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W D Flanders

Publications and source records attributed to W D Flanders.

At least 109 records · Page 6Linked to original sources
PubMed1989

On the measurement of susceptibility in epidemiologic studies.

Although relative effects of risk factors (relative risks) are commonly used in epidemiologic studies of disease, these measures do not provide estimates of the proportion of persons who are "susceptible" to the risk factor. Susceptibility may be defined under a simple sufficient cause model as the underlying factor (or set of factors) sufficient to make a person contract a disease following exposure. The authors derive simple estimates of the proportion of susceptibles in a population based on relative risk, and disease and exposure frequencies. The proportion of susceptibles increases with increasing disease frequency and relative risk but declines at high exposure frequency. For many chronic diseases with a lifetime risk in the range of 1-10 per cent, rare exposures suggest the presence of a large proportion of susceptibles, whereas common exposures suggest fewer susceptibles in the population. The estimation of the proportion of susceptibles is important in the search for genetic and environmental factors that interact with measured risk factors in etiologic studies of disease.

Abnormalities, Drug-Induced↗
PubMed1989

Human teratogens, prenatal mortality, and selection bias.

Etiologic inferences on human teratogens are usually derived from case-control studies conducted either at birth or in spontaneous abortion series. Because both teratogens and defects may be associated with an increased risk of prenatal mortality, the possibility exists that selection bias may affect etiologic inferences. The authors derive relations between the true odds ratio (OR) relating a teratogen and a defect at the time of the occurrence of the defect and the apparent odds ratios observed in spontaneous abortion series and at birth, as functions of prenatal mortality. Depending on the pattern of interaction between the teratogen and the defect in affecting the rate of prenatal mortality, selection bias may lead to overestimation or underestimation of the true odds ratio. With increasing multiplicative effects on prenatal mortality, changes in selection bias tend to increase the observed odds ratio in spontaneous abortion series but to decrease the observed odds ratio at birth. For a range of rates of prenatal mortality, weak associations between exposures and defects (OR = 0.3-3) may well be due to selection bias; conversely, weak teratogens (OR less than 3) may be missed in case-control studies of defects conducted at birth. Selection bias due to prenatal mortality must be considered in the interpretation of etiologic studies of birth defects.

Abortion, Spontaneous↗
PubMed1989

Inappropriate comparisons of incidence and prevalence in epidemiologic research.

Several epidemiologists have published papers in major medical journals in which they compare incidence rates and prevalence and use these comparisons to support conclusions regarding questions of major public health importance. Although these papers have been criticized in published correspondence, we believe that continued use and advocacy of such comparisons by some epidemiologists has created the need for a full discussion of this practice. In this commentary, we review basic differences between incidence and prevalence and show that direct comparison of these two measures is inappropriate for conceptual, theoretical, and practical reasons.

Cohort Studies↗
PubMed1988

Chemical exposures and central nervous system cancers: a case-control study among workers at two nuclear facilities.

In a nested case-control study of workers employed between 1943 and 1977 at two nuclear facilities, we evaluated the possible association of primary CNS cancers with occupational exposure to chemicals. Seventy-two white male and 17 white female workers who, according to the information on death certificates, died of primary CNS cancers were identified as cases. For each case, four controls were matched on race, sex, facility at which initially employed (cohort), year of birth, and year of hire. Each job title/department combination was subjectively evaluated for potential exposure to each of 26 chemicals or chemical groups. Statistically significant associations were not found between CNS cancer deaths and any of the 26 chemicals. An increased risk of CNS cancer occurrence was observed among subjects employed for more than 20 yr (OR = 7.0, 95% CI = 1.2,41.1, cases = 9).

Adult↗
PubMed1988

Penetrance in the presence of genetic susceptibility to environmental factors.

Many single-gene disorders (especially dominant traits) are known to exhibit "incomplete penetrance," a term often criticized as reflecting our ignorance of genetic and environmental factors that may interact with the genotype to determine the ultimate phenotype of the individual. We explore the effects of an environmental factor on penetrance for a simple model of single gene-mediated susceptibility to environmental factors. We show that penetrance of the susceptible genotype increases with increasing frequency of exposure to the factor and the strength of interaction between the factor and the genotype (relative risk). For disorders with disease frequency of 0.001 or less (as seen with many congenital malformations), penetrance is generally low (less than 10%) if the exposure frequency is low (less than 10%) even in the face of strong gene-environment interaction. Such low penetrance can lead to low recurrence risks. Single-gene effects could easily be overlooked in genetic analysis unless specific environmental factors are considered.

Environment↗
PubMed1988

An epidemiologic approach to ecogenetics.

Although "ecogenetics" seeks to examine genetically mediated differences in susceptibility to environmental agents, researchers often examine the relation between genetic markers and disease without regard to environmental determinants. By using epidemiologic definitions of genotype-environment interaction, it can be shown that the relative risk of disease for the genetic marker is a function of the frequency of exposure to the environmental agent, the strength of interaction between the genotype and the agent, and the specificity of the environmental effect vis-à-vis the genotype. Using examples from the literature, we illustrate under six patterns of genotype-environment interaction that the relative risk associated with the marker can fluctuate markedly. However, with infrequent exposures, the relative risk is close to unity (implying no genetic effect) even in the face of strong genotype-environment interaction. Alternatively, elevated relative risks imply a frequent environmental exposure or a strong pattern of interaction. We suggest that genetic marker-disease associations be evaluated within the context of an epidemiologic study design that considers specific environmental determinants of risk.

Disease Susceptibility↗
PubMed1987

Large sample confidence intervals for regression standardized risks, risk ratios, and risk differences.

Several methods have been proposed for standardizing risks, risk ratios, and risk differences based on the results of logistic regression. These methods provide an alternative to direct standardization, a particularly useful approach when there are many covariates. In this paper, methods for calculating approximate confidence limits for these standardized measures are presented. A simple example, in which published data are used, illustrates the techniques and allows comparison with confidence limits calculated from the directly standardized risk ratio.

Aged↗
PubMed1987

A comparison of estrogen and progesterone receptors in black and white breast cancer patients.

After standardization for age and menopausal status, the prevalence of estrogen receptor positivity among 88 White breast cancer patients was about .72 compared with a prevalence of about .54 among Black patients. The prevalence of progesterone receptor positivity was also higher among White than among Black patients, although the magnitude of the difference was smaller. These differences were unchanged after adjustment for tumor size and nodal and distant metastases in addition to age and menopausal status.

Black People↗
PubMed1987

Brain cancer and nonoccupational risk factors: a case-control study among workers at two nuclear facilities.

In a nested case-control study of nuclear workers, 82 brain cancer cases were compared with 328 matched controls to investigate the possible association with nonoccupational risk factors such as histories of epilepsy or head injury. We observed a moderately strong association between brain cancer occurrence and history of epilepsy (OR = 5.7, 95 per cent CI: 1.0, 32.1), but did not find a positive association with previous head injury (OR = 0.9, 95 per cent CI: 0.2, 4.2).

Astrocytoma↗
PubMed1987

CNS cancers and radiation exposure: a case-control study among workers at two nuclear facilities.

A nested case-control study was conducted among workers employed in two nuclear facilities to investigate the possible association of primary CNS cancers with occupational exposure to radiation from external and internal sources. External radiation monitoring data from film badges were available for 27 cases and 90 matched controls. The radiation dose to the lung from internally deposited uranium was estimated for 47 cases and 120 matched controls from area and personnel monitoring data and was used in analyses in lieu of the brain dose. No association was observed between deaths from CNS cancers and exposure to ionizing radiation from external or internal sources. However, due to the small number of monitored subjects and low doses, a modest association could not be ruled out.

Adult↗
PubMed1986

The exposure odds ratio in nested case-control studies with competing risks.

A nested case-control study, also known as an ambidirectional study, is a case-control study within a cohort study. Although distortion by competing risks is well-recognized in follow-up studies, the problem has not been as widely appreciated in nested case-control studies. This paper extends previous work concerning the bias associated with competing risks for nested case-control studies. Specifically, the distorting effect of competing risks is illustrated for three methods of control selection. Assuming the proportional hazards model, the authors derived formulas for the bias of the odds ratio when competing risks cannot be ignored. Examples illustrate the magnitude of bias that occurs when the exposure of interest is associated with competing causes of death or withdrawal.

Epidemiologic Methods↗
PubMed1984

Review: prostate cancer epidemiology.

Prostate cancer is common among men in the United States. Factors of possible importance in the etiology of prostate cancer include diet, primarily implicated by ecologic studies of national, regional, and ethnic variation in rates; endocrine function, implicated by the importance of endocrine function in normal prostatic growth and in the treatment of prostate cancer; genetic susceptibility, supported by familial aggregation; some aspect of sexual behavior, suggested by case-control differences in sexual behavior; and occupational exposure, particularly cadmium exposure. Despite the public health importance of prostate cancer, it has received only moderate epidemiologic study; thus the etiologic importance of these and other possible determinants of prostate cancer risk is uncertain [55].

Aged↗
PubMed1984

Approximate variance formulas for standardized rate ratios.

Some of the techniques which are used to estimate the variance of and confidence intervals for standardized rate ratios either ignore variability of comparison rates or tend to yield confidence intervals which are too narrow when the point estimate is substantially different from one. This paper presents non-iterative, asymptotic formulas for the variance of standardized rate ratios which are applicable when the comparison rates should not be treated as constants, or when the point estimate differs substantially from the null value.

Analysis of Variance↗
PubMed1984

Work-related risk factors for laryngeal cancer.

The authors conducted a case-control study to identify employment-related risk factors for laryngeal cancer. Richmond County, Georgia, and the contiguous counties were chosen as the study area because the 1950-1969 laryngeal cancer mortality rate for white males in Richmond County was almost double the corresponding rate for the entire United States, and because a large proportion of the working population was employed in industries for which excess risk among workers had been reported. All persons with newly diagnosed squamous cell carcinoma of the larynx treated in the area hospitals were identified. Potential controls were selected from patients admitted to these hospitals during the same time period as the cases, excluding those patients admitted for cancer, lung disease, or employment-related disease. Eighty-five control subjects were individually matched to 42 cases for sex, age, area of residence, and smoking and alcohol-drinking history. From lifetime employment histories, laryngeal cancer rate ratios were estimated comparing the incidence rate among subjects who had ever worked in an occupation with the incidence rate among subjects who had never worked in that occupation. Among the 10 occupations in which at least 15 subjects had worked, the authors found rate ratio estimates above 3.0 for farmers, textile processors who separated, filtered or dried textile fibers, and for all laborers and maintenance personnel.

Adult↗
PubMed1982

Interaction of alcohol and tobacco in laryngeal cancer.

Both alcohol and tobacco use are accepted risk factors for laryngeal cancer. The authors used case-control data from previous studies to estimate the value of a previously proposed index of interaction between these two risk factors. In addition to the weighting procedure over exposure categories that was previously proposed for estimating a summary index, they applied maximum-likelihood techniques to facilitate the estimation. Overall, they found moderate synergy between alcohol and tobacco in increasing the risk of laryngeal cancer, in that exposure to both factors increased the risk about 50% more than the increase predicted if the effects of tobacco and alcohol were simply additive.

Adult↗