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W D Flanders

Publications and source records attributed to W D Flanders.

At least 73 records · Page 4Linked to original sources
PubMed1993

Do the medical history and physical examination predict low lung function?

BACKGROUND: We sought to determine whether an abnormal respiratory history or chest physical examination could be used to identify men with low lung function. METHODS: We analyzed pulmonary function, physical examination, and questionnaire data from 4461 middle-aged male Vietnam-era army veterans. MAIN RESULTS: The study sample consisted of 1161 never smokers, 1292 former smokers, and 2008 current smokers. Clinical indicators of respiratory disease (respiratory symptoms, respiratory signs, or a history of respiratory disease), were present in 26.1% of the never smokers, 31.7% of the former smokers, and 47.2% of the current smokers. We defined low forced expiratory volume in 1 second as a value less than 81.2% of the predicted value. Seven percent of the never smokers, 8% of the former smokers, and 17.3% of the current smokers demonstrated low forced expiratory volume in 1 second. Among those with a clinical indicator for spirometry only 11% of the never smokers, 13% of the former smokers, and 21% of the current smokers actually had a low forced expiratory volume in 1 second. Among those without a clinical indicator 6% of the never smokers, 6% of the former smokers, and 14% of the current smokers actually had a low forced expiratory volume in 1 second. CONCLUSIONS: The use of clinical indicators as a basis for obtaining pulmonary function tests in middle-aged men misses many with low lung function, especially current smokers.

Adult↗
PubMed1993

Tryptophan contaminants associated with eosinophilia-myalgia syndrome. The Eosinophilia-Myalgia Studies of Oregon, New York and New Mexico.

Eosinophilia-myalgia syndrome (EMS) has been linked to ingestion of tryptophan contaminated with 1,1'-ethylidene-bis[L-tryptophan] (EBT), but other contaminants have received little study. The authors identified 101 lots of L-tryptophan that had been consumed either by persons with EMS or by asymptomatic tryptophan users and quantified the amounts of EBT and five other contaminants in each lot. After stratification of case and noncase lots by time of manufacture to adjust for the strong sequential pattern over time among case and noncase lots, higher EBT levels were still associated with a lot's case status, but the association lacked statistical significance (p = 0.120, odds ratio = 1.56, 95% confidence interval 0.758-3.23). While these findings do not rule out the possibility that EBT is the etiologic agent in EMS, they raise the possibility that other chemical contaminants in manufactured tryptophan modify the effects of EBT or that the causal agent of EMS is an entirely distinct compound.

Drug Contamination↗
PubMed1993

The lifetime risk of developing breast cancer.

BACKGROUND: The lifetime risk of developing breast cancer in U.S. women, often quoted as one in nine, is a commonly cited cancer statistic. However, many estimates have used cancer rates derived from total rather than the cancer-free population and have not properly accounted for multiple cancers in the same individual. PURPOSE: Our purpose was to provide a revised method for calculating estimates of the lifetime risk of developing breast cancer and to aid in interpretation of the estimates. METHODS: A multiple decrement life table was derived by applying age-specific incidence and mortality rates from cross-sectional data to a hypothetical cohort of women. Incidence, mortality, and population data from 1975-1988 were used, representing the geographic areas of the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program. The incidence rates reflected only the first breast primary cancer; mortality rates reflected causes other than breast cancer. The population denominator used in calculating incidence rates was adjusted to reflect only those women without previously diagnosed breast cancers in the hypothetical cohort. RESULTS: Our calculations showed an overall lifetime risk for developing invasive breast cancer of approximately one in eight with use of 1987-1988 SEER data, although up to age 85, it was still the commonly quoted one in nine. CONCLUSION: Our estimate was calculated assuming constant age-specific rates derived from 1987-1988 SEER data. Because incidence and mortality rates change over time, conditional risk estimates over the short term (10 or 20 years) may be more reliable. A large portion of the rise in the lifetime risk of breast cancer estimated using 1975-1977 data (one in 10.6) to an estimate using 1987-1988 data (one in eight) may be attributed to 1) early detection of prevalent cases due to increased use of mammographic screening and 2) lower mortality due to causes other than breast cancer. A common misperception is that the lifetime risk estimate assumes that all women live to a particular age (e.g., 85 or 95). In fact, the calculation assumes that women can die from causes other than breast cancer at any possible age. Cutting off the lifetime risk calculation at age 85 assumes that no women develop breast cancer after that age. While the lifetime risk of developing breast cancer rose over the period 1976-1977 to 1987-1988, the lifetime risk of dying of breast cancer increased from one in 30 to one in 28, reflecting generally flat mortality trends.

Adolescent↗
PubMed1993

Risk of childhood cancer for infants with birth defects. I. A record-linkage study, Atlanta, Georgia, 1968-1988.

To evaluate the risk of childhood cancer among infants with serious birth defects, the authors linked records of the population-based registry of the Georgia Center for Cancer Statistics for 1975 to 1988 with records of the population-based Metropolitan Atlanta Congenital Defects Program for 1968 to 1987. During the study period, birth defects were diagnosed in 19,373 infants younger than 1 year of age, and cancer was diagnosed in 400 children younger than 15 years of age. The observed number of children with a defect who developed cancer was compared with the number expected on the basis of the cancer registry rates. Of the 19,373 children with birth defects, 31 developed cancer (standardized incidence ratio (SIR) = 2.2, 95% confidence interval (CI) 1.5-3.2). Two associations were found: of 532 children with Down's syndrome (trisomy 21), three developed acute leukemia (SIR = 50.8, 95% CI 10.5-148.5) while of 746 children with pyloric stenosis, four developed cancer (SIR = 7.5, 95% CI 2.0-19.3). These data show that children with selected birth defects are at increased risk for specific childhood cancers. Such record-linkage can reveal new associations, which can in turn help researchers understand underlying mechanisms common to teratogenesis and carcinogenesis.

Acute Disease↗
PubMed1993

Risk of childhood cancer for infants with birth defects. II. A record-linkage study, Iowa, 1983-1989.

To attempt to confirm associations found in a companion study in Atlanta, Georgia between Down's syndrome and acute leukemia and between pyloric stenosis and childhood cancer, the authors used the State Health Registry of Iowa to link the records of infants and children with cancer for 1983 to 1989 with the records of infants with birth defects for 1983 to 1988. During the study period, birth defects were diagnosed in 10,891 infants younger than 1 year of age, and cancer was diagnosed in 396 children younger than 8 years of age. The authors compared the observed number of children with a defect who developed cancer with the number expected on the basis of the cancer registry rates. Of the 10,891 children with birth defects, 16 developed cancer (standardized incidence ratio (SIR) = 2.0, 95% confidence interval (CI) 1.2-3.3). Of 251 children with Down's syndrome (trisomy 21), two developed leukemia (SIR = 32.1, 95% CI 3.9-116.0). None of the infants with cancer had pyloric stenosis (SIR = 0.0, 95% CI 0.0-6.7). The results of this study supported the association found in the Atlanta study between Down's syndrome and leukemia, but did not support the association found there between pyloric stenosis and childhood cancer. This study, however, had a shorter follow-up period and a smaller number of subjects than the Atlanta study.

Acute Disease↗
PubMed1993

Aspirin use and risk of fatal cancer.

Aspirin and other nonsteroidal antiinflammatory drugs inhibit prostaglandin synthesis and tumor growth in many experimental systems, but it is unclear which of these tumor models are relevant to humans. We have reported reduced risk of fatal colon cancer among persons who used aspirin in a large prospective study. This analysis examines other fatal cancers in relation to aspirin among 635,031 adults in that study who provided information in 1982 on the frequency and duration of their aspirin use and did not report cancer. Death rates were measured through 1988. Death rates decreased with more frequent aspirin use for cancers of the esophagus, stomach, colon, and rectum but not generally for other cancers. For each digestive tract cancer, death rates were approximately 40% lower among persons who used aspirin 16 times/month or more for at least 1 year compared to those who used no aspirin. The trend of decreasing risk with more frequent aspirin use was strongest among persons who had used aspirin for 10 years or more; it remained statistically significant, except for esophageal cancer, in multivariate analyses that adjusted for other known risk factors. Biases such as early detection or aspirin avoidance among cases do not appear to explain the results. Our data suggest that regular, prolonged use of aspirin may reduce the risk of fatal cancer of the esophagus, stomach, colon, and rectum. Future epidemiological and basic research should examine all digestive tract cancers in considering the chemopreventive or therapeutic potential of nonsteroidal antiinflammatory drugs.

Acetaminophen↗
PubMed1993

Contaminants in L-tryptophan associated with eosinophilia myalgia syndrome.

In late 1989, an epidemic of eosinophilia-myalgia syndrome (EMS) that resulted in several thousand cases of the syndrome and 36 deaths was recognized in the United States. Physicians in New Mexico linked the epidemic to the ingestion of L-tryptophan (LT). Results of studies indicated that one or more trace contaminants in LT were likely causes of the EMS epidemic. Investigators traced the LT that was taken by most patients with EMS to a single manufacturer, Showa Denko K.K. of Japan. We now report results of high performance liquid chromatographic analysis of LT samples from this manufacturer. Three sets of blind-coded samples were analyzed: the priority case lot set, which included 54 case-associated LT lots and 50 noncase-associated LT lots that were taken by case and control subjects who used only one brand of LT; the single lot case set, which included 73 case-associated LT lots and 25 noncase associated LT lots taken by case and control subjects who used only a single lot of LT; and the South Carolina tablet set, which included LT tablets taken by case subjects (n = 26) and by control subjects (n = 52). We statistically compared the concentration of each contaminant in case-associated, noncase-associated, and control samples of each sample set. The analyses showed that there were more than 60 minor contaminants in the LT from Showa Denko K.K., and that six of these contaminants were associated with EMS. The structures of three contaminants are known, but the identities of the other three contaminants are currently unknown.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacillus↗
PubMed1993

The use of restricted controls to prevent recall bias in case-control studies of reproductive outcomes.

Recall bias or report bias is said to occur when associations are distorted or created because case informants report events differently from controls. Some investigators have suggested that this bias can be prevented by choosing controls who have conditions similar to those found in the case group. We use the term "restricted-control group" for such a control series. Although using a restricted-control series may eliminate differential misclassification, this approach will usually not eliminate nondifferential misclassification and may create selection bias. In this article, we present a way to algebraically examine the effects of misclassification and selection bias on observed associations. We use this method to compare the impact of recall bias in a study using a population control group with the effects of selection bias and nondifferential misclassification if a restricted-control group is used. Our approach is exemplified using data from a case-control study of sudden infant death syndrome. Our findings show that even when recall bias exists, the observed association can be closer to the true association when a population control series is used than when a restricted-control group is used.

Bias↗
PubMed1993

Use of two data sources to estimate odds ratios in case-control studies.

Information bias is among the most serious and common problems in epidemiology. Approaches have been developed to reduce information bias by correcting for known amounts of misclassification. Unfortunately, in most studies, the extent of exposure misclassification cannot be easily estimated. We discuss the application to case-control studies of an approach originally proposed by Hui and Walter in 1980 to estimate the sensitivity and specificity of two independent classification schemes (Hui SL, Walter SD. Biometrics 1980;36:167-171). In this paper, we propose using the EM algorithm to provide a simple numeric technique for implementing their method that seems to converge for most real-world data. Our approach allows inclusion of a measure of non-independence of the two classification schemes, and we assess the influence of non-independence on the odds ratio. Finally, we provide a simple variance estimate for the odds ratio based on the delta method and maximum likelihood theory. We exemplify our results and method with data from a case-control study of sudden infant death syndrome in which data on some variables were obtained from both maternal interviews and medical records.

Algorithms↗
PubMed1993

Confounding by time since hire in internal comparisons of cumulative exposure in occupational cohort studies.

We use a simple, empirical model to describe the healthy worker effect mortality pattern. Under this simple model, internal comparisons of risk with increasing cumulative exposure will tend to be biased away from the null because of the healthy worker effect. We illustrate the potential magnitude of the bias in a simple situation and show that controlling for time since hire, by means of standard epidemiologic methods, eliminates the bias. Time since hire also is a concern of occupational epidemiologists because of the issue of induction time; sufficient time may not have elapsed among recently hired workers for an exposure to manifest its effect on disease occurrence. Provision for an adequate induction period can be addressed, like the concern raised in this paper, by restricting the analysis to workers first employed many years before the start of the follow-up period.

Bias↗
PubMed1993

Demographic predictors of mammography and Pap smear screening in US women.

OBJECTIVES: Proven screening technologies exist for both breast and cervical cancer, but they are underused by many women. We sought to evaluate the effect of demographic characteristics on the underuse of mammography and Pap smear screening. METHODS: We analyzed responses from 12,252 women who participated in the 1987 National Health Interview Survey Cancer Control Supplement. Demographic profiles were produced to target severely underserved groups of women. RESULTS: Low income was a strong predictor of mammography underuse, as was Hispanic ethnicity and other race, low educational attainment, age greater than 65, and residence in a rural area. A strong predictor of never having had a Pap smear was never having been married; however, the importance of this characteristic is difficult to interpret in the absence of data on sexual activity. Hispanic women and women of other races of all ages and all income levels underused Pap smear screening, as did older women, particularly older Black women. CONCLUSIONS: The tendency of women to underuse screening technologies varies greatly across levels of basic demographic characteristics. The importance of these characteristics differs for mammography screening versus Pap smear screening.

Adult↗
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↗