Biomedical subjects

L L Kupper

Publications and source records attributed to L L Kupper.

At least 55 records · Page 3Linked to original sources

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↗

PubMed1990

Sample size determination for pair-matched case-control studies where the goal is interval estimation of the odds ratio.

Samples sizes are calculated for case-control studies where 1:1 matching has been employed, and where the goal is the interval estimation of the odds ratio. The optimal sample size is defined to be the smallest value for which a 100(1 - alpha)% confidence interval for the log odds ratio will not exceed a specified width 2 delta with specified probability (1 - gamma). This approach is similar in spirit to the power-based approach for sample size determination when significance testing is the goal. Tables of sample sizes are presented for various choices of parameters. We also find considerable disagreement with a published method based on expected numbers of discordant pairs.

Case-Control Studies↗

PubMed1990

Sample size requirements for interval estimation of the odds ratio.

Sample sizes are calculated for unmatched case-control (or cohort) studies where the goal is interval estimation of the odds ratio. The procedure used gives the smallest sample size for which a 100(1-alpha)% confidence interval for the log odds ratio will not exceed a specified width with specified probability (1-gamma). Tables of sample sizes for various choices of parameter values are presented. Considerable disagreement is found with a published method which has as its basis expected cell counts.

Case-Control Studies↗

PubMed1990

An exploratory analysis of the occupational correlates of large pigmented nevi at Lawrence Livermore National Laboratory.

To examine the association between exposure to occupational factors and the presence on the body of large pigmented nevi greater than 5 mm, data were collected from 110 employees of Lawrence Livermore National Laboratory employed between 1969 and 1980. In this exploratory prevalent case-control study analysis, 38 employees reported having at least one large pigmented nevus and 72 reported none. Occupational factors associated with the presence of large pigmented nevi (adjusted for age and the number of sunburns per year under age 21) were being an engineer (prevalence odds ratio [POR] = 3.20, 95% confidence interval [CI] = 1.0,10.6) or an electrical engineer (POR = 2.56, 95% CI = 0.3,20.3), being hired at Lawrence Livermore National Laboratory before 1962 (POR = 3.07, 95% CI = 1.2,7.7), and having one's skin exposed to rare earth metals (POR = 3.78, 95% CI = 0.9,15.1).

Adult↗

PubMed1990

Continued fraction representation for expected cell counts of a 2 x 2 table: a rapid and exact method for conditional maximum likelihood estimation.

The expected cell count for a 2 x 2 contingency table, governed by the noncentral (extended) hypergeometric distribution, is expressed as a terminating continued fraction. The coefficients in the continued fraction are better behaved than the multinomial coefficients required for the usual moment calculation. The expected cell count must be calculated repeatedly in a conditional maximum likelihood analysis of K2 x 2 contingency tables. Since the continued fraction can be easily evaluated, a rapid and numerically stable computational algorithm results. Once this first moment is known, higher moments can be obtained as shown by Harkness (1965, Annals of Mathematical Statistics 36, 938-945). A BASIC program to implement the continued fraction algorithm is given in an appendix.

Algorithms↗

PubMed1990

Effective testing of gene-disease associations.

We propose a method for testing any hypothesized association between a candidate allele, for which there is a specific laboratory test, and a common chronic disease. Families in which this allele is segregating are identified through index individuals who are homozygous or heterozygous for the allele. The sample consists of the subset of identified families who also have at least one member with the common disease of interest. For each independent family in this subset, select one person with the disease and determine if he or she is heterozygous for the allele. The observed proportion of heterozygotes in this sample is compared to the proportion expected on the basis of each diseased relative's null probability of being heterozygous for the allele; this null probability depends only on the relative's relationship to the index individual and the population allele frequency. We provide these null probabilities, develop appropriate inference procedures, discuss sample size requirements, and compare this method to a standard case-control design. Results using this method are unlikely to be influenced by confounders, systematic bias, or genetic heterogeneity.

Alleles↗

PubMed1989

On assessing interrater agreement for multiple attribute responses.

New methods are developed for assessing the extent of interrater agreement when each unit to be rated is characterized by a (possibly empty) subset of a specified set of distinct nominal attributes. For such multiple attribute response data, a two-rater concordance statistic is derived, and associated statistical inference-making procedures are provided. This concordance statistic is corrected for chance agreement by using an underlying hypergeometric model. Numerical examples are given to illustrate the proposed methodology, and comparisons to other agreement statistics (e.g., kappa) are made.

Biometry↗

PubMed1988

Development of a Crohn's index for survey research.

Current Crohn's disease activity indices are not suitable for survey research because they rely on information from the laboratory or physical examination. We used data from a multicenter controlled trial of adjuvant sulfasalazine to develop an index of Crohn's disease activity based on information which could be obtained exclusively by interview. The study population consisted of 89 actively symptomatic patients seen on 1082 occasions in eight medical centers. Multiple regression analyses identified three variables which predicted the ratings of physicians: stool frequency, abdominal pain and sense of well-being. The new index correlated very well (r = 0.87, p less than 0.001) with the Crohn's Disease Activity Index from which it was derived. The index may be used in epidemiologic studies to accurately place patients into quartiles of disease severity which correspond to similar quartiles of the CDAI.

Abdomen↗

PubMed1986

Effect of trephine tilt on corneal button dimensions.

Wound disparity, mismatch between the size and shape of the donor corneal button and its wound, probably determines the direction and amount of postkeratoplasty astigmatism. Tilting a hand-held trephine is thought to contribute to an oval wound and to wound disparity. We examined the contribution of trephine tilt to wound size and shape. Eyebank eyes were hand trephined at 0, 5, 10, 15, 20, and 25 degrees of tilt. The button endothelial edges were analyzed by the photogrammetric index method. All index values were significantly different from those for a theoretically circular or symmetric button. Although the most oval buttons were at 20 and 25 degrees, buttons were similarly oval and asymmetric for trephine tilt from 0 to 15 degrees. Neither ovality nor asymmetry correlated with angle of tilt. Even when no attempt is made to tilt a hand-held trephine, oval and irregularly shaped wounds may result.

Corneal Transplantation↗

PubMed1986

Diabetes mellitus in ataxia-telangiectasia, Fanconi anemia, xeroderma pigmentosum, common variable immune deficiency, and severe combined immune deficiency families.

The hypothesis that heterozygous carriers of genes for certain autosomal recessive syndromes may be predisposed to diabetes was tested by comparing diabetes incidence from age 20 to 69 yr in blood relatives to that in spouse controls among 7999 adult family members of patients with one of five autosomal recessive syndromes: ataxia-telangiectasia (A-T), Fanconi anemia (FA), xeroderma pigmentosum (XP), common variable immune deficiency (CVID), and severe combined immune deficiency (SCID). FA and A-T families were studied because earlier findings in family members and the frequency of diabetes in homozygotes suggested that heterozygotes might also be predisposed to diabetes. The XP, CVID, and SCID families were included to see what analysis of family data would reveal when there was no prior evidence for a gene-diabetes association. The diabetes rate ratios of 2.6 and 4.2 among FA and SCID females, respectively, were significantly elevated. For female FA heterozygotes specifically, the estimated relative risk of 5.1 for developing diabetes was also significantly elevated. Among males, the most pronounced, although not statistically significant, findings were an elevated rate ratio of 2.2 for A-T males and a low-rate ratio of 0.5 for CVID males. The results suggest that heterozygotes for some of the diabetes-associated autosomal recessive syndromes may themselves be predisposed to diabetes.

Adult↗

PubMed1986

The impact of litter effects on dose-response modeling in teratology.

The fitting of dose-response models to teratology data involving littermates in order to generate estimates of teratogenic risk is receiving increasing attention as a potential alternative to the "safety-factor" approach to risk estimation. In this paper, we utilize the beta-binomial distribution to introduce varying degrees of intralitter correlation, and, for purposes of illustration, consider a logistic dose-response model that describes the logit of risk as a straight-line function of ln(dose). The biases and (exact and asymptotic) variances of the maximum likelihood estimators of the intercept and slope are studied by simulation as a function of the intralitter correlation structure.

Animals↗

PubMed1985

Statistical age-period-cohort analysis: a review and critique.

Descriptive and statistical age-period-cohort (APC) analysis methods have received considerable attention in the literature. The statistical modeling of APC data often involves the popular multiple classification model, a model containing the effects of age groups (rows), periods of observation (columns), and birth cohorts (diagonals of the age-by-period table). The identifiability problem inherent to this model is discussed, and its adverse effects on the results of APC modeling exercises are illustrated numerically. Potential problems attendant with the use of two-factor models are described, and other possible modeling approaches currently in use are discussed. Interpretational limitations due to certain innate characteristics of typical APC data sets are also detailed. Given all the documented potential sources for error, the current state-of-the-art regarding the statistical modeling of APC data should be considered to be at an early stage of development.

Adult↗

PubMed1984

Laryngeal cancer and occupational exposure to sulfuric acid.

Workers on an ethanol unit which used sulfuric acid in strong concentrations at a large refinery and chemical plant in Baton Rouge, Louisiana were reported, in 1979, at excess risk for upper respiratory cancer. The carcinogen implicated by indirect evidence was diethyl sulfate. However, with the continued use of sulfuric acid in the same plant, and with additional cases not attributable to the ethanol process, the hypothesis of an association between sulfuric acid exposure and upper respiratory cancer was tested. Each of 50 confirmed cases of upper respiratory cancer diagnosed between 1944 and 1980, was matched to at least three controls on sex, race, age, date of initial employment, and duration of employment. Thirty-four of the 50 cases were laryngeal cancers. Data were obtained from existing plant records. Retrospective estimates of exposure were made without regard to case or control status. Findings from conditional logistic regression techniques were supported by other statistical methods. Among workers classified as potentially highly exposed, four-fold relative risks for all upper respiratory cancer sites combined were exceeded by the relative risk for laryngeal cancer specifically. Exposure-response and consistency across various comparisons after controlling statistically for tobacco-use, alcoholism and other previously implicated risk factors, suggest increased cancer risk with higher exposure.

Alcohol Drinking↗

PubMed1984

Effects of the use of unreliable surrogate variables on the validity of epidemiologic research studies.

When certain key factors of interest in epidemiologic research studies cannot be measured directly, epidemiologists often turn to the use of surrogate variables. The potential bias in making statistical inferences about an adjusted exposure-disease association parameter (e.g., a partial correlation) is described as a function of the degree of unreliability in the surrogate variables used in place of the underlying disease, exposure, and confounding factors of real interest. It is shown that unreliability in the surrogate confounder is much more apt to produce seriously misleading inferences than is unreliability in the surrogate measures for disease and exposure. Practical methods are discussed for dealing with less than perfectly reliable surrogate variables.

Epidemiologic Methods↗

PubMed1984

Effect of tissue fit on corneal shape after transplantation.

Postkeratoplasty astigmatism is now a major problem preventing visual recovery. Certain postoperative topographic characteristics are felt to be dictated by the fit of the donor corneal button in its recipient bed. Deficient tissue at the wound is predicted to contribute to the location of the steep meridian and excess tissue to the location of the flat meridian. In an eight-cat sample using our Fit Assessment Method and Photogrammetric Index Method, the authors tested the relationship between button fit in recipient bed and resulting corneal curvature at approximately 42, 161, and 289 postoperative days. Corneal symmetry improved between the first and second postoperative periods. Deficient tissue led to steepened curvature and ample tissue to flattened curvature in the first measurement period. When buttons fit poorly, deficient tissue led to steepness in the first postoperative period, but led to flattened curvature 90 deg away from the deficient tissue meridian in the second and third periods. The relationship between ample tissue and flattest postoperative curvature did not depend on the magnitude of button-fed disparity in any period. Corneal elasticity appeared to influence the way tissue disparity affected postoperative topography. Our findings support Troutman's balloon mode. When there was a large amount of uncompensated tissue disparity, the tissue deficiency exerted a force that shortened the translimbal chord. This produced both steepened curvature parallel to this chord soon after surgery and flattened curvature at 90 deg to the chord in the stable postoperative cornea.

Animals↗

PubMed1984

A new photogrammetric method for quantifying corneal topography.

Attempts to describe normal corneal shape and to represent corneal topography by an array of discrete points have limited usefulness. A quantitative photogrammetric method that produces indices to describe corneal shape was developed. Four indices depict the departure of keratographic rings from circularity, and two indices express the trends and consistencies of all the rings from one keratograph. This photogrammetric index method (PIM) was evaluated against established measurement techniques. Values for the six indices were computed for groups (10 corneas each) of symmetrical, regularly astigmatic, and keratoconic corneas that had been defined by keratometry and clinical criteria. Predictions of the differences among groups were formulated for each index based on group descriptions and anticipated manual tracing and/or digitization error. Parametric and nonparametric tests of significance supported most predictions. The asymmetry of irregularly astigmatic keratoconic corneas, the variability of their orthogonal principal meridians, and an increasing symmetry toward their peripheries were documented clearly. The circularity of symmetrical group rings and the ellipticity of regularly astigmatic group rings were also evident. Preliminary norms are offered to illustrate the usefulness of the PIM in defining groups of corneas with the same histories and in classifying individual corneas.

Adult↗

PubMed1982

In defense of matching.

This paper discusses the simplified situation of an epidemiologic study involving disease, exposure, and a single (possibly confounding) extraneous factor, all of which are dichotomous. The question is: In studying the association between disease and exposure, should the comparison group be selected by random sampling or by matching on the extraneous factor? An example is used to demonstrate the general principle that matching controls confounding in estimating the risk ratio in a follow-up study, but not in estimating the exposure odds ratio in a case-control study. Calculations based on a probability model show that, despite the possible reduction in sample size which may be associated with matching, matching will often lead to a more precise estimate of the effect measure than random sampling and is not likely to result in a significant loss in precision in situations of practical importance. Therefore, selection of the referent group by matching should be given serious consideration for both follow-up and case-control studies.

Epidemiologic Methods↗

PubMed1981

Selection bias in epidemiologic studies.

Consideration of factors involved in the selection of subjects is essential for evaluating the validity of a putative etiologic association. The purpose of this paper is to provide a quantitative conceptual framework for understanding selection bias; this framework integrates both epidemiologic and statistical considerations. Emphasis is given to specifying the conditions under which such bias is likely to occur, identifying the direction and magnitude of the bias, and illustrating how these features differ by type of study design.

Cross-Sectional Studies↗