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W D Flanders

Publications and source records attributed to W D Flanders.

At least 19 recordsLinked to original sources
PubMed1992

Risk factors for fatal colon cancer in a large prospective study.

BACKGROUND: Diet, physical activity, obesity, aspirin use, and family history may all modify the risk of colon cancer, but few epidemiologic studies are large enough to examine these factors simultaneously. PURPOSE: We prospectively assessed the relationship of diet and other factors to risk of fatal colon cancer. METHODS: Using data from Cancer Prevention Study II--an ongoing prospective mortality study--we studied 764,343 adults who, in 1982, completed a questionnaire on diet and other risk factors and did not report cancer or other major illness. We assessed mortality through August 1988 and identified 1150 deaths from colon cancer (611 men and 539 women). Multivariate analyses were used to compare these case patients with 5746 matched control subjects drawn from the cohort. RESULTS: Risk of fatal colon cancer decreased with more frequent consumption of vegetables and high-fiber grains (P for trend = .031 in men and .0012 in women). The relative risk (RR) for the highest versus lowest quintile of vegetable intake was 0.76 in men (95% confidence interval [CI] = 0.57-1.02) and 0.62 in women (95% CI = 0.45-0.86). Dietary consumption of vegetables and grains and regular use of aspirin were the only factors having an independent and statistically significant association with fatal colon cancer. Participants who consumed the least vegetables and grains and no aspirin had a higher risk compared with those who consumed the most vegetables and used aspirin 16 or more times per month. For men in the former category, the RR was 2.4 (95% CI = 1.1-5.3); for women, it was 2.9 (95% CI = 1.3-6.7). Weaker associations were seen for physical inactivity, obesity, total dietary fat, and family history. No associations were seen with consumption of red meat or total or saturated fat in either sex, but this finding must be interpreted cautiously. CONCLUSIONS: These findings support recommendations that increased consumption of vegetables and grains may reduce the risk of fatal colon cancer. Regular use of low doses of aspirin may prove to be an important supplemental measure.

Adult↗
PubMed1992

The relation of prothrombin times to coronary heart disease risk factors among men aged 31-45 years.

Although levels of coagulation factor VII and fibrinogen are predictive of cardiovascular disease, relatively little data describe hemostatic characteristics in healthy populations. The cross-sectional associations between the prothrombin time, a measure of the activity of the extrinsic and common pathways of coagulation, and traits associated with the risk of cardiovascular disease were therefore examined among 3,604 white and 514 black, male, US Army veterans aged 31-45 years. The prothrombin time measurements, performed in 1985 and 1986, were precise, with an intraclass correlation of 0.98 (202 pairs). Overall, the mean prothrombin time was 12.4 seconds (standard deviation, 0.4 seconds), and 11 percent of the men had a value of less than 12 seconds. Many of the observed associations with the prothrombin time paralleled those that have been reported with clotting factor VII and fibrinogen. The mean prothrombin time was 0.15 seconds shorter among whites than among blacks and was 0.2 seconds shorter among current cigarette smokers than among men who had never smoked. Inverse associations were also seen with relative weight and with levels of total cholesterol and triglycerides (r = -0.09 to -0.16). All associations were statistically significant at the 0.01 level, and the examined characteristics could jointly account for about 12 percent of the variability in prothrombin times. Additional data on characteristics related to coagulation may help elucidate the natural history of cardiovascular disease and aid in the design of clinical trials.

Adult↗
PubMed1992

Variable mortality rates among dialysis treatment centers.

OBJECTIVE: To examine the variation in the risk for mortality among patients treated at renal dialysis facilities within a defined geographic area. SETTING: All free-standing and hospital-based dialysis facilities in a single southeastern state reported to the registry. DESIGN: Cohort of dialysis patients followed for 1 year by an end-stage renal disease registry. PATIENTS: Patients (n = 3612) aged 20 years and older receiving treatment at the dialysis facilities reporting to the registry during 1987. MEASUREMENTS: Demographic, comorbid, and severity of illness indicators were abstracted from patient records. Facility-specific risk estimates were derived from a Cox proportional hazards model. RESULTS: Facility-specific mortality rates ranged between 2.0 and 10.5 deaths per 10,000 patient days. Mortality rates were higher among older persons; whites; those with a history of diabetic nephropathy, angina, or congestive heart failure; and patients with either nutritional or functional status impairment. Facility-specific prevalence of each mortality risk factor varied widely. The unadjusted risk for death in a facility at the 75th percentile of risk was 1.3 times that of a facility at the median, whereas at the 25th percentile, it was 0.68 times as likely--a twofold range of risk. Controlling for differences in the prevalence of patient characteristics did not change the interquartile range in risks, and a facility's adjusted risk estimate showed a strong correlation with its unadjusted estimate (R2, 0.566; P less than 0.0001). CONCLUSIONS: Patient attributes associated with increased risk for mortality vary widely among dialysis facilities. Adjustment for these differences did not, however, substantially change either the degree of variation in mortality risks or the relative ranking of a facility's mortality.

Adult↗
PubMed1992

Assessing the direction of causality in cross-sectional studies.

Interpretation of observational studies is difficult, particularly in cross-sectional studies, because the direction of cause and effect may be difficult to assess: Did the "outcome" affect the measured exposure level, or did the exposure affect the outcome? In this paper, the authors describe a pattern, the "checkmark pattern," which can arise in cross-sectional studies. This pattern is characterized by higher levels of the outcome in an unexposed comparison group than in some subgroups of the exposed. The pattern, if seen in certain types of observational studies, suggests that the "outcome" variable may have affected the measured exposure level. Recognition of the pattern may help the epidemiologist to decipher the causal sequence. Two examples illustrate the issues involved.

Adipose Tissue↗
PubMed1992

Interpretation of recurring weak associations obtained from epidemiologic studies of suspected human teratogens.

Epidemiological studies of suspected human teratogens not infrequently lead to recurring weak or moderate associations (relative risks or odds ratios ranging from greater than 1 to 3 for adverse effects and from 1/3 to less than 1 for protective effects) between specific defects and prenatal exposures. Examples of such associations include cigarette smoking and oral clefts (odds ratios between 1 and 2) and periconceptional multivitamin/folic acid supplementation and neural tube defects (odds ratios from 1/3 to 1). In this paper, we illustrate that low relative risk recurring in well-designed studies may reflect underlying biologic mechanisms and should not be readily dismissed. Low relative risks could be the result of a combination of the following factors: 1) unmeasured confounding, 2) exposure misclassification (often related to the inability to pinpoint relevant dose and timing), 3) outcome misclassification (related to the etiologic heterogeneity of birth defects), 4) biologic interactions (related to teratogenic effects in population subgroups defined by genetic susceptibility or the presence of other exposures), and 5) differential prenatal survival (related to the combined impact of the exposure and the defect on prenatal survival). These issues can be addressed in epidemiologic studies by using biological markers of exposure and susceptibility, dysmorphologic evaluation of affected infants, subgroup analysis for etiologic heterogeneity, a search for biologic interactions, and the use of prospective cohort studies. Finally, low relative risks in the face of common exposures can reflect an important public health contribution of the exposure to the occurrence of the defect in the population.

Abnormalities, Drug-Induced↗
PubMed1992

Interpretation of linear regression models that include transformations or interaction terms.

In linear regression analyses, we must often transform the dependent variable to meet the statistical assumptions of normality, variance stability, or linearity. Transformations, however, can complicate the interpretation of results because they change the scale on which the dependent variable is measured. In this setting, the inclusion of product terms or the transformation of some independent (or predictor) variables may further complicate interpretation. In this article, we present some interpretations of linear models that include transformations or product terms. We illustrate these interpretations using regression analyses designed to study determinants of serum testosterone levels. These examples show how one can present results using simple measures, such as medians, and interpret regression parameters.

Epidemiologic Methods↗
PubMed1992

The associations of alcohol drinking and drinking cessation to measures of the immune system in middle-aged men.

To estimate the association between the immunologic responses of the cell-mediated and humoral systems and alcohol drinking, we used data from the Vietnam Experience Study conducted by the Centers for Disease Control. That study, conducted from 1985 to 1986, was based on a random sample of 4462 male, Vietnam-era, U.S. veterans. By using linear regression, we evaluated how (1) the number of alcoholic drinks the subjects consumed per month and (2) the drinking cessation of certain subjects were associated with their relative and absolute T, B, CD4, and CD8 lymphocyte counts and immunoglobulin A (IgA), IgM, and IgG levels. We used geometric means and percentage differences in geometric means of immune status to measure the associations and adjusted these values to account for the effect of covariates. The results indicated that measures of immune status differed among the drinking categories and that, generally, the differences changed after adjustment for covariates. These differences consisted, as alcohol consumption increased, of higher IgA and IgM levels, relative T and CD4 lymphocytes, and the ratio of CD4 to CD8 cells, and of lower IgG levels, relative B and CD8 lymphocytes, absolute lymphocyte, and lymphocyte subset counts after adjusting for other covariates. Among former drinkers, we found no clear-cut pattern in measures of immunity for a few years after cessation and then found that values of former drinkers tended to return toward values of nondrinkers as they continued to abstain.

Adult↗
PubMed1991

A meta-analysis of the effect of estrogen replacement therapy on the risk of breast cancer.

To quantify the effect of estrogen replacement therapy on breast cancer risk, we combined dose-response slopes of the relative risk of breast cancer against the duration of estrogen use across 16 studies. Using this summary dose-response slope, we calculated the proportional increase in risk of breast cancer for each year of estrogen use. For women who experienced any type of menopause, risk did not appear to increase until after at least 5 years of estrogen use. After 15 years of estrogen use, we found a 30% increase in the risk of breast cancer (relative risk, 1.3; 95% confidence interval [CI], 1.2 to 1.6). The increase in risk was largely due to results of studies that included premenopausal women or women using estradiol (with or without progestin), studies for which the estimated relative risk was 2.2 (CI, 1.4 to 3.4) after 15 years. Among women with a family history of breast cancer, those who had ever used estrogen replacement had a significantly higher risk (3.4; CI, 2.0 to 6.0) than those who had not (1.5; CI, 1.2 to 1.7).

Adult↗
PubMed1991

Commentary: the affected sib-pair method in the context of an epidemiologic study design.

The purpose of this commentary is to provide a framework for using the well-known sib-pair methodology in the context of epidemiologic study designs. Using examples from the Pittsburgh family studies of insulin-dependent diabetes mellitus, we illustrate that the sib-pair method can be used in family-based epidemiologic studies. In a cohort study, unaffected relatives of probands ascertained from well-defined populations are followed for disease development. Disease risks are then stratified according to the number of alleles at one or more loci (0, 1, 2) that are identical by descent (ibd) with the proband. In the absence of linkage between the marker locus and the disease locus, disease risks are expected to be identical in the three groups. Measures of relative risk can be computed (with share-0 as baseline group). In a case-control study, relatives of probands that become affected (cases) are compared to a sample of relatives of probands that stay unaffected (controls) with respect to the number of alleles ibd with the proband. Measures of odds ratio can be computed (with share-0 as baseline group). In both cohort and case-control approaches, covariates including other genetic markers and environmental exposures can be evaluated in relation to disease risk and also for evidence of interaction with the specific marker of interest using stratified and multivariate analyses. Family-based epidemiologic studies allow investigators to study, in a single design, the role of environmental factors and specific gene loci in the etiology of diseases.

Alleles↗
PubMed1991

Extensions to methods of sib-pair linkage analyses.

Sib-pair methods provide simple, robust, easily implemented ways to screen for linkage between a marker locus and a suspected disease susceptibility locus. The basic analysis reflects the idea that, in the presence of linkage, siblings who share more alleles at the marker locus should also tend to be concordant for disease. Available sib-pair methods do not lead directly to estimates of risk associated with nongenetic factors, may not account for a variable age-at-onset, or may require that the age-at-onset distribution be known. In this paper, we propose a method for sib-pair linkage analyses that allows for a variable age-at-onset using a logistic model, easily allows modelling of nongenetic factors, reflects the correlation of sibs within a sibship, and allows for nonzero risk in those without the susceptibility genotype. Based on a limited number of simulations, the method has as good or better power than another recently described method that also allows for a variable age-at-onset.

Epidemiologic Methods↗
PubMed1991

Analytic methods for two-stage case-control studies and other stratified designs.

Nested case-control studies, or case-control studies within a cohort, combine the advantages of cohort studies with the efficiency of case-control studies. Case-control studies can often be viewed as having two stages; the first stage consists of vital status, disease, and basic covariate ascertainment, and the second stage consists of detailed covariate and exposure ascertainment. Breslow and Cain (1988) and Breslow and Zhao (1988) recently showed that conventional analyses of such two-stage studies may ignore some of the available information. In this paper, we show how one can adapt the pseudo-likelihood analyses developed by Kalbfleisch and Lawless (1988) to the analysis of data from two-stage case-control studies.

Case-Control Studies↗
PubMed1991

The associations of race, cigarette smoking, and smoking cessation to measures of the immune system in middle-aged men.

To estimate the association between the immunologic responses of the cell-mediated and humoral systems and race or tobacco smoking, we used data from the Vietnam Experience Study conducted by the Centers for Disease Control. That study, done from 1985 to 1986, was based on a random sample of 4462 male, Vietnam-era, U.S. veterans. Racial groups were white, black, Hispanic, Asian, and American Indian. We used linear regression to evaluate how (i) the race of the subjects, (ii) the number of pack-years of cigarettes the subjects smoked, and (iii) the smoking cessation of certain subjects were associated with their relative and absolute T, B, CD4, and CD8 lymphocyte counts and immunoglobulin A (IgA), IgM, and IgG levels. The results indicated that immune status was associated with race and smoking history and that, generally, the associations remained after adjustment for covariates. For example, the average IgA level and absolute CD8 lymphocyte count for blacks were, respectively, 19 and 16% higher than those for whites. On the other hand, smokers had lower immunoglobulin levels and relative CD8 cell counts and higher counts for other lymphocytes of the cell-mediated system than nonsmokers. For example, the average absolute B count of heavy smokers was 37% higher than that of nonsmokers. The pattern after cigarette smoking cessation was consistent with a reversible effect of smoking and a return toward immune levels of nonsmokers.

Adult↗
PubMed1991

Does increased detection account for the rising incidence of breast cancer?

BACKGROUND: The incidence of breast cancer has been increasing over time in the United States. METHODS: To determine the role of screening in this increase, trends in the incidence of in situ and invasive carcinoma of the breast were evaluated using records of the metropolitan Atlanta SEER program between 1979 and 1986. From a sample of records, evidence of symptoms and mammographic screening prior to diagnosis was recorded. RESULTS: The average annual age-adjusted incidence of invasive disease rose 29 percent among Whites and 41 percent among Blacks. Incidence increased in all age groups. A trend towards earlier detection of invasive disease was found. Asymptomatic tumors accounted for only 40 percent of the increased incidence among whites and 25 percent of the increased incidence among blacks, with mammography as the principal contributing procedure. CONCLUSIONS: These data suggest that increased detection accounts for some but not all of the rising incidence of breast cancer in the United States.

Adult↗
PubMed1991

Use of the Mantel-Haenszel chi 2 overestimates precision in studies with sparse data.

Probability values or "test-based" confidence limits computed on the basis of the Mantel-Haenszel chi 2 statistic may be invalid if minimum cell-size requirements are not met. In 30 studies of occupational proportionate mortality published from 1985 through 1987, the Mantel-Haenszel chi 2 was used in potential violation of cell-size requirements in 21 studies. Sixteen (76%) studies included at least one value that, when compared with testing with the Poisson distribution, was erroneously reported as statistically significant at the 0.05 level. We conclude that by using the Mantel-Haenszel chi 2 with sparse data, some epidemiologists overestimate precision.

Bias↗
PubMed1990

Estimation of risk ratios in case-base studies with competing risks.

The case-base study is a recently developed modification of the case-control design that leads to risk ratio estimates. Currently available methods for the analysis of case-base studies lead to estimates of the unconditional risk ratio which may be misleading of censoring occurs. In this manuscript, we describe an approach for the analysis of case-base studies that yields conditional risk ratio estimates which remain valid in the presence of censoring. The approach we propose for estimating risk ratios and their standard errors involves a non-iterative procedure.

Case-Control Studies↗
PubMed1990

Estimating benefits of screening from observational cohort studies.

Analysis and interpretation of observational studies of screening effectiveness is difficult because several biases threaten validity, including the structural healthy screenee bias, length bias, and effects of lead time. Although methods for the analysis of observational studies of screening effectiveness have been proposed, most have limitations such as incomplete control of length bias, or a heavy reliance on distributional assumptions. In this report we present a method for the analysis of observational cohort studies of screening effectiveness. Although developed independently and formulated specifically for estimating benefits of screening, our approach is implied by a more general approach developed previously by Robins. Our approach, in contrast to other available methods, avoids the healthy screenee bias, and length and lead time bias, and allows an empirical approach to analysis that need not depend highly on distributional assumptions. We illustrate application of the approach with analysis of published data from a study of breast cancer screening.

Bias↗