Biomedical subjects

G G Koch

Publications and source records attributed to G G Koch.

At least 37 records · Page 2Linked to original sources

PubMed1999

Gender differences in survival in advanced heart failure. Insights from the FIRST study.

BACKGROUND: Previous natural history studies in broad populations of heart failure patients have associated female gender with improved survival, particularly in patients with a nonischemic etiology of ventricular dysfunction. This study investigates whether a similar survival advantage for women would be evident among patients with advanced heart failure. METHODS AND RESULTS: The study analysis is based on the Flolan International Randomized Survival Trial (FIRST) study which enrolled 471 patients (359 men and 112 women) who had evidence of end-stage heart failure with marked symptoms (60% NYHA class IV) and severe left ventricular dysfunction (left ventricular ejection fraction 18+/-4.9%). A Cox proportional-hazards model, adjusted for age, gender, 6-minute walk, dobutamine use at randomization, mean pulmonary artery blood pressure, and treatment assignment, showed a significant association between female gender and better survival (relative risk of death for men versus women was 2.18, 95% CI 1.39 to 3.41; P<0.001). Although formal interaction testing was negative (P=0.275), among patients with a nonischemic etiology of heart failure, the relative risk of death for men versus women was 3.08 (95% CI 1.56 to 6.09, P=0.001), whereas among those with ischemic heart disease, the relative risk of death for men versus women was 1.64 (95% CI 0.87 to 3.09, P=0.127). CONCLUSIONS: Women with advanced heart failure appear to have better survival than men. Subgroup analysis suggests this finding is strongest among patients with a nonischemic etiology of heart failure.

Aged↗

PubMed1999

Complementary nonparametric analysis of covariance for logistic regression in a randomized clinical trial setting.

In the randomized clinical trial setting, controlling for covariates is expected to produce variance reduction for the treatment parameter estimate and to adjust for random imbalances of covariates between the treatment groups. However, for the logistic regression model, variance reduction is not obviously obtained. This can lead to concerns about the assumptions of the logistic model. We introduce a complementary nonparametric method for covariate adjustment. It provides results that are usually compatible with expectations for analysis of covariance. The only assumptions required are based on randomization and sampling arguments. The resulting treatment parameter is a (unconditional) population average log-odds ratio that has been adjusted for random imbalance of covariates. Data from a randomized clinical trial are used to compare results from the traditional maximum likelihood logistic method with those from the nonparametric logistic method. We examine treatment parameter estimates, corresponding standard errors, and significance levels in models with and without covariate adjustment. In addition, we discuss differences between unconditional population average treatment parameters and conditional subpopulation average treatment parameters. Additional features of the nonparametric method, including stratified (multicenter) and multivariate (multivisit) analyses, are illustrated. Extensions of this methodology to the proportional odds model are also made.

Humans↗

PubMed1999

Nonparametric analysis of covariance for hypothesis testing with logrank and Wilcoxon scores and survival-rate estimation in a randomized clinical trial.

Many clinical trials have time-to-event variables as principal response criteria. When adjustment for covariates is of some importance, the relative role of methods for such analysis may be of some concern. For the Wilcoxon and logrank tests, there is an issue of how covariance adjustment can be nonparametric in the sense of not involving any further assumptions beyond those of the logrank and Wilcoxon test. Also of particular interest in a clinical trial is the estimation of the difference between survival probabilities for the treatment groups at several points in time. As with the Wilcoxon and logrank tests, there is no well known nonparametric way to incorporate covariate adjustment into such estimation of treatment effects for survival rates. We propose a method that enables covariate adjustment for hypothesis testing with logrank or Wilcoxon scores. Related extensions for applying covariate adjustment to estimation of treatment effects are provided for differences in survival-rate counterparts to Kaplan-Meier survival rates. The results represent differences in population average survival rates with adjustment for random imbalance of covariates between treatment groups. The methods are illustrated with a clinical trial example.

Humans↗

PubMed1998

An application of methods for clustered binary responses to a cardiovascular study with small sample size.

This paper discusses statistical methods for a cardiovascular study in which each of eight animals had a dichotomous outcome observed for each of several treatments. There were five treatments in all: shunt, control, two doses of a test drug for potentially causing an unfavorable cardiovascular event, and a combination of the test drug and a counteracting agent. Exact conditional methods were used through LogXact, a statistical software for exact logistic regression and an alternative framework for performing a large class of nonparametric tests performed by StatXact. The results agreed reasonably with asymptotic methods even though the sample size was small.

Animals↗

PubMed1998

A linear model method for rank measures of association from longitudinal studies with fixed conditions (visits) for data collection and more than two groups.

Several statistical methods are available for the analysis of responses with ordinal categories or continuous distributions for the respective visits in longitudinal studies. This paper discusses an alternative nonparametric strategy for studies with more than two groups through Mann-Whitney rank measures of association for all pairs of groups. The proposed method is based on U-statistic theory, and it applies a linear or linear logistic model to the Mann-Whitney estimators for the probabilities of better response for each group relative to each of the others. In addition, the ways of adjusting for covariables and managing stratification factors are explained. Analysis of parallel dose-response relationships for two treatments is illustrated for the proposed method with data from a multicenter study with repeated measurements. A nonparametric estimator for relative potency is provided from the method.

Algorithms↗

PubMed1998

von Willebrand factor does not influence atherogenesis in arteries subjected to altered shear stress.

The role of von Willebrand factor (vWF) in arterial neointimal formation that develops in arteries with altered shear stress was investigated using normal, heterozygous, and homozygous von Willebrand disease pigs (ie, vWD, or lacking vWF) that were fed normal pig chow. Shear stress was applied to carotid and femoral arteries with a Goldblatt clamp for 14 days, producing a > or = 80% stenosis. Neointimal lesion size was measured by computer-assisted morphometry. Expression of proliferative cell nuclear antigen (PCNA) by neointimial and medial cells was used as a relative index of proliferative activity. For shear-stressed arteries, there was no significant difference in the number of smooth muscle cell layers in the lesion, lesion size, and percent of PCNA-positive neointimal or medial cells among normal, heterozygous, and homozygous vWD pigs (P> or =.1, ANOVA). Lesions in pigs that expressed vWF (normals and heterozygotes) contained large amounts of vWF in the neointima, whereas lesions in vWD pigs had no detectable vWF. Moreover, no foam cells were detected in the lesions. Thus, the absence of vWF apparently does not alter the size of lesions in shear-stressed arteries in vWD pigs or the number of neointimal or medial cells expressing PCNA. Mechanism(s) involved with shear-induced modulation of smooth muscle cell proliferation, then, can operate independently of vWF in normolipemic pigs.

Animals↗

PubMed1998

Heart rate variability at rest and during mental stress in patients with coronary artery disease: differences in patients with high and low depression scores.

This study tested the hypothesis that coronary artery disease (CAD) patients with high depressed mood scores differ in sympatho-vagal balance during mental stress compared to patients with low depressed mood scores. Using electrocardiographic monitoring, heart variability data from spectral analysis and hemodynamic parameters were obtained prior to and during mental stress from 34 men and 7 women. A public speaking task was used as the mental stressor. Patients were grouped by a median split of their Minnesota Multiphasic Personality Inventory-Depression score. During mental stress, patients with higher depression scores had greater changes in peak heart rate (p < .05) and low frequency to high frequency power ratio (p < 0.05) than patients with lower scores suggesting a shift toward more sympathetic activity during mental stress. These findings may be related to the reported relation between depression and survival risk in patients with CAD.

Journal Article↗

PubMed1998

An evaluation of Safe Dates, an adolescent dating violence prevention program.

OBJECTIVES: This study assessed the effects of the Safe Dates program on the primary and secondary prevention of adolescent dating violence. METHODS: Fourteen schools were randomly allocated to treatment conditions. Eighty percent (n=1886) of the eighth and ninth graders in a rural county completed baseline questionnaires, and 1700 (90%) completed follow-up questionnaires. RESULTS: Treatment and control groups were comparable at baseline. In the full sample at follow-up, less psychological abuse, sexual violence, and violence perpetrated against the current dating partner were reported in treatment than in control schools. In a subsample of adolescents reporting no dating violence at baseline (a primary prevention subsample), there was less initiation of psychological abuse in treatment than in control schools. In a subsample of adolescents reporting dating violence at baseline (a secondary prevention subsample), there was less psychological abuse and sexual violence perpetration reported at follow-up in treatment than in control schools. Most program effects were explained by changes in dating violence norms, gender stereotyping, and awareness of services. CONCLUSIONS: The Safe Dates program shows promise for preventing dating violence among adolescents.

Adolescent↗

PubMed1997

Unanticipated lessening of the rise in extracellular potassium during ischemia by pinacidil.

BACKGROUND: The efflux of potassium (K) through the ATP-sensitive K channel is considered an important cause of the rise in extracellular K ([K+]e) during no-flow ischemia. We postulated that agents that enhance K conductance in this channel would enhance the rise in [K+]e. METHODS AND RESULTS: We studied the effects of 10 and 25 mumol/L pinacidil, and ATP-sensitive K channel opener that provides metabolic protection to the ischemic myocardium, on the rise in [K+]e recorded by K-sensitive electrodes, the change in action potential duration (APD) recorded by microelectrodes, and the changes in activation during ischemia in in situ pig hearts and Tyrode-perfused rabbit interventricular septa. Pinacidil 25 mumol/L unexpectedly lessened the rise in [K+]e and the activation delay in both preparations. Pinacidil 10 mumol/L had no effect in the rabbit and only a slight effect in the pig. Both concentrations significantly exaggerated the APD shortening induced by ischemia. By varying stimulation frequency, we demonstrated that the rise in [K+]e during ischemia, both before and after pinacidil, correlated with the time that the action potential was at its plateau voltage. CONCLUSIONS: Our results indicate that the rise in [K+]e during ischemia is due to multiple factors, including K conductance across membrane channels, K driving force as reflected by the time that the action potential is at its plateau voltage, and the metabolic effects of ischemia. The unanticipated lessening of the rise in [K+]e by pinacidil reflects the balance of its effects on these several parameters.

Adenosine Triphosphate↗

PubMed1997

Statistical modeling of dose-response relationships in clinical trials--a case study.

This paper presents a model-based assessment of the relationship between the dose of a test treatment and response. The data set used in the analysis describes the results of two clinical trials that were designed to assess the dose-response relationship of a test treatment. The models described in the paper are fit using weighted regression as implemented by the SAS procedure CATMOD. Relationships between weighted regression and other similar procedures are discussed.

Anticholesteremic Agents↗

PubMed1997

Application of rank analysis of covariance methods to analysis of multiple anatomical regions with treatment for seborrheic dermatitis.

This paper presents the advantages of rank analysis of covariance in contrast to the Mantel-Haenszel procedure in the presence of a covariate. In this paper, data from a clinical trial with an indication for seborrheic dermatitis, which afflicts multiple anatomical regions, is presented. This paper presents analysis performed using both the Mantel-Haenszel procedure and rank analysis of covariance for separate anatomical regions, as well as for the combined anatomical regions. The analysis for the combined anatomical regions involves weighted sums over different strata.

Dermatitis, Seborrheic↗

PubMed1997

Statistical strategies for event rate comparisons in dental studies.

Dental researchers are interested in measures of association between explanatory variables and various disease indicators, where both can be measured at the tooth or surface level. The usual chi-square tests for event rate comparisons are inadequate to analyze such data since teeth within the same individual are correlated with one another. This situation may become further complicated when stratification adjustment is of interest, particularly when the stratification factor is also at the tooth or surface level, such as tooth type or presence of previous disease for the tooth. Consequently, statistical methods are needed to control for the correlation of sites in the mouth. A survey sampling approach is suggested; with this method, the sample is managed as a one stage cluster sample of patients to obtain the design base covariance matrix for the cell counts in a contingency table. The covariance matrix for the cell counts can be obtained from statistical software used to analyze data from large sample surveys. Approximate estimates for variance for various measures of association can then be obtained by Taylor series methods. Event rate comparisons through the odds ratio, relative risk, risk difference as well as other measures of association can be made with adjustments for the intra-patient correlation. Methods for summary measures of association across strata are considered as well.

Dental Research↗

PubMed1997

Analytic approaches to longitudinal caries data in adults.

The objective of this paper is to consider current methods for analyzing longitudinal caries data in adults. To illustrate these methods, we used data from the Piedmont dental study, a prospective investigation of the oral health of older adults. Longitudinal dental data sets comprise repeated observations of an outcome (often clustered within randomly selected primary sampling units), and a set of covariates for each of many subjects, in whom clustering can occur as a result of measuring teeth, or surfaces, within people. One objective of statistical analysis is to predict the outcome variable as a function of the covariates, while accounting for the correlation among the repeated observations for a given subject and the effect of clustering within subjects, as well as between subjects within primary sampling units, such as communities, schools, hospitals, or other such units. We considered two statistical approaches: generalized estimating equations and survey regression models. We also examined the impact of varying diagnostic criteria for caries estimation between epidemiologists and clinicians. One approach is to perform the usual time(x) exam score minus time0 score analysis for the baseline and final examinations, while an alternative is to analyze trends among interim examinations. Finally, because caries studies in which the onset of the disease is the endpoint face the problem of censoring due to subject attrition and/or tooth loss, we recommend the incidence density (time-to-event) analytic strategy to address this problem. This approach was found to be most suitable for longitudinal studies of older adults since it accounts for the time each surface remains at risk for the event of interest, making use of interim exam data until the moment the subject and/or the tooth are no longer available for examination. We also included a discussion on biases that occur upon application of the usual methods of estimating caries experience in missing teeth and crowns, which often ignore the classification error in the estimation. We propose a method to adjust for misclassification of the M-component of the DMFS index. In the case where one can observe true reversals or remineralization of caries lesions, we recommend an adjustment formula to account for reversals that are most likely due to examiner misclassification. We provide examples to demonstrate the applicability of the methods for covariates subject to outcome misclassification.

Adult↗

PubMed1997

A study of attachment loss patterns in survivor teeth at 18 months, 36 months and 5 years in community-dwelling older adults.

Most of our knowledge regarding the natural history of periodontitis in adults has come from clinical studies of dental patients. However, it is known that dental patients usually are not representative of what actually happens in the population. This paper presents population-based attachment loss trends in survivor teeth to address the following issues; 1) whether attachment loss during 1 period in time is associated with higher risk for attachment loss at a subsequent period in the same subject; 2) whether sites in survivor teeth with deeper periodontal pockets at baseline are more likely to experience future attachment loss; and 3) whether the effect of regular use of dentists' services on attachment loss are demonstrated in a community-dwelling population. In 1988, the University of North Carolina School of Dentistry initiated the Piedmont 65+ Dental Study, which was designed to elicit 800 dentate respondents in the 5-county area who were examined again at 18, 36 and 60 months. Our findings indicated that, for the 3 time periods investigated, attachment loss during the first period was not related to the incidence of attachment loss at a subsequent period for most people. However, for people who experience multiple episodes, the second episode was likely to immediately follow the first episode. This pattern did not occur at the site level where no site experienced more than 2 successive episodes, and a previous episode did not put a site at higher risk for a subsequent episode. Our data also indicated that both baseline pocket depth and irregular dental visits were positively associated with the proportion of sites that demonstrated break-down over the next 5 yr.

Aged↗

PubMed1997

A 5-year study of attachment loss in community-dwelling older adults: incidence density.

This is the second of three papers that present trends in attachment loss and tooth loss over a 5-yr period in a population of community-dwelling elderly black and whites. The first paper in this series showed that in addition to subject attrition during the 5 yr of the study, teeth also were lost. This loss of subjects and teeth resulted in trends that were not always consistent over time, because people were lost from the study and teeth with more active and advanced periodontal disease were more likely to be lost. In these instances, the incidence density (time-to-event) analytic strategy is useful. Incidence density is the average rate of occurrence for a fixed follow-up period. In 1988, the University of North Carolina School of Dentistry initiated the Piedmont 65+ Dental Study, which was designed to elicit 800 dentate respondents in the 5-county area who were examined again at 18, 36 and 60 months. Our findings indicated that for every 1000 sites followed for 1 yr in this population, 20.6 sites will experience attachment loss of 3+mm. Incidence densities varied greatly by subgroup, indicating that certain characteristics predispose sites for attachment loss. A multivariate logistic regression model indicated that people who are smokers, Porphyromonas gingivalis positive, have 5 or more missing teeth, are not high school graduates, and have not had a dental visit in the last 5 yr are at higher risk of attachment loss. Posterior teeth and mesiobuccal sites are at higher risk. We conclude that incidence density analyses are useful for longitudinal periodontal data and we illustrate the use of incidence density rates to plan clinical trials.

Aged↗

PubMed1997

A 5-year study of attachment loss and tooth loss in community-dwelling older adults.

Tooth loss is a widely recognized endpoint measure for the effects of periodontal diseases and the impact of periodontal therapy. In fact, traditional clinical measures of periodontal status often are considered to be surrogate endpoints in that they are assumed to be related to tooth loss. However, the strength of the relationship between attachment loss and tooth loss in a representative population of untreated subjects has not been studied extensively. The purpose of this paper is to present the trends in attachment loss over a 5-yr period in a population of community-dwelling elderly blacks and whites. Specifically, this paper presents attachment loss trends both at the person and tooth level to address the following issues; 1) whether teeth that experience attachment loss during 1 time period are more likely to be lost at the next time period; and 2) given similar levels of attachment loss, why are some people more likely to lose teeth? In 1988, the University of North Carolina School of Dentistry initiated the Piedmont 65+ Dental Study, which was designed to elicit 800 dentate respondents in the 5-country area who were examined again at 18, 36 and 60 months. Our findings indicated that teeth with poorer attachment level at baseline had a higher probability of being lost during the next 5 yr and teeth that experienced attachment loss during a time period were more likely to be lost during the next time period than teeth without additional attachment loss. In addition, it appears that there are person-level characteristics associated with increasing tendency towards tooth loss in people with similar periodontal status, a finding that may clarify the relationship between attachment loss and tooth loss.

Activities of Daily Living↗

PubMed1997

Categorical data analysis in public health.

A greater variety of categorical data methods are used today than 15 years ago. This article surveys categorical data methods widely applied in public health research. Whereas large sample chi-square methods, logistic regression analysis, and weighted least squares modeling of repeated measures once comprised the primary analytic tools for categorical data problems, today's methodology is comprised of a much broader range of tools made available by increasing computational efficiency. These include computational algorithms for exact inference of small samples and sparsely distributed data, conditional logistic regression for modeling highly stratified data, and generalized estimating equations for cluster samples. The latter, in particular, has found wide use in modeling the marginal probabilities of correlated counted, binary, and multinomial outcomes. The various methods are illustrated with examples including a study of the prevalence of cerebral palsy in very low birthweight infants and a study of cancer screening in primary care settings.

Algorithms↗

PubMed1997

Three-year coronal caries incidence and risk factors in North Carolina elderly.

The data presented in this paper are from the Piedmont 65+ Dental Study (1988-1991), designed to assess the levels of coronal and root caries, periodontal disease, tooth loss, and a variety of dental health-related needs among a representative sample of 234 black and 218 white noninstitutionalized older adults in North Carolina. Of the 452 subjects followed for 3 years, 45% of blacks and 59% of the whites developed new coronal caries when caries was defined as decayed and filled surfaces, decayed root fragments, and crowned surface (p = 0.022). The annualized rate of caries increment for blacks and whites was 0.8 and 1.6 surfaces per 100 at risk (p < 0.001), respectively. The mean 3-year net increment per subject, excluding newly crowned surfaces, was 1.6 and 2.1 (p = 0.025), respectively. Whites had more newly filled and crowned surfaces, whereas blacks had more newly decayed surfaces and more decayed root fragments. Logistic regression models using baseline explanatory variables showed factors related to coronal caries differed between blacks and whites. For blacks, having more teeth, higher concentration of lactobacilli in stimulated saliva, more decayed and filled root surfaces, and smoking were related to the development of new coronal DFS (mostly D). For whites, having more coronal surfaces at risk and having more physical health problems but not seeking medical care in the past 6 months were related to the development of new coronal DFS (mostly F). The study showed the caries attack rate to be higher for whites than blacks, mainly as a result of more crown restorations, whereas blacks appeared to be at greater risk for incident lesions. Thus, in order to obtain more realistic figures for caries risk groups, coronal caries increment can and should be presented including and excluding crowns, since the utilization of dental services is likely to differ between groups of older adults.

Black or African American↗