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W Dana Flanders

Publications and source records attributed to W Dana Flanders.

At least 19 recordsLinked to original sources
PubMed2007

A sequence variation scan of the coagulation factor VIII (FVIII) structural gene and associations with plasma FVIII activity levels.

Plasma factor VIII coagulant activity (FVIII:C) level is a highly heritable quantitative trait that is strongly correlated with thrombosis risk. Polymorphisms within only 1 gene, the ABO blood-group locus, have been unequivocally demonstrated to contribute to the broad population variability observed for this trait. Because less than 2.5% of the structural FVIII gene (F8) has been examined previously, we resequenced all known functional regions in 222 potentially distinct alleles from 137 unrelated nonhemophilic individuals representing 7 racial groups. Eighteen of the 47 variants identified, including 17 single-nucleotide polymorphisms (SNPs), were previously unknown. As the degree of linkage disequilibrium across F8 was weak overall, we used measured-genotype association analysis to evaluate the influence of each polymorphism on the FVIII:C levels in 398 subjects from 21 pedigrees known as the Genetic Analysis of Idiopathic Thrombophilia project (GAIT). Our results suggested that 92714C>G, a nonsynonymous SNP encoding the B-domain substitution D1241E, was significantly associated with FVIII:C level. After accounting for important covariates, including age and ABO genotype, the association persisted with each C-allele additively increasing the FVIII:C level by 14.3 IU dL(-1) (P = .016). Nevertheless, because the alleles of 56010G>A, a SNP within the 3' splice junction of intron 7, are strongly associated with 92714C>G in GAIT, additional studies are required to determine whether D1241E is itself a functional variant.

ABO Blood-Group System↗
PubMed2007

Study design options in evaluating gene-environment interactions: practical considerations for a planned case-control study of pediatric leukemia.

BACKGROUND: We compare methodological approaches for evaluating gene-environment interaction using a planned study of pediatric leukemia as a practical example. We considered three design options: a full case-control study (Option I), a case-only study (Option II), and a partial case-control study (Option III), in which information on controls is limited to environmental exposure only. PROCEDURE: For each design option we determined its ability to measure the main effects of environmental factor E and genetic factor G, and the interaction between E and G. Using the leukemia study example, we calculated sample sizes required to detect and odds ratio (OR) of 2.0 for E alone, an OR of 10 for G alone and an interaction G x E of 3. RESULTS: Option I allows measuring both main effects and interaction, but requires a total sample size of 1,500 cases and 1,500 controls. Option II allows measuring only interaction, but requires just 121 cases. Option III allows calculating the main effect of E, and interaction, but not the main effect of G, and requires a total of 156 cases and 133 controls. CONCLUSIONS: In this case, the partial case-control study (Option III) appears to be more efficient with respect to its ability to answer the research questions for the amount of resources required. The design options considered in this example are not limited to observational epidemiology and may be applicable in studies of pharmacogenomics, survivorship, and other areas of pediatric ALL research.

Age of Onset↗
PubMed2006

Ambient air pollution and cardiovascular emergency department visits in potentially sensitive groups.

Limited evidence suggests that persons with conditions such as diabetes, hypertension, congestive heart failure, and respiratory conditions may be at increased risk of adverse cardiovascular morbidity and mortality associated with ambient air pollution. The authors collected data on over 4 million emergency department visits from 31 hospitals in Atlanta, Georgia, between January 1993 and August 2000. Visits for cardiovascular disease were examined in relation to levels of ambient pollutants by use of a case-crossover framework. Heterogeneity of risk was examined for several comorbid conditions. The results included evidence of stronger associations of dysrhythmia and congestive heart failure visits with comorbid hypertension in relation to increased air pollution levels compared with visits without comorbid hypertension; similar evidence of effect modification by diabetes and chronic obstructive pulmonary disease (COPD) was observed for dysrhythmia and peripheral and cerebrovascular disease visits, respectively. Evidence of effect modification by comorbid hypertension and diabetes was observed in relation to particulate matter less than 10 microm in aerodynamic diameter, nitrogen dioxide, and carbon monoxide, while evidence of effect modification by comorbid COPD was also observed in response to ozone levels. These findings provide further evidence of increased susceptibility to adverse cardiovascular events associated with ambient air pollution among persons with hypertension, diabetes, and COPD.

Air Pollution↗
PubMed2006

Inference for case-control studies when exposure status is both informatively missing and misclassified.

In case-control studies, it is common for a categorical exposure variable to be misclassified. It is also common for exposure status to be informatively missing for some individuals, in that the probability of missingness may be related to exposure. Procedures for addressing the bias due to misclassification via validation data have been extensively studied, and related methods have been proposed for dealing with informative missingness based on supplemental sampling of some of those with missing data. In this paper, we introduce study designs and analytic procedures for dealing with both problems simultaneously in a 2x2 analysis. Results based on convergence in probability illustrate that the combined effects of missingness and misclassification, even when the latter is non-differential, can lead to naïve exposure odds ratio estimates that are inflated or on the wrong side of the null. The motivating example comes from a case-control study of the association between low birth weight and the diagnosis of breast cancer later in life, where self-reported birth weight for some women is supplemented by accurate information from birth certificates.

Adult↗
PubMed2006

On the relationship of sufficient component cause models with potential outcome (counterfactual) models.

The sufficient-component cause (SSC) model provides a useful, concise method to conceptualize and organize ideas concerning biologic effects and interactions of multiple factors. Another type of model, the potential outcome or counterfactual models, has also proved useful in epidemiology, providing insights into definitions of effects, exchangeability and confounding, and selection bias. Prior work has shown important links between these two types of models. Here, we show additional connections between the two types of models. We first review basic concepts for both the SSC model and the potential outcome models. We then indicate additional similarities between them, and derive a quantitative link. Our results show that the SSC model actually corresponds to a unique response pattern in a particular potential outcome model. Recognition of the links between the two models should allow greater insight into use of each model, and allow the strengths of both models to be used jointly.

Causality↗
PubMed2006

Seroprevalence of cytomegalovirus infection in the United States, 1988-1994.

BACKGROUND: Cytomegalovirus (CMV) is a leading cause of congenital illness and disability, including hearing loss and mental retardation. However, there are no nationwide estimates of CMV seroprevalence among pregnant women or the overall population of the United States. METHODS: To determine CMV prevalence in a representative sample of the US population, we tested serum samples for CMV-specific immunoglobulin G from participants aged > or =6 years (n=21,639) in the third National Health and Nutrition Examination Survey (1988-1994). RESULTS: The prevalence of CMV infection was 58.9% in individuals > or =6 years old. CMV seroprevalence increased gradually with age, from 36.3% in 6-11-year-olds to 90.8% in those aged > or =80 years. CMV seroprevalence differed by race and/or ethnicity as follows: 51.2% in non-Hispanic white persons, 75.8% in non-Hispanic black persons, and 81.7% in Mexican Americans. Racial and/or ethnic differences in CMV seroprevalence persisted when controlling for household income level, education, marital status, area of residence, census region, family size, country of birth, and type of medical insurance. Among women, racial and/or ethnic differences were especially significant; between ages 10-14 years and 20-24 years, seroprevalence increased 38% for non-Hispanic black persons, 7% for non-Hispanic white persons, and <1% for Mexican Americans. CONCLUSIONS: On the basis of these results, we estimate that each year in the United States approximately 340,000 non-Hispanic white persons, 130,000 non-Hispanic black persons, and 50,000 Mexican American women of childbearing age experience a primary CMV infection. Given the number of women at risk and the significance of congenital disease, development of programs for the prevention of CMV infection, such as vaccination or education, is of considerable public health importance.

Adolescent↗
PubMed2006

Variations in quality of care for heart failure.

BACKGROUND: The objective of our study was to assess hospital-to-hospital variations for the management and treatment of heart failure (HF) patients. METHODS: We performed a cross-sectional study among randomly selected patients with ICD-10 (International Classification of Disease, 10th revision) HF hospitalised in three Swiss university hospitals in 1999. Demographic characteristics, risk factors, symptoms and findings at admission and discharge medications were abstracted. The main outcome measure was the percentage of patients receiving appropriate management and treatment as defined by quality of care indicators derived from evidence-based guidelines. Quality indicators were considered only when they could be applied (no contra-indications). RESULTS: Among 1153 eligible patients with HF the mean age (SD) was 75.3 (12.7), 54.3% were male. Among potential candidates for specific interventions left ventricular function (LVF) was determined in 68.5% of patients; 53.8% received target dose of angiotensin converting enzyme inhibitors (ACEI), 86.0% any dose of angiotensin receptor blockers; 21.9% b-blockers, and 62.1% anticoagulants at discharge. Compared to hospital B (reference), the adjusted odds ratios (OR) (95% CI) for LVF not determined were 3.82 (2.50 to 5.85) in hospital A and 3.25 (1.78 to 5.93) in hospital C. The adjusted OR (95% CI) for not receiving target dose ACEI was 1.76 (0.95 to 3.26) for hospital A and 3.20 (1.34 to 7.65) for hospital C compared to hospital B. CONCLUSIONS: Apparently, important hospital-to-hospital variations in the quality of care given to patients with HF could have existed between three academic medical centers.

Adrenergic beta-Antagonists↗
PubMed2006

Associations of maternal age- and parity-related factors with trends in low-birthweight rates: United States, 1980 through 2000.

OBJECTIVES: We assessed the effects of changes in the maternal age-parity distribution and age-and parity-specific low-birthweight rates on low-birthweight trends in the United States. METHODS: We used natality file data from 1980 through 2000 to assess very-low-birthweight and low-birthweight rates among singleton live-born infants. RESULTS: Changes in age-and parity-specific low-birthweight rates were the main contributor to the overall trend in rates. However, changes in the age-parity distribution, primarily delayed childbearing, had a smaller but noticeable impact. The very-low-birthweight rate increased 27% among Black women, and changes in the age-parity distribution were associated with, on average, more than 20% of the increased rate during the 1990s. Among Hispanic and non-Hispanic White women, on average, more than 10% of the rate increase observed during the 1990s was associated with changes in the age-parity distribution. CONCLUSIONS: Assuming minimal changes in age-specific rates, delayed childbearing may play an increasingly important role in low-birthweight trends in the United States.

Adolescent↗
PubMed2006

Anemia and chronic kidney disease are associated with poor outcomes in heart failure patients.

BACKGROUND: Chronic kidney disease (CKD) has been linked to higher heart failure (HF) risk. Anemia is a common consequence of CKD, and recent evidence suggests that anemia is a risk factor for HF. The purpose of this study was to examine among patients with HF, the association between CKD, anemia and inhospital mortality and early readmission. METHODS: We performed a retrospective cohort study in two Swiss university hospitals. Subjects were selected based the presence of ICD-10 HF codes in 1999. We recorded demographic characteristics and risk factors for HF. CKD was defined as a serum creatinine > or = 124 956;mol/L for women and > or = 133 micromol/L for men. The main outcome measures were inhospital mortality and thirty-day readmissions. RESULTS: Among 955 eligible patients hospitalized with heart failure, 23.0% had CKD. Twenty percent and 6.1% of individuals with and without CKD, respectively, died at the hospital (p < 0.0001). Overall, after adjustment for other patient factors, creatinine and hemoglobin were associated with an increased risk of death at the hospital, and hemoglobin was related to early readmission. CONCLUSION: Both CKD and anemia are frequent among older patients with heart failure and are predictors of adverse outcomes, independent of other known risk factors for heart failure.

Adolescent↗
PubMed2006

Changes in treatment of advanced laryngeal cancer 1985-2001.

OBJECTIVE: In 1991, a randomized study was published and demonstrated that use of nonsurgical therapy (chemoradiation) provided similar survival to total laryngectomy (the gold standard) for patients with advanced-stage laryngeal cancer. The purpose of this study was to assess how treatment of advanced laryngeal cancer was influenced by such developments in non-surgical therapy. STUDY DESIGN: Patterns of care study using National Cancer Database (1985-2001). RESULTS: The percentage of advanced-stage patients treated with chemoradiation increased from 8.3% to 20.8% while the proportion treated with radiation alone decreased from 38.9% to 23.0%. Use of chemoradiation increased at a significantly faster rate after the 1991 publication at both community cancer centers and teaching research facilities. The use of total laryngectomy decreased slightly during this period. CONCLUSIONS: The use of chemoradiation increased after the 1991 publication. It was impossible to determine from the NCDB whether additional patients who could benefit from chemo-RT were not offered or did not complete this treatment option. We recommend that treatment recommendations discussed at tumor boards be recorded in cancer registries.

Aged↗
PubMed2005

How many genes underlie the occurrence of common complex diseases in the population?

BACKGROUND: Most common human diseases are due to complex interactions among multiple genetic variants and environmental risk factors. There is debate over whether variants of a relatively small number of genes, each with weak or modest individual effects, account for a large proportion of common diseases in the population, or whether a large number of rare variants with large effects underlie genetic susceptibility to these diseases. It is not clear how many genes are necessary to account for an appreciable population-attributable fraction of these diseases. METHODS: In this analysis, we estimated the number of disease susceptibility genes needed to account for varying population attributable fractions of a common complex disease, taking into account the genotype prevalence, risk ratios for individual genes, and the model of gene-gene interactions (additive or multiplicative). RESULTS: Very large numbers of rare genotypes (e.g. those with frequencies of 1 per 5000 or less) are needed to explain 50% of a common disease in the population, even if the individual risk ratios are large (RR = 10-20). On the other hand, only approximately 20 genes are usually needed to explain 50% of the burden of a disease in the population if the predisposing genotypes are common (> or = 25%), even if the individual risk ratios are relatively small (RR = 1.2-1.5). CONCLUSIONS: Our results suggest that a limited number of disease susceptibility genes with common variants can explain a major proportion of common complex diseases in the population. Our findings should help focus the search for common genetic variants that provide the most important predispositions to complex human diseases.

Algorithms↗
PubMed2005

Variations in the quality of care of patients with acute myocardial infarction among Swiss university hospitals.

OBJECTIVE: The objective of our study was to assess hospital variations in the quality of care delivered to acute myocardial infarction (AMI) patients among three Swiss academic medical centres. DESIGN: Cross-sectional study. SETTING: Three Swiss university hospitals. STUDY PARTICIPANTS: We selected 1129 eligible patients discharged from these hospitals from 1 January to 31 December 1999, with a primary or secondary diagnosis code [International Classification of Diseases, 10th revision (ICD-10)] of AMI. We abstracted medical records for information on demographic characteristics, risk factors, symptoms, and findings at admission. We also recorded the main ECG and laboratory findings, as well as hospital and discharge management and treatment. We excluded patients transferred to another hospital and who did not meet the clinical definition of AMI. MAIN OUTCOME MEASURES: Percentage of patients receiving appropriate intervention as defined by six quality of care indicators derived from clinical practical guidelines. RESULTS: Among 577 eligible patients with AMI in this study, the mean (SD) age was 68.2 (13.9), and 65% were male. In the assessment of the quality indicators we excluded patients who were not eligible for the procedure. Among cohorts of 'ideal candidates' for specific interventions, 64% in hospital A and 73% in hospital C had reperfusion within 12 hours either with thrombolytics or percutaneous transluminal coronary angioplasty (P = 0.367). Further, in hospitals A, B, and C, respectively 97, 94, and 84% were prescribed aspirin during the initial hospitalization (P = 0.0002), and respectively 68, 91, and 75% received angiotensin converting enzyme inhibitors at discharge in the case of left ventricular systolic dysfunction (P = 0.003). CONCLUSIONS: Our results showed important hospital-to-hospital variations in the quality of care provided to patients with AMI between these three university hospitals.

Acute Disease↗
PubMed2005

Meat consumption and risk of colorectal cancer.

CONTEXT: Consumption of red and processed meat has been associated with colorectal cancer in many but not all epidemiological studies; few studies have examined risk in relation to long-term meat intake or the association of meat with rectal cancer. OBJECTIVE: To examine the relationship between recent and long-term meat consumption and the risk of incident colon and rectal cancer. DESIGN, SETTING, AND PARTICIPANTS: A cohort of 148 610 adults aged 50 to 74 years (median, 63 years), residing in 21 states with population-based cancer registries, who provided information on meat consumption in 1982 and again in 1992/1993 when enrolled in the Cancer Prevention Study II (CPS II) Nutrition Cohort. Follow-up from time of enrollment in 1992/1993 through August 31, 2001, identified 1667 incident colorectal cancers. Participants contributed person-years at risk until death or a diagnosis of colon or rectal cancer. MAIN OUTCOME MEASURE: Incidence rate ratio (RR) of colon and rectal cancer. RESULTS: High intake of red and processed meat reported in 1992/1993 was associated with higher risk of colon cancer after adjusting for age and energy intake but not after further adjustment for body mass index, cigarette smoking, and other covariates. When long-term consumption was considered, persons in the highest tertile of consumption in both 1982 and 1992/1993 had higher risk of distal colon cancer associated with processed meat (RR, 1.50; 95% confidence interval [CI], 1.04-2.17), and ratio of red meat to poultry and fish (RR, 1.53; 95% CI, 1.08-2.18) relative to those persons in the lowest tertile at both time points. Long-term consumption of poultry and fish was inversely associated with risk of both proximal and distal colon cancer. High consumption of red meat reported in 1992/1993 was associated with higher risk of rectal cancer (RR, 1.71; 95% CI, 1.15-2.52; P = .007 for trend), as was high consumption reported in both 1982 and 1992/1993 (RR, 1.43; 95% CI, 1.00-2.05). CONCLUSIONS: Our results demonstrate the potential value of examining long-term meat consumption in assessing cancer risk and strengthen the evidence that prolonged high consumption of red and processed meat may increase the risk of cancer in the distal portion of the large intestine.

Aged↗
PubMed2005

mtDNA mutations increase tumorigenicity in prostate cancer.

Mutations in the mtDNA have been found to fulfill all of the criteria expected for pathogenic mutations causing prostate cancer. Focusing on the cytochrome oxidase subunit I (COI) gene, we found that 11-12% of all prostate cancer patients harbored COI mutations that altered conserved amino acids (mean conservation index=83%), whereas <2% of no-cancer controls and 7.8% of the general population had COI mutations, the latter altering less conserved amino acids (conservation index=71%). Four conserved prostate cancer COI mutations were found in multiple independent patients on different mtDNA backgrounds. Three other tumors contained heteroplasmic COI mutations, one of which created a stop codon. This latter tumor also contained a germ-line ATP6 mutation. Thus, both germ-line and somatic mtDNA mutations contribute to prostate cancer. Many tumors have been found to produce increased reactive oxygen species (ROS), and mtDNA mutations that inhibit oxidative phosphorylation can increase ROS production and thus contribute to tumorigenicity. To determine whether mutant tumors had increased ROS and tumor growth rates, we introduced the pathogenic mtDNA ATP6 T8993G mutation into the PC3 prostate cancer cell line through cybrid transfer and tested for tumor growth in nude mice. The resulting mutant (T8993G) cybrids were found to generate tumors that were 7 times larger than the wild-type (T8993T) cybrids, whereas the wild-type cybrids barely grew in the mice. The mutant tumors also generated significantly more ROS. Therefore, mtDNA mutations do play an important role in the etiology of prostate cancer.

Adenosine Triphosphatases↗
PubMed2005

Ambient air pollution and respiratory emergency department visits.

BACKGROUND: A number of emergency department studies have corroborated findings from mortality and hospital admission studies regarding an association of ambient air pollution and respiratory outcomes. More refined assessment has been limited by study size and available air quality data. METHODS: Measurements of 5 pollutants (particulate matter [PM10], ozone, nitrogen dioxide [NO2], carbon monoxide [CO], and sulfur dioxide [SO2]) were available for the entire study period (1 January 1993 to 31 August 2000); detailed measurements of particulate matter were available for 25 months. We obtained data on 4 million emergency department visits from 31 hospitals in Atlanta. Visits for asthma, chronic obstructive pulmonary disease, upper respiratory infection, and pneumonia were assessed in relation to air pollutants using Poisson generalized estimating equations. RESULTS: In single-pollutant models examining 3-day moving averages of pollutants (lags 0, 1, and 2): standard deviation increases of ozone, NO2, CO, and PM10 were associated with 1-3% increases in URI visits; a 2 microg/m increase of PM2.5 organic carbon was associated with a 3% increase in pneumonia visits; and standard deviation increases of NO2 and CO were associated with 2-3% increases in chronic obstructive pulmonary disease visits. Positive associations persisted beyond 3 days for several of the outcomes, and over a week for asthma. CONCLUSIONS: The results of this study contribute to the evidence of an association of several correlated gaseous and particulate pollutants, including ozone, NO2, CO, PM, and organic carbon, with specific respiratory conditions.

Adolescent↗
PubMed2005

Residual spatial correlation between geographically referenced observations: a Bayesian hierarchical modeling approach.

BACKGROUND: Analytic methods commonly used in epidemiology do not account for spatial correlation between observations. In regression analyses, this omission can bias parameter estimates and yield incorrect standard error estimates. We present a Bayesian hierarchical model (BHM) approach that accounts for spatial correlation, and illustrate its strengths and weaknesses by applying this modeling approach to data on Wuchereria bancrofti infection in Haiti. METHODS: A program to eliminate lymphatic filariasis in Haiti assessed prevalence of W. bancrofti infection in 57 schools across Leogane Commune. We analyzed the spatial pattern in the prevalence data using semi-variograms and correlograms. We then modeled the data using (1) standard logistic regression (GLM); (2) non-Bayesian logistic generalized linear mixed models (GLMMs) with school-specific nonspatial random effects; (3) BHMs with school-specific nonspatial random effects; and (4) BHMs with spatial random effects. RESULTS: An exponential semi-variogram with an effective range of 2.15 km best fit the data. GLMM and nonspatial BHM point estimates were comparable and also were generally similar with the marginal GLM point estimates. In contrast, compared with the nonspatial mixed model results, spatial BHM point estimates were markedly attenuated. DISCUSSION: The clear spatial pattern evident in the Haitian W. bancrofti prevalence data and the observation that point estimates and standard errors differed depending on the modeling approach indicate that it is important to account for residual spatial correlation in analyses of W. bancrofti infection data. Bayesian hierarchical models provide a flexible, readily implementable approach to modeling spatially correlated data. However, our results also illustrate that spatial smoothing must be applied with care.

Animals↗
PubMed2005

Predictors of improved HbA1c testing by primary care physicians.

Measurement of glycosylated hemoglobin (HbA1c) among patients with diabetes mellitus contributes to attaining control of blood glucose, which in turn is associated with fewer complications. Here, we seek to identify physician and county level characteristics that predict increased HbA1c testing among Medicare beneficiaries with diabetes who did not have testing in the baseline year. Physicians in counties with more people on Medicaid, or with fewer physicians per capita tended to have less improvement in HbA1c testing among Medicare beneficiaries over the three year study period.

Aged↗