Biomedical subjects

L L Kupper

Publications and source records attributed to L L Kupper.

At least 19 recordsLinked to original sources

PubMed1997

A lognormal distribution-based exposure assessment method for unbalanced data.

We present a generalization of existing statistical methodology for assessing occupational exposures while explicitly accounting for between- and within-worker sources of variability. The approach relies upon an intuitively reasonable model for shift-long exposures, and requires repeated exposure measurements on at least some members of a random sample of workers from a job group. We make the methodology more readily applicable by providing the necessary details for its use when the exposure data are unbalanced (that is, when there are varying numbers of measurements per worker). The hypothesis testing strategy focuses on the probability that an arbitrary worker in a job group experiences a long-term mean exposure above the occupational exposure limit (OEL). We also provide a statistical approach to aid in the determination of an appropriate intervention strategy in the event that exposure levels are deemed unacceptable for a group of workers. We discuss important practical considerations associated with the methodology, and we provide several examples using unbalanced sets of shift-long exposure data-taken on workers in various sectors of the nickel-producing industry. We conclude that the statistical methods discussed afford sizable practical advantages, while maintaining similar overall performance to that of existing methods appropriate for balanced data only.

Air Pollutants, Occupational↗

PubMed1997

Is incarceration during pregnancy associated with infant birthweight?

OBJECTIVES: This study examined whether incarceration during pregnancy is associated with infant birthweight. METHODS: Multivariable analyses compared infant birthweight outcomes among three groups of women: 168 women incarcerated during pregnancy, 630 women incarcerated at a time other than during pregnancy, and 3910 women never incarcerated. RESULTS: After confounders were controlled for, infant birthweights among women incarcerated during pregnancy were not significantly different from women never incarcerated; however, infant birthweights were significantly worse among women incarcerated at a time other than during pregnancy than among never-incarcerated women and women incarcerated during pregnancy. CONCLUSIONS: Certain aspects of the prison environment (shelter, food, etc.) may be health-promoting for high-risk pregnant women.

Adult↗

PubMed1997

A detailed evaluation of adjustment methods for multiplicative measurement error in linear regression with applications in occupational epidemiology.

It is often appropriately assumed, based on both theoretical and empirical considerations, that airborne exposures in the workplace are lognormally distributed, and that a worker's mean exposure over a reference time period is a key predictor of subsequent adverse health effects for that worker. Unfortunately, it is generally impossible to accurately measure a worker's true mean exposure. We begin by introducing a familiar model for exposure that views this true mean, as well as logical surrogates for it, as lognormal random variables. In a more general context, we then consider the linear regression of a continuous health outcome on a lognormal predictor measured with multiplicative error. We discuss several candidate methods of adjusting for the measurement error to obtain consistent estimators of the true regression parameters. These methods include a simple correction of the ordinary least squares estimator based on the surrogate regression, the regression of the outcome on the covariates and on the conditional expectation of the true predictor given the observed surrogate, and a quasi-likelihood approach. By means of a simulation study, we compare the various methods for practical sample sizes and discuss important issues relevant to both estimation and inference. Finally, we illustrate promising adjustment strategies using actual lung function and dust exposure data on workers in the Dutch animal feed industry.

Analysis of Variance↗

PubMed1996

Micronutrients and the risk of colorectal adenomas.

Recent studies suggest that micronutrients, especially folate, calcium, iron, and antioxidant vitamins, affect the risk of colorectal neoplasia. The objective of this case-control study was to examine the association between these micronutrients and the risk of colorectal adenomas. The study was based on 236 cases with adenomatous polyps or cancer and 409 controls, all colonoscopy patients at University of North Carolina Hospitals between July 1988 and March 1991. After colonoscopy, subjects were interviewed using a semi-quantitative food frequency questionnaire, and average daily nutrient intakes were calculated. Sex-specific odds ratios relative to the lowest quartile of intake for each micronutrient were determined using unconditional logistic regression while adjusting for a number of potential confounders. In women, folate, iron, and vitamin C were inversely related to the risk of adenomas. Folate appeared to be most protective, with women in the highest quartile only 40% as likely to develop adenomas compared with women in the lowest (odds ratio = 0.39, 95% confidence interval 0.15-1.01). In men, greater vitamin E and calcium intakes were associated with reduced risk of adenomas, with vitamin E showing the strongest inverse association. Men in the highest vitamin E quartile had a risk of 0.35 (95% confidence interval 0.14-0.92) relative to those in the lowest. These study results support previous research findings that selected micronutrients protect against colorectal neoplasia.

Adenoma↗

PubMed1996

An investigation of systematic changes in occupational exposure.

Nonstationary behavior in occupational exposure was examined among a number of job groups from different industries. A change in the mean level of exposure between two survey periods was evaluated by applying mixed-effects models. Overall, differences between surveys were observed in slightly more than one-third of the industries analyzed and in about one-quarter of the total number of comparisons performed. Exposures in the majority of cases decreased in the later survey. Further analyses examined the impact of nonstationary exposures on the estimation of the between- and within-worker components of variance. When changes in the mean exposure level were detected, point estimates of the variance components generated under the mixed model were compared with those estimates obtained under the one-way random-effects model, which assumes that the mean exposure level remains constant over time. The results indicate that the magnitude of the bias in the variance component estimates can be substantial when the misspecified model is applied. It is concluded that, in the absence of changes known to affect exposure, data collected within a year are likely to result in relatively valid inferences about mean and variance parameters using models that assume stationarity; for periods extending beyond a year, systematic changes in exposure are more likely to occur. Thus, exposure assessment strategies should be designed so that sufficient data are collected among groups of workers to investigate systematic changes and to ensure that appropriate statistical models are applied. In this way, occupational hygienists will be able to make reliable inferences about the underlying distribution of exposures pertinent to each occupational group.

Analysis of Variance↗

PubMed1996

On strategies for comparing occupational exposure data to limits.

Parametric statistical approaches to assessing workplace exposure levels have typically focused either on the probability that a single measurement exceeds a limit or on whether the mean exposure for a population of workers exceeds a limit. This article reviews and clarifies some methods that have been proposed for each of these two approaches, on the assumption that the exposure data represent a random sample from a lognormal distribution. For tests concerning the mean exposure level, the authors developed a potentially useful new procedure based on a bound for noncentral t critical values. Appropriate sample size calculations are emphasized, and computer simulation is used to compare competing methods for assessing mean exposure. The authors conclude that the new proposed method offers an appealing alternative to existing methods in many cases. The importance of employing an exposure assessment strategy that is in concert with underlying etiologic considerations is stressed.

Humans↗

PubMed1996

Comparison of average estimated metabolic rates for styrene in previously exposed and unexposed groups with pharmacokinetic modelling.

OBJECTIVE: To understand whether previous styrene exposure increases the human liver's ability to convert styrene into styrene oxide. METHODS: The hypothesis was tested that the average linear metabolic rate constant kappa was the same in both exposed and unexposed groups, when the exposed group comprised people with a history of styrene exposure and the unexposed group had no exposure. In an experimental chamber, these two groups of subjects were exposed to a concentration of 80 ppm styrene for two hours. A three compartment pharmacokinetic model was used to define kappa. Based on large sample theory, the comparison of estimated mean values of kappa in the exposed and unexposed groups was shown to be equivalent to a comparison of the estimated mean values of the hepatic clearance X in the two groups. A method was developed to estimate X for each subject in both groups from the subject's height, weight, and estimated asymptotic styrene decay constant alpha. Here, alpha was estimated individually from observed blood concentrations over time when sufficient time had elapsed after the controlled exposure. RESULTS: The proposed methodology of comparing the estimated mean values of kappa in exposed and unexposed groups reduced the number of specific physiological variables involved to three, all of which were estimable from data based on simple direct measurements. In contrast, other methods based on pharmacokinetic models usually involved many variables that were non-estimable on an individual basis. Consequently, statistical comparisons were impossible. These methods were applied to analyse previously published data on the time course of styrene concentrations in arterial blood of subjects in both exposed and unexposed groups. A Wilcoxon non-parametric rank sum test with the individually estimated X values was used, and no significant difference in the means of X in the two groups was found. CONCLUSION: The linear metabolic rate constant kappa for humans is probably not altered by previous exposure to styrene. This result is in agreement with some experimental studies on animals. However, in the data analysis, it was noted that the number of subjects in each group was small (6-7) and that the styrene concentration data did not exactly reflect true behaviour of asymptotic decay. Further studies are still needed to draw more definitive conclusions.

Adipose Tissue↗

PubMed1996

Antidepressant-treated patients in ambulatory care long-term use of non-psychotropic and psychotropic drugs.

BACKGROUND: Despite the problems involved in treating depression and concomitant medical disease, there are virtually no longitudinal studies on drug utilisation among depressed patients. METHOD: Use of prescription drugs among all first-time users of antidepressants in a defined population five years before and six years after the index (first) treatment was compared to a referent group without antidepressant treatment. The generalised estimating equations (GEE) method was used for analysis. RESULTS: The antidepressant-treated group used considerably more non-psychotropic drugs during the whole study period than the referent group. They also used more psychotropic drugs, a use which increased in connection with the initiation of antidepressant treatment, and stayed high for a further five years. CONCLUSIONS: The high use of prescription drugs indicated widespread somatic and psychiatric health problems during the whole study period. Antidepressant-treated patients are at risk for drug interactions and adverse effects, and would benefit from a closer collaboration between psychiatry and medicine.

Adolescent↗

PubMed1996

Violence and substance use among North Carolina pregnant women.

OBJECTIVES: Prenatal patients were studied to examine the proportion of women who had been violence victims, women's patterns of substance use (cigarettes, alcohol, and illegal drugs) before and during pregnancy, and relationships between violence and substance use. METHODS: More than 2000 prenatal patients in North Carolina were screened for violence and substance use. Relationships between violence and patterns of substance use before and during pregnancy were examined, as well as women's continuation of substance use during pregnancy as a function of violence and sociodemographic factors. RESULTS: Twenty-six percent of the women had been violence victims during their lives. Before pregnancy, 62% of the women had used one or more substances; during pregnancy, 31% had used one or more substances. Both before and during pregnancy, violence victims were significantly more likely to use multiple substances than nonvictims. Continuation of substance use during pregnancy was significantly more likely among violence victims than nonvictims. CONCLUSIONS: Care providers should screen women for violence as well as for substance use and should ensure that women are provided with appropriate interventions.

Adult↗

PubMed1995

An exposure-assessments strategy accounting for within- and between-worker sources of variability.

A strategy is presented for comparing exposures to an occupational exposure limit (OEL) and for suggesting appropriate interventions when exposures are unacceptable. The major departure from previous approaches is the explicit recognition that exposures vary both within and between workers in a given occupational group. The primary goal is to determine whether the probability of overexposure is acceptably small (a value of 0.10 or less is recommended), with overexposure being defined as the likelihood that a randomly selected worker's true mean exposure exceeds the OEL. The exposure-assessment protocol contains five levels. It is suggested that at least two shift-long measurements be randomly collected from each of 10 workers for preliminary analysis. If the logged exposure data appear to be appropriate for testing (Level 1), the probability of overexposure is compared to the pre-determined value via a rigorous test of statistical significance (Level 2). Based upon published data, this test is likely to classify exposures as acceptable with 20 measurements when the group mean exposure is less than one-fifth of the OEL. However, if exposure is found to be unacceptable, re-sampling can be considered to increase the power of the test (Level 3). Otherwise, it is necessary to reduce exposures and then to re-apply the protocol. If it appears that all persons in the group have essentially the same predicted mean exposures (Level 4), then engineering or administrative controls are recommended. If, on the other hand, substantial differences appear to exist amongst these predicted mean values, regrouping and/or modifications of tasks and work practices should be considered (Level 5). Application of the protocol is illustrated with samples of data from four groups of workers exposed to inorganic nickel in the nickel-producing industry.

Analysis of Variance↗

PubMed1995

The relationship between environmental monitoring and biological markers in exposure assessment.

The poor quality of traditional assessments of exposure has encouraged epidemiologists to explore biological monitoring in studies of chronic diseases. Yet, despite theoretical advantages, biomarkers have not been widely used in such applications. This article compares the general utility of a biomarker with that of the measurement of exposure per se. Points are illustrated with a longitudinal study of boat workers in which levels of styrene in the breathing zone and in exhaled air were compared to sister chromatid exchanges (SCEs) in peripheral lymphocytes. First, the linear relationship is explored between personal exposure and the levels of a biomarker in the cohort. A good fit to the straight-line relationship reflected by a correlation coefficient which is close to 1, such as observed with styrene in exhaled air (r2 = 0.83), suggests linear kinetics, that the appropriate route of exposure was measured by personal monitoring, small interindividual differences, adequate sample sizes, and a specific biomarker. However, a small correlation coefficient, as observed between SCEs and styrene exposure (r2 = 0.11), indicates that either kinetics were nonlinear or that more complex issues were involved with one or more of these factors. Second, environmental and biologic measurements are compared for use as independent variables in establishing a straight-line relationship between exposure and the health effect. If the ratio of the within-person to the between-person components of variance of the independent variable is large, then significant attenuation results when estimating the slope of the line.(ABSTRACT TRUNCATED AT 250 WORDS)

Biomarkers↗

PubMed1994

Exposure to ionizing radiation and risk of cutaneous malignant melanoma. Search for error and bias.

In a 1984 case-control study of cutaneous malignant melanoma (CMM) among workers at the Lawrence Livermore National Laboratory, Austin and Reynolds found an association between reported employment in proximity to ionizing radiation and CMM (odds ratio (OR) = 5.4; 95% confidence interval (CI): 1.4, 20.7). But in a preliminary study in 1981, they found no association between individual radiation dosimetry readings and CMM. We reanalyzed the 1984 Austin-Reynolds case-control data to determine whether error or bias explain the inconsistency between reported employment in proximity to radiation and individual radiation dosimetry readings. Using individual radiation dosimetry readings, we developed an index of occupation-specific radiation. This index was associated with case status (OR = 10.8; 95% CI: 1.4, 85.1). No definitive evidence for influential matched sets, confounding, recall bias, or any other sources of bias was identified. These results suggest that the odds ratio for reported employment in proximity to radiation may be valid.

Bias↗

PubMed1994

Limitations of relative sensitivity in detecting differential misclassification in case-control studies.

Apparent relative sensitivity, based on an investigator's external standard, is the ratio of observed case to control exposure sensitivity. An apparent relative sensitivity different from 1.0 is usually interpreted as evidence for differential misclassification of exposure status. We undertook this investigation to determine the conditions under which an apparent relative sensitivity exceeding 1.0 is actually due to differential misclassification. We also consider whether apparent relative sensitivity correctly quantifies the degree of differential misclassification. To achieve these goals, we derived an algebraic relation involving apparent relative sensitivity, true sensitivities and specificities, true odds ratio, an index of how well the external standard classifies true exposure, and the incidence of the disease among the nonexposed. We found that an apparent relative sensitivity greater than 1.0 correctly indicates differential misclassification when either (1) the investigator's external standard classifies true exposure perfectly, or (2) the investigator's external standard is imperfect, but the true odds ratio equals 1.0, true relative sensitivity is greater than 1.0, and true relative specificity is less than 1.0. We also found that apparent relative sensitivity greater than 1.0 falsely suggests differential misclassification when true relative sensitivity equals 1.0, the investigator's external standard is imperfect, and the true odds ratio is greater than 1.0. Furthermore, even when apparent relative sensitivity correctly detects the presence of differential misclassification, it may misrepresent the degree.

Bias↗

PubMed1993

Diet and risk of colorectal adenomas: macronutrients, cholesterol, and fiber.

BACKGROUND: Diet is thought to be important in the etiology of colorectal cancer. Studies suggest that a diet high in red meat and saturated fat and low in dietary fiber and vegetables may increase cancer risk. Diet may also be important in the development of colorectal adenomas that are precursors of most colorectal cancers, but this hypothesis has not been well studied. PURPOSE: This case-control study was designed to examine the effects of dietary consumption of cholesterol, fiber (vegetables, fruits, beans, and grains), and macronutrients (protein, carbohydrate, and fat) on risk for colorectal adenomas. METHODS: Analyses were based on data from 236 subjects (105 men and 131 women) with histologically confirmed adenomas (cases) and 409 adenoma-free control subjects (165 men and 244 women), all of whom had had colonoscopy. Case and control subjects were similar with respect to gender, body mass, race, marital status, education, and indications for colonoscopy. Using a validated quantitative food-frequency questionnaire, an experienced graduate nutritionist interviewed each subject by telephone. Sex-specific analyses were conducted because the ranges of nutrient intake were substantially different for men and women. Odds ratios (ORs) were calculated according to quintiles of nutrient intake. RESULTS: Carbohydrate intake was inversely related to adenoma risk in women (P for trend = .002). Compared with women in the lowest quintile of carbohydrate consumption, those in the highest quintile were 60% less likely to develop adenomas (OR = 0.39; 95% confidence interval [CI] = 0.19-0.80). Intake of fruit (P for trend = .028) and intake of fiber derived from vegetables and fruits (P for trend = .012) were also inversely related to adenomas in women. Total fat showed a positive association in women (P for trend = .004), with an OR of 2.69 for the highest versus the lowest quintile (95% CI = 1.31-5.50). Results were comparable for saturated fat (P for trend = .027). The risks in men were generally similar in direction and magnitude but were not statistically significant. CONCLUSIONS: These data support the hypothesis that a diet high in fat and low in carbohydrates, fruits, and fruit and vegetable fiber increases risk not only for colorectal cancer but also for precursor colorectal adenomas. IMPLICATIONS: These results, which are consistent with findings of other investigators, suggest that environmental factors, influencing risk for colorectal cancer, such as a high-risk diet, may lead to development of the precursor adenomas.

Adenoma↗

PubMed1993

Cigarette smoking, alcohol, and the risk of colorectal adenomas.

BACKGROUND: The present study was designed to further assess the reported association between cigarette smoking, alcohol, and colorectal adenomas. METHODS: A number of environmental and life-style risk factors were examined in 236 patients with histologically proven adenomas and 409 controls with no adenomas. RESULTS: Age, sex, race, and indication for procedure were similar in cases and controls. Those who had ever smoked were not at increased risk for adenomas compared with those who had never smoked. Years of smoking, cigarettes per day, and total pack-years showed no dose-response effect. Results for men and women were similar. Alcohol was a significant risk factor for men but not for women. Men in the highest quartile of daily caloric intake from alcohol were more than four times more likely than nondrinkers to develop adenomas, with a statistically significant trend in risk from the lowest to the highest quartile. These findings persisted after controlling for other potential risk factors for adenomas. The risk for colon and rectal polyps were similar. Men in the highest tertile of beer consumption were nearly six times more likely to develop adenomas than nondrinkers. CONCLUSIONS: Beer drinking is a risk factor for colorectal adenomas in this population.

Adenoma↗

PubMed1993

Conditional regression analysis of the exposure-disease odds ratio using known probability-of-exposure values.

Conditional inference methods are proposed for the odds ratio between binary exposure and disease variables when only the probability of exposure is known for each study subject. We develop a conditional likelihood approach that removes nuisance parameters and permits inferences to be made about important parameters in log odds ratio regression models. We also discuss a heuristic procedure based on estimating the (unknown) number of truly exposed individuals; this procedure provides a simple framework for interpreting our likelihood-based statistics, and leads to a Mantel-Haenszel-type estimator and a goodness-of-fit test. As an example of the use of this methodology, we present an analysis of some genetic data of Swift et al. (1976, Cancer Research 36, 209-215).

Adult↗

PubMed1991

Confidence intervals for post-test probability.

Confidence intervals are a natural way to describe the uncertainty of post-test probability in diagnostic tests. We consider confidence intervals for two different scenarios. At a site, for example, hospital emergency room or student health centre, with measured values of disease prevalence, sensitivity and specificity available, the confidence interval is similar to results in the literature, but at a site where measured values of these indices are unavailable, we develop a method, using the values of disease prevalence, sensitivity and specificity from other sites, to obtain a confidence interval for post-test probability. We use the diagnosis of strep throat to illustrate the results. We also obtain confidence intervals from simulations to compare with the results of both scenarios.

Adult↗

PubMed1991

Effects of exposure misclassification on regression analyses of epidemiologic follow-up study data.

In epidemiologic studies, subjects are often misclassified as to their level of exposure. Ignoring this misclassification error in the analysis introduces bias in the estimates of certain parameters and invalidates many hypothesis tests. For situations in which there is misclassification of exposure in a follow-up study with categorical data, we have developed a model that permits consideration of any number of exposure categories and any number of multiple-category covariates. When used with logistic and Poisson regression procedures, this model helps assess the potential for bias when misclassification is ignored. When reliable ancillary information is available, the model can be used to correct for misclassification bias in the estimates produced by these regression procedures.

Biometry↗