Biomedical subjects

S R Lipsitz

Publications and source records attributed to S R Lipsitz.

At least 37 records · Page 2Linked to original sources

PubMed1997

Arsenic in drinking water and incidence of urinary cancers.

The associations between arsenic ingestion and cancers of the bladder and kidney have been documented in Taiwan. To evaluate further such associations for urinary cancers of various cell types, we conducted an ecologic study encompassing 243 townships using cancer registry data of patients diagnosed between 1980 and 1987. We used the proportions of wells with various specified arsenic levels in each township as indicators of exposure and evaluated the effects of urbanization and smoking by an urbanization index and the number of cigarettes sold per capita. In both genders, we observed associations of high arsenic levels in drinking water with transitional cell carcinomas of the bladder, kidney, and ureter and all urethral cancers combined. We also observed such associations in adenocarcinomas of the bladder in males, but not in squamous cell carcinomas of the bladder or renal cell carcinomas or nephroblastomas of the kidney. There was also a positive association between the urbanization index and transitional cell carcinomas of the ureter in males. The number of cigarettes sold per capita was not a good predictor for urinary cancers. The results indicate that the carcinogenicity of arsenic may be cell type specific.

Adolescent↗

PubMed1997

Weighted estimating equations with nonignorably missing response data.

We propose weighted estimating equations for data with nonignorable nonresponse in order to reduce the bias that can occur with a complete case analysis. A survey concerning medical practice guidelines, malpractice litigation, and settlement provides the framework. The survey was sent to recipients in two waves: those who responded on the first or second wave are used to estimate a nonignorable nonresponse model, while the fraction of recipients who never responded is used to allow the percentage of missing data to change with each wave. We use the structure of the GEE of Liang and Zeger (1986, Biometrika 73, 13-22), adding weights equal to the inverse probability of being observed. We present simulations demonstrating the bias that can occur with an unweighted analysis and use the survey data to illustrate the methods.

Bias↗

PubMed1996

Initial results of a phase II trial of high dose radiation therapy, 5-fluorouracil, and cisplatin for patients with anal cancer (E4292): an Eastern Cooperative Oncology Group study.

PURPOSE: A prospective clinical trial was performed to assess the response and toxicity associated with the use of high dose radiation therapy, 5-fluorouracil, and cisplatin in patients with anal cancer. METHODS AND MATERIALS: Patients with anal cancer without distant metastasis were eligible for this study. Radiation therapy consisted of 59.4 Gy in 33 fractions; a 2 week break in treatment was taken after 36 Gy had been given. A treatment of 5-fluorouracil, 1,000 mg/m2 per day intravenously, was given for the first 4 days of radiation therapy, and cisplatin, 75 mg/m2 intravenously, was given on day 1 of radiation therapy. A second course of 5-fluorouracil and cisplatin was given after 36 Gy of radiation, when the radiation therapy was resumed. RESULTS: Nineteen patients entered this study and received treatment. Thirteen (68%) had a complete response, 5 (26%) had a partial response, and 1 (5%) had stable disease. The patient with stable disease and one of the patients with a partial response had complete disappearance of tumor more than 8 weeks after completion of radiation therapy. Fifteen patients had toxicity of Grade 3 or higher: the worst toxicity was Grade 3 in eight patients, Grade 4 in six patients, and Grade 5 in one patient. The most common form of toxicity of Grade 3 or higher was hematologic. The one lethal toxicity was due to pseudomembranous colitis, which was a complication of antibiotic therapy for a urinary tract infection. CONCLUSION: Radiation therapy, cisplatin, and 5-fluorouracil resulted in an overall response rate of 95%. Significant toxicity occurred, an indication that this regimen is near the maximal tolerated dose. A Phase III clinical trial is planned in which radiation therapy, cisplatin, and 5-fluorouracil will be used as an experimental arm.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1996

Using the EM-algorithm for survival data with incomplete categorical covariates.

Incomplete covariate data is a common occurrence in many studies in which the outcome is survival time. With generalized linear models, when the missing covariates are categorical, a useful technique for obtaining parameter estimates is the EM by the method of weights proposed in Ibrahim (1990). In this article, we extend the EM by the method of weights to survival outcomes whose distributions may not fall in the class of generalized linear models. This method requires the estimation of the parameters of the distribution of the covariates. We present a clinical trials example with five covariates, four of which have some missing values.

Algorithms↗

PubMed1996

The score test for independence in R x C contingency tables with missing data.

In this paper, the score test statistic for testing independence in R x C contingency tables with missing data is proposed. Under the null hypothesis of independence, the statistic has an approximate chi-squared distribution with (R - 1)(C - 1) degrees of freedom. The proposed test statistic is quite similar to the Pearson chi-squared statistic with complete data and, unlike the likelihood ratio statistic for testing independence, its computation is simple and noniterative. In addition, a score test statistic is proposed for testing independence when the rows and columns of the R x C table are ordinal. Finally, extensions of the score statistics to test for conditional independence in a set of (R x C) contingency tables with missing data are described. This yields score test statistics that are natural extensions of the Mantel-Haenszel statistic. An example, using a subset of data from the Six Cities Study, is presented to illustrate the methods.

Air Pollution↗

PubMed1996

Estimating equations for measures of association between repeated binary responses.

Moment-based methods for analyzing repeated binary responses using the marginal odds ratio as a measure of association have been proposed by a number of authors. Carey, Zeger, and Diggle (1993, Biometrika 80, 517-526) have recently described how the marginal odds ratio can be estimated using generalized estimating equations (GEE) based on conditional residuals (deviations about conditional expectations). In this paper, we show that other measures of association between pairs of binary responses, e.g., the correlation, can also be estimated using conditional residuals. We demonstrate that the estimator of the correlation based on conditional residuals is nearly efficient when compared with maximum likelihood or second order estimating equations (GEE2) except when the correlation is large. This estimator also yields more efficient estimates of the correlation than the usual GEE estimator that is based on unconditional residuals. Furthermore, the gains in efficiency can be quite considerable when some of the responses are missing or incomplete, or, alternatively, when cluster sizes are unequal (in the clustered data setting).

Air Pollution↗

PubMed1996

Parameter estimation from incomplete data in binomial regression when the missing data mechanism is nonignorable.

We propose a method for estimating parameters in binomial regression models when the response variable is missing and the missing data mechanism is nonignorable. We assume throughout that the covariates are fully observed. Using a logit model for the missing data mechanism, we show how parameter estimation can be accomplished using the EM algorithm by the method of weights proposed in Ibrahim (1990, Journal of the American Statistical Association 85, 765-769). An example from the Six Cities Study (Ware et al., 1984, American Review of Respiratory Diseases 129, 366-374) is presented to illustrate the method.

Air Pollution↗

PubMed1996

A jackknife estimator of variance for Cox regression for correlated survival data.

Studies in the health sciences often give rise to correlated survival data. Wei, Lin, and Weissfeld (1989, Journal of the American Statistical Association 84, 1065-1073) and Lee, Wei, and Amato (1992, in Survival Analysis: State of the Art) showed that, if the marginal distributions of the correlated survival times follow a proportional hazards model, then the estimates from Cox's partial likelihood (Cox, D.R., 1972, Journal of the Royal Statistical Society, Series B 24, 187-220), naively treating the correlated survival times as independent, give consistent estimates of the relative risk parameters. However, because of the correlation between survival times, the inverse of the information matrix may not be a consistent estimate of the asymptotic variance. Wei et al. (1989) and Lee et al. (1992) proposed a robust variance estimate that is consistent for the asymptotic variance. We show that a "one-step" jackknife estimator of variance is asymptotically equivalent to their variance estimator. The jackknife variance estimator may be preferred because an investigator needs only to write a simple loop in a computer package instead of a more involved program to compute Wei et al. (1989) and Lee et al.'s (1992) estimator.

Acquired Immunodeficiency Syndrome↗

PubMed1995

Results of combined modality therapy for patients with anal cancer (E7283). An Eastern Cooperative Oncology Group study.

BACKGROUND: This prospective study assessed combined modality therapy of patients with International Union Against Cancer classification T1-4 N0 M0 anal cancer. METHODS: Protocol therapy consisted of a dose of 4000 cGy to the pelvis, anus, and perineum, followed by a 1000-1300 cGy boost. Infusions of 5-fluorouracil and mitomycin-C were administered when radiation therapy began. A second infusion of 5-fluorouracil was administered 28 days later. Biopsy was performed 6-8 weeks after completion of treatment. Positive biopsy findings resulted in abdominal-perineal resection. RESULTS: Survival at 7 years for 50 eligible patients was 58%. White patients and those with favorable performance status had significantly better survival. Of the 46 patients evaluable for response, 34 had a complete response, 11 had a partial response, and 1 had no response. Seven-year survival for partial responders was 53%. Freedom from locoregional progression was 80% at 7 years. CONCLUSION: Treatment with a combination of chemotherapy and radiation therapy is effective for patients with anal cancer. The investigation of methods of improving therapy is warranted.

Adult↗

PubMed1995

Female sex and higher drug dose as risk factors for late cardiotoxic effects of doxorubicin therapy for childhood cancer.

BACKGROUND: Late cardiotoxic effects of doxorubicin are increasingly a problem for patients who survive childhood cancer. Cardiotoxicity is often progressive, and some patients have disabling symptoms. Our objective was to identify risk factors for late cardiotoxicity. METHODS: We examined echocardiograms from 120 children and adults who had received cumulative doses of 244 to 550 mg of doxorubicin per square meter of body-surface area for the treatment of acute lymphoblastic leukemia or osteogenic sarcoma in childhood, a mean of 8.1 years earlier. Measurements of blood pressure and left ventricular function, contractility (measured as the stress-velocity index), end-diastolic posterior-wall thickness, end-diastolic dimension, mass, and afterload (measured as end-systolic wall stress) were compared with sex-specific values from a cohort of 296 normal subjects. RESULTS: All echocardiographic measurements were abnormal at follow-up a minimum of two years after the end of therapy, with more frequent and severe abnormalities in female patients. In a multivariate analysis, female sex and a higher cumulative dose of doxorubicin were associated with depressed contractility (P < or = 0.001), and there was an interaction between these two variables. Independent and significant associations were found between a higher rate of administration of doxorubicin and increased afterload (P < or = 0.001), left ventricular dilatation, and depressed left ventricular function; between a higher cumulative dose and depressed left ventricular function (P < or = 0.001); between a younger age at diagnosis and reduced left-ventricular-wall thickness and mass and increased afterload; and between a longer time since the completion of doxorubicin therapy and reduced left-ventricular-wall thickness and increased afterload (P < or = 0.001). CONCLUSIONS: Female sex and a higher rate of administration of doxorubicin were independent risk factors for cardiac abnormalities after treatment with doxorubicin for childhood cancer; the prevalence and severity of abnormalities increased with longer follow-up.

Adolescent↗

PubMed1995

Practice guidelines and malpractice litigation: a two-way street.

OBJECTIVE: To understand how practice guidelines are used in malpractice litigation. DESIGN: Review of the open and closed malpractice claims of two medical malpractice insurance companies, and a mailed survey of attorneys who litigate malpractice claims. SETTING: United States. PARTICIPANTS: Two insurance companies and 960 randomly selected malpractice attorneys. MEASUREMENTS: Frequency and nature of the use of practice guidelines in litigation; understanding and frequency of the use of practice guidelines by attorneys in malpractice cases. RESULTS: 259 claims opened in 1990-1992 at two insurance companies, including all obstetrics and anesthesia claims and a random sample of other claims, were reviewed. Seventeen of these claims involved practice guidelines, which were used as exculpatory evidence (exonerating the defendant physician) in 4 cases and as inculpatory evidence (implicating the defendant physician) in 12 cases. The only physician or patient factors associated with use of a guideline was a longer physician-patient relationship (P = 0.021). Nine hundred and sixty surveys were mailed and 578 were returned (response rate, 60.1%). Attorneys reported that once a suit is initiated, practice guidelines are likely to be used for inculpatory purposes (inculpatory in 54% of cases; exculpatory in 22.7% of cases). However, guidelines that seem to offer exculpatory value induce attorneys not to bring suits. The only attorney factor associated with increased use of guidelines was a practice in which more than 50% of business was in medical malpractice. CONCLUSIONS: Guidelines are used both by plaintiffs' and defendants' attorneys in malpractice cases. The emphasis in health reform proposals on guidelines as exculpatory evidence should be carefully considered.

Humans↗

PubMed1995

Estimation methods for the join distribution of repeated binary observations.

The joint distribution of repeated binary observations is multinomial, and can be specified using a representation first suggested by Bahadur (1961, in Studies in Item Analysis and Prediction,158-168. Stanford, California: Stanford University Press), and later by Cox (1972, Applied Statistics 21, 13-120). Using the Bahadur representation, the marginal probabilities of success can be related to a set of covariates using the logistic link function, or any other suitable link function. Besides the parameters of the marginal regression model, we may also have interest in the probability of success on any of the repeated measures. For example, in the Six Cities study, a longitudinal study of the health effects of air pollution, we have interest in both the marginal probability of a child wheezing at age t (t = 10, 11, 12), and the union probability of wheezing at any of the three ages. This "union" probability can be specified in terms of the joint probabilities and the second higher-order correlations. We discuss several methods of estimating the parameters of the Bahadur model.

Adult↗

PubMed1994

Sample size for repeated measures studies with binary responses.

We consider the sample size required for repeated measures studies when the response variable is binary. We propose the use of weighted least squares (WLS) for calculating the minimum sample size required to detect some minimum clinically important treatment effect. We provide tabulated values of the estimated sample sizes for a simple example and we discuss some practical considerations in determination of sample size with repeated binary responses.

Bias↗

PubMed1994

Analysis of repeated categorical data using generalized estimating equations.

Moment methods for analysing repeated binary responses have been proposed by Liang and Zeger, and extended by Prentice and Zhao and Prentice. In these estimating equations, models are proposed for the correlation between the repeated binary responses. We extend Liang and Zeger's method to models for the correlation between repeated nominal or ordinal categorical responses; in particular, when the repeated responses are binary, our methods reduce to Liang and Zeger's method. Our method is illustrated with two datasets. One dataset contains repeated observations of self-assessment of arthritis, an ordered variable with three categories, collected during a randomized comparative study of alternative treatments of patients with rheumatoid arthritis. The second dataset is a longitudinal study of the health effects of air pollution, in which the repeated ordered multinomial response is the wheezing status (no wheeze, wheeze with cold, wheeze apart from cold) of a child at ages 9, 10, 11 and 12 years.

Adult↗

PubMed1994

A robust goodness-of-fit test statistic with application to ordinal regression models.

We propose a goodness-of-fit test statistic for linear regression with heterogeneous variance, which is asymptotically chi-square if the given model is correct. The test statistic is computed as a quadratic form of observed minus predicted responses. We apply the method to a linear regression for an ordinal categorical response, the wheezing status of a child (no wheeze, wheeze with cold, wheeze apart from cold) as a function of maternal smoking and city of residence.

Child↗

PubMed1994

Analysing incomplete longitudinal binary responses: a likelihood-based approach.

In this paper, we describe a likelihood-based method for analysing balanced but incomplete longitudinal binary responses that are assumed to be missing at random. Following the approach outlined in Zhao and Prentice (1990, Biometrika 77, 642-648), we focus on "marginal models" in which the marginal expectation of the response variable is related to a set of covariates. The association between binary responses is modelled in terms of conditional log odds-ratios. We describe a set of scoring equations for jointly estimating both the marginal parameters and the conditional association parameters. An outline of the EM algorithm used to obtain the maximum likelihood estimates is presented. This approach yields valid and efficient estimates when the responses are missing at random, but not necessarily missing completely at random. An example, using data from the Muscatine Coronary Risk Factor Study, is presented to illustrate this methodology.

Age Factors↗

PubMed1994

Jackknife estimators of variance for parameter estimates from estimating equations with applications to clustered survival data.

An estimate of a parameter vector beta is often obtained by setting a "score" vector equal to zero and solving for beta. Estimating equations of this type include maximum likelihood, quasi-likelihood (McCullagh, 1983, Annals of Statistics 11, 59-67), and generalized estimating equations (Liang and Zeger, 1986, Biometrika 73, 13-22). White (1982, Econometrica 50, 1-26) proposed a variance estimator for beta that is robust to model misspecification. We show that a "one-step" jackknife estimator of variance is asymptotically equivalent to the variance estimator proposed by White. The one-step variance estimator may be preferred when the appropriate computer packages are not available to compute White's estimator directly. This jackknife estimator is very useful in our example with clustered survival data.

Analysis of Variance↗

PubMed1994

An extension of Yule's Q to multivariate binary data.

In this note we describe a summary measure of pairwise association for multivariate binary data based on the conditional odds ratio. The proposed measure is an extension of Yule's Q to more than two binary random variables. Unlike marginal measures of association, this measure is not constrained by the marginal probabilities of success. For example, when each binary variable has a different probability of success, the upper limit of the pairwise marginal correlation coefficient is constrained to be less than 1. If one prefers a measure of association that is unconstrained, then with only two binary variables, Bishop, Feinberg, and Holland (1975, Discrete Multivariate Analysis: Theory and Practice, Cambridge, Massachusetts: MIT Press) suggest the use of the odds ratio or, equivalently, Yule's Q. Yule's Q transforms the odds ratio between the two binary variables from [0, infinity) to [-1, 1]. We propose an extension of Yule's Q to more than two binary random variables. This measure of pairwise association is based on the conditional odds ratio from a log-linear model.

Animals↗