Showing papers in "American Journal of Epidemiology in 2007"

Relaxing the Rule of Ten Events per Variable in Logistic and Cox Regression

Abstract: The rule of thumb that logistic and Cox models should be used with a minimum of 10 outcome events per predictor variable (EPV), based on two simulation studies, may be too conservative. The authors conducted a large simulation study of other influences on confidence interval coverage, type I error, relative bias, and other model performance measures. They found a range of circumstances in which coverage and bias were within acceptable levels despite less than 10 EPV, as well as other factors that were as influential as or more influential than EPV. They conclude that this rule can be relaxed, in particular for sensitivity analyses undertaken to demonstrate adequate control of confounding.

Systematic Review of Type 1 and Type 2 Diabetes Mellitus and Risk of Fracture

Abstract: The authors conducted a systematic review of published data on the association between diabetes mellitus and fracture. The authors searched MEDLINE through June 2006 and examined the reference lists of pertinent articles (limited to studies in humans). Summary relative risks and 95% confidence intervals were calculated with a random-effects model. The 16 eligible studies (two case-control studies and 14 cohort studies) included 836,941 participants and 139,531 incident cases of fracture. Type 2 diabetes was associated with an increased risk of hip fracture in both men (summary relative risk (RR) = 2.8, 95% confidence interval (CI): 1.2, 6.6) and women (summary RR = 2.1, 95% CI: 1.6, 2.7). Results were consistent between studies of men and women and between studies conducted in the United States and Europe. The association between type of diabetes and hip fracture incidence was stronger for type 1 diabetes (summary RR = 6.3, 95% CI: 2.6, 15.1) than for type 2 diabetes (summary RR = 1.7, 95% CI: 1.3, 2.2). Type 2 diabetes was weakly associated with fractures at other sites, and most effect estimates were not statistically significant. These findings strongly support an association between both type 1 and type 2 diabetes and increased risk of hip fracture in men and women.

The Third Generation Cohort of the National Heart, Lung, and Blood Institute's Framingham Heart Study: Design, Recruitment, and Initial Examination

Abstract: For nearly 60 years, the Framingham Heart Study has examined the natural history, risk factors, and prognosis of cardiovascular, lung, and other diseases. Recruitment of the Original Cohort began in 1948. Twenty-three years later, 3,548 children of the Original Cohort, along with 1,576 of their spouses, enrolled in the Offspring Cohort. Beginning in 2002, 4,095 adults having at least one parent in the Offspring Cohort enrolled in the Third Generation Cohort, along with 103 parents of Third Generation Cohort participants who were not previously enrolled in the Offspring Cohort. The objective of new recruitment was to complement phenotypic and genotypic information obtained from prior generations, with priority assigned to larger families. From a pool of 6,553 eligible individuals, 1,912 men and 2,183 women consented and attended the first examination (mean age: 40 (standard deviation: 9) years; range: 19-72 years). The examination included clinical and laboratory assessments of vascular risk factors and imaging for subclinical atherosclerosis, as well as assessment of cardiac structure and function. The comparison of Third Generation Cohort data with measures previously collected from the first two generations will facilitate investigations of genetic and environmental risk factors for subclinical and overt diseases, with a focus on cardiovascular and lung disorders.

Smoking as a Risk Factor for Dementia and Cognitive Decline: A Meta-Analysis of Prospective Studies

Abstract: The authors assessed the association of smoking with dementia and cognitive decline in a meta-analysis of 19 prospective studies with at least 12 months of follow-up. Studies included a total of 26,374 participants followed for dementia for 2-30 years and 17,023 participants followed up for 2-7 years to assess cognitive decline. Mean study age was 74 years. Current smokers at baseline, relative to never smokers, had risks of 1.79 (95% confidence interval (CI): 1.43, 2.23) for incident Alzheimer's disease, 1.78 (95% CI: 1.28, 2.47) for incident vascular dementia, and 1.27 (95% CI: 1.02, 1.60) for any dementia. Compared with those who never smoked, current smokers at baseline also showed greater yearly declines in Mini-Mental State Examination scores over the follow-up period (effect size (beta)=-0.13, 95% CI: -0.18, -0.08). Compared with former smokers, current smokers at baseline showed an increased risk of Alzheimer's disease (relative risk=1.70, 95% CI: 1.25, 2.31) and an increased decline in cognitive abilities (effect size (beta)=-0.07, 95% CI: -0.11, -0.03), but the groups were not different regarding risk of vascular dementia or any dementia. The authors concluded that elderly smokers have increased risks of dementia and cognitive decline.

Birth weight and subsequent risk of type 2 diabetes: a meta-analysis

Abstract: The "small baby syndrome hypothesis" suggests that an inverse linear relation exists between birth weight and risk of type 2 diabetes. The authors conducted a meta-analysis to examine this association. They included studies that reported odds ratios and 95% confidence intervals (or data with which to calculate them) for the association of type 2 diabetes with birth weight. Fourteen studies involving a total of 132,180 persons were identified. Low birth weight ( /=2,500 g, was associated with increased risk of type 2 diabetes (odds ratio (OR) = 1.32, 95% confidence interval (CI): 1.06, 1.64). High birth weight (>4,000 g), as compared with a birth weight of

Assessing the measurement properties of neighborhood scales: from psychometrics to ecometrics

Abstract: Most studies examining the relation between residential environment and health have used census-derived measures of neighborhood socioeconomic position (SEP). There is a need to identify specific features of neighborhoods relevant to disease risk, but few measures of these features exist, and their measurement properties are understudied. In this paper, the authors 1) develop measures (scales) of neighborhood environment that are important in cardiovascular disease risk, 2) assess the psychometric and ecometric properties of these measures, and 3) examine individual- and neighborhood-level predictors of these measures. In 2004, data on neighborhood conditions were collected from a telephone survey of 5,988 residents at three US study sites (Baltimore, Maryland; Forsyth County, North Carolina; and New York, New York). Information collected covered seven dimensions of neighborhood environment (aesthetic quality, walking environment, availability of healthy foods, safety, violence, social cohesion, and activities with neighbors). Neighborhoods were defined as census tracts or census clusters. Cronbach's alpha coefficient ranged from 0.73 to 0.83, with test-retest reliabilities of 0.60-0.88. Intraneighborhood correlations were 0.28-0.51, and neighborhood reliabilities were 0.64-0.78 for census tracts for most scales. The neighborhood scales were strongly associated with neighborhood SEP but also provided information distinct from neighborhood SEP. These results illustrate a methodological approach for assessing the measurement properties of neighborhood-level constructs and show that these constructs can be measured reliably.

Age, Gene/Environment Susceptibility–Reykjavik Study: Multidisciplinary Applied Phenomics

Abstract: In anticipation of the sequencing of the human genome and description of the human proteome, the Age, Gene/Environment Susceptibility-Reykjavik Study (AGES-Reykjavik) was initiated in 2002. AGES-Reykjavik was designed to examine risk factors, including genetic susceptibility and gene/environment interaction, in relation to disease and disability in old age. The study is multidisciplinary, providing detailed phenotypes related to the cardiovascular, neurocognitive (including sensory), and musculoskeletal systems, and to body composition and metabolic regulation. Relevant quantitative traits, subclinical indicators of disease, and medical diagnoses are identified by using biomarkers, imaging, and other physiologic indicators. The AGES-Reykjavik sample is drawn from an established population-based cohort, the Reykjavik Study. This cohort of men and women born between 1907 and 1935 has been followed in Iceland since 1967 by the Icelandic Heart Association. The AGES-Reykjavik cohort, with cardiovascular risk factor assessments earlier in life and detailed late-life phenotypes of quantitative traits, will create a comprehensive study of aging nested in a relatively genetically homogeneous older population. This approach should facilitate identification of genetic factors that contribute to healthy aging as well as the chronic conditions common in old age.

The Impact of Residual and Unmeasured Confounding in Epidemiologic Studies: A Simulation Study

Abstract: Measurement error in explanatory variables and unmeasured confounders can cause considerable problems in epidemiologic studies. It is well recognized that under certain conditions, nondifferential measurement error in the exposure variable produces bias towards the null. Measurement error in confounders will lead to residual confounding, but this is not a straightforward issue, and it is not clear in which direction the bias will point. Unmeasured confounders further complicate matters. There has been discussion about the amount of bias in exposure effect estimates that can plausibly occur due to residual or unmeasured confounding. In this paper, the authors use simulation studies and logistic regression analyses to investigate the size of the apparent exposure-outcome association that can occur when in truth the exposure has no causal effect on the outcome. The authors consider two cases with a normally distributed exposure and either two or four normally distributed confounders. When the confounders are uncorrelated, bias in the exposure effect estimate increases as the amount of residual and unmeasured confounding increases. Patterns are more complex for correlated confounders. With plausible assumptions, effect sizes of the magnitude frequently reported in observational epidemiologic studies can be generated by residual and/or unmeasured confounding alone.

Should Meta-Analyses of Interventions Include Observational Studies in Addition to Randomized Controlled Trials? A Critical Examination of Underlying Principles

Abstract: Some authors argue that systematic reviews and meta-analyses of intervention studies should include only randomized controlled trials because the randomized controlled trial is a more valid study design for causal inference compared with the observational study design. However, a review of the principal elements underlying this claim (randomization removes the chance of confounding, and the double-blind process minimizes biases caused by the placebo effect) suggests that both classes of study designs have strengths and weaknesses, and including information from observational studies may improve the inference based on only randomized controlled trials. Furthermore, a review of empirical studies suggests that meta-analyses based on observational studies generally produce estimates of effect similar to those from meta-analyses based on randomized controlled trials. The authors found that the advantages of including both observational studies and randomized studies in a meta-analysis could outweigh the disadvantages in many situations and that observational studies should not be excluded a priori.

Flavonoid Intake and Cognitive Decline over a 10-Year Period

Abstract: In the PAQUID (Personnes Agees Quid) study, the authors prospectively examined flavonoid intake in relation to cognitive function and decline among subjects aged 65 years or older. A total of 1,640 subjects free from dementia at baseline in 1990 and with reliable dietary assessment were reexamined four times over a 10-year period. Cognitive functioning was assessed through three psychometric tests (Mini-Mental State Examination, Benton's Visual Retention Test, "Isaacs" Set Test) at each visit. Information on flavonoid intake was collected at baseline. A linear mixed model was used to analyze the evolution of cognitive performance according to quartiles of flavonoid intake. After adjustment for age, sex, and educational level, flavonoid intake was associated with better cognitive performance at baseline (p = 0.019) and with a better evolution of the performance over time (p = 0.046). Subjects included in the two highest quartiles of flavonoid intake had better cognitive evolution than did subjects in the lowest quartile. After 10 years' follow-up, subjects with the lowest flavonoid intake had lost on average 2.1 points on the Mini-Mental State Examination, whereas subjects with the highest quartile had lost 1.2 points. This gradient persisted after adjustment for several other potential confounders. This study raises the possibility that dietary flavonoid intake is associated with better cognitive evolution.

A Prospective Study of Tobacco, Alcohol, and the Risk of Esophageal and Gastric Cancer Subtypes

Abstract: Rates of esophageal adenocarcinoma and gastric cardia adenocarcinoma have increased, while rates of esophageal squamous cell carcinoma (ESCC) and gastric noncardia adenocarcinoma have decreased, suggesting distinct etiologies. The authors prospectively investigated the associations of alcohol and tobacco with these cancers in 474,606 US participants using Cox models adjusted for potential confounders. Between 1995/1996 and 2000, 97 incident cases of ESCC, 205 of esophageal adenocarcinoma, 188 of gastric cardia, and 187 of gastric noncardia cancer occurred. Compared with nonsmokers, current smokers were at increased risk for ESCC (hazard ratio (HR) = 9.27, 95% confidence interval (CI): 4.04, 21.29), esophageal adenocarcinoma (HR = 3.70, 95% CI: 2.20, 6.22), gastric cardia (HR = 2.86, 95% CI: 1.73, 4.70), and gastric noncardia (HR = 2.04, 95% CI: 1.32, 3.16). Assuming causality, ever smoking had population attributable risks of 77% (95% CI: 0.55, 0.89) for ESCC, 58% (95% CI: 0.38, 0.72) for esophageal adenocarcinoma, 47% (95% CI: 0.27, 0.63) for gastric cardia, and 19% (95% CI: 0.00, 0.37) for gastric noncardia. For drinkers of more than three alcoholic beverages per day, compared with those whose intake was up to one drink per day, the authors found significant associations between alcohol intake and ESCC risk (HR = 4.93, 95% CI: 2.69, 9.03) but not risk for esophageal, gastric cardia, or gastric noncardia adenocarcinoma.

Adherence to Lipid-lowering Therapy and the Use of Preventive Health Services: An Investigation of the Healthy User Effect

Abstract: Patients who adhere to preventive therapies may be more likely to engage in a broad spectrum of behaviors consistent with a healthy lifestyle. Because many of these behaviors cannot be measured easily, observational studies of outcomes associated with the long-term use of preventive therapies are subject to the so-called ‘‘healthy user bias.’’ To better understand this effect, the authors examined the association between adherence to statin therapy and the use of preventive health services in a Pennsylvania cohort of 20,783 new users of statins between 1996 and 2004. After adjustment for age, gender, and various comorbid conditions, patients who filled two or more prescriptions for a statin during a 1-year ascertainment period were more likely than patients who filled only one prescription to receive prostate-specific antigen tests (hazard ratio (HR) ¼ 1.57, 95% confidence interval (CI): 1.17, 2.19), fecal occult blood tests (HR ¼ 1.31, 95% CI: 1.12, 1.53), screening mammograms (HR ¼ 1.22, 95% CI: 1.09, 1.38), influenza vaccinations (HR ¼ 1.21, 95% CI: 1.12, 1.31), and pneumococcal vaccinations (HR ¼ 1.46, 95% CI: 1.17, 1.83) during follow-up. These results suggest that patients who adhere to chronic therapies are more likely to seek out preventive health services, such as screening tests and vaccinations. Further work is needed to identify study design and analysis methods that can be used to minimize the healthy user bias in studies of preventive therapies.

Association of Black Carbon with Cognition among Children in a Prospective Birth Cohort Study

Abstract: While studies show that ultrafine and fine particles can be translocated from the lungs to the central nervous system, the possible neurodegenerative effect of air pollution remains largely unexplored. The authors examined the relation between black carbon, a marker for traffic particles, and cognition among 202 Boston, Massachusetts, children (mean age = 9.7 years (standard deviation, 1.7)) in a prospective birth cohort study (1986-2001). Local black carbon levels were estimated using a validated spatiotemporal land-use regression model (mean predicted annual black carbon level, 0.56 mug/m(3) (standard deviation, 0.13)). The Wide Range Assessment of Memory and Learning and the Kaufman Brief Intelligence Test were administered for assessment of cognitive constructs. In analysis adjusting for sociodemographic factors, birth weight, blood lead level, and tobacco smoke exposure, black carbon (per interquartile-range increase) was associated with decreases in the vocabulary (-2.2, 95% confidence interval (CI): -5.5, 1.1), matrices (-4.0, 95% CI: -7.6, -0.5), and composite intelligence quotient (-3.4, 95% CI: -6.6, -0.3) scores of the Kaufman Brief Intelligence Test and with decreases on the visual subscale (-5.4, 95% CI: -8.9, -1.9) and general index (-3.9, 95% CI: -7.5, -0.3) of the Wide Range Assessment of Memory and Learning. Higher levels of black carbon predicted decreased cognitive function across assessments of verbal and nonverbal intelligence and memory constructs.

Genetic and Environmental Influences on Birth Weight, Birth Length, Head Circumference, and Gestational Age by Use of Population-based Parent-Offspring Data

Abstract: Familial correlations in birth weight and gestational age have been explained by fetal and maternal genetic factors, mainly in studies on offspring of twins. The aim of the present intergenerational study was to estimate and compare fetal and maternal genetic effects and shared sibling environmental effects on birth weight and gestational age and also on crown-heel length and head circumference. The authors used path analysis and maximum likelihood principles to estimate these effects and, at the same time, to adjust for covariates. Parent-offspring data were obtained from the Medical Birth Registry of Norway from 1967 to 2004. For the analysis of birth weight and crown-heel length, 101,748 families were included; for gestational age, 91,617 families; and for head circumference, 77,044 families. Assuming no cultural transmission and random mating, the authors found that fetal genetic factors explained 31% of the normal variation in birth weight and birth length, 27% of the variation in head circumference, and 11% of the variation in gestational age. Maternal genetic factors explained 22% of the variation in birth weight, 19% of the variation in birth length and head circumference, and 14% of the variation in gestational age. Relative to the proportion of explained variation, fetal genes were most important for birth length and head circumference.

Ambient Air Pollution and Preterm Birth in the Environment and Pregnancy Outcomes Study at the University of California, Los Angeles

Abstract: The authors conducted a case-control survey nested within a birth cohort and collected detailed risk factor information to assess the extent to which residual confounding and exposure misclassification may impact air pollution effect estimates. Using a survey of 2,543 of 6,374 women sampled from a cohort of 58,316 eligible births in 2003 in Los Angeles County, California, the authors estimated with logistic regression and two-phase models the effects of pregnancy period-specific air pollution exposure on the odds of preterm birth. For the first trimester, the odds of preterm birth consistently increased with increasing carbon monoxide exposures and also at high levels of exposure to particulate matter less than or equal to 2.5 microm in diameter (>21.4 microg/m(3)), regardless of type of data (cohort/sample) or covariate adjustment (carbon monoxide exposures of >1.25 ppm increased the odds by 21-25%). Women exposed to carbon monoxide above 0.91 ppm during the last 6 weeks of pregnancy experienced increased odds of preterm birth. Crude and birth certificate covariate-adjusted results for carbon monoxide differed from each other. However, further adjustment for risk factors assessed in the survey did not change effect estimates for short-term pollutant averages appreciably, except for time-activity patterns, which strengthened the observed associations. These results confirm the importance of reducing exposure misclassification when evaluating the effect of traffic-related pollutants that vary spatially.

Prospective Effect of Job Strain on General and Central Obesity in the Whitehall II Study

Abstract: Positive energy balance is the major cause of obesity, and chronic stress may be a contributory factor. The authors examined cumulative work stress, using the Job Strain Questionnaire on four occasions, as a predictor of obesity in a prospective 19-year study of 6,895 men and 3,413 women (aged 35–55 years) in the Whitehall II cohort in London, United Kingdom (baseline: 1985–1988). A dose-response relation was found between work stress and risk of general obesity (body mass index 30 kg/m2) and central obesity (waist circumference >102 cm in men, >88 cm in women) that was largely independent of covariates. The imputed odds ratios of body mass index obesity for one, two, and three or more reports of work stress adjusted for age, sex, and social position were 1.17, 1.24, and 1.73 (trend p < 0.01), respectively. For waist obesity, the corresponding findings were 1.17, 1.41, and 1.61 (trend p < 0.01). Work stress effect was modestly attenuated after exclusion of obese individuals at baseline and further adjustments for smoking; intakes of dietary fiber, fruits and vegetables, and alcohol; and levels of physical activity during follow-up. This study provides prospective, population-based evidence that chronic work stress predicts general and central obesity.

Oral Health and Risk of Squamous Cell Carcinoma of the Head and Neck and Esophagus: Results of Two Multicentric Case-Control Studies

Abstract: Poor oral health has been reported as a risk factor in the etiology of head and neck cancer. Data on oral health were ascertained as part of two multicenter case-control studies comprising 924 cases and 928 controls in central Europe and 2,286 cases and 1,824 controls in Latin America. Incident cases of squamous cell carcinoma of the head and neck (oral cavity, pharynx, larynx) and esophagus, as well as age (in quinquennia)- and sex frequency-matched controls, were enrolled from 1998 to 2003. Poor condition of the mouth (central Europe: odds ratio (OR) = 2.89, 95% confidence interval (CI): 1.74, 4.81; Latin America: OR = 1.89, 95% CI: 1.47, 2.42), lack of toothbrush use (Latin America: OR = 2.36, 95% CI: 1.28, 4.36), and daily mouthwash use (Latin America: OR = 3.40, 95% CI: 1.96, 5.89) emerged as risk factors for head and neck cancer, independent of tobacco use and alcohol consumption. Missing between six and 15 teeth was an independent risk factor for esophageal cancer (central Europe: OR = 2.84, 95% CI: 1.26, 6.41; Latin America: OR = 2.18, 95% CI: 1.04, 4.59). These results indicate that periodontal disease (as indicated by poor condition of the mouth and missing teeth) and daily mouthwash use may be independent causes of cancers of the head, neck, and esophagus.

Plasma Urate and Risk of Parkinson's Disease

Abstract: Oxidative stress contributes to dopaminergic neuron degeneration in Parkinson’s disease (PD).Urate, a potent antioxidant, could be neuroprotective. To determine whether higher plasma concentrations of urate predict a reduced risk of PD, we conducted a nested case-control study among participants in the Health Professional Follow-up Study, a cohort comprising over 18,000 men who provided blood samples in 1993–95. 84 incident cases of PD were diagnosed through 2000 and each was randomly matched to two controls by year of birth, race, and time of blood collection. Rate ratios (RR) of PD according to quartile of uricemia were estimated using conditional logistic regression. The mean urate concentration was 5.7mg/dL among cases and 6.1mg/dL among controls (p=0.01). After adjusting for age, smoking, and caffeine, the RR (95 percent confidence interval [CI]) of PD for the highest quartile of uricemia compared to the lowest was 0.43 (0.18, 1.02; p-for-trend=0.017). This association was stronger in analyses excluding cases diagnosed within 4 years (median) from blood collection (RR=0.17; 95 percent CI: 0.04, 0.69; p-for-trend=0.010). These results suggest that high plasma urate concentrations may decrease risk of PD and raise the possibility that interventions to increase plasma urate may reduce risk and delay the progression of PD.

Influence of Exercise, Walking, Cycling, and Overall Nonexercise Physical Activity on Mortality in Chinese Women

Abstract: This investigation described the effects of exercise, walking, and cycling for transportation, as well as the effect of overall nonexercise physical activity, on mortality in the Shanghai Women's Health Study (1997-2004). Women without heart disease, stroke, or cancer were followed for an average of 5.7 years (n = 67,143), and there were 1,091 deaths from all causes, 537 deaths from cancer, and 251 deaths from cardiovascular diseases. Information about physical activity and relevant covariates was obtained by interview. Proportional hazards models were used to estimate adjusted hazard ratios and 95% confidence intervals. Exercise and cycling for transportation were both inversely and independently associated with all-cause mortality (p(trend) < 0.05), but walking for transportation was less strongly associated with reduced risk (p(trend) = 0.07). Women reporting no regular exercise but who reported 10 or more metabolic equivalent (MET)-hours/day of nonexercise activity were at 25-50% reduced risk (p(trend) < 0.01) relative to less active women (0-9.9 MET-hours/day). Among women reporting the least nonexercise activity (0-9.9 MET-hours/day) but reporting regular exercise participation, exercise was associated with reduced mortality (hazard ratio = 0.78, 95% confidence interval: 0.62, 0.99). These findings add new evidence that overall physical activity levels are an important determinant of longevity, and that health benefit can be obtained through an active lifestyle, exercise, or combinations of both.

Influence of exercise, walking, cycling, and overall nonexercise physical activity on mortality in Chinese women. Commentary and Authors'reply.

Abstract: This investigation described the effects of exercise, walking, and cycling for transportation, as well as the effect of overall nonexercise physical activity, on mortality in the Shanghai Women's Health Study (1997-2004). Women without heart disease, stroke, or cancer were followed for an average of 5.7 years (n = 67,143), and there were 1,091 deaths from all causes, 537 deaths from cancer, and 251 deaths from cardiovascular diseases. Information about physical activity and relevant covariates was obtained by interview. Proportional hazards models were used to estimate adjusted hazard ratios and 95% confidence intervals. Exercise and cycling for transportation were both inversely and independently associated with all-cause mortality (p(trend) < 0.05), but walking for transportation was less strongly associated with reduced risk (p(trend) = 0.07). Women reporting no regular exercise but who reported 10 or more metabolic equivalent (MET)-hours/day of nonexercise activity were at 25-50% reduced risk (p(trend) < 0.01) relative to less active women (0-9.9 MET-hours/day). Among women reporting the least nonexercise activity (0-9.9 MET-hours/day) but reporting regular exercise participation, exercise was associated with reduced mortality (hazard ratio = 0.78, 95% confidence interval: 0.62, 0.99). These findings add new evidence that overall physical activity levels are an important determinant of longevity, and that health benefit can be obtained through an active lifestyle, exercise, or combinations of both.

Motor Vehicle Crash Injury Rates by Mode of Travel, United States: Using Exposure-Based Methods to Quantify Differences

Abstract: The authors used traffic exposure data to calculate exposure-based fatal and nonfatal traffic injury rates in the United States. Nationally representative data were used to identify fatal and nonfatal traffic injuries that occurred from 1999 to 2003, and the 2001 National Household Travel Survey was used to estimate traffic exposure (i.e., person-trips). Fatal and nonfatal traffic injury rates per 100 million person-trips were calculated by mode of travel, sex, and age group. The overall fatal traffic injury rate was 10.4 per 100 million person-trips. Fatal injury rates were highest for motorcyclists, pedestrians, and bicyclists. The nonfatal traffic injury rate was 754.6 per 100 million person-trips. Nonfatal injury rates were highest for motorcyclists and bicyclists. Exposure-based traffic injury rates varied by mode of travel, sex, and age group. Motorcyclists, pedestrians, and bicyclists faced increased injury risks. Males, adolescents, and the elderly were also at increased risk. Effective interventions are available and should be implemented to protect these vulnerable road users.

Prediction of Coronary Heart Disease Risk using a Genetic Risk Score: The Atherosclerosis Risk in Communities Study

Abstract: Recent studies have evaluated whether incorporating nontraditional risk factors improves coronary heart disease (CHD) prediction models. This 1986–2001 US study aggregated the contribution of multiple single nucleotide polymorphisms into a genetic risk score (GRS) and assessed whether the GRS plus traditional risk factors predict CHD better than traditional risk factors alone. The Atherosclerosis Risk in Communities (ARIC) cohort was followed for a median of 13 years for CHD events (n ¼ 1,452). Individuals were genotyped for 116 single nucleotide polymorphisms associated with CHD in multiple case-control studies. Single nucleotide polymorphisms nominally predicting incident CHD in the ARIC study were included in the GRS. The GRS was significantly associated with incident CHD in Blacks (hazard rate ratio ¼ 1.20, 95% confidence interval: 1.11, 1.29) and Whites (hazard rate ratio ¼ 1.10, 95% confidence interval: 1.06, 1.14) as well as in each tertile defined by the traditional cardiovascular risk score (p � 0.02). When receiver operating characteristic curves based on traditional risk factors were recalculated after the GRS was added, the increase in the area under the receiver operating characteristic curve was statistically significant for Blacks and suggestive of improved CHD prediction for Whites. This study demonstrates the concept of aggregating information from multiple single nucleotide polymorphisms into a risk score and indicates that it can improve prediction of incident CHD in the ARIC study.

Seasonality of influenza in Brazil: a traveling wave from the Amazon to the subtropics

Abstract: Influenza circulation and mortality impact in tropical areas have not been well characterized. The authors studied the seasonality of influenza throughout Brazil, a geographically diverse country, by modeling influenza-related mortality and laboratory surveillance data. Monthly time series of pneumonia and influenza mortality were obtained from 1979 to 2001 for each of the 27 Brazilian states. Detrended time series were analyzed by Fourier decomposition to describe the amplitude and timing of annual and semiannual epidemic cycles, and the resulting seasonal parameters were compared across latitudes, ranging from the equator (+5 degrees N) to the subtropics (-35 degrees S). Seasonality in mortality was most pronounced in southern states (winter epidemics, June-July), gradually attenuated toward central states (15 degrees S) (p < 0.001), and remained low near the equator. A seasonal southward traveling wave of influenza was identified across Brazil, originating from equatorial and low-population regions in March-April and moving toward temperate and highly populous regions over a 3-month period. Laboratory surveillance data from recent years provided independent confirmation that mortality peaks coincided with influenza virus activity. The direction of the traveling wave suggests that environmental forces (temperature, humidity) play a more important role than population factors (density, travel) in driving the timing of influenza epidemics across Brazil.

Vitamin K and Vitamin D Status: Associations with Inflammatory Markers in the Framingham Offspring Study

Abstract: In vitro data suggest protective roles for vitamins K and D in inflammation. To examine associations between vitamins K and D and inflammation in vivo, the authors used multiple linear regression analyses, adjusted for age, sex, body mass index, triglyceride concentrations, use of aspirin, use of lipid-lowering medication, season, menopausal status, and hormone replacement therapy. Participants were from the Framingham Offspring Study (1997-2001; n = 1,381; mean age = 59 years; 52% women). Vitamin K status, measured by plasma phylloquinone concentration and phylloquinone intake, was inversely associated with circulating inflammatory markers as a group and with several individual inflammatory biomarkers (p < 0.01). Percentage of undercarboxylated osteocalcin, a functional measure of vitamin K status, was not associated with overall inflammation but was associated with C-reactive protein (p < 0.01). Although plasma 25-hydroxyvitamin D was inversely associated with urinary isoprostane concentration, an indicator of oxidative stress (p < 0.01), overall associations between vitamin D status and inflammation were inconsistent. The observation that high vitamin K status was associated with lower concentrations of inflammatory markers suggests that a possible protective role for vitamin K in inflammation merits further investigation.

Why Do Children from Socioeconomically Disadvantaged Families Suffer from Poor Health When They Reach Adulthood? A Life-Course Study

Abstract: The authors investigated what risk factors contribute to an excess risk of poor adult health among children who experience socioeconomic disadvantage. Data came from 1,037 children born in Dunedin, New Zealand, in 1972-1973, who were followed from birth to age 32 years (2004-2005). Childhood socioeconomic status (SES) was measured at multiple points between birth and age 15 years. Risk factors evaluated included a familial liability to poor health, childhood/adolescent health characteristics, low childhood intelligence quotient (IQ), exposure to childhood maltreatment, and adult SES. Adult health outcomes evaluated at age 32 years were major depressive disorder, anxiety disorders, tobacco dependence, alcohol or drug dependence, and clustering of cardiovascular disease risk factors. Results showed that low childhood SES was associated with an increased risk of substance dependence and poor physical health in adulthood (for tobacco dependence, sex-adjusted relative risk (RR) = 2.27, 95% confidence interval (CI): 1.41, 3.65; for alcohol or drug dependence, RR = 2.11, 95% CI: 1.16, 3.84; for cardiovascular risk factor status, RR = 2.55, 95% CI: 1.46, 4.46). Together, the risk factors studied here accounted for 55-67% of poor health outcomes among adults exposed to low SES as children. No single risk factor emerged as the prime explanation, suggesting that the processes mediating the link between childhood low SES and adult poor health are multifactorial.

Peripheral Inflammatory Biomarkers and Risk of Parkinson's Disease

Abstract: Experimental and postmortem evidence indicates a role of neuroinflammation in the pathogenesis of Parkinson’s disease. The authors prospectively examined whether plasma concentrations of inflammatory biomarkers assessed before Parkinson’s disease diagnosis were predictive of future risk of the disease in a nested case-control study in the United States (1993–2002), including 84 incident cases and 165 matched controls. Blood was collected from patients on average 4.3 years before the diagnosis. After adjustment for potential confounders, higher level of interleukin-6 was associated with a greater risk of Parkinson’s disease. Compared with the lowest quintile, the odds ratios were 1.5 for the second, 1.6 for the third, 2.7 for the fourth, and 3.4 for the fifth quintiles (p for trend ¼ 0.03). In contrast, concentrations of other inflammatory biomarkers including C-reactive protein, fibrinogen, and tumor necrosis factor-a receptors were not related to the risk. These data suggest that men with high plasma concentrations of interleukin-6 have an increased risk of developing Parkinson’s disease. However, this finding should be interpreted with caution because of the small sample size and the lack of associations with other biomarkers of inflammation. biological markers; C-reactive protein; inflammation; interleukin-6; odds ratio; Parkinson disease; tumor necrosis factor-a Abbreviations: IL, interleukin; TNF, tumor necrosis factor. Microglia-mediated neuroinflammation has been hypothesized to play an important role in the pathogenesis of Parkinson’s disease, primarily based on findings from postmortem studies and animal experiments (1, 2). Consistently, concentrations of proinflammatory cytokines such as interleukin (IL)-1b, IL-2, IL-6, and tumor necrosis factor (TNF)-a were elevated in the brain and cerebral spinal fluid of Parkinson’s disease patients (3). Two small studies further showed plasma elevations of some of these cytokines when comparing Parkinson’s disease patients with controls (4, 5). However, these studies involved prevalent cases and provided little information on whether prediagnostic levels of inflammatory biomarkers are predictive of future risk of Parkinson’s disease. Therefore, by taking advantage of the prospective Health Professionals Follow-up Study, we conducted a nested case-control investigation to examine whether peripheral elevations in inflammatory biomarkers assessed years before disease diagnoses were associated with greater risk of Parkinson’s disease.

Integrating the Predictiveness of a Marker with Its Performance as a Classifier

Abstract: There are two popular statistical approaches to biomarker evaluation. One models the risk of disease (or disease outcome) with, for example, logistic regression. A marker is considered useful if it has a strong effect on risk. The second evaluates classification performance by use of measures such as sensitivity, specificity, predictive values, and receiver operating characteristic curves. There is controversy about which approach is more appropriate. Moreover, the two approaches can give contradictory results on the same data. The authors present a new graphic, the predictiveness curve, which complements the risk modeling approach. It assesses the usefulness of a risk model when applied to the population. Although the predictiveness curve relates to classification performance measures, it also displays essential information about risk that is not displayed by the receiver operating characteristic curve. The authors propose that the predictiveness and classification performance of a marker, displayed together in an integrated plot, provide a comprehensive and cohesive assessment of a risk marker or model. The methods are demonstrated with data on prostate-specific antigen and risk factors from the Prostate Cancer Prevention Trial, 1993-2003.

Self-reported Racial Discrimination and Substance Use in the Coronary Artery Risk Development in Adults Study

Abstract: The authors investigated whether substance use and self-reported racial discrimination were associated in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Smoking status, alcohol consumption, and lifetime use of marijuana, amphetamines, and opiates were ascertained in 2000–2001, 15 years after baseline(1985–1986). Most of the 1,507 African Americans reported having experienced racial discrimination, 79.5% at year 7 and 74.6% at year 15, compared with 29.7% and 23.7% among the 1,813 Whites. Compared with African Americans experiencing no discrimination, African Americans reporting any discrimination had more education and income, while the opposite was true for Whites (all p < 0.001). African Americans experiencing racial discrimination in at least three of seven domains in both years had 1.87 (95% confidence interval (CI): 1.18, 2.96) and 2.12 (95% CI: 1.42, 3.17) higher odds of reporting current tobacco use and having any alcohol in the past year than did their counterparts experiencing no discrimination. With control for income and education, African Americans reporting discrimination in three or more domains in both years had 3.31 (95% CI: 1.90, 5.74) higher odds of using marijuana 100 or more times in their lifetime, relative to African Americans reporting no discrimination. These associations were similarly positive in Whites but not significant. Substance use may be an unhealthy coping response to perceived unfair treatment for some individuals, regardless of their race/ethnicity.

Green Tea Consumption and Prostate Cancer Risk in Japanese Men: A Prospective Study

Abstract: The incidence of prostate cancer is much lower in Asian than Western populations. Given that environmental factors such as dietary habits may play a major role in the causation of prostate cancer and the high consumption of green tea in Asian populations, this low incidence may be partly due to the effects of green tea. The JPHC Study (Japan Public Health Center-based Prospective Study) was established in 1990 for cohort I and in 1993 for cohort II. The subjects were 49,920 men aged 40-69 years who completed a questionnaire that included their green tea consumption habit at baseline and were followed until the end of 2004. During this time, 404 men were newly diagnosed with prostate cancer, of whom 114 had advanced cases, 271 were localized, and 19 were of an undetermined stage. Green tea was not associated with localized prostate cancer. However, consumption was associated with a dose-dependent decrease in the risk of advanced prostate cancer. The multivariate relative risk was 0.52 (95% confidence interval: 0.28, 0.96) for men drinking 5 or more cups/day compared with less than 1 cup/day (p(trend) = 0.01). Green tea may be associated with a decreased risk of advanced prostate cancer.

Risk Factors for Inguinal Hernia among Adults in the US Population

Abstract: The authors examined risk factors for incident inguinal hernia among US adults (5,316 men and 8,136 women) participating in the First National Health and Nutrition Examination Survey (1971-1975) who were followed through 1992-1993 for a hospital (International Classification of Diseases, Ninth Revision, Clinical Modification, code 550) or physician diagnosis of inguinal hernia. Ninety-six percent of the baseline cohort was recontacted, with a median follow-up of 18.2 years (range, 0.02-22.1 years). Because the cumulative incidence of inguinal hernia was higher among men (13.9%) than among women (2.1%), more detailed analyses were conducted in men. Among men in multivariate analysis, a higher incidence (p < 0.05) of inguinal hernia was associated with an age of 40-59 years (hazard ratio (HR) = 2.2, 95% confidence interval (CI): 1.7, 2.8), an age of 60-74 years (HR = 2.8, 95% CI: 2.2, 3.6), and hiatal hernia (HR = 1.8, 95% CI: 1.2, 2.7), while Black race (HR = 0.58, 95% CI: 0.42, 0.79), being overweight (HR = 0.79, 95% CI: 0.66, 0.95), and obesity (HR = 0.51, 95% CI: 0.36, 0.71) were associated with a lower incidence. Among women, older age, rural residence, greater height, chronic cough, and umbilical hernia were associated with inguinal hernia. In the United States, inguinal hernias are common among men, especially with aging. The lower risk among heavier men was unexpected and bears further study.