Biomedical subjects

C S Weng

Publications and source records attributed to C S Weng.

6 recordsLinked to original sources

PubMed1998

Transdermal nitroglycerin patch therapy improves left ventricular function and prevents remodeling after acute myocardial infarction: results of a multicenter prospective randomized, double-blind, placebo-controlled trial.

BACKGROUND: Nitrates are widely used in the treatment of angina in patients with acute myocardial infarction (AMI). Short-term administration prevents left ventricular (LV) dilation and infarct expansion. However, little information is available regarding their long-term effects on LV remodeling in patients surviving Q-wave AMI. METHODS AND RESULTS: This was a randomized, double-blind, placebo-controlled trial designed to investigate the long-term (6-month) efficacy of intermittent transdermal nitroglycerin (NTG) patches on LV remodeling in 291 survivors of AMI. Patients meeting entry criteria had baseline gated radionuclide angiography (RNA) followed by randomization to placebo or active NTG patches delivering 0.4-, 0.8-, or 1.6-mg/h. RNA was repeated at 6 months and 6.5 days after withdrawal of double-blind medication. The primary study end point was the change in end-systolic volume index (ESVI). Both ESVI and end-diastolic volume index (EDVI) were significantly reduced with 0.4-mg/h NTG patches (-11.4 and -11.6 mL/m2, respectively, P<.03). This beneficial effect was observed primarily in patients with a baseline LV ejection fraction < or =40% (deltaESVI, -31 mL/m2; deltaEDVI, -33 mL/m2; both P<.05) and only at the 0.4-mg/h dose. After NTG patch withdrawal, ESVI significantly increased but did not reach pretreatment values. CONCLUSIONS: Transdermal NTG patches prevent LV dilation in patients surviving AMI. The beneficial effects are limited to patients with depressed LV function and only at the lowest (0.4-mg/h) dose. Continued administration is necessary to maintain efficacy. Whether these remodeling effects confer a clinical or survival advantage will need to be addressed in an adequately powered cardiac event trial.

Administration, Cutaneous↗

PubMed1998

Hepatitis C infection risk analysis: who should be screened? Comparison of multiple screening strategies based on the National Hepatitis Surveillance Program.

OBJECTIVES: Hepatitis C, an infection of high prevalence worldwide, is insidiously progressive in many. Reduction of person-to-person spread is possible, and treatment is possible for many, particularly if offered before cirrhosis develops. Screening for hepatitis C (HCV) would be appropriate if strategies could be developed to afford adequate sensitivity and specificity at reasonable cost. We evaluated the performance characteristics of several screening strategies to determine the best balance between cost and performance. METHODS: The database of a national hepatitis screening program was used to define risk factors for HCV. Features associated with increased risk for HCV by multivariable analysis were combined in various ways to construct HCV screening models. Screening Model 1 employed a mathematical model constructed to predict the probability of hepatitis C. Using this model, testing for HCV was done if the probability of HCV was determined to be higher than 7%. Models 2 and 3 called for HCV testing if certain risk factors, stratified as socially intrusive, or nonintrusive in nature, were present. Model 4 calls for testing for HCV only when ALT values are elevated. Costs per case discovered were calculated for each model. RESULTS: Nine thousand two-hundred sixty-nine individuals from a database of 13,997 has sufficient information to be included in the modeling studies. Risk factors considered socially intrusive were intravenous (i.v.) drug use and sex with an i.v. drug user. Risk factors considered not socially intrusive were: history of blood transfusion, age 30-49 yrs, and male gender. The sensitivity of Models 1-4 were 65%, 69%, 53%, and 63%, respectively. Specificities were 84%, 74%, 77%, and 92%, respectively. The cost per case detected was lowest when Models 1 or 2 were used ($357 and $439, respectively) and higher for models 3 and 4 ($487 and $1047, respectively). CONCLUSIONS: The yield and cost of screening for HCV compares favorably with accepted current screening practices for other diseases. Models 1, 2, and 3 may be appropriate in certain clinical and epidemiological settings. Selective screening by a risk factor questionnaire (first three models) is more cost-effective than blood testing with ALT (Model 4).

Adult↗

PubMed1995

Bias of two one-sided tests procedures in assessment of bioequivalence.

The current applications of Schuirmann's two one-sided tests procedure for the original scale ignore the variability of the least squares mean of the reference formulation when it substitutes for the unknown reference average of pharmacokinetic responses. We propose a modified two one-sided test procedure that takes into account the variability of the least squares mean of the reference formulation. The non-parametric version of the modified procedure is also available. We conducted a simulation study to examine the true level of significance and empirical power of four current parametric and non-parametric two one-sided tests procedures under a 2 x 2 crossover design with different combinations of sample size, intrasubject variability, and correlation between the two responses from a subject. Both theoretical results and empirical evidence show that the true level of significance of the current two one-sided tests procedures converges to 0.5 when the correlation of the two responses approaches 1. However, not only is the modified two one-sided tests procedure a test of size alpha, but empirical evidence indicates it is also an unbiased test. The modified non-parametric procedure also controls the size of the tests and is competitive even under normality assumption.

Bias↗

PubMed1993

Evaluation of parametric and nonparametric two one-sided tests procedures for assessing bioequivalence of average bioavailability.

A simulation study was conducted to compare the levels of significance and power between Schuirmann's and nonparametric two one-sided tests procedures for a 2 x 2 crossover design under different combinations of sample sizes, intrasubject variabilities, and underlying distributions. Empirical results suggest that Schuirmann's two one-sided tests procedure is robust to minor departure from the assumption of normality.

Chemistry, Pharmaceutical↗

PubMed1992

Estimation of direct formulation effect under log-normal distribution in bioavailability/bioequivalence studies.

This paper considers estimation of a measure of relative bioavailability of a test formulation to a reference formulation, on the original scale, under the assumption of a log-normal distribution for the data from a 2 x 2 crossover bioavailability/bioequivalence study. We propose the minimum variance unbiased estimator which is equal to the maximum likelihood estimator adjusted for bias by a correction factor. We also derive the variance of the minimum variance unbiased estimator and its unbiased estimator. We derive the biases and mean square errors of the maximum likelihood estimator, the ratio of the least square means, and the least squares mean of individual subject ratios, with respect to this measure, and compare them in a simulation study. Both theoretical and empirical results strongly suggest that one always consider the minimum variance unbiased estimator. A numerical example illustrates the proposed estimation procedure.

Bias↗

PubMed1991

Detection of outlying data in bioavailability/bioequivalence studies.

This paper considers the problem of detecting outlying data in bioavailability/bioequivalence studies. We define outlying subjects as those whose responses in bioavailability to all formulations differ from the rest of the subjects. We also define an outlying observation as the response in bioavailability of a subject to a particular formulation which is grossly different from the average bioavailability of that formulation calculated from all subjects. We propose two test procedures. The first, based on two-sample Hotelling T2, is to detect possible outlying subjects. The second, based on residuals from formulation means, is to identify possible outlying observations within subjects. Both procedures take into account the covariance structure of the responses to formulations, dependence of test statistics, and multiplicity of test procedures. We apply the Monte Carlo or bootstrap simulation to evaluate the sampling distributions of test statistics. An example from a 3-way crossover bioequivalence study illustrates the two procedures.

Biological Availability↗