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R F Woolson

Publications and source records attributed to R F Woolson.

At least 55 records · Page 3Linked to original sources
PubMed1993

On the efficacy of the rank transformation in stepwise logistic and discriminant analysis.

We have evaluated the performance of four stepwise variable selection procedures commonly used in medical and epidemiologic research. The four procedures are discriminant and logistic regression and their rank transformed versions, where the independent variables are replaced by their ranks. We generated, by computer, data for two groups from several distributions with a variety of sample sizes and covariance matrices. The two ranking procedures each increased the chance of correctly selecting those variables related to group membership for data generated from log-normal or contaminated distributions. For normally distributed data the ranking procedure had little effect on variable selection. Rank transformed discriminant analysis and rank transformed logistic regression were equally effective in selecting variables when sample sizes exceeded 100. Rank transformed discriminant analysis was superior for smaller data sets. We discuss the implications of the results of this study for clinical and epidemiologic research.

Case-Control Studies↗
PubMed1993

The prognostic value of tumor blood vessel morphology in primary uveal melanoma.

BACKGROUND: It is possible to identify at least nine vascular patterns in melanomas of the ciliary body and choroid from histologic sections. An association between the presence of at least one closed vascular loop and death from metastases was shown in a matched-pair, case-control study of 40 patients whose eyes were removed for ciliary body or choroidal melanomas. METHODS: Two independent observers who were masked to the follow-up of patients examined histologic preparations of 234 eyes removed for ciliary body or choroidal melanomas for the presence of each of the tumor vascular patterns. Statistical analyses included tests for interobserver reliability, Kaplan-Meier survival curves, and the fitting of Cox regression models. RESULTS: The detection of each of the nine vascular patterns is highly reproducible. The Cox model indicates that the presence of vascular networks, defined as at least three back-to-back closed vascular loops, is the feature most strongly associated with death from metastatic melanoma. Other significant factors in the Cox model include (in descending order of importance) largest tumor dimension, mitoses, the parallel with cross-linking vascular pattern, age, the presence of tumor-infiltrating lymphocytes, and male gender. CONCLUSIONS: The presence of vascular networks provides the most significant association with death from metastatic melanoma of all variables tested. The presence of this pattern should be recorded on pathology reports. If it becomes possible to detect this vascular pattern clinically using a noninvasive imaging technique, then ophthalmologists may be able to determine the likely biologic behavior of a melanoma before resorting to the removal of tissue.

Adolescent↗
PubMed1993

Interphysician agreement in the diagnosis of subtypes of acute ischemic stroke: implications for clinical trials. The TOAST Investigators.

To test interphysician agreement on the diagnosis of subtype of ischemic stroke, we sent subtype definitions and 18 case summaries (clinical features and pertinent laboratory data) to 24 neurologists who have a special interest in stroke, and asked them to determine the most likely subtype diagnosis. The overall agreement was 0.64 (Kappa [K] = 0.54). Interphysician agreement was highest for the diagnoses of stroke secondary to cardioembolism (K = 0.75) or to large-artery atherosclerosis (K = 0.69). Individual physicians varied widely; four agreed with the consensus diagnosis in all 18 cases, while six others disagreed with the consensus diagnosis in three to five cases. Our level of interphysician agreement is greater than that reported in other studies and was substantial. However, despite using subtype definitions and being given extensive information often not available in the acute setting, physicians still disagree about the etiology of stroke, particularly in regard to stroke due to small-artery occlusion or of undetermined etiology. Physicians seem reluctant not to attribute stroke to a specific etiology. The uncertainty about subtype diagnosis will affect interpretation of the results of clinical trials in patients selected by the subtype of ischemic stroke and also suggests that results of treatment as affected by subtype should be cautiously interpreted unless efforts to assure uniformity are included in the trial's operations. Refinement of algorithms for determining subtype of ischemic stroke do improve interphysician agreement. Such criteria should be applied strictly, and trials should include measures to assure the most uniform diagnosis of stroke subtype possible.

Aged↗
PubMed1993

Adequacy of prenatal care and risk of pre term rupture of amniotic sac membranes.

Premature rupture of amniotic membranes (PROM) is associated with perinatal morbidity and mortality. A matched case-control study was undertaken to determine whether adequacy of prenatal care was associated with increased risk for PROM. Three study groups were defined, consisting of women delivering pre term with PROM, full term with PROM, and pre term without PROM. Cases were singly matched by race, age, and parity with women having full term deliveries without PROM. Data were collected by face-to-face structured interviews with eligible subjects and by medical records abstraction. Conditional multiple logistic regression indicated that among women with inadequate levels of prenatal care during pregnancy the risk for pre term PROM was 3.11 (CI = 1.10-8.78) and for pre term without PROM 2.18 (CI = 1.05-4.53) times higher than for their matched controls, even when adjusted for other sociodemographic, behavioral, index pregnancy, and medical history factors. We conclude that inadequate prenatal care may be a marker for less healthy behaviors, lifestyles, and environmental factors among women at increased risk for pre term delivery.

Adolescent↗
PubMed1992

A double-blind, placebo-controlled multicenter study of tacrine for Alzheimer's disease. The Tacrine Collaborative Study Group.

BACKGROUND: In Alzheimer's disease, there is a marked decline in the function of cholinergic neurons in the brain. However, studies of treatment with cholinesterase inhibitors have produced conflicting results. We conducted a multicenter trial to evaluate whether the cholinesterase inhibitor tacrine (1,2,3,4-tetrahydro-9-acridinamine monohydrochloride monohydrate) could improve cognition in patients with Alzheimer's disease. METHODS: Of 632 eligible patients with probable Alzheimer's disease, 215 improved while receiving tacrine during a preliminary crossover phase to determine responsiveness and the best dose. The 215 patients were randomly assigned to receive either placebo or their best dose of tacrine (10 or 20 mg four times a day) in a six-week, double-blind trial. The primary measures of efficacy were the cognitive subscale of the Alzheimer's Disease Assessment Scale and the Clinical Global Impression of Change scale; the secondary measures included the Mini-Mental State Examination and the assessment of the activities of daily living. RESULTS: At the end of the six-week trial, the patients receiving tacrine had a mean adjusted cognitive-subscale score of 30.3 (Alzheimer's Disease Assessment Scale) as compared with 32.7 in patients receiving placebo. This represents a smaller decline (by 2.4 points) in cognitive performance in the tacrine group (P < 0.001). There were no differences between the groups in their global-rating scores. The tacrine group had a significantly smaller decline in the activities of daily living. The results of the Mini-Mental State Examination favored tacrine, but the differences were small and not statistically significant (a score of 16.0 with tacrine vs. 15.3 with placebo; P = 0.08). Gastrointestinal symptoms, elevation of aminotransferase levels, and headache were the most frequent side effects; all could be reversed by reducing the dose or discontinuing treatment. CONCLUSIONS: In this short-term study in patients with Alzheimer's disease who were selected for apparent responsiveness to tacrine, treatment with tacrine resulted in a statistically significant reduction in the decline of cognitive function, although this reduction was not large enough to be detected by the study physicians' global assessments of the patients.

Activities of Daily Living↗
PubMed1992

A comparison of several tests for censored paired data.

This paper reviews several tests for censored paired data and uses Monte Carlo methods to evaluate their sizes and powers. Each of the tests maintains its size. The Akritas test and the paired Prentice-Wilcoxon test are somewhat more powerful than the Gehan statistic or the generalized signed rank test for most of the distributions studied. If the survival times follow an exponential distribution, then the Gehan and the generalized signed rank tests are more powerful against a location shift alternative.

Computer Simulation↗
PubMed1992

Application of empirical Bayes inference to estimation of rate of change in the presence of informative right censoring.

We apply parametric empirical Bayes inference of Morris to the estimation of rate of change from incomplete longitudinal studies where the right censoring process is considered informative, that is, the length of time the subjects participate in the study is associated with level of the study variable. Ignoring such an association can result in a biased estimate of rate of change. The proposed method provides estimates of rate of change for individual subjects as well as for the entire group, adjusted for informative right censoring. The method is considered more robust than those based on a specific parametric model for the censoring distribution. Under non-informative right censoring these estimators of slopes are equivalent to the Bayes estimators derived by Fearn. We illustrate the method with an example involving renal transplant data. We evaluate the method's performance through a simulation study.

Bayes Theorem↗
PubMed1992

The morphologic characteristics of tumor blood vessels as a marker of tumor progression in primary human uveal melanoma: a matched case-control study.

Nine morphologic patterns of tumor vessels were identified in eyes removed for ciliary body or choroidal melanoma by the examination of tissue sections stained with fluorescein-conjugated Ulex europaeus I using laser scanning confocal microscopy. This technique also highlights intravascular tumor invasion. Each of these nine morphologic patterns of tumor vessels also may be demonstrated by a modification of the periodic acid-Schiff reaction, viewed with a green narrow band pass filter, but this modified histochemical technique does not accurately identify intravascular tumor invasion. Most tumors have a heterogeneous distribution of vascular patterns. Melanomas in two groups of 20 tumors each were matched by tumor size and location (one group of tumors from patients who survived at least 15 years free of metastatic melanoma after enucleation and one group of tumors from patients who died of metastatic melanoma). A matched case-control analysis indicates that the presence of at least one closed vascular loop in a uveal melanoma is the most significant vascular pattern associated with death from metastatic melanoma after enucleation. Closed loops are associated with other histologic features that are predictive of an unfavorable outcome after enucleation: epithelioid cells and mitotic figures. In this preliminary study the formation of closed vascular loops is a marker of tumor progression in ciliary body and choroidal melanomas.

Adult↗
PubMed1992

Studies of Org 10172 in patients with acute ischemic stroke. TOAST Study Group.

This report presents data from pilot studies of Org 10172 in the management of patients with acute ischemic stroke. The studies have established a potentially optimal dosage and treatment regimen and have provided information for the development of a large randomized trial. The trial of Org 10172 in acute stroke treatment is now underway in the United States.

Brain Ischemia↗
PubMed1992

Dietary habits, prepregnancy weight, and weight gain during pregnancy. Risk of pre term rupture of amniotic sac membranes.

BACKGROUND: Premature rupture of amniotic sac membranes (PROM) is associated with perinatal morbidity and mortality. A matched case-control study was undertaken to determine whether dietary habits, prepregnancy weight, and weight gain during pregnancy were associated with increased risks for PROM. METHODS: Three study groups were defined, consisting of women delivering pre term with PROM (PP), full term with PROM (FP), and pre term without PROM (PWP). Cases were singly matched by race, age, and parity with women having full term deliveries without PROM. Data were collected by face-to-face structured interviews with eligible subjects and by medical records abstraction. RESULTS: Conditional multiple logistic regression indicated that during pregnancy, PP cases were significantly more likely to have gained less than 21 pounds (9.5 kg) (OR = 2.7, CI = 1.14-6.36) and were only half as likely as controls to have improved their diet (OR = 0.43, CI = 0.18-0.99) while controlling for cigarette smoking, urinary tract infection, chorioamnionitis, chlamydia, and a history of previous PROM. FP cases were significantly less likely than controls to have gained 31-40 pounds (14-18 kg) while pregnant (OR = 0.56, CI = 0.33-0.94) and were significantly more likely than controls to have a somewhat inadequate pregnancy diet (OR = 2.05, CI = 1.11-3.77) while controlling for a history of previous PROM. PWP cases were significantly less likely to have gained 31-40 pounds (14-18 kg) (OR = 0.42, CI = 0.21-0.84) or greater than 40 pounds (18 kg) (OR = 0.37, CI = 0.17-0.80) while pregnant or to have had adequate dairy products intake (OR = 0.60, CI = 0.36-0.99) while controlling for cigarette usage. CONCLUSION: Maternal dietary habits, weight gain during pregnancy, and supplement intake are associated with the occurrence of both pre term and full term PROM and pre term delivery without PROM.

Adult↗
PubMed1990

Variability in expression of common fragile sites: in search of a new criterion.

Fragile sites are nonrandom, heritable sites on chromosomes that can be induced to form gaps, breaks, and rearrangements under specific conditions. There is currently no established criterion to define a common fragile site. We applied seven published criteria to our data from three groups of subjects: (1) three pairs of like-sexed twins, (2) four unaffected von Hippel-Lindau (VHL) family members, and (3) six patients affected with VHL disease. Substantial differences were present in the numbers of sites considered positive by these criteria. While some of this variability can be attributed to technical factors, our data illustrate the problems in comparing results from different studies to assess the significance of fragile sites. A recently published criterion is based upon the Poisson distribution. We found this criterion to be flawed in its presentation, and furthermore, the Poisson distribution did not provide an adequate approximation to our data. We propose here an alternative approach based upon the negative binomial distribution.

Binomial Distribution↗
PubMed1990

Statistical analysis of K 2 x 2 tables: a comparative study of estimators/test statistics for association and homogeneity.

In order to control for confounding variables, epidemiologists often obtain data in the form of a 2 x 2 table. One variable is usually the disease status, while the other variable represents a dichotomous exposure variable that is suspected of being a risk factor. If a confounding variable is present, the data are often stratified into several 2 x 2 tables. The objectives of the analysis are to test for the association between the suspected risk factor and the disease and to estimate the strength of this relationship. Before estimating a common odds ratio, it is important to check whether the odds ratios are homogeneous. This paper presents the results of a Monte Carlo study that was performed to determine the size and power of a number of tests of association and homogeneity when the data are sparse. We also evaluated the performance of three estimators of the common odds ratio. For the Monte Carlo studies, equal numbers of cases and controls were used in a wide variety of sparse data situations. On the basis of these studies, we recommend the Breslow-Day test for nonsparse data, and the T4 and T5 statistics for sparse data to test for homogeneity. The Mantel-Haenszel test of association is recommended for sparse and nonsparse data sets. With sparse data, none of the odds ratio estimators are entirely satisfactory.

Case-Control Studies↗
PubMed1989

In-vitro susceptibility of nosocomial gram-negative bloodstream pathogens to quinolones and other antibiotics--a statistical approach.

We examined the in-vitro activity of 12 antibiotics against Gram-negative bacillary isolates from 141 distinct episodes of nosocomial bloodstream infection occurring from July 1984 through November 1986. At least ten strains of each of the seven most frequently encountered species were tested. Relative potency was carefully assessed by extending the concentrations from 0.004 to 64 mg/l in microdilution tests performed in duplicate. We estimated MIC50 and MIC90 and, importantly, calculated 95% confidence intervals (CI95) for MIC90. Against all isolates, ciprofloxacin, the most potent antibiotic, had an MIC50 of 0.03 and an MIC90 of 0.13 (CI95 0.11 to 0.16 mg/l). Norfloxacin and enoxacin had MIC90 of 0.50 and 0.71 mg/l, respectively. Imipenem, ceftazidime, aztreonam, and cefoperazone had MIC90 of 1.0, 2.0, 5.3, and 5.7 mg/l, respectively. Both cefotaxime and ceftriaxone had MIC90 of 16 mg/l (CI95 13-19.7 mg/l). For tobramycin, gentamicin and amikacin, the MIC90 values were 1.4, 5.7, and 8 mg/l, respectively. Against Pseudomonas aeruginosa (n = 26), Serratia marcescens (n = 19), and Klebsiella pneumoniae (n = 26), the CI95s about the MIC90 for ciprofloxacin were 0.31-0.81, 0.07-0.23, and 0.04-0.10 mg/l, respectively. For optimal comparison of antibiotics used to treat hospital-acquired bacteraemias, only clinically significant nosocomial bloodstream isolates should be studied with regard to their antibiotic susceptibilities; the isolates should be unique (only one isolate per episode of bacteraemia occurring over a defined period of time); an adequate number of isolates of a particular species should be studied; MICs should be determined over a wide range of concentrations; and both the MIC90 and the CI95 should be reported.

4-Quinolones↗
PubMed1989

Hospital-acquired pneumonia. Attributable mortality and morbidity.

A total of 1,001 consecutive episodes of nosocomial pneumonia in 901 patients was identified by routine surveillance at the University of Virginia Medical Center between 1979 and 1983 (8.6 episodes/1,000 admissions). When only initial episodes were examined, 890 patients comprised the study sample. The overall case fatality rate was 30%. Stepwise logistic regression indicated that time from admission to pneumonia (p = 0.0006), age (p less than 0.0001), prior use of mechanical ventilation (p = 0.0032), and neoplastic disease (p = 0.0062) were associated with mortality. Multiple regression analysis indicated that the factors associated with increased length of hospitalization included posttracheostomy status (p = 0.0001), prior mechanical ventilation (p = 0.0001), immunosuppressive or leukopenic status (p = 0.0009), nasogastric intubation (p = 0.0003), and prior bacteremia (p = 0.0127). A sampled, individually matched cohort study (n = 74 pairs) was conducted to determine the proportion of mortality in cases that was attributable to infections (33%) and to determine excess hospital stay (seven days) among the patients with nosocomial pneumonia. Excess stay was statistically significant (p less than 0.0001), but proportional mortality was only marginally significant (p = 0.0892). Our findings suggest that nosocomial pneumonia accounts for approximately 33% of the crude mortality and contributes significantly to the economic burden associated with prolonged hospitalization.

Cohort Studies↗
PubMed1989

Perspectives on statistical significance testing.

The question of whether statistical significance testing should be used for the analysis of public health and epidemiologic data has received considerable attention in recent years. In this paper we have described some of the arguments for and against the use of hypothesis testing for the analysis of biomedical data. In addition, we have reviewed the literature from related fields, in particular sociology and psychology, in which similar discussions have taken place within the last 30 years. Many of the significance testing criticisms in these scientific fields have been raised in the more recent discussions taking place in the biomedical field. We present an example that emphasizes the use of both confidence interval estimation and significance testing. The example is particularly pertinent because it represents a more complex problem than has generally been discussed by critics of significance testing. Much of the discussion on this topic has focused on simple data analysis, such as the analysis of a 2 x 2 table or problems involving simple linear regression. Most epidemiologic data are far more complicated and warrant the use of both confidence interval estimation and significance testing for statistical analysis. Both of these techniques have no doubt been misused in the analysis of data. These misuses may have arisen from a lack of understanding of the role of statistical methods in data analysis and the choice of such methods for data analysis. If used prudently and judiciously, significance testing can help reduce the number of variables involved in a statistical analysis, thereby resulting in shorter confidence intervals for the models presented. Both significance testing and confidence interval estimation can serve and have served very useful functions for the analysis of public health and biomedical data.

Data Interpretation, Statistical↗
PubMed1989

A Monte Carlo investigation of homogeneity tests of the odds ratio under various sample size configurations.

Epidemiologic data for case-control studies are often summarized into K 2 x 2 tables. Given a fixed number of cases and controls, the degree of sparseness in the data depends on the number of strata, K. The effect of increasing stratification on size and power of seven tests of homogeneity of the odds ratio is studied using Monte Carlo methods. In all the designs considered here, the numbers of cases and controls per stratum are the same. Considering both size and power in non-sparse-data settings, we recommend the Breslow-Day statistic (1980, Statistical Methods in Cancer Research, 1. The Analysis of Case-Control Studies, p. 142; Lyon: International Agency for Research on Cancer) for general use. In sparse-data settings the T4 statistic of Liang and Self (1985, Biometrika 72, 353-358) performs the best when all tables, regardless of sample size, have odds ratios generated from the same distribution. In sparse-data settings characterized by a large table with an odds ratio of 1 and many small tables with odds ratios greater than 1, the T5 statistic of Liang and Self (1985) performs the best. One of the most important results of this study is the generally low power for all homogeneity tests especially when the data are sparse.

Computer Simulation↗
PubMed1989

Risk factors for hospital-acquired candidemia. A matched case-control study.

Nosocomial candidemia has become an important infection not only because of an apparently increasing incidence but also because of its high fatality rate. We studied 28 risk factors through a matched case-control study that included 88 pairs of patients hospitalized between July 1983 and December 1986. The strongest single risk factor found in the univariate analysis was the number of prior antibiotics administered: the exposure odds ratio (OR) was 12.50 when patients who received three to five antibiotics were compared with those who received none to two antibiotics. A multiple logistic regression analysis using a conditional likelihood method was performed to evaluate several risk factors simultaneously. The final model selected by a stepwise procedure included the following variables: number of antibiotics received prior to infection (OR, 1.73 per unit increase), isolation of Candida species from sites other than blood (OR, 10.37), prior hemodialysis (OR, 18.13), and prior use of a Hickman catheter (OR, 7.23). It remains to be shown in controlled clinical trials whether limiting the number of antibiotics or instituting prophylaxis and/or early treatment for high-risk patients will reduce the incidence of nosocomial candidemia.

Anti-Bacterial Agents↗