios were increased for TNF –308A carriers (NHL: ORallelic = 1.13, Ptrend = 0.0001; DLBCL: ORallelic = 1.25, Ptrend = 3.7 x 10–6; marginal zone lymphoma: ORallelic = 1.35, Ptrend = 0.004) and LTA 252G carriers (DLBCL: ORallelic = 1.12, Ptrend = 0.006; mycosis fungoides: ORallelic = 1.44, Ptrend = 0.015). The LTA 252A>G/TNF –308G>A haplotype containing the LTA/TNF variant alleles was strongly associated with DLBCL (P = 2.9 x 10–8). Results suggested associations between IL10 –3575T>A and DLBCL (Ptrend = 0.02) and IL10 –1082A>G and mantle cell lymphoma (Ptrend = 0.04). These findings strengthen previous results for DLBCL and the LTA 252A>G/TNF –308A locus and provide robust evidence that these TNF/LTA gene variants, or others in linkage disequilibrium, are involved in NHL etiology.

A Prospective Study of Albuminuria and Cognitive Function in Older Adults: The Rancho Bernardo Study

Chronic kidney disease is a risk factor for cognitive impairment. Albuminuria is an early manifestation of chronic kidney disease and a marker of endothelial dysfunction and vascular risk. Results of prior studies of albuminuria and cognitive function are contradictory. The authors studied 1,345 community-dwelling women and men in southern California (mean age, 75 years) at a 1992–1996 research clinic visit, when urine albumin/creatinine ratio (ACR) was measured in spot morning urine and cognitive function was evaluated by using the Mini-Mental State Examination Trail-Making Test B, and category fluency test. An ACR of ≥30 mg/g was found in 17% of women and 15% of men in 1992–1996. Analysis of covariance was used to compare cognitive function score by categorical ACR. Between 1999 and 2002, 759 participants returned for repeat cognitive function testing. For men, but not women, baseline albuminuria, but not estimated glomerular filtration rate, was associated with reduced cognitive function at follow-up on all tests (P's < 0.05). An ACR of ≥30 mg/g was associated with greater annual decline in Mini-Mental State Examination and category fluency scores. Albuminuria may be an easily measured marker predicting future cognitive function decline. Results imply a common underlying mechanism affecting the renal and cerebral microvasculature.

Invited Commentary: Albuminuria and Microvascular Disease of the Brain--A Shared Pathophysiology

This commentary considers the implications of the association between albuminuria and cognitive decline described by Jassal et al. in this issue of the Journal (Am J Epidemiol. 2010;171(3):290–291). The authors report that men with albuminuria had a greater likelihood than men without albuminuria of experiencing declines in cognitive function over a 6.6-year period. Albuminuria is the result of endothelial damage in the kidney, which, in turn, is the result of microvascular disease. If one of the key mechanisms of brain microvascular disease is leakage of serum proteins into the brain extracellular space, in a fashion parallel to albuminuria that occurs in nephrosclerosis, several facets of cerebrovascular disease and cognitive decline are explained. First, brain microvascular disease would not be recognized by traditional clinical features of cerebrovascular disease because brain microvascular disease occurs gradually and insidiously. Second, the extravasation of serum proteins as a result of brain microvascular disease would account for the perivascular distribution of white matter hyperintensities on magnetic resonance imaging. Albuminuria might be a useful screening test for generalized microvascular disease and, if detected, might reasonably prompt brain imaging and more intensive therapeutic efforts to forestall further endothelial dysfunction in the kidney, brain, and elsewhere.

Jassal et al. Respond to "Microalbuminuria and Brain Vascular Disease"

Secondhand Smoke, Vascular Disease, and Dementia Incidence: Findings From the Cardiovascular Health Cognition Study

Recent studies have found that smoking is associated with an increased risk of dementia, but the effects of secondhand smoke (SHS) on dementia risk are not known to have previously been studied. The authors used Cox proportional hazards marginal structural models to examine the association between self-reported lifetime household SHS exposure and risk of incident dementia over 6 years among 970 US participants in the Cardiovascular Health Cognition Study (performed from 1991 to 1999) who were never smokers and were free of clinical cardiovascular disease (CVD), dementia, and mild cognitive impairment at baseline. In addition, because prior studies have found that SHS is associated with increased risk of CVD and that CVD is associated with increased risk of dementia, the authors tested for interactions between SHS and measures of clinical and subclinical CVD on dementia risk. Moderate (16–25 years) and high (>25 years) SHS exposure levels were not independently associated with dementia risk; however, subjects with >25 years of SHS exposure and >25% carotid artery stenosis had a 3-fold increase (hazard ratio = 3.00, 95% confidence interval: 1.03, 9.72) in dementia risk compared with subjects with no/low (0–15 years) SHS exposure and ≤25% carotid artery stenosis. High lifetime SHS exposure may increase the risk of dementia in elderly with undiagnosed CVD.

Effects of Externally Rated Job Demand and Control on Depression Diagnosis Claims in an Industrial Cohort

This study examined whether externally rated job demand and control were associated with depression diagnosis claims in a heavy industrial cohort. The retrospective cohort sample consisted of 7,566 hourly workers aged 18–64 years who were actively employed at 11 US plants between January 1, 1996, and December 31, 2003, and free of depression diagnosis claims during an initial 2-year run-in period. Logistic regression analysis was used to model the effect of tertiles of demand and control exposure on depression diagnosis claims. Demand had a significant positive association with depression diagnosis claims in bivariate models and models adjusted for demographic (age, gender, race, education, job grade, tenure) and lifestyle (smoking status, body mass index, cholesterol level) variables (high demand odds ratio = 1.39, 95% confidence interval: 1.04, 1.86). Control was associated with greater risk of depression diagnosis at moderate levels in unadjusted models only (odds ratio = 1.47, 95% confidence interval: 1.12, 1.93), while low control, contrary to expectation, was not associated with depression. The effects of the externally rated demand exposure were lost with adjustment for location. This may reflect differences in measurement or classification of exposure, differences in depression diagnosis by location, or other location-specific factors.

Diet, Lifestyle, and Acute Myeloid Leukemia in the NIH-AARP Cohort

The relation between diet, lifestyle, and acute myeloid leukemia was assessed in a US cohort of 491,163 persons from the NIH–AARP Diet and Health Study (1995–2003). A total of 338 incident cases of acute myeloid leukemia were ascertained. Multivariate Cox models were utilized to estimate hazard ratios and 95% confidence intervals. Compared with those for never smokers, hazard ratios were 1.29 (95% confidence interval: 0.95, 1.75), 1.79 (95% confidence interval: 1.32, 2.42), 2.42 (95% confidence interval: 1.63, 3.57), and 2.29 (85% confidence interval: 1.38, 3.79) for former smokers who smoked ≤1 or >1 pack/day and for current smokers who smoked ≤1 or >1 pack/day, respectively. Higher meat intake was associated with an increased risk of acute myeloid leukemia (hazard ratio = 1.45, 95% confidence interval: 1.02, 2.07 for the fifth vs. first quintile; P for trend = 0.06); however, there were no clear effects of meat-cooking method or doneness level. Individuals who did not drink coffee appeared to have a higher risk of acute myeloid leukemia than those who drank various quantities of coffee. Neither fruit nor vegetable intake was associated with acute myeloid leukemia. This large prospective study identified smoking and meat intake as risk factors for acute myeloid leukemia.

Lung Cancer and Occupation in a Population-based Case-Control Study

The authors examined the relation between occupation and lung cancer in the large, population-based Environment And Genetics in Lung cancer Etiology (EAGLE) case-control study. In 2002–2005 in the Lombardy region of northern Italy, 2,100 incident lung cancer cases and 2,120 randomly selected population controls were enrolled. Lifetime occupational histories (industry and job title) were coded by using standard international classifications and were translated into occupations known (list A) or suspected (list B) to be associated with lung cancer. Smoking-adjusted odds ratios and 95% confidence intervals were calculated with logistic regression. For men, an increased risk was found for list A (177 exposed cases and 100 controls; odds ratio = 1.74, 95% confidence interval: 1.27, 2.38) and most occupations therein. No overall excess was found for list B with the exception of filling station attendants and bus and truck drivers (men) and launderers and dry cleaners (women). The authors estimated that 4.9% (95% confidence interval: 2.0, 7.8) of lung cancers in men were attributable to occupation. Among those in other occupations, risk excesses were found for metal workers, barbers and hairdressers, and other motor vehicle drivers. These results indicate that past exposure to occupational carcinogens remains an important determinant of lung cancer occurrence.

Age at Menarche and Risk of Type 2 Diabetes: Results From 2 Large Prospective Cohort Studies

The authors investigated the association between age at menarche and risk of type 2 diabetes mellitus (T2DM) among 101,415 women from the Nurses’ Health Study (NHS) aged 34–59 years (1980–2006) and 100,547 women from Nurses’ Health Study II (NHS II) aged 26–46 years (1991–2005). During 2,430,274 and 1,373,875 person-years of follow-up, respectively, 7,963 and 2,739 incident cases of T2DM were documented. Young age at menarche was associated with increased risk of T2DM after adjustment for potential confounders, including body figure at age 10 years and body mass index (BMI; weight (kg)/height (m)2) at age 18 years. Relative risks of T2DM across age-at-menarche categories (≤11, 12, 13, 14, and ≥15 years) were 1.18 (95% confidence interval (CI): 1.10, 1.27), 1.09 (95% CI: 1.02, 1.17), 1.00 (referent), 0.92 (95% CI: 0.83, 1.01), and 0.95 (95% CI: 0.84, 1.06), respectively, in the NHS (P for trend < 0.0001) and 1.40 (95% CI: 1.24, 1.57), 1.13 (95% CI: 1.00, 1.27), 1.00 (referent), 0.98 (95% CI: 0.82, 1.18), and 0.96 (95% CI: 0.78, 1.19), respectively, in NHS II (P for trend < 0.0001). Associations were substantially attenuated after additional control for updated time-varying BMI. These data suggest that early menarche is associated with increased risk of T2DM in adulthood. The association may be largely mediated through excessive adult adiposity. The association was stronger among younger women, supporting a role for sex hormones in younger onset of T2DM, in addition to BMI.

How Does Socioeconomic Development Affect Risk of Mortality? An Age-Period-Cohort Analysis From a Recently Transitioned Population in China

During the 20th century, the Hong Kong Chinese population experienced 2 abrupt but temporally distinct macroenvironmental changes: The transition from essentially preindustrial living conditions to a rapidly developing economy through mass migration in the late 1940s was followed by the emergence of an infant and childhood adiposity epidemic in the 1960s. The authors aimed to delineate the effects of these 2 aspects of economic development on mortality, thus providing a sentinel for other rapidly developing economies. Sex-specific Poisson models were used to estimate effects of age, calendar period, and birth cohort on Hong Kong adult mortality between 1976 and 2005. All-cause and cause-specific mortality, including mortality from ischemic heart disease (IHD), cardiovascular disease excluding IHD, lung cancer, other cancers, and respiratory disease, were considered. Male mortality from IHD and female mortality from other cancers increased with birth into a more economically developed environment. Cardiovascular disease mortality increased with birth after the start of the infant and childhood adiposity epidemic, particularly for men. Macroenvironmental changes associated with economic development had sex-specific effects over the life course, probably originating in early life. The full population health consequences of these changes are unlikely to manifest until persons who have spent their early lives in such environments reach an age at which they become vulnerable to chronic diseases.

Correlates for Human Papillomavirus Vaccination of Adolescent Girls and Young Women in a Managed Care Organization

The authors studied the characteristics of those who initiated the human papillomavirus (HPV) vaccine versus those who did not. Female members of Kaiser Permanente Southern California aged 9–26 years were identified and assessed for HPV vaccination between October 2006 and March 2008. Multivariable log-binomial regression was used to examine the association of the following factors with vaccine initiation: 1) demographics, 2) provider characteristics, 3) health care utilization, 4) women's health-related conditions, and 5) selected immune-related conditions. The study included 285,265 females. All analyses were stratified by 2 age groups: 9–17 years and 18–26 years. Black race (relative risk (RR)9–17 years = 0.93, RR18–26 years = 0.82), having a male primary care provider (RR9–17 years = 0.93, RR18–26 years = 0.84), and history of hospitalizations were associated with a lower likelihood of vaccine initiation. Higher neighborhood income level, physician office visits, and history of influenza vaccination (RR9–17 years = 1.20, RR18–26 years = 1.34) were associated with higher HPV vaccine uptake. Those with a history of sexually transmitted diseases were more likely and those with immune-related conditions were not less likely to initiate the HPV vaccine. These findings are helpful for interpreting the results of observational safety studies and providing insights for developing targeted HPV vaccination programs.

The Relevance of Different Methods of Calculating the Ankle-Brachial Index: The Multi-Ethnic Study of Atherosclerosis

The authors aimed to determine differences in the prevalence of peripheral arterial disease (PAD) and its associations with cardiovascular disease (CVD) risk factors, using different methods of calculating the ankle-brachial index (ABI). Using measurements taken in the bilateral brachial, dorsalis pedis, and posterior tibial arteries, the authors calculated ABI in 3 ways: 1) with the lowest ankle pressure (dorsalis pedis artery or posterior tibial artery) ("ABI-LO"), 2) with the highest ankle pressure ("ABI-HI"), and 3) with the mean of the ankle pressures ("ABI-MN"). For all 3 methods, the index ABI was the lower of the ABIs calculated from the left and right legs. PAD was defined as an ABI less than 0.90. Among 6,590 subjects from a multiethnic cohort (baseline examination: 2000–2002), in comparison with ABI-HI, the relative prevalence of PAD was 3.95 times higher in women and 2.74 times higher in men when ABI-LO was used. The relative magnitudes of the associations were largest between PAD and both subclinical atherosclerosis and CVD risk factors when ABI-HI was used, except when risk estimates for PAD were less than 1.0, where the largest relative magnitudes of association were found using ABI-LO. PAD prevalence and its associations with CVD risk factors and subclinical atherosclerosis measures depend on the ankle pressure used to compute the ABI.

Fitting General Relative Risk Models for Survival Time and Matched Case-Control Analysis

Cox proportional hazards regression analysis of survival data and conditional logistic regression analysis of matched case-control data are methods that are widely used by epidemiologists. Standard statistical software packages accommodate only log-linear model forms, which imply exponential exposure-response functions and multiplicative interactions. In this paper, the authors describe methods for fitting non-log-linear Cox and conditional logistic regression models. The authors use data from a study of lung cancer mortality among Colorado Plateau uranium miners (1950–1982) to illustrate these methods for fitting general relative risk models to matched case-control control data, countermatched data with weights, d:m matching, and full cohort Cox regression using the SAS statistical package (SAS Institute Inc., Cary, North Carolina).

Smallpox--The Death of a Disease: The Inside Story of Eradicating a Worldwide Killer: By D. A. Henderson

Getting What We Deserve: Health & Medical Care in America: By Alfred Sommer

Re: "Vitamin C Deficiency in a Population of Young Canadian Adults"

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Re: "Chronic Particulate Exposure, Mortality, and Coronary Heart Disease in the Nurses' Health Study"

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The Association Between Obesity and Low Back Pain: A Meta-Analysis

This meta-analysis assessed the association between overweight/obesity and low back pain. The authors systematically searched the Medline (National Library of Medicine, Bethesda, Maryland) and Embase (Elsevier, Amsterdam, the Netherlands) databases until May 2009. Ninety-five studies were reviewed and 33 included in the meta-analyses. In cross-sectional studies, obesity was associated with increased prevalence of low back pain in the past 12 months (pooled odds ratio (OR) = 1.33, 95% confidence interval (CI): 1.14, 1.54), seeking care for low back pain (OR = 1.56, 95% CI: 1.46, 1.67), and chronic low back pain (OR = 1.43, 95% CI: 1.28, 1.60). Compared with nonoverweight people, overweight people had a higher prevalence of low back pain but a lower prevalence of low back pain compared with obese people. In cohort studies, only obesity was associated with increased incidence of low back pain for ≥1 day in the past 12 months (OR = 1.53, 95% CI: 1.22, 1.92). Results remained consistent after adjusting for publication bias and limiting the analyses to studies that controlled for potential confounders. Findings indicate that overweight and obesity increase the risk of low back pain. Overweight and obesity have the strongest association with seeking care for low back pain and chronic low back pain.

Impact of Improved Classification on the Association of Human Papillomavirus With Cervical Precancer

Misclassification of exposure and surrogate endpoints of disease can obscure causal relations. Using data from the Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study (ALTS, 1997–2001), the authors explored the impact of exposure (human papillomavirus (HPV) detection) and endpoint (histologic cervical precancer) classification on their mutual association. Women referred into this study with an atypical squamous cells of undetermined significance Papanicolaou test with satisfactory results for all 4 HPV tests were included in this analysis (n = 3,215; 92.2%). HPV testing results were related to different definitions of cervical precancer, based on paired, worst 2-year histologic diagnoses, by calculating clinical sensitivity, specificity, and odds ratios. The authors found that HPV test sensitivity increased and specificity decreased with increasing certainty of cervical precancer, with HPV testing having the highest sensitivity (92%–98%) and lowest specificity (46%–54%) for consensus cervical intraepithelial neoplasia grade 3 (CIN 3). The overall accuracy of each HPV test, as measured by odds ratios, was greatest for consensus CIN-3 diagnoses, from 2- to 4-fold greater than for a less stringent precancer definition of any diagnosis of CIN 2 or more severe. In summary, there was convergence of greater certainty of carcinogenic HPV with greater certainty of a precancerous diagnosis, such that all 4 HPV tests almost always tested positive in women most likely to have cervical precancer. Finding increasingly strong associations when both test and diagnostic misclassification are reduced is a useful sign of "true association" in molecular epidemiology.

Invited Commentary: Human Papillomavirus Infection and Risk of Cervical Precancer--Using the Right Methods to Answer the Right Questions

Epidemiologists are well aware of the negative consequences of measurement error in exposure and outcome variables to their ability to detect putative causal associations. However, empirical proof that remedying the misclassification problem improves estimates of epidemiologic effect is seldom examined in detail. Of all areas in cancer epidemiology, perhaps the best example of the consequences of misclassification and of the steps taken to circumvent them was the pursuit, beginning in the mid-1980s, of the human papillomavirus (HPV) infection–cervical cancer association. The stakes were high: Had the wrong conclusions been reached epidemiologists would have been led astray in the search for competing hypotheses for the sexually transmissible agent causing cervical cancer or in ascribing to HPV infection a mere ancillary role among many lifestyle, hormonal, and environmental factors. The article by Castle et al. in this issue of the Journal (Am J Epidemiol. 2010;171(2):155–163) provides a detailed account of the joint influences of improved HPV and cervical precancer measurements in gradually unveiling the strong magnitude of the underlying association between viral exposure and cervical lesion risk. In this commentary, the authors extend the findings of Castle et al. by providing additional empirical evidence in support of their arguments.

Between-Strain Competition in Acquisition and Clearance of Pneumococcal Carriage--Epidemiologic Evidence From a Longitudinal Study of Day-Care Children

The state of pneumococcal carriage—that is, pneumococcal colonization in the nasopharynx of healthy persons—represents a reservoir for the spread of pneumococci among individuals. In light of the introduction of new pneumococcal conjugate vaccines, further knowledge on the dynamics of pneumococcal carriage is important. Different serotypes (strains) of pneumococcus are known to compete with each other in colonizing human hosts. Understanding the strength and mode of between-serotype competition is important because of its implications for vaccine-induced changes in the ecology of pneumococcal carriage. Competition may work through reduced acquisition of new serotypes, due to concurrent carriage in the individual, or through enhanced clearance of serotypes in carriers who harbor more than 1 serotype simultaneously. The authors employed longitudinal data (1999–2001) on pneumococcal carriage in Danish day-care children to analyze between-serotype competition. The data included observations of carriage in children who had not been vaccinated against pneumococcus, and the level of pneumococcal antibiotic resistance and antibiotic usage in the community was very low. Clearance of any single serotype was not affected by simultaneous carriage of other serotypes. In contrast, acquisition of other serotypes in already-colonized hosts was weak (relative rate of acquisition = 0.09, 95% credible interval: 0.05, 0.15).

Near Real-Time Surveillance for Influenza Vaccine Safety: Proof-of-Concept in the Vaccine Safety Datalink Project

The emergence of pandemic H1N1 influenza in 2009 has prompted public health responses, including production and licensure of new influenza A (H1N1) 2009 monovalent vaccines. Safety monitoring is a critical component of vaccination programs. As proof-of-concept, the authors mimicked near real-time prospective surveillance for prespecified neurologic and allergic adverse events among enrollees in 8 medical care organizations (the Vaccine Safety Datalink Project) who received seasonal trivalent inactivated influenza vaccine during the 2005/06–2007/08 influenza seasons. In self-controlled case series analysis, the risk of adverse events in a prespecified exposure period following vaccination was compared with the risk in 1 control period for the same individual either before or after vaccination. In difference-in-difference analysis, the relative risk in exposed versus control periods each season was compared with the relative risk in previous seasons since 2000/01. The authors used Poisson-based analysis to compare the risk of Guillian-Barré syndrome following vaccination in each season with that in previous seasons. Maximized sequential probability ratio tests were used to adjust for repeated analyses on weekly data. With administration of 1,195,552 doses to children under age 18 years and 4,773,956 doses to adults, no elevated risk of adverse events was identified. Near real-time surveillance for selected adverse events can be implemented prospectively to rapidly assess seasonal and pandemic influenza vaccine safety.

Longitudinal Data Analysis for Generalized Linear Models Under Participant-Driven Informative Follow-up: An Application in Maternal Health Epidemiology

It is common in longitudinal studies for scheduled visits to be accompanied by as-needed visits due to medical events occurring between scheduled visits. If the timing of these as-needed visits is related to factors that are associated with the outcome but are not among the regression model covariates, naively including these as-needed visits in the model yields biased estimates. In this paper, the authors illustrate and discuss the key issues pertaining to inverse intensity rate ratio (IIRR)-weighted generalized estimating equations (GEE) methods in the context of a study of Kenyan mothers infected with human immunodeficiency virus type 1 (1999–2005). The authors estimated prevalences and prevalence ratios for morbid conditions affecting the women during a 1-year postpartum follow-up period. Of the 484 women under study, 62% had at least 1 as-needed visit. Use of a standard GEE model including both scheduled and unscheduled visits predicted a pneumonia prevalence of 2.9% (95% confidence interval: 2.3%, 3.5%), while use of the IIRR-weighted GEE predicted a prevalence of 1.5% (95% confidence interval: 1.2%, 1.8%). The estimate obtained using the IIRR-weighted GEE approach was compatible with estimates derived using scheduled visits only. These results highlight the importance of properly accounting for informative follow-up in these studies.

Copy-Years Viremia as a Measure of Cumulative Human Immunodeficiency Virus Viral Burden

Plasma human immunodeficiency virus type 1 (HIV-1) viral load is a valuable tool for HIV research and clinical care but is often used in a noncumulative manner. The authors developed copy-years viremia as a measure of cumulative plasma HIV-1 viral load exposure among 297 HIV seroconverters from the Multicenter AIDS Cohort Study (1984–1996). Men were followed from seroconversion to incident acquired immunodeficiency syndrome (AIDS), death, or the beginning of the combination antiretroviral therapy era (January 1, 1996); the median duration of follow-up was 4.6 years (interquartile range (IQR), 2.7–6.5). The median viral load and level of copy-years viremia over 2,281 semiannual follow-up assessments were 29,628 copies/mL (IQR, 8,547–80,210) and 63,659 copies x years/mL (IQR, 15,935–180,341). A total of 127 men developed AIDS or died, and 170 survived AIDS-free and were censored on January 1, 1996, or lost to follow-up. Rank correlations between copy-years viremia and other measures of viral load were 0.56–0.87. Each log10 increase in copy-years viremia was associated with a 1.70-fold increased hazard (95% confidence interval: 0.94, 3.07) of AIDS or death, independently of infection duration, age, race, CD4 cell count, set-point, peak viral load, or most recent viral load. Copy-years viremia, a novel measure of cumulative viral burden, may provide prognostic information beyond traditional single measures of viremia.

C-Reactive Protein and Retinal Microvascular Caliber in a Multiethnic Asian Population

Retinal microvascular caliber is a risk marker for cardiovascular disease. The authors examined the relation between high-sensitivity C-reactive protein (hsCRP) and retinal microvascular caliber in a multiethnic Asian population (n = 3,583) of Chinese, Malays, and Indians aged 24–95 years residing in Singapore (2003–2007). Retinal arteriolar and venular diameters were measured and summarized as central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE), respectively. Persons with higher levels of hsCRP had wider CRVE (Ptrend < 0.001). In subgroup analysis stratified for different cardiovascular disease risk factors, the association between hsCRP and CRVE was seen in persons without diabetes (Ptrend < 0.001) but was absent in persons with diabetes (Ptrend = 0.200; Pinteraction = 0.004). No significant interaction between race/ethnicity and hsCRP in relation to retinal vascular caliber was observed. These data suggest that retinal venular caliber is associated with higher levels of hsCRP in Asians, which is consistent with studies in white Caucasian populations, further supporting the concept that retinal venular caliber may be a marker for low-grade systemic inflammation.

Red Blood Cell Distribution Width and Risk of Cardiovascular Events and Mortality in a Community Cohort in Taiwan

The authors investigated whether red blood cell distribution width (RDW) was associated with the development of cardiovascular disease (CVD) events and mortality in a community cohort in Taiwan. The influence of anemia on the association was also assessed. RDW levels were measured in 3,226 participants aged 35 years or older who reported no CVD or cancer at baseline in 1990. During a median follow-up period of 15.9 years (1990–2007), 358 participants experienced stroke and/or coronary heart disease, and 810 participants died. The multivariate-adjusted hazard ratio for subjects in the highest RDW quartile as compared with the lowest quartile was 1.46 for both all-cause mortality (95% confidence interval: 1.17, 1.81) and non-CVD mortality (95% confidence interval: 1.13, 1.88) (P for trend < 0.01 for both) but was not significant for CVD morbidity and mortality. Further analyses showed that in comparison with participants with low RDW and no anemia, persons with high RDW but no anemia had elevated risks of all-cause mortality and non-CVD mortality. The authors conclude that elevated RDW values are associated with increased risk of mortality but not the development of CVD in the general population. RDW may precede anemia in predicting the risk of non-CVD death.

A Prospective Study of Dairy Intake and Risk of Uterine Leiomyomata

Rates of uterine leiomyomata are 2–3 times higher among black women than white women. Dietary factors that differ in prevalence between these populations that could contribute to the disparity include dairy intake. During 1997–2007, the authors followed 22,120 premenopausal US Black Women's Health Study participants to assess dairy intake in relation to uterine leiomyomata risk. Because soy may be substituted for dairy, the effect of soy intake was also evaluated. Diet was estimated by using food frequency questionnaires in 1995 and 2001. Incidence rate ratios and 95% confidence intervals were estimated with Cox regression. There were 5,871 incident cases of uterine leiomyomata diagnosed by ultrasound (n = 3,964) or surgery (n = 1,907). Multivariable incidence rate ratios comparing 1, 2, 3, and ≥4 servings/day with <1 serving/day of total dairy were 0.94 (95% confidence interval (CI): 0.88, 1.00), 0.87 (95% CI: 0.78, 0.98), 0.84 (95% CI: 0.70, 1.01), and 0.70 (95% CI: 0.58, 0.86), respectively (P-trend <0.001). Incidence rate ratios comparing the highest (≥2 servings/day) with the lowest (<1 serving/week) intake categories were 0.81 (95% CI: 0.66, 0.99) for high-fat dairy, 0.80 (95% CI: 0.70, 0.91) for low-fat dairy, and 0.78 (95% CI: 0.68, 0.89) for milk. Soy intake was unrelated to uterine leiomyomata risk. This large prospective study of black women provides the first epidemiologic evidence of reduced uterine leiomyomata risk associated with dairy consumption.

A Prospective Study of Magnesium and Iron Intake and Pancreatic Cancer in Men

Many studies have investigated the relation between magnesium and iron intake and diabetes and, separately, between diabetes and pancreatic cancer. However, no known study has examined the direct association of magnesium and iron intake with pancreatic cancer risk. The authors obtained magnesium and iron intake data using food frequency questionnaires from the US male Health Professionals Follow-up Study, which began in 1986. During 851,476 person-years and 20 years of follow-up, 300 pancreatic cancer cases were documented. Cox proportional hazards models were used to estimate relative risks, adjusting for age, smoking, and body mass index. No associations were observed between magnesium or iron intake and pancreatic cancer (highest vs. lowest quintile: relative risk (RR) = 0.94, 95% confidence interval (CI): 0.66, 1.32 and RR = 0.93, 95% CI: 0.65, 1.34, respectively). Similarly, iron or magnesium supplement use was not related to pancreatic cancer. A statistically significant inverse relation was noted between magnesium and pancreatic cancer for subjects with a body mass index of ≥25 kg/m2 (RR = 0.67, 95% CI: 0.46, 0.99; P-trend = 0.04). Although, overall, no relation between magnesium or iron intake and pancreatic cancer was observed in this cohort of men, an inverse association with magnesium was suggested among overweight individuals, which should be examined in other studies.

Nonradiation Risk Factors for Thyroid Cancer in the US Radiologic Technologists Study

The incidence of thyroid cancer has been rapidly increasing in the United States, but few risk factors have been established. The authors prospectively examined the associations of self-reported medical history, anthropometric factors, and behavioral factors with thyroid cancer risk among 90,713 US radiologic technologists (69,506 women and 21,207 men) followed from 1983 through 2006. Incident thyroid cancers in 242 women and 40 men were reported. Elevated risks were observed for women with benign thyroid conditions (hazard ratio (HR) = 2.35, 95% confidence interval (CI): 1.73, 3.20), benign breast disease (HR = 1.56, 95% CI: 1.08, 2.26), asthma (HR = 1.68, 95% CI: 1.00, 2.83), and body mass index ≥35.0 versus 18.5–24.9 kg/m2 (HR = 1.74, 95% CI: 1.03, 2.94; P-trend = 0.04). Current smoking was inversely associated with thyroid cancer risk (HR = 0.54). No clear associations emerged for reproductive factors, other medical conditions, alcohol intake, or physical activity. Despite few thyroid cancers in men, men with benign thyroid conditions had a significantly increased risk of thyroid cancer (HR = 4.65, 95% CI: 1.62, 13.34), and results for other risk factors were similar to those for women. Consistent with prior studies, obesity and benign thyroid conditions increased and current smoking decreased the risk of thyroid cancer. The novel findings for benign breast disease and asthma warrant further investigation.

An Exploration of Shared Genetic Risk Factors Between Periodontal Disease and Cancers: A Prospective Co-Twin Study

Biologic mechanisms underlying associations of periodontal disease with cancers remain unknown. The authors propose that both conditions share common genetic risk factors. They analyzed associations between baseline periodontal disease, measured by questionnaire-recorded tooth mobility, and incident cancers, identified by linkage with national registries, between 1963 and 2004 in 15,333 Swedish twins. The authors used co-twin analyses to control for familial factors and undertook analyses restricted to monozygotic twins to further control for confounding by genetic factors. They observed 4,361 cancer cases over 548,913 person-years. After adjustment for covariates, baseline periodontal disease was associated with increased risk of several cancers ranging from 15% for total cancer (proportional hazard ratio (HR) = 1.15, 95% confidence interval (CI): 1.01, 1.32) to 120% for corpus uterine cancer (HR = 2.20, 95% CI: 1.16, 4.18). Periodontal disease was also associated with increased risk of colorectal (HR = 1.62, 95% CI: 1.13, 2.33), pancreatic (HR = 2.06, 95% CI: 1.14, 3.75), and prostate (HR = 1.47, 95% CI: 1.04, 2.07) cancers. In co-twin analyses, dizygotic twins with baseline periodontal disease showed a 50% increase in total cancer risk (HR = 1.50, 95% CI: 1.04, 2.17), but in monozygotic twins this association was markedly attenuated (HR = 1.07, 95% CI: 0.63, 1.81). Similar patterns emerged for digestive tract cancers, suggesting that shared genetic risk factors may partially explain associations between periodontal disease and cancers.

Generational Differences in the Prevalence of Hearing Impairment in Older Adults

There were significant changes in health and lifestyle throughout the 20th century which may have changed temporal patterns of hearing impairment in adults. In this study, the authors aimed to assess the effect of birth cohort on the prevalence of hearing impairment in an adult population aged 45–94 years, using data collected between 1993 and 2008 from 3 cycles of the Epidemiology of Hearing Loss Study (n = 3,753; ages 48–92 years at baseline) and a sample of participants from the Beaver Dam Offspring Study (n = 2,173; ages ≥45 years). Hearing impairment was defined as a pure-tone average of thresholds at 0.5, 1, 2, and 4 kHz greater than 25-dB HL [hearing level]. Descriptive analysis, generalized additive models, and alternating logistic regression models were used to examine the birth cohort effect. Controlling for age, with every 5-year increase in birth year, the odds of having hearing impairment were 13% lower in men (odds ratio = 0.87, 95% confidence interval: 0.83, 0.92) and 6% lower in women (odds ratio = 0.94, 95% confidence interval: 0.89, 0.98). These results suggest that 1) older adults may be retaining good hearing longer than previous generations and 2) modifiable factors contribute to hearing impairment in adults.

Volume 138 Issue 03

Epidemiology and Infection, Volume 138 Issue 03 Increased frequency in 2007 - now 8 issues per year! Epidemiology and Infection publishes original reports and reviews on all aspects of infection in humans and animals. Particular emphasis is given to the epidemiology, prevention and control of infectious diseases. The field covered is broad and includes the zoonoses, tropical infections, food hygiene, vaccine studies, statistics and the clinical, social and public-health aspects of infectious disease. Papers covering microbiology and immunology which have an epidemiological relevance are part of this broad field. Papers come from medical and veterinary scientists worldwide. It has become the key periodical in which to find the latest reports on recently discovered infections and new technology. For those concerned with policy and planning for the control of infections, the papers on mathematical modelling of epidemics caused by historical, current and emergent infections, will be of particular value. To celebrate 100 years of the journal, a series of important papers has been selected and each, together with a modern commentary on the paper by an expert, will be published on-line. This journal has now moved over to electronic submission, using the Scholar One system. Click here to go to the submission website. Guidance on how to upload your manuscript is available on the site by clicking "User Tutorials". Online manuscript submission (now) available, please go to http://mc.manuscriptcentral.com/cup/hyg

Rabies epidemiology and control in Turkey: past and present

Review ArticlesN. JOHNSON, H. UN, A. R. FOOKS, C. FREULING, T. MÜLLER, O. AYLAN, A. VOS, Epidemiology and Infection, Volume 138 Issue 03 , pp 305-312Abstract

Staphylococcus aureus is the most common identified cause of cellulitis: a systematic review

Brief ReportS. CHIRA, L. G. MILLER, Epidemiology and Infection, Volume 138 Issue 03 , pp 313-317Abstract

Salmonella enterica serovar Typhi in Japan, 2001–2006: emergence of high-level fluoroquinolone-resistant strains

Brief ReportM. MORITA, K. HIROSE, N. TAKAI, J. TERAJIMA, H. WATANABE, H. SAGARA, T. KURAZONO, M. YAMAGUCHI, Y. KANAZAWA, T. OYAIZU, H. IZUMIYA, Epidemiology and Infection, Volume 138 Issue 03 , pp 318-321Abstract

Salmonella enterica serotypes and antibiotic susceptibility in New Zealand, 2002–2007

Research ArticlesE. I. BROUGHTON, H. M. HEFFERNAN, C. L. COLES, Epidemiology and Infection, Volume 138 Issue 03 , pp 322-329Abstract

Sensitivity of environmental sampling methods for detecting Salmonella Enteritidis in commercial laying flocks relative to the within-flock prevalence

Research ArticlesM. E. ARNOLD, J. J. CARRIQUE-MAS, R. H. DAVIES, Epidemiology and Infection, Volume 138 Issue 03 , pp 330-339Abstract

Sporadic Salmonella enterica serotype Javiana infections in Georgia and Tennessee: a hypothesis-generating study

Research ArticlesL. S. CLARKSON, M. TOBIN-D'ANGELO, C. SHULER, S. HANNA, J. BENSON, A. C. VOETSCH, Epidemiology and Infection, Volume 138 Issue 03 , pp 340-346Abstract

El Tor cholera with severe disease: a new threat to Asia and beyond

Research ArticlesA. K. SIDDIQUE, G. B. NAIR, M. ALAM, D. A. SACK, A. HUQ, A. NIZAM, I. M. LONGINI, F. QADRI, S. M. FARUQUE, R. R. COLWELL, S. AHMED, A. IQBAL, N. A. BHUIYAN, R. B. SACK, Epidemiology and Infection, Volume 138 Issue 03 , pp 347-352Abstract

Flock management and histomoniasis in free-range turkeys in France: description and search for potential risk factors

Research ArticlesM. P. CALLAIT-CARDINAL, E. GILOT-FROMONT, L. CHOSSAT, A. GONTHIER, C. CHAUVE, L. ZENNER, Epidemiology and Infection, Volume 138 Issue 03 , pp 353-363Abstract

Risk factors for sanitary condemnation in broiler chickens and their relative impact: application of an original multiblock approach

Research ArticlesC. LUPO, S. BOUGEARD, L. BALAINE, V. MICHEL, I. PETETIN, P. COLIN, S. LeBOUQUIN, C. CHAUVIN, Epidemiology and Infection, Volume 138 Issue 03 , pp 364-375Abstract

The role of birds in dissemination of Francisella tularensis : first direct molecular evidence for bird-to-human transmission

Brief ReportP. I. PADESHKI, I. N. IVANOV, B. POPOV, T. V. KANTARDJIEV, Epidemiology and Infection, Volume 138 Issue 03 , pp 376-379Abstract

Zoonotic Dirofilaria immitis infections in a province of Northern Spain

Brief ReportR. MORCHÓN, I. MOYA, J. GONZÁLEZ-MIGUEL, M. N. MONTOYA, F. SIMÓN, Epidemiology and Infection, Volume 138 Issue 03 , pp 380-383Abstract

The impact of sheep breed on the risk of classical scrapie

Research ArticlesK. M. McINTYRE, H. TREWBY, S. GUBBINS, M. BAYLIS, Epidemiology and Infection, Volume 138 Issue 03 , pp 384-392Abstract

Diagnosis of hepatitis C virus infection in Scotland's injecting drug user population

Research ArticlesS. A. McDONALD, S. J. HUTCHINSON, P. R. MILLS, S. M. BIRD, C. ROBERTSON, J. F. DILLON, A. SPRINGBETT, D. J. GOLDBERG, Epidemiology and Infection, Volume 138 Issue 03 , pp 393-402Abstract

Seroepidemiology of human herpesvirus 8 (HHV-8) infection in injecting drug users

Research ArticlesA. ZAVITSANOU, M. MALLIORI, V. SYPSA, M. PETRODASKALAKI, M. PSICHOGIOU, C. ROKKA, A. GIANNOPOULOS, V. KALAPOTHAKI, D. WHITBY, A. HATZAKIS, Epidemiology and Infection, Volume 138 Issue 03 , pp 403-408Abstract

Dirty hands: bacteria of faecal origin on commuters' hands

Research ArticlesG. JUDAH, P. DONACHIE, E. COBB, W. SCHMIDT, M. HOLLAND, V. CURTIS, Epidemiology and Infection, Volume 138 Issue 03 , pp 409-414Abstract

Measles outbreak linked to a minority group in Austria, 2008

Research ArticlesD. SCHMID, H. HOLZMANN, K. SCHWARZ, S. KASPER, H-W. KUO, S. W. ABERLE, M. REDLBERGER-FRITZ, W. HAUTMANN, S. SANTIBANEZ, A. MANKERTZ, C. KÖNIG, E. MAGNET, S. REICHART, S. MEUSBURGER, A. LUCKNER-HORNISCHER, A. DE MARTIN, E. BECHTER, J. STIRLING, F. ALLERBERGER, Epidemiology and Infection, Volume 138 Issue 03 , pp 415-425Abstract

The utility of seroepidemiology for tracking trends in pertussis infection

Research ArticlesH. E. QUINN, P. B. McINTYRE, J. L. BACKHOUSE, H. F. GIDDING, J. BROTHERTON, G. L. GILBERT, Epidemiology and Infection, Volume 138 Issue 03 , pp 426-433Abstract

A spatial analysis of the spread of mumps: the importance of college students and their spring-break-associated travel

Research ArticlesP. M. POLGREEN, L. C. BOHNETT, M. YANG, M. A. PENTELLA, J. E. CAVANAUGH, Epidemiology and Infection, Volume 138 Issue 03 , pp 434-441Abstract

Anti-VP6 IgG antibodies against group A and group C rotaviruses in South India

Research ArticlesI. MUKHOPADHYA, D. ANBU, M. ITURRIZA-GOMARA, J. J. GRAY, D. W. BROWN, O. KAVANAGH, M. K. ESTES, G. KANG, Epidemiology and Infection, Volume 138 Issue 03 , pp 442-447Abstract

Editorial - ETOX turned twenty

Pathogenomics of mobile genetic elements of toxigenic bacteria

Host cell modulation by human, animal and plant pathogens

In silico identification of novel bacterial ADP-ribosyltransferases

The multi-talented bacterial adenylate cyclases

Pathways followed by protein toxins into cells

Retrograde transport of cholera toxin into the ER of host cells

Analysing the action of bacterial toxins in living cells with fluorescence resonance energy transfer (FRET)

The Pasteurella multocida toxin interacts with signalling pathways to perturb cell growth and differentiation

E. coli CNF1 toxin: a two-in-one system for host-cell invasion

Molecular and cell biology of Legionella pneumophila

Superantigens: Structure-function relationships

Novel activities of the Helicobacter pylori vacuolating cytotoxin: from epithelial cells towards the immune system

Exploitation of host cells by Burkholderia pseudomallei

Clostridium botulinum C2 toxin - New insights into the cellular up-take of the actin-ADP-ribosylating toxin

Inverted pathogenicity: the use of pathogen-specific molecular mechanisms for prevention or therapy of disease

The adenylate cyclase toxin from Bordetella pertussis - a novel promising vehicle for antigen delivery to dendritic cells

Recombinant immunotoxins for treating cancer

Bordetella pertussis: from functional genomics to intranasal vaccination

The multiple cellular activities of the VacA cytotoxin of Helicobacter pylori

Pore worms: Using Caenorhabditis elegans to study how bacterial toxins interact with their target host

Enterococcal cytolysin: activities and association with other virulence traits in a pathogenicity island

In vivo Bacillus anthracis gene expression requires PagR as an intermediate effector of the AtxA signalling cascade

Microbiology RSS : Gourt

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Table of contents

Neighborhood Poverty and Injection Cessation in a Sample of Injection Drug Users

Variation in Child Cognitive Ability by Week of Gestation Among Healthy Term Births

Maternal Dietary Glycemic Intake and the Risk of Neural Tube Defects

Menopausal Hormone Therapy Use and Risk of Invasive Colon Cancer: The California Teachers Study

Cardiorespiratory Fitness Levels Among US Adults 20-49 Years of Age: Findings From the 1999-2004 National Health and Nutrition Examination Survey

Dairy Intake and the Risk of Bladder Cancer in the Netherlands Cohort Study on Diet and Cancer

Presence of Gallstones or Kidney Stones and Risk of Type 2 Diabetes

Pesticide Use and Thyroid Disease Among Women in the Agricultural Health Study

Estimates of the Transmissibility of the 1968 (Hong Kong) Influenza Pandemic: Evidence of Increased Transmissibility Between Successive Waves

Comparing 3 Dietary Pattern Methods--Cluster Analysis, Factor Analysis, and Index Analysis--With Colorectal Cancer Risk: The NIH-AARP Diet and Health Study

Biochemical Validation of Food Frequency Questionnaire-Estimated Carotenoid, {alpha}-Tocopherol, and Folate Intakes Among African Americans and Non-Hispanic Whites in the Southern Community Cohort Study

A Comparison of Sample Size and Power in Case-Only Association Studies of Gene-Environment Interaction

Marginal Structural Models for Sufficient Cause Interactions

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Editorial Board

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Neighborhood Poverty and Injection Cessation in a Sample of Injection Drug Users

Variation in Child Cognitive Ability by Week of Gestation Among Healthy Term Births

Maternal Dietary Glycemic Intake and the Risk of Neural Tube Defects

Menopausal Hormone Therapy Use and Risk of Invasive Colon Cancer: The California Teachers Study

Cardiorespiratory Fitness Levels Among US Adults 20-49 Years of Age: Findings From the 1999-2004 National Health and Nutrition Examination Survey

Dairy Intake and the Risk of Bladder Cancer in the Netherlands Cohort Study on Diet and Cancer

Presence of Gallstones or Kidney Stones and Risk of Type 2 Diabetes

Pesticide Use and Thyroid Disease Among Women in the Agricultural Health Study

Estimates of the Transmissibility of the 1968 (Hong Kong) Influenza Pandemic: Evidence of Increased Transmissibility Between Successive Waves

Comparing 3 Dietary Pattern Methods--Cluster Analysis, Factor Analysis, and Index Analysis--With Colorectal Cancer Risk: The NIH-AARP Diet and Health Study

Biochemical Validation of Food Frequency Questionnaire-Estimated Carotenoid, {alpha}-Tocopherol, and Folate Intakes Among African Americans and Non-Hispanic Whites in the Southern Community Cohort Study

A Comparison of Sample Size and Power in Case-Only Association Studies of Gene-Environment Interaction

Marginal Structural Models for Sufficient Cause Interactions

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Editorial Board

Subscriptions

Table of contents

Tumor Necrosis Factor (TNF) and Lymphotoxin-{alpha} (LTA) Polymorphisms and Risk of Non-Hodgkin Lymphoma in the InterLymph Consortium

A Prospective Study of Albuminuria and Cognitive Function in Older Adults: The Rancho Bernardo Study

Invited Commentary: Albuminuria and Microvascular Disease of the Brain--A Shared Pathophysiology

Jassal et al. Respond to "Microalbuminuria and Brain Vascular Disease"

Secondhand Smoke, Vascular Disease, and Dementia Incidence: Findings From the Cardiovascular Health Cognition Study

Effects of Externally Rated Job Demand and Control on Depression Diagnosis Claims in an Industrial Cohort

Diet, Lifestyle, and Acute Myeloid Leukemia in the NIH-AARP Cohort

Lung Cancer and Occupation in a Population-based Case-Control Study

Age at Menarche and Risk of Type 2 Diabetes: Results From 2 Large Prospective Cohort Studies

How Does Socioeconomic Development Affect Risk of Mortality? An Age-Period-Cohort Analysis From a Recently Transitioned Population in China

Correlates for Human Papillomavirus Vaccination of Adolescent Girls and Young Women in a Managed Care Organization

The Relevance of Different Methods of Calculating the Ankle-Brachial Index: The Multi-Ethnic Study of Atherosclerosis

Fitting General Relative Risk Models for Survival Time and Matched Case-Control Analysis

Smallpox--The Death of a Disease: The Inside Story of Eradicating a Worldwide Killer: By D. A. Henderson

Getting What We Deserve: Health & Medical Care in America: By Alfred Sommer

Re: "Vitamin C Deficiency in a Population of Young Canadian Adults"

The Authors Reply

Re: "Chronic Particulate Exposure, Mortality, and Coronary Heart Disease in the Nurses' Health Study"

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The Association Between Obesity and Low Back Pain: A Meta-Analysis

Impact of Improved Classification on the Association of Human Papillomavirus With Cervical Precancer

Invited Commentary: Human Papillomavirus Infection and Risk of Cervical Precancer--Using the Right Methods to Answer the Right Questions

Between-Strain Competition in Acquisition and Clearance of Pneumococcal Carriage--Epidemiologic Evidence From a Longitudinal Study of Day-Care Children

Near Real-Time Surveillance for Influenza Vaccine Safety: Proof-of-Concept in the Vaccine Safety Datalink Project

Longitudinal Data Analysis for Generalized Linear Models Under Participant-Driven Informative Follow-up: An Application in Maternal Health Epidemiology

Copy-Years Viremia as a Measure of Cumulative Human Immunodeficiency Virus Viral Burden

C-Reactive Protein and Retinal Microvascular Caliber in a Multiethnic Asian Population

Red Blood Cell Distribution Width and Risk of Cardiovascular Events and Mortality in a Community Cohort in Taiwan

A Prospective Study of Dairy Intake and Risk of Uterine Leiomyomata

A Prospective Study of Magnesium and Iron Intake and Pancreatic Cancer in Men

Nonradiation Risk Factors for Thyroid Cancer in the US Radiologic Technologists Study

An Exploration of Shared Genetic Risk Factors Between Periodontal Disease and Cancers: A Prospective Co-Twin Study

Generational Differences in the Prevalence of Hearing Impairment in Older Adults

Volume 138 Issue 03

Rabies epidemiology and control in Turkey: past and present

Staphylococcus aureus is the most common identified cause of cellulitis: a systematic review

Salmonella enterica serovar Typhi in Japan, 2001–2006: emergence of high-level fluoroquinolone-resistant strains

Salmonella enterica serotypes and antibiotic susceptibility in New Zealand, 2002–2007