American journal of epidemiology (Am J Epidemiol)

Publications in this journal

• Article: Area deprivation across the life course and physical capability in mid-life: findings from the 1946 British Birth Cohort.

  Murray ET, Ben-Shlomo Y, Tilling K, Southall H, Aucott P, Kuh D, Hardy R
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  ABSTRACT: Physical capability in later life is influenced by factors occurring across life, yet exposures to area conditions have only been examined cross-sectionally. Data from the Medical Research Council National Survey of Health and Development, a representative sample of all births in England, Scotland and Wales over two weeks in March 1946, were used to estimate associations of area deprivation (indicated by % of employed people in each area in partly- or un-skilled occupations) at ages 4, 26 and 53 years (residential addresses linked to census data in 1950, 1972 and 1999) with three measures of physical capability at age 53 years: grip strength, standing balance and chair rise time. Cross-classified multilevel models with individuals nested within areas at three ages showed that models assessing a single time-point underestimate total area contributions to physical capability. For balance and chair rise performance, associations with area deprivation in mid-life were robust to adjustment for individual socioeconomic position (SEP) and prior area deprivation [mean percentage change for 1-standard deviationSD increase (95% confidence interval): balance -7.4% (-12.8, -2.8), chair rise 2.1% (-0.1, 4.3)]. In addition, area deprivation in childhood was related to balance after adjustment for childhood socioeconomic positionSEP [(-5.1% (-8.7, -1,6)]. Interventions aimed at reducing mid-life disparities in physical capability should target the socioeconomic environment of individuals, for standing balance as early as childhood [IN PRESS]
  American journal of epidemiology 06/2013;
• Article: Anthropometric Measures and the Risk of Endometrial Cancer, Overall and by Tumor Microsatellite Status and Histological Subtype.

  Ernest K Amankwah, Christine M Friedenreich, Anthony M Magliocco, Rollin Brant, Kerry S Courneya, Thomas Speidel, Wahida Rahman, Annie R Langley, Linda S Cook
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  ABSTRACT: Obesity is an established risk factor for endometrial cancer, but this association is not well understood for subtypes of endometrial cancer. We evaluated the association of recent and adult-life obesity with subtypes of endometrial cancer based on microsatellite status (microsatellite-stable (MSS) vs. microsatellite-instable (MSI)) and histology (type I vs. type II). Analyses were based on a population-based case-control study (524 cases and 1,032 controls) conducted in Alberta, Canada (2002-2006) and included the following groupings of subtypes: MSS = 337 and MSI = 130; type I = 458 and type II = 66. Logistic and polytomous logistic regression were used to estimate odds ratios and 95% confidence intervals for overall endometrial cancer and subtypes of endometrial cancer, respectively. The risks of all subtypes of endometrial cancer, except type II, increased with an increase in all of the anthropometric characteristics examined. The risks for MSI tumors were suggestively stronger than those for MSS tumors; the risk with high (≥30) body mass index (weight (kg)/height (m)(2)) was significantly stronger for MSI tumors (odds ratio = 4.96, 95% confidence interval: 2.76, 8.91) than for MSS tumors (odds ratio = 2.33, 95% confidence interval: 1.66, 3.28) (P-heterogeneity = 0.02). Obesity is associated with most subtypes of endometrial cancer, and further studies are warranted to elucidate the biological mechanisms underlying the stronger risk for the MSI subtype with a high body mass index.
  American journal of epidemiology 05/2013;
• Article: Invited Commentary: Quantifying Salt in Urine--A Complex Solution.

  Ian H de Boer, Bryan Kestenbaum
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  ABSTRACT: Reduction of dietary sodium intake has been identified as a priority to reduce the worldwide burden of hypertension and cardiovascular disease. Dietary sodium intake is most precisely ascertained by using timed urine collection. Casual urine sodium measurements are relatively easy to perform, but their relationship to timed urine sodium measurements is unclear. In this issue of the Journal, Brown et al. (Am J Epidemiol. 2013;000(00):000-000) report the development and validation of equations to estimate 24-hour urine sodium excretion from casual urine samples. Their study included a large number of participants on 2 continents, a well-collected gold standard, separate discovery and validation samples, and relevant covariates. The resulting equations represent the best available methods to estimate dietary sodium intake from casual urine samples. However, the study is limited by evidence of a suboptimal model fit, restriction to people 20-59 years of age in North America and Europe, and exclusion and adjustment that further limit external validity. In addition, individual-level correlations of estimated and measured 24-hour urine sodium excretion were modest. Properly applied, the results will facilitate tracking of dietary sodium intake within populations over time and identification of communities for which dietary sodium restriction is most likely to be beneficial. Further work is needed to extend estimation to additional populations and improve individual-level assessment.
  American journal of epidemiology 05/2013;
• Article: Trends in C-Reactive Protein Levels in US Adults From 1999 to 2010.

  Kwok Leung Ong, Matthew A Allison, Bernard M Y Cheung, Ben J Wu, Philip J Barter, Kerry-Anne Rye
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  ABSTRACT: C-reactive protein (CRP) is a well-known biomarker of systemic inflammation and cardiovascular disease. We investigated the trends in prevalence of elevated CRP levels (>3.0 mg/L) in a general population of US adults. Data from 27,214 subjects aged ≥20 years in the 1999-2010 National Health and Nutrition Examination Survey were analyzed. After adjustment for age, sex, race/ethnicity, body mass index (weight (kg)/height (m)(2)), and medications for lowering blood pressure, glucose, and lipids, the prevalence of elevated CRP decreased significantly from 36.7% in 1999-2002 to 32.0% in 2007-2010, corresponding to a decrease in mean CRP level from 1.92 to 1.66 mg/L (both P < 0.001). The trend remained significant after additional adjustment for several traditional cardiovascular risk factors and use of different medications, including statins. However, the decreasing trends were attenuated after additional adjustment for total bilirubin (P = 0.08 and 0.02), which increased from 0.62 to 0.73 mg/dL over 12 years (P < 0.001). The decreasing trend of CRP levels is encouraging and may be related to the increase in total bilirubin levels. Such trends may be explained in part by the increasing use of medications such as statins, which can increase bilirubin levels and decrease CRP levels.
  American journal of epidemiology 05/2013;
• Article: Chicago Healthy Aging Study: Objectives and Design.

  Amber Pirzada, Kathryn Reid, Daniel Kim, Daniel B Garside, Brandon Lu, Thanh-Huyen T Vu, Donald M Lloyd-Jones, Phyllis Zee, Kiang Liu, Jeremiah Stamler, Martha L Daviglus
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  ABSTRACT: Investigators in the Chicago Healthy Aging Study (CHAS) reexamined 1,395 surviving participants aged 65-84 years (28% women) from the Chicago Heart Association Detection Project in Industry (CHA) 1967-1973 cohort whose cardiovascular disease (CVD) risk profiles were originally ascertained at ages 25-44 years. CHAS investigators reexamined 421 participants who were low-risk (LR) at baseline and 974 participants who were non-LR at baseline. LR was defined as having favorable levels of 4 major CVD risk factors: serum total cholesterol level <200 mg/dL and no use of cholesterol-lowering medication; blood pressure <120/≤80 mm Hg and no use of antihypertensive medication; no current smoking; and no history of diabetes or heart attack. While the potential of LR status in overcoming the CVD epidemic is being recognized, the long-term association of LR with objectively measured health in older age has not been examined. It is hypothesized that persons who were LR in 1967-1973 and have survived to older age will have less clinical and subclinical CVD, lower levels of inflammatory markers, and better physical performance/functioning and sleep quality. Here we describe the rationale, objectives, design, and implementation of this longitudinal epidemiologic study, compare baseline and follow-up characteristics of participants and nonparticipants, and highlight the feasibility of reexamining study participants after an extended period postbaseline with minimal interim contact.
  American journal of epidemiology 05/2013;
• Article: Neonatal Outcomes and Birth Weight in Pregnancies Complicated by Maternal Thyroid Disease.

  Tuija Männistö, Pauline Mendola, Uma Reddy, S Katherine Laughon
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  ABSTRACT: Maternal hypothyroidism has previously been shown to increase risk for neonatal intensive care treatment, but otherwise the association between thyroid diseases and neonatal morbidity is understudied. The Consortium on Safe Labor, a retrospective cohort (2002-2008), included 223,512 singleton deliveries of which 0.2% had hyperthyroidism, 1.4% primary and 0.1% iatrogenic hypothyroidism, and 1.3% other/unspecified thyroid disease. Logistic regression with generalized estimating equations estimated adjusted odds ratios of adverse outcomes. Intensive care treatment was more common for neonates of women with thyroid disease. Hyperthyroidism and primary hypothyroidism were associated with sepsis, respiratory distress syndrome, transient tachypnea, and apnea. Iatrogenic hypothyroidism was associated with sepsis and neonatal anemia. Hyperthyroidism was also associated with rare outcomes (prevalence, <1%) including cardiomyopathy, retinopathy of prematurity, and neonatal thyroid diseases. Hyperthyroid non-Hispanic black women had higher odds of term infants that weighed <2,500 g, and hypothyroid non-Hispanic white women had higher odds of large-for-gestational-age infants. These analyses were stratified by race/ethnicity due to interaction. Associations were similar in analyses restricted to term infants. In conclusion, thyroid diseases were associated with increased neonatal morbidity. Although we lacked data on treatment during pregnancy, these nationwide data suggest a need for better thyroid disease management to reduce neonatal morbidity.
  American journal of epidemiology 05/2013;
• Article: Neighborhood Amenities and Mobility in Older Adults.

  Andrea L Rosso, Tony H Grubesic, Amy H Auchincloss, Loni P Tabb, Yvonne L Michael
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  ABSTRACT: Diversity of neighborhood amenities may promote the mobility of older adults. A 2010 community-based sample of 510 adults aged ≥65 years in Philadelphia, Pennsylvania, and geospatial data from the Esri Business Analyst database (Esri, Inc., Redlands, California) were used to assess associations of neighborhood amenity diversity with mobility. Neighborhoods were defined by census tract, and diversity of amenities was derived by using the Leadership in Energy and Environmental Design's neighborhood development index (US Green Building Council, Washington, DC). Generalized estimating equations adjusted for demographic, socioeconomic, and neighborhood characteristics were used to estimate differences in mobility score by tertile of amenity diversity. Analyses were stratified by participants' routine travel habits (stayed at home, stayed in home zip code, or traveled beyond home zip code). We found that for those who spent most of their time in their home neighborhoods, mobility scores (from the Life-Space Assessment, which ranges from 0 to 104 points) were 8.3 points higher (95% confidence interval: 0.1, 16.6) among those who lived in neighborhoods with the most amenity diversity compared with those who lived in neighborhoods with the least amenity diversity. No significant associations between amenity diversity and mobility were observed for those who did not leave home or who regularly traveled outside their neighborhoods. Neighborhoods with a high diversity of amenities may be important promoters of mobility in older adults who do not routinely travel outside their neighborhoods.
  American journal of epidemiology 05/2013;
• Article: Internal Validation of Risk Models in Clustered Data: A Comparison of Bootstrap Schemes.

  W Bouwmeester, K G M Moons, T H Kappen, W A van Klei, J W R Twisk, M J C Eijkemans, Y Vergouwe
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  ABSTRACT: Internal validity of a risk model can be studied efficiently with bootstrapping to assess possible optimism in model performance. Assumptions of the regular bootstrap are violated when the development data are clustered. We compared alternative resampling schemes in clustered data for the estimation of optimism in model performance. A simulation study was conducted to compare regular resampling on only the patient level with resampling on only the cluster level and with resampling sequentially on both the cluster and patient levels (2-step approach). Optimism for the concordance index and calibration slope was estimated. Resampling of only patients or only clusters showed accurate estimates of optimism in model performance. The 2-step approach overestimated the optimism in model performance. If the number of centers or intraclass correlation coefficient was high, resampling of clusters showed more accurate estimates than resampling of patients. The 3 bootstrap schemes also were applied to empirical data that were clustered. The results presented in this paper support the use of resampling on only the clusters for estimation of optimism in model performance when data are clustered.
  American journal of epidemiology 05/2013;
• Article: The Co-Seasonality of Pneumonia and Influenza With Clostridium difficile Infection in the United States, 1993-2008.

  Kevin A Brown, Nick Daneman, Paul Arora, Rahim Moineddin, David N Fisman
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  ABSTRACT: Seasonal variations in the incidence of pneumonia and influenza are associated with nosocomial Clostridium difficile infection (CDI) incidence, but the reasons why remain unclear. Our objective was to consider the impact of pneumonia and influenza timing and severity on CDI incidence. We conducted a retrospective cohort study using the US National Hospital Discharge Survey sample. Hospitalized patients with a diagnosis of CDI or pneumonia and influenza between 1993 and 2008 were identified from the National Hospital Discharge Survey data set. Poisson regression models of monthly CDI incidence were used to measure 1) the time lag between the annual pneumonia and influenza prevalence peak and the annual CDI incidence peak and 2) the lagged effect of pneumonia and influenza prevalence on CDI incidence. CDI was identified in 18,465 discharges (8.52 per 1,000 discharges). Peak pneumonia prevalence preceded peak CDI incidence by 9.14 weeks (95% confidence interval: 4.61, 13.67). A 1% increase in pneumonia prevalence was associated with a cumulative effect of 11.3% over a 6-month lag period (relative risk = 1.113, 95% confidence interval: 1.073, 1.153). Future research could seek to understand which mediating pathways, including changes in broad-spectrum antibiotic prescribing and hospital crowding, are most responsible for the associated changes in incidence.
  American journal of epidemiology 05/2013;
• Article: Socioeconomic Factors in Childhood and the Risk of Multiple Sclerosis.

  Nete Munk Nielsen, Kristian T Jørgensen, Peter Bager, Egon Stenager, Bo V Pedersen, Henrik Hjalgrim, Nils Koch-Henriksen, Morten Frisch
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  ABSTRACT: In a national cohort comprising 1.5 million Danes born from 1966 to 1992, we studied the association between childhood socioeconomic status (SES) and the risk of multiple sclerosis (MS) from 1981 to 2007 using information about household income and parental educational levels at the person's 15th birthday. The association between childhood SES and MS was evaluated using MS incidence rate ratios with 95% confidence intervals obtained in log-linear Poisson regression analyses. We found no strong association between childhood SES and MS but did observe a tendency toward a reduced risk of MS among children from households with more highly educated parents, particularly mothers. Children whose mothers had a secondary (rate ratio = 0.95, 95% confidence interval: 0.86, 1.04) or higher (rate ratio = 0.86, 95% confidence interval: 0.76, 0.97) education had reduced risks of MS (5% and 14%, respectively) compared with children of mothers with a basic education (P for trend = 0.02). Results were practically unchanged in an analysis restricted to persons aged 15-29 years, among whom the possible effect of own SES on MS risk is considered limited. Overall, SES in childhood seems of no major importance for the subsequent risk of MS; however, offspring of well-educated mothers may be at a slightly reduced risk of MS.
  American journal of epidemiology 05/2013;
• Article: Plasma Vitamin D Biomarkers and Leukocyte Telomere Length.

  Jason J Liu, Jennifer Prescott, Edward Giovannucci, Susan E Hankinson, Bernard Rosner, Jiali Han, Immaculata De Vivo
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  ABSTRACT: Vitamin D may reduce telomere shortening through anti-inflammatory and anti-cell proliferation mechanisms. In the present study, we examined the association between vitamin D and relative leukocyte telomere length by using both plasma 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)2D) biomarkers. Vitamin D biomarker levels and leukocyte telomere length were measured using plasma samples collected in 1989-1990 from participants of the Nurses' Health Study, a study of nurses from 11 US states. In total, 1,424 participants had their 25(OH)D levels assessed and 837 had their 1,25(OH)2D levels assessed. Genotyping was performed on 480 participants on 12 single nucleotide polymorphisms in vitamin D-related genes. Linear and logistic regression models were used. Higher 25(OH)D levels were significantly associated with longer telomere length (P for trend = 0.05), and the odds ratio increased from 1.07 (P = 0.65) when comparing the second lowest quartile of 25(OH)D with the lowest to 1.59 (P = 0.01) when comparing the highest quartile with the lowest. Vitamin D-related single nucleotide polymorphisms and 1,25(OH)2D levels were not significantly associated with telomere length. Total calcium intake significantly modified the association between 25(OH)D and telomere length (P for interaction = 0.05). Higher plasma 25(OH)D levels may be associated with longer telomeres, and this association may be modified by calcium intake.
  American journal of epidemiology 05/2013;
• Article: A Modeling Framework for the Evolution and Spread of Antibiotic Resistance: Literature Review and Model Categorization.

  Ian H Spicknall, Betsy Foxman, Carl F Marrs, Joseph N S Eisenberg
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  ABSTRACT: Antibiotic-resistant infections complicate treatment and increase morbidity and mortality. Mathematical modeling has played an integral role in improving our understanding of antibiotic resistance. In these models, parameter sensitivity is often assessed, while model structure sensitivity is not. To examine the implications of this, we first reviewed the literature on antibiotic-resistance modeling published between 1993 and 2011. We then classified each article's model structure into one or more of 6 categories based on the assumptions made in those articles regarding within-host and population-level competition between antibiotic-sensitive and antibiotic-resistant strains. Each model category has different dynamic implications with respect to how antibiotic use affects resistance prevalence, and therefore each may produce different conclusions about optimal treatment protocols that minimize resistance. Thus, even if all parameter values are correctly estimated, inferences may be incorrect because of the incorrect selection of model structure. Our framework provides insight into model selection.
  American journal of epidemiology 05/2013;
• Article: Epidemiologic Approaches to Evaluating the Potential for Human Papillomavirus Type Replacement Postvaccination.

  Joseph E Tota, Agnihotram V Ramanakumar, Mengzhu Jiang, Joakim Dillner, Stephen D Walter, Jay S Kaufman, François Coutlée, Luisa L Villa, Eduardo L Franco
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  ABSTRACT: Currently, 2 vaccines exist that prevent infection by the genotypes of human papillomavirus (HPV) responsible for approximately 70% of cervical cancer cases worldwide. Although vaccination is expected to reduce the prevalence of these HPV types, there is concern about the effect this could have on the distribution of other oncogenic types. According to basic ecological principles, if competition exists between ≥2 different HPV types for niche occupation during natural infection, elimination of 1 type may lead to an increase in other type(s). Here, we discuss this issue of "type replacement" and present different epidemiologic approaches for evaluation of HPV type competition. Briefly, these approaches involve: 1) calculation of the expected frequency of coinfection under independence between HPV types for comparison with observed frequency; 2) construction of hierarchical logistic regression models for each vaccine-targeted type; and 3) construction of Kaplan-Meier curves and Cox models to evaluate sequential acquisition and clearance of HPV types according to baseline HPV status. We also discuss a related issue concerning diagnostic artifacts arising when multiple HPV types are present in specific samples (due to the inability of broad-spectrum assays to detect certain types present in lower concentrations). This may result in an apparent increase in previously undetected types postvaccination.
  American journal of epidemiology 05/2013;
• Article: ABO Blood Group and Risk of Pancreatic Cancer: A Study in Shanghai and Meta-Analysis.

  Harvey A Risch, Lingeng Lu, Jing Wang, Wei Zhang, Quanxing Ni, Yu-Tang Gao, Herbert Yu
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  ABSTRACT: Studies over 5 decades have examined ABO blood groups and risk of pancreatic cancer in Western, Asian, and other populations, though no systematic review has been published. We studied data from 908 pancreatic cancer cases and 1,067 population controls collected during December 2006-January 2011 in urban Shanghai, China, and reviewed the literature for all studies of this association. Random-effects meta-analysis provided summary odds ratio estimates according to blood group and by populations endemic versus nonendemic for cytotoxin-associated gene A (CagA)-positive Helicobacter pylori. In our Shanghai study, versus group O, only ABO group A was associated with risk (odds ratio (OR) = 1.60, 95% confidence interval (CI): 1.27, 2.03). In 24 pooled studies, group A showed increased risk in both CagA-nonendemic and -endemic populations (ORpooled = 1.40, 95% CI: 1.32, 1.49). In nonendemic populations, groups B and AB were also associated with higher risk (OR = 1.38, 95% CI: 1.16, 1.64; and OR = 1.52, 95% CI: 1.24, 1.85, respectively). However, in CagA-endemic populations, groups B and AB were not associated with risk (OR = 1.05, 95% CI: 0.92, 1.19; and OR = 1.13, 95% CI: 0.92, 1.38, respectively). These population differences were significant. One explanation for contrasts in associations of blood groups B and AB between CagA-endemic and -nonendemic populations could involve gastric epithelial expression of A versus B antigens on colonization behaviors of CagA-positive and CagA-negative H. pylori strains.
  American journal of epidemiology 05/2013;
• Article: Dietary Flavonoid Intake and Esophageal Cancer Risk in the European Prospective Investigation into Cancer and Nutrition Cohort.

  Esther Vermeulen, Raul Zamora-Ros, Eric J Duell, Leila Luján-Barroso, Heiner Boeing, Krasimira Aleksandrova, H Bas Bueno-de-Mesquita, Augustin Scalbert, Isabelle Romieu, Veronika Fedirko, [......], Anne M May, Elisabete Weiderpass, Guri Skeie, Anette Hjartåker, Rikard Landberg, Ingegerd Johansson, Emily Sonestedt, Ulrika Ericson, Elio Riboli, Carlos A González
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  ABSTRACT: We prospectively investigated dietary flavonoid intake and esophageal cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The study included 477,312 adult subjects from 10 European countries. At baseline, country-specific validated dietary questionnaires were used. During a mean follow-up of 11 years (1992-2010), there were 341 incident esophageal cancer cases, of which 142 were esophageal adenocarcinoma (EAC), 176 were esophageal squamous cell carcinoma (ESCC), and 23 were other types of esophageal cancer. In crude models, a doubling in total dietary flavonoid intake was inversely associated with esophageal cancer risk (hazard ratio (HR) (log2) = 0.87, 95% confidence interval (CI): 0.78, 0.98) but not in multivariable models (HR (log2) = 0.97, 95% CI: 0.86, 1.10). After covariate adjustment, no statistically significant association was found between any flavonoid subclass and esophageal cancer, EAC, or ESCC. However, among current smokers, flavonols were statistically significantly associated with a reduced esophageal cancer risk (HR (log2) = 0.72, 95% CI: 0.56, 0.94), whereas total flavonoids, flavanols, and flavan-3-ol monomers tended to be inversely associated with esophageal cancer risk. No associations were found in either never or former smokers. These findings suggest that dietary flavonoid intake was not associated with overall esophageal cancer, EAC, or ESCC risk, although total flavonoids and some flavonoid subclasses, particularly flavonols, may reduce the esophageal cancer risk among current smokers.
  American journal of epidemiology 05/2013;
• Article: Chart-Confirmed Guillain-Barre Syndrome After 2009 H1N1 Influenza Vaccination Among the Medicare Population, 2009-2010.

  Laura L Polakowski, Sukhminder K Sandhu, David B Martin, Robert Ball, Thomas E Macurdy, Riley L Franks, Jonathan M Gibbs, Garner F Kropp, Armen Avagyan, Jeffrey A Kelman, Christopher M Worrall, Guoying Sun, Rebecca E Kliman, Dale R Burwen
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  ABSTRACT: Given the increased risk of Guillain-Barré Syndrome (GBS) found with the 1976 swine influenza vaccine, both active surveillance and end-of-season analyses on chart-confirmed cases were performed across multiple US vaccine safety monitoring systems, including the Medicare system, to evaluate the association of GBS after 2009 monovalent H1N1 influenza vaccination. Medically reviewed cases consisted of H1N1-vaccinated Medicare beneficiaries who were hospitalized for GBS. These cases were then classified by using Brighton Collaboration diagnostic criteria. Thirty-one persons had Brighton level 1, 2, or 3 GBS or Fisher Syndrome, with symptom onset 1-119 days after vaccination. Self-controlled risk interval analyses estimated GBS risk within the 6-week period immediately following H1N1 vaccination compared with a later control period, with additional adjustment for seasonality. Our results showed an elevated risk of GBS with 2009 monovalent H1N1 vaccination (incidence rate ratio = 2.41, 95% confidence interval: 1.14, 5.11; attributable risk = 2.84 per million doses administered, 95% confidence interval: 0.21, 5.48). This observed risk was slightly higher than that seen with previous seasonal influenza vaccines; however, additional results that used a stricter case definition (Brighton level 1 or 2) were not statistically significant, and our ability to account for preceding respiratory/gastrointestinal illness was limited. Furthermore, the observed risk was substantially lower than that seen with the 1976 swine influenza vaccine.
  American journal of epidemiology 05/2013;
• Article: Evaluating the Impact of Database Heterogeneity on Observational Study Results.

  David Madigan, Patrick B Ryan, Martijn Schuemie, Paul E Stang, J Marc Overhage, Abraham G Hartzema, Marc A Suchard, William Dumouchel, Jesse A Berlin
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  ABSTRACT: Clinical studies that use observational databases to evaluate the effects of medical products have become commonplace. Such studies begin by selecting a particular database, a decision that published papers invariably report but do not discuss. Studies of the same issue in different databases, however, can and do generate different results, sometimes with strikingly different clinical implications. In this paper, we systematically study heterogeneity among databases, holding other study methods constant, by exploring relative risk estimates for 53 drug-outcome pairs and 2 widely used study designs (cohort studies and self-controlled case series) across 10 observational databases. When holding the study design constant, our analysis shows that estimated relative risks range from a statistically significant decreased risk to a statistically significant increased risk in 11 of 53 (21%) of drug-outcome pairs that use a cohort design and 19 of 53 (36%) of drug-outcome pairs that use a self-controlled case series design. This exceeds the proportion of pairs that were consistent across databases in both direction and statistical significance, which was 9 of 53 (17%) for cohort studies and 5 of 53 (9%) for self-controlled case series. Our findings show that clinical studies that use observational databases can be sensitive to the choice of database. More attention is needed to consider how the choice of data source may be affecting results.
  American journal of epidemiology 05/2013;
• Article: Regional and Neighborhood Disparities in the Odds of Type 2 Diabetes: Results From 5 Population-Based Studies in Germany (DIAB-CORE Consortium).

  Grit Müller, Alexander Kluttig, Karin Halina Greiser, Susanne Moebus, Uta Slomiany, Sabine Schipf, Henry Völzke, Werner Maier, Christa Meisinger, Teresa Tamayo, Wolfgang Rathmann, Klaus Berger
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  ABSTRACT: The objective of this study was to investigate the association between residential environment and type 2 diabetes. We pooled cross-sectional data from 5 population-based German studies (1997-2006): the Cardiovascular Disease, Living and Ageing in Halle Study, the Dortmund Health Study, the Heinz Nixdorf Recall Study, the Cooperative Health Research in the Region of Augsburg Study, and the Study of Health in Pomerania. The outcome of interest was the presence of self-reported type 2 diabetes. We conducted mixed logistic regression models in a hierarchical data set with 8,879 individuals aged 45-74 years on level 1; 226 neighborhoods on level 2; and 5 study regions on level 3. The analyses were adjusted for age, sex, social class, and employment status. The odds ratio for type 2 diabetes was highest in eastern Germany (odds ratio = 1.98, 95% confidence interval: 1.81, 2.14) and northeastern Germany (odds ratio = 1.58, 95% confidence interval: 1.40, 1.77) and lowest in southern Germany (reference) after adjustment for individual variables. Neighborhood unemployment rates explained a large proportion of regional differences. Individuals residing in neighborhoods with high unemployment rates had elevated odds of type 2 diabetes (odds ratio = 1.62, 95% confidence interval: 1.25, 2.09). The diverging levels of unemployment in neighborhoods and regions are an independent source of disparities in type 2 diabetes.
  American journal of epidemiology 05/2013;
• Article: Biological and Statistical Approaches for Modeling Exposure to Specific Trihalomethanes and Bladder Cancer Risk.

  Lucas A Salas, Kenneth P Cantor, Adonina Tardon, Consol Serra, Alfredo Carrato, Reina Garcia-Closas, Nathaniel Rothman, Núria Malats, Debra Silverman, Manolis Kogevinas, Cristina M Villanueva
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  ABSTRACT: Lifetime exposure to trihalomethanes (THM) has been associated with increased risk of bladder cancer. We explored methods of analyzing bladder cancer risk associated with 4 THM (chloroform, bromodichloromethane, dibromochloromethane, and bromoform) as surrogates for disinfection by-product (DBP) mixtures in a case-control study in Spain (1998-2001). Lifetime average concentrations of THM in the households of 686 incident bladder cancer cases and 750 matched hospital-based controls were calculated. Several exposure metrics were modeled through conditional logistic regression, including the following analyses: total THM (μg/L), cytotoxicity-weighted sum of total THM (pmol/L), 4 THM in separate models, 4 THM in 1 model, chloroform and the sum of brominated THM in 1 model, and a principal-components analysis. THM composition, concentrations, and correlations varied between areas. The model for total THM was stable and showed increasing dose-response trends. Models for separate THM provided unstable estimates and inconsistent dose-response relationships. Risk estimation for specific THM is hampered by the varying composition of the mixture, correlation between species, and imprecision of historical estimates. Total THM (μg/L) provided a proxy measure of DBPs that yielded the strongest dose-response relationship with bladder cancer risk. A variety of metrics and statistical approaches should be used to evaluate this association in other settings.
  American journal of epidemiology 05/2013;
• Article: Breast Cancer Risk Prediction with Heterogeneous Risk Profiles According to Breast Cancer Tumor Markers.

  Bernard Rosner, Robert J Glynn, Rulla M Tamimi, Wendy Y Chen, Graham A Colditz, Walter C Willett, Susan E Hankinson
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  ABSTRACT: Relationships between some risk factors and breast cancer incidence are known to vary by tumor subtype. However, breast tumors can be classified according to a number of markers, which may be correlated, making it difficult to identify heterogeneity of risk factors with specific tumor markers when using standard competing-risk survival analysis. In this paper, we propose a constrained competing-risk survival model that allows for assessment of heterogeneity of risk factor associations according to specific tumor markers while controlling for other markers. These methods are applied to Nurses' Health Study data from 1980-2006, during which 3,398 incident invasive breast cancers occurred over 1.4 million person-years of follow-up. Results suggested that when estrogen receptor (ER) and progesterone receptor (PR) status are mutually considered, some risk factors thought to be characteristic of "estrogen-positive tumors," such as high body mass index during postmenopause and increased height, are actually significantly associated with PR-positive tumors but not ER-positive tumors, while other risk factors thought to be characteristic of "estrogen-negative tumors," such as late age at first birth, are actually significantly associated with PR-negative rather than ER-negative breast cancer. This approach provides a strategy for evaluating heterogeneity of risk factor associations by tumor marker levels while controlling for additional tumor markers.
  American journal of epidemiology 05/2013;