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American Journal of Epidemiology - RSS feed of recent issues (covers the latest 3 issues, including the current issue)

Cover 25 Aug 2010

Editorial Board 25 Aug 2010

Subscriptions 25 Aug 2010

Table of contents 25 Aug 2010

Blood 25-Hydroxyvitamin D3 Concentrations and Incident Sporadic Colorectal Adenoma Risk: A Pooled Case-Control Study 25 Aug 2010

The authors examined the association between circulating 25-hydroxyvitamin D₃ (25(OH)D₃), the best indicator of total vitamin D exposure, and incident, sporadic colorectal adenoma risk in a pooled analysis of primary data from 3 colonoscopy-based case-control studies conducted in Minnesota, North Carolina, and South Carolina between 1991 and 2002. The pooled study included 616 colorectal adenoma cases and 770 polyp-free controls. Multivariable logistic regression was used to estimate the association between circulating 25(OH)D₃ and colorectal adenoma risk. Stratified analyses and the likelihood ratio test were used to examine effect modification by various risk factors. In the pooled analysis, higher circulating 25(OH)D₃ concentrations were statistically significantly associated with decreased colorectal adenoma risk (highest vs. lowest quartile odds ratio = 0.59, 95% confidence interval: 0.41, 0.84). The observed inverse association was stronger among participants who used nonsteroidal antiinflammatory drugs regularly (highest vs. lowest quartile odds ratio = 0.33, 95% confidence interval: 0.19, 0.56). Inverse associations between 25(OH)D₃ and colorectal adenoma did not differ substantially by other risk factors or by adenoma characteristics. These findings support the hypothesis that greater vitamin D exposure may reduce the risk of colorectal adenoma and suggest that it may do so more strongly in combination with antiinflammatory agents.

Community Programs for the Prevention of Cardiovascular Disease: A Systematic Review 25 Aug 2010

In this systematic review, the authors aimed to assess the effectiveness of community programs for prevention of cardiovascular disease (CVD). They searched numerous electronic databases (CDSR, DARE, HTA, EED, and CENTRAL via the Cochrane Library, MEDLINE, MEDLINE In Process, EMBASE, CINAHL, PsycINFO, HMIC, and ASSIA) and relevant Web sites from January 1970 to mid-July 2008. Controlled studies of community programs for the primary prevention of CVD were included. Net changes in CVD risk factors were used to generate an overall index for net change in 10-year CVD risk. The authors identified 36 relevant community programs that took place between 1970 and 2008. These programs were multifaceted interventions employing combinations of media, screening, and counseling activities and environmental changes and were primarily evaluated using controlled before-after studies. In 7 studies, investigators reported changes in CVD/total mortality rates, and in 5 they reported net changes. In all cases, these net changes were positive but were largely nonsignificant. In 22 studies, investigators reported changes in physiologic CVD risk factors, and there was a positive trend in the calculated CVD risk score. The average net reduction in 10-year CVD risk was 0.65%. Community programs for CVD prevention appear to have generally achieved favorable changes in overall CVD risk and, with adaptation to current circumstances, deserve continued consideration as possible approaches to preventing CVD.

The Emergence of Translational Epidemiology: From Scientific Discovery to Population Health Impact 25 Aug 2010

Recent emphasis on translational research (TR) is highlighting the role of epidemiology in translating scientific discoveries into population health impact. The authors present applications of epidemiology in TR through 4 phases designated T1–T4, illustrated by examples from human genomics. In T1, epidemiology explores the role of a basic scientific discovery (e.g., a disease risk factor or biomarker) in developing a "candidate application" for use in practice (e.g., a test used to guide interventions). In T2, epidemiology can help to evaluate the efficacy of a candidate application by using observational studies and randomized controlled trials. In T3, epidemiology can help to assess facilitators and barriers for uptake and implementation of candidate applications in practice. In T4, epidemiology can help to assess the impact of using candidate applications on population health outcomes. Epidemiology also has a leading role in knowledge synthesis, especially using quantitative methods (e.g., meta-analysis). To explore the emergence of TR in epidemiology, the authors compared articles published in selected issues of the Journal in 1999 and 2009. The proportion of articles identified as translational doubled from 16% (11/69) in 1999 to 33% (22/66) in 2009 (P = 0.02). Epidemiology is increasingly recognized as an important component of TR. By quantifying and integrating knowledge across disciplines, epidemiology provides crucial methods and tools for TR.

Invited Commentary: The Epicenter of Translational Science 25 Aug 2010

Epidemiology is at the center of translational science. Uniquely among biomedical disciplines, the methods and perspective of epidemiology span research from discovery to effective interventions and ultimately to their dissemination and implementation. However, shorthand designations for various phases of translational science, such as "T1, T2, T3, and T4," may be proliferating past the level of their usefulness. It is worthwhile to reflect on the actual nature of the science undertaken by epidemiologists along the continuum of discovery to application. The new challenge for epidemiology is the integration of knowledge and effective interventions into various societal settings working with allied disciplines not necessarily in the biomedical domain to ensure that these interventions have their intended effects on individual and public health.

Khoury et al. Respond to "The Epicenter of Translational Science": Crossing All the T's 25 Aug 2010

Birth Weight Standardized to Gestational Age and Intelligence in Young Adulthood: A Register-based Birth Cohort Study of Male Siblings 25 Aug 2010

The authors aimed to determine the relation between birth-weight variations within the normal range and intelligence in young adulthood. A historical birth cohort study was conducted. Data from the Medical Birth Register of Norway were linked with register data from the Norwegian National Conscript Service. The sample comprised 52,408 sibships of full brothers who were born singletons at 37–41 completed weeks’ gestation during 1967–1984 in Norway and were intelligence-tested at the time of mandatory military conscription. Generalized estimating equations were used to fit population-averaged panel data models. The analyses showed that in men with birth weights within the 10th–90th percentile range, a within-family difference of 1 standard deviation in birth weight standardized to gestational age was associated with a within-family difference of 0.07 standard deviation (99% confidence interval: 0.03, 0.09) in intelligence score, after adjustment for a range of background factors. There was no significant between-family association after adjustment for background factors. In Norwegian males, normal variations in intrauterine growth are associated with differences in intelligence in young adulthood. This association is probably not due to confounding by familial and parental characteristics.

Invited Commentary: The Use of Sibship Studies to Detect Familial Confounding 25 Aug 2010

The authors discuss how the sibship design can be used to detect and control for familial confounding. Family-level confounding is especially problematic when estimating modest individual-level effects in the presence of familial confounders with large effects. This circumstance arises frequently in studies which relate indicators of fetal growth, such as birth weight, to outcomes that are strongly associated with parental socioeconomic status and genes. The study by Eriksen et al. in this issue of the Journal (Am J Epidemiol. 2010;172(5):530–536) uses the sibship design to capture the relation between birth weight, gestational age, and intelligence score among Norwegian males born as singletons at 37–41 completed weeks’ gestation during 1967–1984. Their study illustrates how valuable the design can be in this kind of scenario. It also illustrates the potential complexity of sibship studies and the challenges they present for appropriate interpretation.

Midlife Health and Socioeconomic Consequences of Persistent Overweight Across Early Adulthood: Findings From a National Survey of American Adults (1986-2008) 25 Aug 2010

The health consequences of obesity and overweight have been well documented, but less research has examined their social and economic consequences. This paper examines the long-term consequences of early adult overweight for midlife health and socioeconomic attainment using prospective nationally representative panel data from American adults in the Monitoring the Future Study (1986–2008). Growth mixture models identified 2 distinct latent classes of trajectories of body mass index (BMI) from age 19 to 35 years: a persistently overweight class (BMI >25 kg/m²) and a second class exhibiting more moderate growth in BMI to age 35 years. Women (odds ratio (OR) = 2.16, 95% confidence interval (CI): 1.39, 3.36) and those from a lower childhood socioeconomic position (OR = 1.71, 95% CI: 1.30, 2.24) were more likely to be in the persistently overweight class. Compared with those in the moderately increasing BMI class, those in the persistently overweight class were more likely to have a chronic health problem at age 40 years (OR = 2.74, 95% CI: 2.20, 3.43), to have no further education beyond high school (OR = 1.33, 95% CI: 1.04, 1.69), and to have a higher odds of receiving welfare or unemployment compensation at age 40 years (OR = 1.76, 95% CI: 1.49, 2.04). These findings highlight the importance of addressing persistent obesity and overweight early in the life course.

A Study of the Birth Weight-Obesity Relation Using a Longitudinal Cohort and Sibling and Twin Pairs 25 Aug 2010

Sibling and twin study designs provide control for confounding factors that are typically unmeasured in traditional cohort studies. Using nationally representative data from the National Longitudinal Study of Adolescent Health collected at 3 visits during 1994–2002, the authors evaluated the longitudinal association between birth weight and later obesity in a traditional cohort study (n = 13,763; ages 11–21 years at baseline), controlling for sex, age, race/ethnicity, and parental education. Among persons with a nonobese mother, high birth weight (>4 kg) participants were more likely than normal birth weight (≥2.5–≤4 kg) participants to become obese later in life (incidence rate ratio = 1.46, 95% confidence interval: 1.28, 1.67). In a matched sibling pair sample (full siblings: n = 513; monozygotic twins: n = 207; dizygotic twins: n = 189), the authors examined longitudinal within-pair differences. Birth weight difference was positively associated with body mass index difference later in life for female monozygotic pairs only (β = 2.67, 95% confidence interval: 0.99, 4.35). Given the null associations observed in the sibling sample, the commonly observed positive association between birth weight and later obesity from cohort analyses may be attributed to confounding by maternal characteristics. Further research is needed to identify specific factors that contribute to the birth weight–obesity relation.

Changes in Weight at the End of Life: Characterizing Weight Loss by Time to Death in a Cohort Study of Older Men 25 Aug 2010

The purpose of this analysis was to characterize the natural history of weight change in the years prior to death among older persons and to examine how this pattern varies according to longevity and cause of death. Weight trajectories were analyzed by using data from 800 male decedents from the Baltimore Longitudinal Study of Aging (Maryland, 1958–2005) observed beginning an average of 19 years before death. A model including 3 distinct periods of weight change (weight stability/gain, mild weight loss, and accelerated weight loss before death) provided the best fit for all age-at-death groups. Approximately 9 years before death, the rate of weight loss increased to an average of 0.39 kg/year (P < 0.001) for all-cause mortality. For cancer deaths, weight loss accelerated significantly 3 years before death, regardless of age group. For cardiovascular deaths, the best-fitting inflection point increased with age, from 5 years for participants aged 60–69 years to 9–10 years before death for those aged 80 years or older. Results suggest that weight loss in older persons may begin earlier than previously believed. The duration of weight loss for noncancer deaths suggests that even distal changes in energy balance may be linked to risk of death.

Diet, Supplement Use, and Prostate Cancer Risk: Results From the Prostate Cancer Prevention Trial 25 Aug 2010

The authors examined nutritional risk factors for prostate cancer among 9,559 participants in the Prostate Cancer Prevention Trial (United States and Canada, 1994–2003). The presence or absence of cancer was determined by prostate biopsy, which was recommended during the trial because of an elevated prostate-specific antigen level or an abnormal digital rectal examination and was offered to all men at the trial's end. Nutrient intake was assessed using a food frequency questionnaire and a structured supplement-use questionnaire. Cancer was detected in 1,703 men; 127 cancers were high-grade (Gleason score 8–10). There were no associations of any nutrient or supplement with prostate cancer risk overall. Risk of high-grade cancer was associated with high intake of polyunsaturated fats (quartile 4 vs. quartile 1: odds ratio = 2.41, 95% confidence interval (CI): 1.33, 4.38). Dietary calcium was positively associated with low-grade cancer but inversely associated with high-grade cancer (for quartile 4 vs. quartile 1, odds ratios were 1.27 (95% CI: 1.02, 1.57) and 0.43 (95% CI: 0.21, 0.89), respectively). Neither dietary nor supplemental intakes of nutrients often suggested for prostate cancer prevention, including lycopene, long-chain n-3 fatty acids, vitamin D, vitamin E, and selenium, were significantly associated with cancer risk. High intake of n-6 fatty acids, through their effects on inflammation and oxidative stress, may increase prostate cancer risk.

Use of Aspirin and Other Nonsteroidal Antiinflammatory Medications in Relation to Prostate Cancer Risk 25 Aug 2010

Recent interest has focused on the role that inflammation may play in the development of prostate cancer and whether use of aspirin or other nonsteroidal antiinflammatory drugs (NSAIDs) affects risk. In a population-based case-control study designed to investigate the relation between these medications and prostate cancer risk, detailed exposure data were analyzed from 1,001 cases diagnosed with prostate cancer between January 1, 2002, and December 31, 2005, and 942 age-matched controls from King County, Washington. A significant 21% reduction in the risk of prostate cancer was observed among current users of aspirin compared with nonusers (95% confidence interval (CI): 0.65, 0.96). Long-term use of aspirin (>5 years: odds ratio = 0.76, 95% CI: 0.61, 0.96) and daily use of low-dose aspirin (odds ratio = 0.71, 95% CI: 0.56, 0.90) were also associated with decreased risk. There was no evidence that the association with aspirin use varied by disease aggressiveness, but there was effect modification (P_interaction = 0.02) with a genetic variant in prostaglandin-endoperoxide synthase 2 (PTGS2) (rs12042763). Prostate cancer risk was not related to use of either nonaspirin NSAIDs or acetaminophen. These results contribute further evidence that aspirin may have chemopreventive activity against prostate cancer and highlight the need for additional research.

Cigarette Smoking in Relation to Risk of Ductal Carcinoma In Situ of the Breast in a Cohort of Postmenopausal Women 25 Aug 2010

In numerous studies, investigators have examined the association of active smoking with risk of invasive breast cancer, but to the authors’ knowledge, no cohort study has assessed smoking in relation to the risk of in situ breast cancer, the postulated penultimate stage preceding invasive breast cancer. The authors examined the latter association using data collected at baseline from 63,393 women in the Women's Health Initiative Clinical Trial. A total of 486 cases of ductal carcinoma in situ (DCIS) of the breast were identified during 8 years of follow-up between 1993 and 2005. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals. For the primary analysis, invasive breast cancer was treated as a competing risk. After adjustment for covariates, associations with smoking status, smoking intensity, duration, pack-years, and age at quitting were all close to the null value and showed few meaningful trends. Sensitivity analyses performed to address different possibilities with respect to the natural history of breast cancer also did not provide consistent evidence of an association of smoking with DCIS. The results of this large cohort study provide little support for an association of cigarette smoking with risk of DCIS in postmenopausal women.

Risk of Incident Cardiovascular Disease Among Users of Smokeless Tobacco in the Atherosclerosis Risk in Communities (ARIC) Study 25 Aug 2010

Use of smokeless tobacco in the United States has been relatively constant in recent years, as tobacco companies continue aggressive marketing campaigns. The health effects of smokeless tobacco use need further documentation. Thus, the authors examined whether current use of smokeless tobacco was associated with increased incidence of cardiovascular disease (CVD) in 14,498 men and women aged 45–64 years at baseline (1987–1989) in the Atherosclerosis Risk in Communities (ARIC) Study. There were 2,572 incident CVD events (myocardial infarction, coronary revascularization, coronary death, or stroke) during a median of 16.7 years of follow-up (maximum = 19.1 years). Current use of smokeless tobacco at baseline was associated with 1.27-fold greater CVD incidence (95% confidence interval: 1.06, 1.52) than was nonuse, independently of demographic, socioeconomic, and lifestyle and other tobacco-related variables. Past use of smokeless tobacco was not associated with CVD incidence. In conclusion, current use of smokeless tobacco was associated with increased risk of CVD incidence in ARIC cigarette nonsmokers. Current users of smokeless tobacco should be informed of its harm and advised to quit the practice. Current cigarette smokers should also be given sufficient information on safe, therapeutic methods of quitting which do not include switching to smokeless tobacco.

Assessment of Changes in Condom Use Among Female Sex Workers in a Prospective Cohort Study Introducing Diaphragm Use for Disease Prevention 25 Aug 2010

Changes in the rates of condom use and number of sexual partners were evaluated among 140 female sex workers in Kibera, Kenya, participating in a 6-month study of diaphragm safety and acceptability for prevention of sexually transmitted infections conducted in 2004–2005. Analyses were stratified by partner type. Multivariable Tobit regression modeling was used to assess the association between study visit and proportion of acts protected. Participants completed 140 baseline visits and 390 bimonthly follow-up visits. The mean percentage of coital acts reported as protected by a condom increased from 56% at baseline to 68% at the 6-month visit (P < 0.01). Similar increases were observed for condom use by all partner types. Additionally, the mean number of sexual partners decreased over the study. Furthermore, consistent (i.e., 100%) diaphragm use during follow-up was associated with a higher proportion of coital acts protected by a condom in analyses adjusted for study visit and coital frequency. These findings suggest that, despite concerns that introduction of the diaphragm would result in more risky sexual behaviors, reported condom use increased and number of partners decreased.

From Cancer to Transplantation: An Evaluation of Period Analysis for Calculating Up-to-date Long-term Survival Estimates 25 Aug 2010

The timeliness of survival monitoring is particularly important in a field such as transplantation medicine, where progress occurs rapidly. Period analysis, a method successfully applied for improving the timeliness of survival monitoring in population-based cancer survival analysis, could potentially be useful in the field of transplantation as well. Using data from the Collaborative Transplant Study, the authors compared the ability of traditional, cohort-based analysis methods and the period analysis method to provide timely 5-year graft and patient survival estimates for kidney, heart, and liver transplants in 6 age groups (0–17, 18–29, 30–39, 40–49, 50–59, ≥60 years) on 378 occasions between 1990–1992 and 2000–2002. Overall, period estimates provided superior predictions for the survival of most recent transplants on 344 of 378 occasions (91%); in the organ-specific analysis, this proportion ranged between 83% for heart and 100% for kidney graft survival. This evaluation provides evidence that the period analysis method can improve the timeliness of survival monitoring in solid organ transplantation. The method appears useful for providing more up-to-date long-term survival estimates than traditional methods, and its use in pertinent studies is encouraged.

Cover 10 Aug 2010

Editorial Board 10 Aug 2010

Subscriptions 10 Aug 2010

Table of contents 10 Aug 2010

Cytomegalovirus Antibody Levels, Inflammation, and Mortality Among Elderly Latinos Over 9 Years of Follow-up 10 Aug 2010

This study examined the relation between immune response to cytomegalovirus (CMV) and all-cause and cardiovascular disease (CVD) mortality, and possible mediating mechanisms. Data were derived from the Sacramento Area Latino Study on Aging, a population-based study of older Latinos (aged 60–101 years) in California followed in 1998–2008. CMV immunoglobulin G (IgG), tumor necrosis factor, and interleukin-6 were assayed from baseline blood draws. Data on all-cause and CVD mortality were abstracted from death certificates. Analyses included 1,468 of 1,789 participants. For individuals with CMV IgG antibody titers in the highest quartile compared with lower quartiles, fully adjusted models showed that all-cause mortality was 1.43 times (95% confidence interval: 1.14, 1.79) higher over 9 years. In fully adjusted models, the hazard of CVD mortality was also elevated (hazard ratio = 1.35, 95% confidence interval: 1.01, 1.80). A composite measure of tumor necrosis factor and interleukin-6 mediated a substantial proportion of the association between CMV and all-cause (18.9%, P < 0.001) and CVD (29.0%, P = 0.02) mortality. This study is the first known to show that high CMV IgG antibody levels are significantly related to mortality and that the relation is largely mediated by interleukin-6 and tumor necrosis factor. Further studies investigating methods for reducing IgG antibody response to CMV are warranted.

Invited Commentary: Human Cytomegalovirus, Inflammation, Cardiovascular Disease, and Mortality 10 Aug 2010

Human cytomegalovirus (CMV) is a human herpesvirus, and infection is widespread in the human population. Prevalence of seropositivity for human CMV increases with age. CMV establishes persistent infection in vascular arterial and venous endothelial tissue. It has been associated with atherosclerosis and graft rejection in heart transplant recipients. The antiviral drug ganciclovir prevents CMV disease in heart transplant patients, and valganciclovir and CMV immune globulin reduce rejection rates and cardiovascular disease. Human CMV infection has been associated with proinflammatory cytokine increases and nonresponsiveness to antiinfluenza vaccine in the elderly. Enhanced expression of proinflammatory cytokines has also been associated with enhanced mortality in the elderly. In this issue of the Journal, Roberts et al. (Am J Epidemiol. 2010;000(00):000–000) report that, in a large population-based cohort of elderly Sacramento area Latino subjects in California followed from 1998 to 2008, more than 95% were seropositive for human CMV. In that study, Kaplan-Meier survival curves suggested worse cardiovascular disease survival for individuals in the highest quartile of human CMV immunoglobulin G antibody titers over 9 years of follow-up. Theirs is the first study known to report a relation between high human CMV antibody levels and mortality.

Roberts et al. Respond to "Human CMV, Inflammation, and Mortality" 10 Aug 2010

Personality Traits and Cancer Risk and Survival Based on Finnish and Swedish Registry Data 10 Aug 2010

Personality traits have been studied extensively as risk and prognostic factors for cancer; however, the association remains unclear. This prospective, population-based cohort study comprised 59,548 Swedish (1974–1999) and Finnish (1976–2004) participants who completed a questionnaire eliciting information for the Eysenck Personality Inventory and on health behavior at baseline. To analyze the association of personality traits extraversion and neuroticism with risk of cancer, the authors identified 4,631 cancer cases for a maximum 30 years of follow-up. To assess the association with cancer survival among the Finnish participants, they identified 2,733 cancer cases and, later, 1,548 deaths for a maximum 29 years of follow-up. Hazard ratios were estimated by treating the personality scales as continuous variables and are presented per one increase in score on each scale. In multivariate analyses, extraversion and neuroticism were not significantly associated with risk of cancers at all sites (extraversion: hazard ratio = 0.99, 95% confidence interval: 0.98, 1.01; neuroticism: hazard ratio = 1.00, 95% confidence interval: 0.99, 1.02). Results showed no significant association between these traits and the hazard ratio for death after cancers at all sites, and they do not support the hypothesis that extraversion and neuroticism are direct risk factors for cancer or survival after cancer.

Invited Commentary: Personality as a Causal Factor in Cancer Risk and Mortality--Time to Retire a Hypothesis? 10 Aug 2010

In this issue of the Journal, Nakaya et al. (Am J Epidemiol. 2010;172(4):377–385) report null findings from a large-scale prospective study of the prognostic value of 2 personality dimensions, neuroticism and extraversion, for cancer risk and mortality. The study stands out because of its exceptionally large sample size and its methodological strengths. The authors discuss the Nakaya et al. study in the context of persistent beliefs about the role of personality in cancer onset and survival despite a pattern of null findings in the literature, as well as the influence of extreme outlier findings from one investigator group that continue to be cited. They question whether it is time for the field to move on from considering a role for personality in cancer to more promising and modifiable factors.

Long-term Harm of Low Preparedness for a Wife's Death From Cancer--A Population-based Study of Widowers 4-5 Years After the Loss 10 Aug 2010

The authors examined the impact of a widower's preparedness before his wife's death from cancer on his risk of long-term morbidity. In a population-based study, 691 (76%) of 907 Swedish men who lost a wife to breast, ovarian, or colon cancer in 2000 or 2001 answered an anonymous questionnaire in 2004 or 2005 measuring preparedness at the time of the wife's death and psychological well-being at follow-up. Men aged 38–61 years with a low degree of preparedness at the time of their spouse's death had increased risk of psychological morbidity and other symptoms, such as anxiety (adjusted relative risk (aRR) = 2.1, 95% confidence interval (CI): 1.0, 4.3), a heightened startle response (aRR = 5.3, 95% CI: 1.2, 23.6), emotional numbness (aRR = 2.1, 95% CI: 1.2, 3.6), little or no grief resolution (aRR = 2.7, 95% CI: 1.3, 5.4), and sleep disorders (aRR = 2.3, 95% CI: 1.2, 4.3), 4–5 years after the loss. For older widowers (aged 62–80 years), a low degree of preparedness increased the risk of having repeated painful memories (aRR = 2.8, 95% CI: 1.5, 5.2) and a heightened startle response (aRR = 5.7, 95% CI: 1.5, 21.4) at follow-up. These results show that to improve the long-term psychological well-being of widowers, it may be fruitful to identify care-related facilitators and inhibitors of preparedness.

Fruit and Vegetable Consumption and Risk of Distal Gastric Cancer in the Shanghai Women's and Men's Health Studies 10 Aug 2010

Results from case-control and cohort studies of the association between fruit and vegetable consumption and gastric cancer risk have been inconsistent. Cases for the current study consisted of incident distal gastric cancers identified between 1996 and 2007 among members of the Shanghai Women's Health Study (n = 206) and the Shanghai Men's Health Study (n = 132). Intakes of fruits, vegetables, and select micronutrients were assessed on the basis of validated food frequency questionnaires. Multivariate-adjusted hazards ratios and 95% confidence intervals were calculated by Cox proportional hazards regression. For women, no associations were found between gastric cancer risk and the highest intake of fruits (hazard ratio (HR) = 1.02, 95% confidence interval (CI): 0.68, 1.54; P_trend = 0.87) or vegetables (HR = 0.89, 95% CI: 0.60, 1.31; P_trend = 0.32). For men, increased fruit intake was associated with decreased risk of distal gastric cancer (for the highest quartile of intake, HR = 0.50, 95% CI: 0.29, 0.84; P_trend = 0.004), but no association was seen with increased intake of vegetables (HR = 1.00, 95% CI: 0.59, 1.68; P_trend = 0.87). The inverse association with fruit intake for men was more evident among ever smokers (P_trend = 0.001) than never smokers (P_trend = 0.67). No associations between dietary intakes of select antioxidant micronutrients were seen for men or women. Fruit intake is inversely associated with distal gastric cancer risk among men in Shanghai, China.

Circulating C-Reactive Protein Concentrations and Risks of Colon and Rectal Cancer: A Nested Case-Control Study Within the European Prospective Investigation into Cancer and Nutrition 10 Aug 2010

The authors investigated associations between serum C-reactive protein (CRP) concentrations and colon and rectal cancer risk in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (1992–2003) among 1,096 incident cases and 1,096 controls selected using risk-set sampling and matched on study center, age, sex, time of blood collection, fasting status, menopausal status, menstrual cycle phase, and hormone replacement therapy. In conditional logistic regression with adjustment for education, smoking, nutritional factors, body mass index, and waist circumference, CRP showed a significant nonlinear association with colon cancer risk but not rectal cancer risk. Multivariable-adjusted relative risks for CRP concentrations of ≥3.0 mg/L versus <1.0 mg/L were 1.36 (95% confidence interval (CI): 1.00, 1.85; P-trend = 0.01) for colon cancer and 1.02 (95% CI: 0.67, 1.57; P-trend = 0.65) for rectal cancer. Colon cancer risk was significantly increased in men (relative risk = 1.74, 95% CI: 1.11, 2.73; P-trend = 0.01) but not in women (relative risk = 1.06, 95% CI: 0.67, 1.68; P-trend = 0.13). Additional adjustment for C-peptide, glycated hemoglobin, and high density lipoprotein cholesterol did not attenuate these results. These data provide evidence that elevated CRP concentrations are related to a higher risk of colon cancer but not rectal cancer, predominantly among men and independently of obesity, insulin resistance, and dyslipidemia.

Leisure Time Spent Sitting in Relation to Total Mortality in a Prospective Cohort of US Adults 10 Aug 2010

The obesity epidemic is attributed in part to reduced physical activity. Evidence supports that reducing time spent sitting, regardless of activity, may improve the metabolic consequences of obesity. Analyses were conducted in a large prospective study of US adults enrolled by the American Cancer Society to examine leisure time spent sitting and physical activity in relation to mortality. Time spent sitting and physical activity were queried by questionnaire on 53,440 men and 69,776 women who were disease free at enrollment. The authors identified 11,307 deaths in men and 7,923 deaths in women during the 14-year follow-up. After adjustment for smoking, body mass index, and other factors, time spent sitting (≥6 vs. <3 hours/day) was associated with mortality in both women (relative risk = 1.34, 95% confidence interval (CI): 1.25, 1.44) and men (relative risk = 1.17, 95% CI: 1.11, 1.24). Relative risks for sitting (≥6 hours/day) and physical activity (<24.5 metabolic equivalent (MET)-hours/week) combined were 1.94 (95% CI: 1.70, 2.20) for women and 1.48 (95% CI: 1.33, 1.65) for men, compared with those with the least time sitting and most activity. Associations were strongest for cardiovascular disease mortality. The time spent sitting was independently associated with total mortality, regardless of physical activity level. Public health messages should include both being physically active and reducing time spent sitting.

Influence of Endogenous Reproductive Hormones on F2-Isoprostane Levels in Premenopausal Women: The BioCycle Study 10 Aug 2010

Endogenous reproductive hormones and oxidative stress have been independently linked to risk of chronic disease but mostly in postmenopausal women. The interplay between endogenous reproductive hormones and oxidative stress among premenopausal women, however, has yet to be clearly elucidated. The objective of this study was to investigate the association between endogenous reproductive hormones and F₂-isoprostanes in the BioCycle Study. Women aged 18–44 years from western New York State were followed prospectively for up to 2 menstrual cycles (n = 259) during 2005–2007. Estradiol, progesterone, luteinizing hormone, follicle-stimulating hormone, sex hormone-binding globulin, F₂-isoprostanes, and thiobarbituric acid-reactive substances were measured up to 8 times per cycle at clinic visits timed by using fertility monitors. F₂-Isoprostane levels had an independent positive association with estradiol (β = 0.02, 95% confidence interval: 0.01, 0.03) and inverse associations with sex hormone-binding globulin and follicle-stimulating hormone (β = –0.04, 95% confidence interval: –0.07, –0.003; β = –0.02, 95% confidence interval: –0.03, –0.002, respectively) after adjustment for age, race, age at menarche, -tocopherol, beta-carotene, total cholesterol, and homocysteine by inverse probability weighting. Thiobarbituric acid-reactive substances, a less specific marker of oxidative stress, had similar associations. If F₂-isoprostanes are specific markers of oxidative stress, these results call into question the commonly held hypothesis that endogenous estradiol reduces oxidative stress.

Association Between Left Ventricular Mass and Telomere Length in a Population Study 10 Aug 2010

Experimental studies have implicated telomere dynamics in cardiomyocyte size and replication potential; shorter telomeres mark attenuated proliferation and increased apoptosis. The authors examined whether this translates into an impact of telomere length (TL) on left ventricular (LV) mass in the general population. In 334 randomly selected Flemish participants (mean age = 46.5 years; 52.5% women), they measured TL in circulating leukocytes using quantitative polymerase chain reaction, expressing it as telomere/genomic DNA ratio (T/S). After a median 7.4 years of follow-up (interquartile range, 6.2–8.5) during 1996–2007, they measured LV mass by echocardiography. In multivariable-adjusted analyses accounting for sex, age, body weight and height, systolic blood pressure, and antihypertensive drug use, LV mass and LV mass index significantly increased with mean leukocyte TL in the entire population and in the 198 normotensive subjects. For a 1-standard-deviation increment in T/S ratio, LV mass (mean = 170 g) and LV mass index (mean = 92 g/m²) increased by 5.20 g (P = 0.003) and 2.70 g/m² (P = 0.004), respectively, in all subjects and by 8.03 g (P = 0.0001) and 3.74 g/m² (P = 0.0007) in normotensive subjects. There were corresponding associations with LV wall thicknesses (P < 0.007) but not LV internal diameter (P = 0.26) in normotensive subjects. Longer mean leukocyte TL is associated with increased LV mass, particularly in normotensive subjects. This association could have a biologic basis related to the role of TL in determining cardiomyocyte size and replication potential.

Home Dampness and Molds as Determinants of Allergic Rhinitis in Childhood: A 6-Year, Population-based Cohort Study 10 Aug 2010

The authors assessed the relation between exposure to dampness and molds in dwellings and the development of allergic rhinitis in childhood in a 6-year, population-based prospective cohort study of 1,863 children aged 1–7 years at baseline in 1991 (follow-up rate, 77%) from Espoo, Finland. The studied exposures were history of water damage, presence of moisture and visible mold, and perceived mold odor in the home, based on parent-administered questionnaire. A total of 246 (13.2%) children developed physician-diagnosed allergic rhinitis during the study period, resulting in an incidence rate of 440 cases per 10,000 person-years (95% confidence interval (CI): 387, 499). In logistic regression adjusting for confounding, any mold or dampness exposure indicator at baseline (adjusted odds ratio = 1.55, 95% CI: 1.10, 2.18), at follow-up (adjusted odds ratio = 1.62, 95% CI: 1.21, 2.18), or both (adjusted odds ratio = 1.96, 95% CI: 1.29, 2.98) was an important independent determinant of the risk of allergic rhinitis. Of the individual indicators, water damage and moisture on the surfaces were consistent determinants of allergic rhinitis. The results of this cohort study, which assessed exposure before the onset of allergic rhinitis, strengthen considerably the evidence of the role of indoor dampness problems as determinants of allergic rhinitis in children.

Epidemiology of Antiretroviral Multiclass Resistance 10 Aug 2010

Given the recent evolution of therapeutic trends, the frequency and determinants of multiclass-resistant HIV infection in the modern combination highly active antiretroviral therapy (HAART) era are less well understood. In this study, the authors characterize the epidemiology of antiretroviral multiclass resistance among HAART-naïve patients enrolled in a province-wide HAART distribution program in British Columbia, Canada. HAART and resistance testing are free to eligible individuals in British Columbia. This study was based on patients who initiated naïve on HAART and were followed during January 1, 2000–June 30, 2007. Explanatory logistic and survival models were built to identify those factors most influential in the emergence of multiclass resistance. Among the 1,820 individuals in our study, 833 (46%) were tested for antiretroviral resistance at least once during their follow-up. Multiclass resistance was observed in 142 individuals (n = 833; 17%) during a median follow-up of 14 months (interquartile range, 3–34 months) (incidence rate, 0.8 cases/1,000 person-months). The authors found that initial nonnucleoside reverse transcriptase inhibitor-based HAART was the main determinant of multiclass resistance. Given that these inhibitors are still widely used, priority should be given to make resistance testing and viral load monitoring a standard part of human immunodeficiency virus care to maximize the long-term efficacy and efficiency of HAART.

Strategies for Using the National Death Index and the Social Security Administration for Death Ascertainment in Large Occupational Cohort Mortality Studies 10 Aug 2010

This paper describes a multistage process to improve the completeness and time-/cost-effectiveness of ascertaining deaths in large employee cohorts. The process uses the vital status data service of the Social Security Administration (SSA) to identify people who can be confirmed as living, in order to reduce the number of records submitted for a National Death Index (NDI) search. The accuracy of SSA results is verified by submitting a sample of known-living and known-deceased people. For the NDI search results, an algorithm based on a discrete combination of matching variables is applied to distinguish NDI records as true, false, or questionable matches to reduce the number of death certificate requests to state offices. Subsequent decision making is based on manual reviews at various stages. In a cohort of over 200,000 employees, an SSA vital status search reduced the size of the NDI death record search by 85%. The algorithm sorted thousands of NDI records into 15 distinct strata and reduced the number of death certificate requests by 76%. The authors believe that the matching process is enhanced by obtaining paper copies of death certificates from the states, because death certificates often provide additional information and aid in determining true matches to company employees.

Strategies for Multiple Imputation in Longitudinal Studies 10 Aug 2010

Multiple imputation is increasingly recommended in epidemiology to adjust for the bias and loss of information that may occur in analyses restricted to study participants with complete data ("complete-case analyses"). However, little guidance is available on applying the method, including which variables to include in the imputation model and the number of imputations needed. Here, the authors used multiple imputation to analyze the prevalence of wheeze among 81-month-old children in the Avon Longitudinal Study of Parents and Children (Avon, United Kingdom; 1991–1999) and the association of wheeze with gender, maternal asthma, and maternal smoking. The authors examined how inclusion of different types of variables in the imputation model affected point estimates and precision, and assessed the impact of number of imputations on Monte Carlo variability. Inclusion of variables associated with the outcome in the imputation model increased odds ratios and reduced standard errors. When only 5 or 10 imputations were used, variability due to the imputation procedure was substantial enough to affect conclusions. Careful preliminary analysis identified the scope for multiple imputation to reduce bias and improve efficiency and provided guidance for building the imputation model. When data are missing, such preliminary analyses should be routinely undertaken and reported, regardless of whether multiple imputation is used in the final analysis.

Social Networks and Health: Models, Methods, and Applications: By Thomas W. Valente 10 Aug 2010

Cover 23 Jul 2010

Editorial Board 23 Jul 2010

Subscriptions 23 Jul 2010

Table of contents 23 Jul 2010

Pelvic Endometriosis Diagnosed in an Entire Nation Over 20 Years 23 Jul 2010

The annual incidence of pelvic endometriosis among women aged 15–49 years and up to age 69 years was ascertained for the Icelandic population between 1981 and 2000 by using Iceland's extensive record linkage systems. Comprehensive, state-financed health care and unique personal identification numbers enabled care to be tracked from first diagnosis. To identify cases, a centralized discharge-code registry was searched, as well as all hospital databases and, for individual patients, all hospital records. Each case of visually diagnosed and histologically verified endometriosis was cross-checked against the nationwide pathology registry. The revised American Society for Reproductive Medicine classification system was used for staging. Recorded was type of operation at diagnosis and presence of disease at 5 sites: deep pelvis, appendages, central pelvis, vesicouterine pouch, and ovaries. A total of 1,383 women were diagnosed surgically, with histologic verification of 811 (58.6%). All but 6 cases could be staged; 297 (36.9%) had minimal/mild and 508 (63.1%) had moderate/severe disease. The estimates of crude annual incidence were 0.1% for visually confirmed and 0.06% for histologically verified endometriosis, and respective age-standardized annual incidence was 0.1% and 0.05% for women aged 15–49 years. The most common site was the ovary, followed by deep pelvis, central pelvis, appendages, and vesicouterine pouch.

Evaluation of Genetic Susceptibility Loci for Obesity in Chinese Women 23 Jul 2010

Recent genome-wide association (GWA) studies have identified 18 genetic loci for obesity. Using directly observed and imputed GWA genotyping data on approximately 5,000 Chinese women (1996–2007), the authors evaluated 17 single nucleotide polymorphisms (SNPs) that represent 17 distinct obesity loci. Two SNPs near the BAT2 and MC4R genes and 3 SNPs within the FTO, SEC16B, and SH2B1 genes were significantly associated with body mass index (weight (kg)/height (m)²), body weight, and the prevalence of obesity. The per-allele increase in body mass index ranged from 0.16 units (BAT2) to 0.38 units (SH2B1). Odds ratios for obesity ranged from 1.46 (95% confidence interval (CI): 1.12, 1.92) for BAT2 to 2.16 (95% CI: 1.39, 3.37) for MC4R. A genetic risk score calculated by summing the number of risk-increasing alleles that each woman carried at these 5 loci was significantly associated with the prevalence of obesity. Women carrying 5 or more risk alleles had a 3.13-fold (95% CI: 2.06, 4.77) higher prevalence of obesity than women carrying 1 or no risk alleles. Results from this study extend some previous GWA findings to Chinese women and show the need for additional studies to identify susceptibility loci in Chinese and other Asian populations.

Teens and Screens: The Influence of Screen Time on Adiposity in Adolescents 23 Jul 2010

The effect of screen time during secondary school on percent body fat was examined in a cohort of 744 Canadian adolescents aged 12–13 years at baseline. Participants completed self-reported questionnaires on television viewing and computer use in 19 survey cycles over 57 months from 1999 to 2005. Triceps skinfold thickness and subscapular skinfold thickness were measured in survey cycles 1 and 19. Four screen-time trajectory groups identified in growth mixture modeling included steady-low screen time (73% of the sample), steady-high (10%), increasers (9%), and decreasers (8%). The effect of screen-time trajectory on percent body fat at survey cycle 19 was modeled in boys and girls separately by using linear regression, adjusting for baseline percent body fat and physical activity. Relative to that of steady-low screen-time trajectory group boys, percent body fat was 2.9 (95% confidence interval: 0.7, 5.0) and 2.4 (95% confidence interval: 0.5, 4.2) percentage units higher on average among "increasers" and "steady-high" trajectory group boys, respectively. There was no evidence that screen time has an effect on percent body fat in girls overall, although physical activity modified the association between screen time and percent body fat in both sexes. Efforts to prevent obesity in youth should emphasize reducing screen time.

Weight Change and Incident Diabetes: Addressing an Unresolved Issue 23 Jul 2010

The impact of weight change on diabetes incidence remains unclear. To clarify the role of weight change as a risk factor for diabetes, the authors assessed the association between weight change and diabetes incidence conditional upon either initial or attained body mass index (BMI). They used 7,837 observations available from repeated measurements of 4,259 participants (men and women aged 20–59 years) in the Dutch population-based Doetinchem Cohort Study (1987–2007) to analyze the association between 5-year weight change and diabetes incidence (n = 124) in the subsequent 5 years. When adjusted for initial BMI, 5-year weight change was a significant risk factor for diabetes (odds ratio = 1.08, 95% confidence interval: 1.04, 1.13 per kilogram of weight change). However, no significant association was found between weight change and diabetes if the association was adjusted for attained BMI (odds ratio = 0.99, 95% confidence interval: 0.94, 1.04 per kilogram of weight change). Results suggest that weight change is associated with diabetes incidence because, conditional upon initial BMI, weight change determines attained BMI. This finding implies that lifestyle interventions can contribute to diabetes prevention because they affect attained BMI. Weight change appears to have no effect on diabetes incidence beyond its effect on attained BMI.

Urinary 8-Hydroxy-2-deoxyguanosine and Cognitive Function in Puerto Rican Adults 23 Jul 2010

DNA oxidative stress has been suggested as an important pathogenic mechanism in cognitive impairment and dementia. With baseline data collected from 2004 to 2008, the authors examined whether urinary 8-hydroxy-2-deoxyguanosine (8-OHdG), a biomarker of global DNA oxidation, was associated with cognitive function in a sample of 1,003 Puerto Rican adults, aged 45–75 years, living in Boston, Massachusetts, and the surrounding area. Cognitive function was measured by using a battery of 7 tests: the Mini-Mental State Examination, word list learning, digit span, clock drawing and figure copying, Stroop, and verbal fluency tests. The primary outcome was a global cognitive score, averaging standardized scores across all cognitive tests. A higher 8-OHdG concentration was significantly associated with lower global cognitive scores, after adjustment for age, education, status of the gene for apolipoprotein E (APOE), and other covariates (P_trend = 0.01). The difference in the global score, comparing participants in the 2 extreme 8-OHdG quartiles, was –0.11 (95% confidence interval: –0.20, –0.02), which was equivalent to accelerating cognitive aging by about 4 years, as observed in this population. Prospective studies are needed to elucidate whether elevated urinary 8-OHdG concentrations can predict the rate of cognitive decline and incident dementia.

Effect of Teenage Parenthood on Mental Health Trajectories: Does Sex Matter? 23 Jul 2010

Rates of teenage pregnancy and parenthood in the United States remain high. Although many consequences of teenage parenthood have been well studied, little prospective research has examined its effect on mental health. This study aims to better understand the impact of teenage parenthood on mental health and to determine whether sex modifies this relation. Using data from the National Longitudinal Survey of Youth, 1997 (1997–2006), and a matched cohort design, the authors compared changes in the mental health of parenting teenagers and nonparenting teenagers over 6 years of follow-up with mixed-effects regression. The results indicate that mental health improved for all teenagers over 6 years of follow-up. Furthermore, overall, teenage parenthood was not associated with changes in mental health; however, sex modified this relation. Although the mental health of teenage fathers improved at a faster rate compared with nonparenting teenage males, teenage mothers improved at a slower rate compared with nonparenting teenage females. Psychological health has important implications for both the teenage parent and the child. Future studies should aim to better understand the mechanisms through which teenage parenthood impacts mental health among both males and females, and interventions should be developed to ensure mental health among young parents.

Do Neighborhood Socioeconomic Deprivation and Low Social Cohesion Predict Coronary Calcification?: The CARDIA Study 23 Jul 2010

Growing evidence suggests that neighborhood characteristics may influence the risk of coronary heart disease. No studies have yet explored associations of neighborhood attributes with subclinical atherosclerosis in younger adult populations. Using data on 2,974 adults (1,699 women, 1,275 men) aged 32–50 years in 2000 from the Coronary Artery Disease Risk Development in Young Adults (CARDIA) Study and 2000 US Census block-group-level data, the authors estimated multivariable-adjusted associations of neighborhood socioeconomic deprivation and perceived neighborhood cohesion with odds of coronary artery calcification (CAC) 5 years later. Among women, the quartiles of highest neighborhood deprivation and lowest cohesion were associated with higher odds of CAC after adjustment for individual-level demographic and socioeconomic factors (for deprivation, odds ratio = 2.49, 95% confidence interval: 1.22, 5.08 (P for trend = 0.03); for cohesion, odds ratio = 1.87, 95% confidence interval: 1.10, 3.16 (P for trend = 0.02)). Associations changed only slightly after adjustment for behavioral, psychosocial, and biologic factors. Among men, neither neighborhood deprivation nor cohesion was related to CAC. However, among men in deprived neighborhoods, low cohesion predicted higher CAC odds (for interaction between neighborhood deprivation and cohesion, P = 0.03). This study provides evidence on associations of neighborhood deprivation and cohesion with CAC in younger, asymptomatic adults. Neighborhood attributes may contribute to subclinical atherosclerosis.

Chronic Disease in Men With Newly Diagnosed Cancer: A Nested Case-Control Study 23 Jul 2010

The authors performed a matched case-control study (1982–2007) nested in a prospective cohort of 22,071 US men to determine the prevalence of chronic diseases of aging in those with newly diagnosed cancer. They matched one control by age to each of 5,622 men who developed cancer over the 25 years of follow-up, as of the date of cancer diagnosis. A modified Charlson score was calculated that reflected comorbidities prior to the matching date, and the authors used conditional logistic regression to determine the odds ratios of various diseases. No substantial differences were found between the scores of cases and controls overall, by cancer subtype, or by age at diagnosis. Overall, men who developed cancer were less likely to have had hypercholesterolemia (odds ratio (OR) = 0.79, 95% confidence interval (CI): 0.72, 0.87) or coronary artery disease (OR = 0.85, 95% CI: 0.77, 0.96). Compared with controls, men with cancers for which there is routine screening had fewer diseases, whereas those with smoking-related cancers had more. Prostate cancer was inversely associated with both coronary artery disease (OR = 0.72, 95% CI: 0.62, 0.84) and diabetes (OR = 0.72, 95% CI: 0.58, 0.89). Overall, men who developed cancer had no more comorbidity or frequent history of chronic disease than their age-matched controls.

Long-Term Mortality in Patients Diagnosed With Pneumococcal Meningitis: A Danish Nationwide Cohort Study 23 Jul 2010

The objective of the study was to determine the long-term mortality and the causes of death in patients diagnosed with pneumococcal meningitis. The authors performed a nationwide, population-based cohort study including all Danish patients diagnosed with pneumococcal meningitis from 1977 through 2006 and alive 1 year after diagnosis. Data were retrieved from medical databases in Denmark. The absolute and relative risks of all-cause and cause-specific death were analyzed by using Kaplan-Meier survival curves, Poisson regression analysis, Cox regression analysis, and cumulative incidence functions. The authors identified 2,131 pneumococcal meningitis patients and an age- and gender-matched, population-based cohort of 8,524 individuals. Compared with the background population, the pneumococcal meningitis patients had an increased long-term mortality varying from an 8-fold increased mortality in the age category 0–<20 years to a 1.5-fold increased mortality in those aged 60–<80 years. The increased risk of death stemmed from neoplasms, liver diseases, and nervous system diseases. The excess mortality due to neoplasms stemmed mainly from a 5-fold increased risk of death due to hematologic neoplasms. To improve survival in patients surviving the acute phase of pneumococcal meningitis, physicians should meticulously screen this patient population for neurologic sequelae and comorbidity predisposing to the disease.

How Close Is Close Enough? Exploring Matching Criteria in the Estimation of Recent Transmission of Tuberculosis 23 Jul 2010

If Mycobacterium tuberculosis isolates from 2 people have the same genotype, transmission may have occurred between them. Genotyping based on the insertion sequence IS6110 uses identical restriction fragment length polymorphisms ("fingerprints") to infer transmission. However, once transmission has occurred, the genotypes may mutate, resulting in divergent fingerprints. Estimation of the proportion of tuberculosis (TB) cases due to recent transmission includes 3 approaches to determine if genotypes match: exact matching (assumes no fingerprint change); band-addition, band-loss, band-shift matching (ad hoc attempt to account for fingerprint changes); and genetic distance (directly accounts for fingerprint changes). Via simulation study, the authors varied the fingerprint change rate, level of recent transmission, and background genetic heterogeneity and estimated sensitivity, specificity, and bias of the recent transmission index by matching method. For exact matching, specificity was always high, but sensitivity decreased as the change rate increased. For band-addition, band-loss, band-shift matching, specificity decreased as genetic diversity decreased, and sensitivity remained high as the change rate increased. Genetic distance offered a compromise between the 2. Results from this study suggest that interpretation of the recent transmission index and the resulting necessary public health interventions will vary according to how researchers account for spontaneous mutation when estimating transmission from genotyping data.

Linking the Iowa Women's Health Study Cohort to Medicare Data: Linkage Results and Application to Hip Fracture 23 Jul 2010

This study linked the Iowa Women's Health Study cohort to Medicare administrative data and assessed the value of using Medicare and survey-based sources to study hip fracture incidence. The authors used Social Security number to combine the Iowa Women's Health Study cohort Medicare enrollment and claims data for 1986–2004. Hip fractures were identified from Medicare and follow-up-mail, survey-based sources. Estimates of hip fracture incidence after age 65 years and postfracture mortality were compared. The authors were able to match to Medicare 99.2% of the 40,978 Iowa Women's Health Study participants who survived to age 65 years. Although both Medicare and survey-based hip fracture incidence showed the expected positive association with age and negative association with body mass index, hip fracture incidence was considerably underestimated by self-report (2.61 per 1,000 person-years of observation vs. 4.20 per 1,000 person-years of observation from Medicare-based estimates). Similarly, 1-year postfracture mortality was significantly underestimated by survey-based measures (1% vs. 14% for Medicare-based estimates). Medicare data are an outstanding source of health care information to supplement for older cohorts that have identifiers such as Social Security numbers. These data are useful for studying clinically unambiguous and high morbidity and mortality conditions. They enable less-biased collection of health data.

A Simple Approach to the Estimation of Incidence Rate Difference 23 Jul 2010

The incidence rate difference (IRD) is a parameter of interest in many medical studies. For example, in vaccine studies, it is interpreted as the vaccine-attributable reduction in disease incidence. This is an important parameter, because it shows the public health impact of an intervention. The IRD is difficult to estimate for various reasons, especially when there are quantitative covariates or the duration of follow-up is variable. In this paper, the authors propose an approach based on weighted least-squares regression for estimating the IRD. It is very easy to implement because it boils down to performing ordinary least-squares regression analysis of transformed variables. Furthermore, if the outcome events are repeatable, the authors propose that data on all events be analyzed instead of first events only. Four versions of the Huber-White robust standard error are considered for statistical inference. Simulation studies are used to examine the performance of the proposed method. In a variety of scenarios simulated, the method provides an unbiased estimate for the IRD, and the empirical coverage proportion of the 95% confidence interval is very close to the nominal level. The method is illustrated with data from a vaccine trial carried out in the Gambia in 2001–2004.

Regression Calibration for Classical Exposure Measurement Error in Environmental Epidemiology Studies Using Multiple Local Surrogate Exposures 23 Jul 2010

Environmental epidemiologic studies are often hierarchical in nature if they estimate individuals’ personal exposures using ambient metrics. Local samples are indirect surrogate measures of true local pollutant concentrations which estimate true personal exposures. These ambient metrics include classical-type nondifferential measurement error. The authors simulated subjects’ true exposures and their corresponding surrogate exposures as the mean of local samples and assessed the amount of bias attributable to classical and Berkson measurement error on odds ratios, assuming that the logit of risk depends on true individual-level exposure. The authors calibrated surrogate exposures using scalar transformation functions based on observed within- and between-locality variances and compared regression-calibrated results with naive results using surrogate exposures. The authors further assessed the performance of regression calibration in the presence of Berkson-type error. Following calibration, bias due to classical-type measurement error, resulting in as much as 50% attenuation in naive regression estimates, was eliminated. Berkson-type error appeared to attenuate logistic regression results less than 1%. This regression calibration method reduces effects of classical measurement error that are typical of epidemiologic studies using multiple local surrogate exposures as indirect surrogate exposures for unobserved individual exposures. Berkson-type error did not alter the performance of regression calibration. This regression calibration method does not require a supplemental validation study to compute an attenuation factor.

Improvement of Risk Prediction by Genomic Profiling: Reclassification Measures Versus the Area Under the Receiver Operating Characteristic Curve 23 Jul 2010

Reclassification is observed even when there is no or minimal improvement in the area under the receiver operating characteristic curve (AUC), and it is unclear whether it indicates improved clinical utility. The authors investigated total reclassification, net reclassification improvement, and integrated discrimination improvement for different AUC using empirical and simulated data. Empirical analyses compared prediction of type 2 diabetes risk based on age, sex, and body mass index with prediction updated with 18 established genetic risk factors. Simulated data were used to investigate measures of reclassification against AUCs of 0.005, 0.05, and 0.10. Total reclassification and net reclassification improvement were calculated for all possible cutoff values. The AUC of type 2 diabetes risk prediction improved from 0.63 to 0.66 when 18 polymorphisms were added, whereas total reclassification ranged from 0% to 22.5% depending on the cutoff value chosen. In the simulation study, total reclassification, net reclassification improvement, and integrated discrimination improvement increased with higher AUC. When AUC was low (0.005), net reclassification improvement values were close to zero, integrated discrimination improvement was 0.08% (P > 0.05), but total reclassification ranged from 0 to 6.7%. Reclassification increases with increasing AUC but predominantly varies with the cutoff values chosen. Reclassification observed in the absence of AUC increase is unlikely to improve clinical utility.

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