Biomedical subjects

Stuart R Lipsitz

Publications and source records attributed to Stuart R Lipsitz.

33 records · Page 2Linked to original sources

PubMed2003

Analysis of clustered matched-pair data for a non-inferiority study design.

Hypothesis testing of matched-pair data has been adapted for equivalence (one- and two-sided) study designs; however, a statistical problem arises when more than one measurement is recorded for each study subject. Ignoring the correlation between the repeated measurements per subject may underestimate the standard error of the parameter estimate. A method of testing for non-inferiority or equivalence of clustered matched-pair data is not yet available. This paper proposes a Wald-type test statistic for a non-inferiority hypothesis and applies it to the comparison of two diagnostic procedures.

Computer Simulation↗

PubMed2003

Cholesterol measures to identify and treat individuals at risk for coronary heart disease.

BACKGROUND: Low-density lipoprotein (LDL)-based guidelines are currently used to initiate and monitor cholesterol-lowering therapy. METHODS: Using stratified analyses, data from the Framingham Heart Study and the Coronary Primary Prevention Trial were evaluated to determine whether (1) cholesterol levels (total cholesterol [TC] or LDL [low-density lipoprotein]) better discriminated risk for coronary heart disease (CHD) than cholesterol ratios (LDL/HDL [high-density lipoprotein] or TC/HDL); and (2) whether changes in ratios better predicted risk reduction than changes in levels. RESULTS: Individuals with similar LDL/HDL ratios had similar risks for CHD regardless of whether they had high LDL levels or low LDL levels (23% vs 23% for the CPPT, 13.8% vs 14% for FHS men, and 8.6% vs 10.9% for FHS women). Among men with similar initial LDL/HDL ratios and similar changes in LDL/HDL ratios, risks for CHD did not differ (20.3% compared with 21.0%; p =0.96) between those with the largest and smallest reductions in LDL levels (21.3% compared with 6.5%). Among men with similar initial LDL levels and similar LDL reductions, a 20% reduction in risk for CHD was seen (19.5% compared with 24.5%; p =0.005) between those with the largest and smallest reductions in LDL/HDL ratios (23% compared with 4.6%). TC/HDL had predictive ability similar to LDL/HDL. CONCLUSIONS: Cholesterol levels do not provide incremental predictive value over cholesterol ratios in identifying people at risk for CHD. Changes in ratios are better predictors of successful CHD risk reduction than changes in levels. Future guidelines should consider incorporating ratios in initiating and monitoring successful lipid-lowering therapy.

Cholesterol, HDL↗

PubMed2003

Serum cardiac troponin and subclinical cardiac status in pediatric chronic renal failure.

BACKGROUND: Patients with uremia often have elevated serum cardiac troponin T (cTnT) even without clinical heart damage. Pediatric patients are ideal for studies of the relationship between uremia and heart disease because they are unlikely to have cardiac risk factors other than uremia. OBJECTIVE: To determine the relationship between uremia and cTnT levels. DESIGN: Echocardiograms and blood chemistry results were obtained from 50 pediatric patients with chronic renal failure and without clinical heart disease. Levels of cTnT were tested for correlation with cardiac dysfunction. In multivariate analysis, biochemical aspects of renal disease and its treatment were tested for correlation with cardiac dysfunction. RESULTS: Forty-nine patients had cardiovascular abnormalities, including increased left ventricular function and mass, elevated heart rate and blood pressure, and reduced LV afterload. LV contractility was inversely correlated with cTnT level (r = -0.36). Higher cTnT also correlated with higher serum creatine kinase-MB mass, lower serum parathyroid hormone, higher blood urea nitrogen and bicarbonate levels, and the use of diuretics, but not with higher cardiac troponin I. Left ventricular contractility was inversely related to serum creatinine, phosphorus, and the use of beta-blockers. CONCLUSIONS: Elevated cTnT levels are not artifactual, but are genuine indicators of cardiomyocyte damage. Cardiac damage, indicated by either elevated cTnT or low LV contractility, is related to uremia, deranged calcium and phosphorus metabolism, and bicarbonate levels. Serum cTnT and LV contractility identify subclinical cardiac damage that could be treated to hopefully reduce cardiovascular morbidity and mortality in this high-risk population.

Adolescent↗

PubMed2002

Long-term enalapril therapy for left ventricular dysfunction in doxorubicin-treated survivors of childhood cancer.

PURPOSE: A common late effect of doxorubicin therapy for childhood cancer is reduced left-ventricular (LV) wall thickness resulting in elevated LV afterload and depressed LV function. Many children are given angiotensin-converting enzyme inhibitors, which have been studied primarily in adults. We document the long-term effects of angiotensin-converting enzyme inhibitors in doxorubicin-treated survivors of childhood cancer. PATIENTS AND METHODS: In this retrospective study, we reviewed records of 18 children who had regular echocardiographic examinations during enalapril therapy (mean age at cancer diagnosis, 8 years; mean time between completion of doxorubicin therapy and start of enalapril, 7 years; median follow-up since the start of enalapril, 10 years). RESULTS: Over the first 6 years of enalapril therapy, there was progressive improvement toward normal values in LV dimension, afterload, fractional shortening, and mass, but all these parameters deteriorated between 6 and 10 years. LV wall thickness deteriorated throughout the study period, as did LV contractility and systolic blood pressure. Diastolic blood pressure fell slightly. By 6 years on enalapril, all six patients who had had congestive heart failure at the start of enalapril therapy had either died or undergone cardiac transplantation, compared with three of the 12 asymptomatic patients. CONCLUSION: In doxorubicin-treated long-term survivors of childhood cancer, enalapril-induced improvement in LV structure and function is transient. The primary defect, which is LV wall thinning, continues to deteriorate, and thus the short-term improvement was mostly related to lowered diastolic blood pressure.

Adolescent↗

PubMed2002

A weighted estimating equation for linear regression with missing covariate data.

Linear regression is one of the most popular statistical techniques. In linear regression analysis, missing covariate data occur often. A recent approach to analyse such data is a weighted estimating equation. With weighted estimating equations, the contribution to the estimating equation from a complete observation is weighted by the inverse 'probability of being observed'. In this paper, we propose a weighted estimating equation in which we wrongly assume that the missing covariates are multivariate normal, but still produces consistent estimates as long as the probability of being observed is correctly modelled. In simulations, these weighted estimating equations appear to be highly efficient when compared to the most efficient weighted estimating equation as proposed by Robins et al. and Lipsitz et al. However, these weighted estimating equations, in which we wrongly assume that the missing covariates are multivariate normal, are much less computationally intensive than the weighted estimating equations given by Lipsitz et al. We compare the weighted estimating equations proposed in this paper to the efficient weighted estimating equations via an example and a simulation study. We only consider missing data which are missing at random; non-ignorably missing data are not addressed in this paper.

Adolescent↗

PubMed2002

The reliability of medical record review for estimating adverse event rates.

BACKGROUND: The data used by the U.S. Institute of Medicine to estimate deaths from medical errors come from a study that relied on nurse and physician reviews of medical records to detect the errors. OBJECTIVE: To measure the reliability of medical record review for detecting adverse events and negligent adverse events. DESIGN: Medical record review. SETTING: Hospitalizations in Utah and Colorado in 1992. MEASUREMENTS: After three independent reviews of 500 medical records, the following were measured: reliability and the effect of varying criteria for reviewer confidence in and reviewer agreement about the presence of adverse events. RESULTS: For agreements in judgments of adverse events among the three sets of reviews, the kappa statistics ranged from 0.40 to 0.41 (95% CIs ranged from 0.30 to 0.51) for adverse events and from 0.19 to 0.23 (CIs, 0.05 to 0.37) for negligent adverse events. Rates for adverse events and for negligent adverse events varied substantially depending on the degree of agreement and the level of confidence that was required among reviewers. CONCLUSION: Estimates of adverse event rates from medical record review, including those reported by the Institute of Medicine in its 2000 report on medical errors, are highly sensitive to the degree of consensus and confidence among reviewers.

Colorado↗

PubMed2002

Prediction of survival and opportunistic infections in HIV-infected patients: a comparison of imputation methods of incomplete CD4 counts.

In evaluating the risk of mortality or development of opportunistic infections in HIV-infected patients, the number of CD4 lymphocyte cells per cubic millimetre of blood is widely recognized as one of the best available predictors of such future events. However, its usefulness is limited by the incompleteness and variability of such CD4 measurements during follow-up. Because of these limitations, analysis of such data requires the missing measurements to be 'filled in' or the patients without them to be excluded. We consider multiple imputation of CD4 values based partly on information from other health status measures such as haemoglobin, as well as on the event status of interest. These alternative health status measures are also considered as possible independent predictors of survival endpoints. Our work is motivated by a cohort of 1530 patients enrolled in two AIDS clinical trials. We compare our approach to other strategies such as basing evaluation of risk on baseline CD4, the last measured CD4 before an event, or a time-dependent covariate based on carrying the last CD4 value forward; we conclude with a strong recommendation for multiple imputation.

AIDS-Related Opportunistic Infections↗

PubMed2002

Doxorubicin administration by continuous infusion is not cardioprotective: the Dana-Farber 91-01 Acute Lymphoblastic Leukemia protocol.

PURPOSE: Acute doxorubicin-induced cardiotoxicity can be prevented in adults by continuous infusion of the drug, but mechanisms of cardiotoxicity are different in children. We compared cardiac outcomes in children receiving bolus or continuous infusion of doxorubicin. PATIENTS AND METHODS: In a randomized study, children with high-risk acute lymphoblastic leukemia received doxorubicin 360 mg/m(2) in 30-mg/m(2) doses every 3 weeks either by bolus (within 1 hour, n = 57) or by continuous infusion (over 48 hours, n = 64). Echocardiograms obtained before doxorubicin and at longest follow-up times were centrally remeasured, and z scores of cardiac measurements were calculated based on a healthy population. RESULTS: The groups were similar in age, sex distribution, doxorubicin dose, and duration of follow-up. Before treatment, measures of left ventricular (LV) structure and function did not reveal dilated cardiomyopathy and were not statistically different between bolus and continuous-infusion groups. The follow-up echocardiograms demonstrated no significant difference between the two groups for any cardiac characteristic, but both groups showed significant abnormalities of LV structure and function compared with normal and with baseline. For example, the mean LV fractional shortening fell by approximately two SD in both groups between the two echocardiograms. LV contractility was depressed in both groups (for bolus patients, median z score = -0.70 SD, P =.006; for continuous-infusion patients, median z score = -0.765, P =.005). Dilated cardiomyopathy and inadequate LV hypertrophy were noted in both groups. Clinical cardiac manifestations and event-free survival did not differ. CONCLUSION: Continuous doxorubicin infusion over 48 hours for childhood leukemia did not offer a cardioprotective advantage over bolus infusion. Both regimens were associated with progressive subclinical cardiotoxicity. Other cardioprotective strategies should be explored.

Adolescent↗

PubMed2002

Self-report of high cholesterol: determinants of validity in U.S. adults.

BACKGROUND: Hypercholesterolemia is a major cardiovascular risk factor, and cholesterol awareness is important in both clinical practice and in public health. We evaluated the validity of self-reported hypercholesterolemia and identified determinants of validity. METHODS: The study design was a cross-sectional survey, from 1988 to 1994, of adult participants (N=8236) from the Third National Health and Nutrition Examination Survey for whom self-report of hypercholesterolemia and serum measurement were available. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for self-reported hypercholesterolemia were calculated using total cholesterol > or =5.17 mmol/L (200 mg/dL) and/or taking cholesterol-lowering medication as the criterion standard. RESULTS: Overall test characteristics for self-report were sensitivity, 51%; specificity, 89%; PPV, 87%; and NPV, 55%. Sensitivity of self-report was higher among older subjects and non-Hispanic whites, specificity was higher among subjects with >12 years of education, PPV was higher in older subjects, and NPV was higher in younger subjects and in those with >12 years of education. Using higher cholesterol thresholds to define hypercholesterolemia led to higher sensitivity, lower specificity, lower PPV, and higher NPV. Sociodemographic and anthropometric predictors of validity were identified by logistic regression. CONCLUSIONS: Due to low sensitivity, self-reported hypercholesterolemia should be used with caution, both during the patient encounter and for surveillance of trends in hypercholesterolemia in the absence of measured cholesterol levels. Specificity is consistently much higher than sensitivity. The high PPV may be of use in certain clinical situations. Such validation studies should form the foundation for future research based on self-report.

Adult↗

PubMed2002

Bayesian methods for missing covariates in cure rate models.

We propose methods for Bayesian inference for missing covariate data with a novel class of semiparametric survival models with a cure fraction. We allow the missing covariates to be either categorical or continuous and specify a parametric distribution for the covariates that is written as a sequence of one dimensional conditional distributions. We assume that the missing covariates are missing at random (MAR) throughout. We propose an informative class of joint prior distributions for the regression coefficients and the parameters arising from the covariate distributions. The proposed class of priors are shown to be useful in recovering information on the missing covariates especially in situations where the missing data fraction is large. Properties of the proposed prior and resulting posterior distributions are examined. Also, model checking techniques are proposed for sensitivity analyses and for checking the goodness of fit of a particular model. Specifically, we extend the Conditional Predictive Ordinate (CPO) statistic to assess goodness of fit in the presence of missing covariate data. Computational techniques using the Gibbs sampler are implemented. A real data set involving a melanoma cancer clinical trial is examined to demonstrate the methodology.

Bayes Theorem↗

PubMed2002

Frailty models with missing covariates.

We present a method for estimating the parameters in random effects models for survival data when covariates are subject to missingness. Our method is more general than the usual frailty model as it accommodates a wide range of distributions for the random effects, which are included as an offset in the linear predictor in a manner analogous to that used in generalized linear mixed models. We propose using a Monte Carlo EM algorithm along with the Gibbs sampler to obtain parameter estimates. This method is useful in reducing the bias that may be incurred using complete-case methods in this setting. The methodology is applied to data from Eastern Cooperative Oncology Group melanoma clinical trials in which observations were believed to be clustered and several tumor characteristics were not always observed.

Clinical Trials, Phase III as Topic↗

PubMed2002

Parameter estimation in longitudinal studies with outcome-dependent follow-up.

In many observational studies, individuals are measured repeatedly over time, although not necessarily at a set of prespecified occasions. Instead, individuals may be measured at irregular intervals, with those having a history of poorer health outcomes being measured with somewhat greater frequency and regularity; i.e., those individuals with poorer health outcomes may have more frequent follow-up measurements and the intervals between their repeated measurements may be shorter. In this article, we consider estimation of regression parameters in models for longitudinal data where the follow-up times are not fixed by design but can depend on previous outcomes. In particular, we focus on general linear models for longitudinal data where the repeated measures are assumed to have a multivariate Gaussian distribution. We consider assumptions regarding the follow-up time process that result in the likelihood function separating into two components: one for the follow-up time process, the other for the outcome process. The practical implication of this separation is that the former process can be ignored when making likelihood-based inferences about the latter; i.e., maximum likelihood (ML) estimation of the regression parameters relating the mean of the longitudinal outcomes to covariates does not require that a model for the distribution of follow-up times be specified. As a result, standard statistical software, e.g., SAS PROC MIXED (Littell et al., 1996, SAS System for Mixed Models), can be used to analyze the data. However, we also demonstrate that misspecification of the model for the covariance among the repeated measures will, in general, result in regression parameter estimates that are biased. Furthermore, results of a simulation study indicate that the potential bias due to misspecification of the covariance can be quite considerable in this setting. Finally, we illustrate these results using data from a longitudinal observational study (Lipshultz et al., 1995, New England Journal of Medicine 332, 1738-1743) that explored the cardiotoxic effects of doxorubicin chemotherapy for the treatment of acute lymphoblastic leukemia in children.

Adolescent↗

PubMed2002

Improving family practice residents' compliance with asthma practice guidelines.

OBJECTIVES: This study primarily determined the effect of an educational and system intervention on residents' documentation of the severity classification of asthma. Secondarily, the study assessed the effect of classification on pharmacologic treatment, as outlined by national asthma treatment guidelines. METHODS: We reviewed the charts of all patients with asthma seen by the residents in the Center for Family Medicine (CFM) between October 1, 1998, and March 31, 1999. Data gathered from each chart included, but was not limited to, disease severity classification and medication regimen. Between July 1999 and October 1999, efforts at increasing residents' knowledge of asthma severity classification were made via formal and informal teaching. A post-intervention chart review was performed on all patients with asthma seen by the residents in the CFM between October 1, 1999, and March 31, 2000. RESULTS: A total of 8.5% of 198 and 51% of 271 patient visits were classified with respect to asthma severity in the pre- and post-intervention periods, respectively. Classified patients were treated appropriately 100% of the time in the pre-intervention period and 76% of the time in the post-intervention period. CONCLUSIONS: A comprehensive protocol significantly improved compliance with national asthma treatment guidelines with respect to severity classification but not pharmacologic treatment.

Asthma↗

PubMed2002

Serum antibodies to Helicobacter pylori and the CagA antigen do not explain differences in the prevalence of precancerous gastric lesions in two Chinese populations with contrasting gastric cancer rates.

Incidence and mortality rates for gastric cancer in rural People's Republic of China differ greatly over short distances. In Shandong Province, we studied asymptomatic adult subjects from Bei Duan village (n = 196) in Linqu County (a high-risk area for gastric cancer) and from Shi Huang village (n = 192) in Cangshan County (a low-risk area for gastric cancer). The prevalence of advanced precancerous gastric lesions (APGL) was assessed by microscopic examination of endoscopic stomach biopsies. ELISAs were used to detect serum IgG to Helicobacter pylori whole-cell antigen and to the CagA protein. A logistic regression model was used to quantify the role of the two H. pylori seromarkers in explaining the differences in prevalence of APGL between the two villages after adjusting for age and sex. The prevalence of APGL was much greater in Bei Duan than in Shi Huang. Although H. pylori seroprevalence by the whole-cell ELISA was similar in the two populations, seroprevalence of CagA was significantly greater in Bei Duan. Although age, sex, and both H. pylori seromarkers were associated with APGL in the logistic regression model, the effect of village of residence remained strong after adjustment for all four covariates. Only a relatively small proportion of the difference in prevalence of APGL between these two rural Chinese populations can be explained by differences in H. pylori or CagA seroprevalence.

Antibodies, Bacterial↗

PubMedDate not supplied

The association of low birthweight and chronic renal failure among Medicaid young adults with diabetes and/or hypertension.

OBJECTIVE: The purpose of this study was to assess the effect of low birthweight on chronic renal failure among young Medicaid patients with diabetes and/or hypertension. METHODS: The study included Caucasian and African American young adults, aged 18-50, who enrolled in the Medicaid program from 1993 to 1996 in South Carolina and were diagnosed with diabetes and/or hypertension. The odds of chronic renal failure by low birthweight (< 2,500 grams) was estimated using logistic regression. RESULTS: Of the 7,505 Medicaid patients with diabetes and/or hypertension, 179 (2.4%) were diagnosed with chronic renal failure. These patients were younger (mean age of 33.9 vs. 37.6, p = 0.0024) and had a higher proportion of low birthweight (15.1% vs. 11.4%, p = 0.07) compared with the 7,326 patients without renal failure. The odds ratio of chronic renal failure for low birthweight was significantly higher compared with normal birthweight (2,500-3,999 grams) (adjusted odds ratio [OR] 1.56, 95% confidence interval [95% CI] 1.0, 2.4). The association between low birthweight and chronic renal failure was stronger among the 888 patients with both diabetes and hypertension (OR 2.6, 95% Cl 1.3, 5.7) than the 1,812 diabetes or the 4,805 hypertension patients. CONCLUSIONS: The odds of chronic renal failure by low birthweight was highest in patients with both diabetes and hypertension, suggesting that the mechanism(s) involved in the disease progression to chronic renal failure may have a fetal early life origin.

Adolescent↗