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Biomedical subjects

W W Hauck

Publications and source records attributed to W W Hauck.

At least 19 recordsLinked to original sources
PubMed1992

An annotated bibliography of methods for analysing correlated categorical data.

This paper provides an annotated bibliography of over 100 articles concerning methods for analysing correlated categorical response data. Most of the papers listed here concern categorical regression models and estimation, with particular emphasis on binary responses. The papers are classified by several characteristics which group them according to common themes. The bibliography serves as a reference of methods for analysts of correlated categorical data, as well as for persons interested in methodologic work in this active area of statistical research.

Clinical Trials as Topic↗
PubMed1992

Histopathology of smokeless tobacco lesions in professional baseball players. Associations with different types of tobacco.

We examined 142 biopsy specimens of smokeless tobacco-associated oral mucosal lesions from 133 professional baseball players. Four types of epithelial change were observed in the specimens: hyperparakeratosis, hyperorthokeratosis, pale surface staining, and basal cell hyperplasia. These types of epithelial change were associated with the type of smokeless tobacco used (snuff or chewing tobacco) but not with the duration (years) or amount (hours per day) of use. The thickness of hyperkeratosis in a specimen correlated directly with the amount of smokeless tobacco use. The use of snuff was more frequently associated with development of oral mucosal lesions than was the use of chewing tobacco, and snuff appeared to cause a greater variety and severity of epithelial change than did chewing tobacco.

Adult↗
PubMed1992

Bioequivalence studies of topical preparations: statistical considerations.

To be approved for marketing, a potential generic pharmaceutical product must demonstrate bioequivalence, that is, a rate and extent of absorption similar to those of the currently marketed ("innovator") product. For oral products, design and statistical analysis for studies conducted to determine whether two products are bioequivalent have become reasonably standardized; the design is crossover, and analysis is based on the two one-sided tests principle. The purpose of this overview is to consider whether the practices for oral products apply to topical products, and where different procedures may be required. The principles behind the practices for oral products are seen, largely, to carry over to topical products.

Administration, Topical↗
PubMed1992

Reduction of Langerhans cells in smokeless tobacco-associated oral mucosal lesions.

Localized absence of epithelial Langerhans cells (LC) has been shown to affect systemic immune responses, allow microbial colonization and play a possible role in carcinogenesis. Because use of smokeless tobacco is associated with abnormal oral mucosal changes and development of carcinoma, we examined lesion and control specimens from 17 current users of smokeless tobacco to determine whether lesions showed changes in LC number or antigen expression. We identified LC by immunohistochemistry with antibodies to the antigens T6, HLA-DR, HLA-DQ, and HLA-DP. Lesion specimens contained fewer LC (means of 6 LC/mm and 10 LC/mm2) than did the corresponding control specimens (means of 14 LC/mm and 30 LC/mm2), and in each pair of lesion and autologous control specimens the reduction in LC was on average 58% (range, 3% to 95%). There were no apparent differences between lesion and control specimens in the number of LC expressing each of the four marker antigens. Reductions in LC occurred in all types of smokeless tobacco-associated lesions, regardless of increased epithelial thickness or changes in keratinization. Our data indicate that smokeless tobacco reduces the number of Langerhans cells at its site of contact with the oral mucosa.

Antigens, Surface↗
PubMed1992

Smokeless tobacco, cardiovascular risk factors, and nicotine and cotinine levels in professional baseball players.

BACKGROUND: The use of smokeless tobacco (ST), which has increased in popularity over the past 2 decades, results in considerable systemic exposure to nicotine. Nicotine might contribute to atherosclerosis by an effect on cardiovascular risk factors. METHODS: The effects of ST use on cardiovascular risk factors and cotinine and nicotine levels were studied in 1061 professional baseball players during spring training in 1988 and 1989. RESULTS: Of the study participants 477 (45%) were users. ST use was more common among Whites (55%) than among Blacks (29%) or Hispanics (21%), and users reported heavier consumption of alcohol (p less than .001) and had higher mean serum caffeine levels (p less than .001) than nonusers. ST users did not differ from nonusers in adjusted levels of systolic and diastolic blood pressure, pulse, and total or HDL-cholesterol. Among ST users, participants using snuff had higher mean serum cotinine levels than those who used chewing tobacco (p less than .001). There was no association between serum cotinine levels and adjusted levels of any cardiovascular risk factor studied. However, higher diastolic blood pressures were associated with higher mean serum nicotine levels (p = .02). CONCLUSIONS: Smokeless tobacco use has at most a modest effect on cardiovascular risk factors in young physically fit men.

Adult↗
PubMed1992

Effect of changing the bioequivalence range from (0.80, 1.20) to (0.80, 1.25) on the power and sample size.

International harmonization of guidelines for bioequivalence assessment has led to a wide acceptance of the multiplicative model for the extent and rate characteristics AUC and Cmax and--in consistency with this--of the bioequivalence range (0.80, 1.25). The effect of this change from (0.80, 1.20) on the power of the two one-sided test procedure and the sample sizes based thereon is investigated as a function of the within-subject coefficient of variation (CV) and the ratio mu T/mu R of expected medians for test and reference. The relative reduction in sample size is practically zero for mu T/mu R < or = 0.9 and then gradually increases as mu T/mu R approaches 1.2. At mu T/mu R = 1, the reduction is up to 20%. For a fixed ratio mu T/mu R this reduction increases with the coefficient of variation, reaching a plateau at a CV of about 25%.

Models, Statistical↗
PubMed1992

Types of bioequivalence and related statistical considerations.

Approval of a generic alternative to an existing formulation carries the implication that the two formulations are "equivalent". However, there are many notions of equivalent. Current practice in bioequivalence studies defines equivalence solely in terms of average (or median) measures of bioavailability. Current methods for this average bioequivalence approach are commonly based on the two one-sided tests principle. Average bioequivalence is the special case of population bioequivalence, where the entire distribution of bioavailabilities is considered. Statistical approaches for population bioequivalence are suggested. Population bioequivalence is an improvement over average bioequivalence, because average bioequivalence does not consider the variabilities of the formulations. However, population bioequivalence is still not sufficient to ensure that an individual will respond similarly to the two formulations; that requires individual bioequivalence. Again, statistical approaches are suggested, one of which, a tolerance interval approach, appears to directly address the clinical question of switchability of formulations. We conclude that population bioequivalence is sufficient for marketing approval, but that individual bioequivalence is necessary for switchability.

Biological Availability↗
PubMed1992

Decreased fecundability in Hutterite couples sharing HLA-DR.

To study the effects of parental HLA sharing on pregnancy outcome, we initiated population-based studies in the Hutterites. We previously reported longer intervals from marriage to each birth among couples sharing HLA, particularly HLA-DR. In the present report, we present the results of a prospective, 5-year study of fecundability and fetal loss rates in this population. Between April 1986 and April 1991, 154 pregnancies were observed in 104 couples. The median number of months of unprotected intercourse to a positive pregnancy test was significantly longer among couples sharing HLA-DR who stopped nursing prior to the first menses as compared with couples not sharing HLA-DR who stopped nursing prior to the first menses (5.1 vs. 2.0 mo, respectively; P = .016). Fetal loss rates were increased among couples sharing HLA-B as compared with couples not sharing HLA-B (.23 vs. .12, respectively; P = .041, adjusted for age, gravidity, and kinship). These data suggest that our earlier observations of increased birth interval lengths among Hutterite couples sharing HLA were predominantly due to longer intervals until a clinical pregnancy among couples sharing HLA-DR and, to a lesser degree, were due to increased fetal loss rates among couples sharing HLA-B.

Abortion, Spontaneous↗
PubMed1991

Statistical analysis of outcomes from repeated pregnancies: effects of HLA sharing on fetal loss rates.

As part of our ongoing studies of genetic markers of reproductive outcome in the Hutterites, we have been analyzing potential risk factors for pregnancy outcomes. In particular, we are interested in the effects of HLA sharing between parents on fetal loss rates. Pregnancy outcome data such as these have two characteristics that create statistical challenges, i.e., repeated observations per couple and between-couple heterogeneity in risk. We critically examine four approaches based on the logistic model for the analysis of this and similar data: 1) unconditional likelihood analysis with and without fixed cluster effects; 2) conditional likelihood analysis; 3) mixed-effects analysis with random cluster effects; and 4) the robust generalized estimating equation (GEE) procedure. Of these approaches, the GEE method of Liang and Zeger would be best suited for the analysis of our data when the question of interest concerns a variable that is constant over all pregnancies, such as HLA sharing. If the question concerns a couple's risk associated with a changing variable such as maternal age, the mixed-effects analysis is the more appropriate.

Cluster Analysis↗
PubMed1991

A proposal for examining and reporting stepwise regressions.

A common mode of regression analysis is a stepwise regression. One of the problems associated with the stepwise algorithm is that the data analyst may wrongly identify the selected variables as the important variables. We propose a simple table as an aid in examining and reporting stepwise regression analyses. The key to our proposal is recognition of 'close alternatives', that is, those variables excluded from selection by the inclusion of another variable. This presentation should encourage the analyst and reader to think in terms of sets of variables that, together, represent factors associated with the outcome.

Adult↗
PubMed1991

Individual bioequivalence: what matters to the patient.

Current procedures for assessing the bioequivalence of two formulations are based on the concept of average bioequivalence. That is, they assess whether the average responses between individuals on the two formulations are similar. We show first that average bioequivalence is not sufficient to assure that an individual patient could be expected to respond similarly to the two formulations. To have such reasonable assurance requires a different notion of bioequivalence; individual (or within-subject) bioequivalence. Second, we propose a simple statistical procedure for assessing individual bioequivalence. This decision rule, TIER (test of individual equivalence ratios) requires the specification of the minimum proportion of subjects in the applicable population for which the two formulations being tested must be bioequivalent (a regulatory decision). The TIER rule is summarized in terms of the minimum number of subjects with bioavailability ratios falling within the specified equivalence interval necessary to be able to claim bioequivalence for given sample size and type I error. We recommend that the corresponding lower bounds (one-sided confidence intervals) for the proportion of bioequivalent subjects be calculated.

Chemistry, Pharmaceutical↗
PubMed1991

A consequence of omitted covariates when estimating odds ratios.

In the epidemiologic literature, one finds three criteria for confounding, which we will call the classical (marginal), operational (change-in-estimate) and conditional criteria. We define mavericks to be covariates that satisfy the operational criterion, but not the classical criterion. We present what is known about the problems of mavericks for estimating odds ratios and clarify the interpretation of odds ratios. Key results are: (1) omitting mavericks biases odds ratios towards 1; (2) omitting mavericks cannot artificially introduce an effect in contrast to omitting classical confounders; (3) the operational criterion for confounding corresponds to the conditional criterion when estimating odds ratios, but for relative risks, there are no mavericks (i.e. the classical and operational criterion correspond); and (4) the interpretation of odds ratios obtained from standard methods is that of comparing proportions, not of individual risk.

Confounding Factors, Epidemiologic↗
PubMed1991

Confidence intervals for seroprevalence determined from pooled sera.

In population surveys of seroprevalence, it may not be most efficient to test all individual samples. The laboratory and statistical issues encountered when one first pools individual samples into groups of samples before laboratory analyses were discussed recently in relation to the seroprevalence of human immunodeficiency virus. In particular, point and confidence interval estimates for seroprevalence from pooled sera were derived. A potential problem with these confidence intervals is that they may contain negative values. This problem is most likely to occur in low-prevalence populations where pooling is most efficient. An alternative method of obtaining confidence intervals that cannot contain negative values is proposed and an example provided.

Confidence Intervals↗
PubMed1991

Design and organization of the herpetic eye disease study (HEDS).

The Herpetic Eye Disease Study (HEDS) includes three double-masked, placebo-controlled clinical trials for potentially blinding herpes simplex virus (HSV) eye infections. One study compares a tapering dosage of topical prednisolone or placebo eye drops for HSV stromal keratitis (HEDS-SKN). Two other trials compare oral acyclovir to placebo capsules for HSV stromal keratitis (HEDS-SKS) or iridocyclitis (HEDS-IRT) in patients on a tapering dosage of topical prednisolone drops. All medications are administered for 10 weeks. Outcome is judged by time to recurrent disease or treatment failure. This paper presents the design, estimated sample size and recruitment as of July 25, 1990.

Acyclovir↗
PubMed1990

Smokeless tobacco use and health effects among baseball players.

The effects of smokeless tobacco (ST) use were studied in 1109 members of major and minor league professional baseball teams during spring training in 1988. The prevalence of current ST use was 39%. The median age at initiation among users was 18 years, and the median duration of use was 5 years. Among users, 75% cited a snuff brand as their usual ST product. Oral leukoplakia was present in 46% (196/423) of current-week ST users and 1.4% (7/493) of nonusers (odds ratio, 60; 95% confidence interval, 28 to 130). Prevalence of oral leukoplakia among ST users increased with hours used per day and decreased with time lapsed since last use, and was higher in snuff users than in chewing tobacco users. Of the subjects with oral leukoplakia who underwent punch biopsy, 91 had benign hyperkeratosis and one had mild dysplasia. Overall prevalence of dental caries, gingivitis, and plaque did not differ between ST users and nonusers. In analyses confined to facial surfaces of mandibular incisor teeth, where ST is most commonly used, there were significant increases among users in both gingival recession and attachment loss. Users of ST did not differ from nonusers in blood pressure, pulse, total or high-density lipoprotein cholesterol level, or white blood cell count, but among users high-density lipoprotein cholesterol levels were inversely associated with serum cotinine levels. The major health effects of ST use among professional baseball players are oral leukoplakia and localized periodontal disease. The study population was young, physically fit, and characterized by relatively moderate short-term ST use.

Adolescent↗
PubMed1990

Consideration of individual bioequivalence.

Current procedures for assessing the bioequivalence of two formulations are based on the concept of average bioequivalence. That is, they assess whether the average responses between individuals on the two formulations are similar. Average bioequivalence, however, is not sufficient to guarantee that an individual patient could be expected to respond similarly to the two formulations. To have reasonable assurance that an individual patient could be switched from a therapeutically successful formulation to a different formulation (e.g., a generic substitute) requires a different notion of bioequivalence. We propose a simple, valid statistical procedure for assessing individual bioequivalence. The decision rule, TIER (Test of Individual Equivalence Ratios), requires the specification of the minimum proportion of subjects in the applicable population for which the two formulations being tested must be bioequivalent (a regulatory decision). The TIER rule is summarized in terms of the minimum number of subjects with bioavailability ratios falling within the specified equivalence interval necessary to be able to claim bioequivalence for given sample size and Type I (alpha) error. We recommend that the corresponding lower bounds (one-sided confidence intervals) for the proportion of bioequivalent subjects be calculated. TIER is partly motivated by the U.S. FDA's 75/75 Rule (at least 75% of the individual subject bioavailability ratios must be within 75-125%). TIER retains the sensible idea of considering the individual ratios but, unlike the 75/75 rule, is a statistically valid procedure.

Humans↗
PubMed1990

Factors associated with obtaining nipple aspirate fluid: analysis of 1428 women and literature review.

Studies of cytologic and biochemical constituents of nipple aspirates of breast fluid have contributed to understanding the natural history of benign and malignant breast disease. We conducted multivariate analyses using 1428 women from a recent case-control study of breast disease to determine which factors were independently associated with the ability to obtain breast fluid from nonlactating women. We then compared results from these analyses to the results from five previous studies that also used the aspiration technique of Sartorius. Four factors were consistently associated across studies with increased ability to obtain breast fluid: 1) age up to 35 to 50 years; 2) earlier age at menarche; 3) non-Asian compared to Asian ethnicity; and 4) history of lactation. Exogenous estrogen use, endogenous estrogen concentrations, phase of menstrual cycle, family history of breast cancer, type of menopause, and less than full-term pregnancy consistently did not influence ability to obtain fluid. New findings from this study shed light on some apparently contradictory findings from the previous studies. In particular, this study showed that the effects of age on ability to obtain fluid appeared to be independent of the effects of menopause. Furthermore, discrepancies in previous findings on the effects of parity on ability to obtain fluid may be explained by our finding that the increased ability to obtain fluid from parous compared to nulliparous women applied only to parous women who had breastfed.

Adult↗