Biomedical subjects

X H Zhou

Publications and source records attributed to X H Zhou.

At least 37 records · Page 2Linked to original sources

PubMed1999

Zinc ligand-disrupted recombinant human Endostatin: potent inhibition of tumor growth, safety and pharmacokinetic profile.

Endostatin, a potent endogenous inhibitor of angiogenesis, inhibits the growth of primary tumors without induction of acquired drug resistance in mice. We report that a soluble recombinant human (rh) Endostatin produced with characteristics of the native Endostatin, effectively inhibited the growth of primary tumors and pulmonary metastases in a dose-dependent manner. We also show that deletion of two of the four zinc ligands of rhEndostatin did not affect this potent tumor inhibiton. The growth of established Lewis lung primary tumors implanted into mice was inhibited (80-90%) upon systemic treatment with 50 mg/kg/12 h of rhEndostatin. Using the B16-BL6 murine experimental pulmonary metastases model, rhEndostatin administered at 1.5 mg/kg/day or 4.5 mg/kg/day beginning 3- or 11-days post tumor cell injection, respectively, resulted in an approximate 80% inhibition of tumor growth. At effective anti-tumor doses of 1.5 and 50 mg/kg, pharmacokinetic modeling in mice showed (a) the protein was 100% bioavailable, (b) the AUC ranged from 16 to 700 ng ml/h and (c) the Cmax ranged from 161 to 4582 ng/ml. At the highest dose tested (300 mg/kg), delivered as a single bolus, no drug-related toxicity was observed in a Cynomolgus monkey infused with rhEndostatin. No toxicity was observed even at AUC and Cmax values that were 1.3- to 56-fold higher than those observed in mice with tumors that were potently inhibited. Our production system yields a well characterized, soluble and potent rhEndostatin at quantities sufficient for human use. The preclinical studies described herein are an important first step toward the assessment of Endostatin in the clinic.

Journal Article↗

PubMed1999

Mailed reminders for area-wide influenza immunization: a randomized controlled trial.

OBJECTIVE: To determine if mailed reminders would increase area-wide influenza immunization for persons aged 65 and older. DESIGN: A randomized, controlled trial. SETTING: Ten counties in Indiana. PARTICIPANTS: Using a Medicare database, 10,000 subjects were selected randomly from 10 counties in Indiana and randomized for the study. Using pre-established criteria, 4503 persons in the control group and 4508 in the intervention group were eligible for study. INTERVENTION: Intervention subjects received mailed reminders during the immunization season of 1995. MEASUREMENTS: Data from mailed surveys, Medicare claims, and phone calls were used to determine immunization rates. RESULTS: Of those surveyed who received immunization, only 63.4% filed a Medicare claim. Immunization rates were high in both groups but higher in the intervention group, 69.0% versus 64.2%. Age, presence of lung disease, assignment to the intervention group, presence of heart disease, and an age-sex interaction term were significantly and independently related to immunization. CONCLUSIONS: The Healthy People Year 2000 goal (60% immunization for persons 65 and older) was exceeded in this population. Medicare claims data do not reflect immunization rates accurately. Mailed reminders, an inexpensive intervention, increased immunization rates area-wide and have potential for cost savings.

Age Factors↗

PubMed1998

Endochondral ossification is dependent on the mechanical properties of cartilage tissue and on intracellular signals in chondrocytes.

Skeletal elements are formed either by replacing a performed cartilagenous matrix template in a process called endochondral ossification or directly from mesenchyme by a process known as membranous ossification. Longitudinal growth of bones is achieved by growth plates where calcified cartilage is converted into bone. To investigate the role of extracellular matrix as well as intracellular signaling pathways in the formation and growth of bone, the genes coding for type II collagen and cyclic guanosine 3',5'-monophosphate (cGMP)-dependent protein kinase (cGK) II, were disrupted. It is demonstrated that loss of Col2a1 or cGKII led to abnormal endochondral ossification and skeletal development. In cGKII -/- mice, bones derived by membranous ossification developed normally while bones derived by endochondral ossification were shortened. This growth defect was not associated with a general metabolic disturbance. In Col2a1 knockout mice, endochondral ossification was completely absent, whereas membraneous ossification was not affected. Despite the defects in bone formation, invasion of blood vessels into bone cavities and formation of bone marrow occurred in Col2a1-null mice. Taken together, the phenotypes of these two knockout mice show that chondrocytes need a well-functioning extracellular matrix scaffold and a normal cGMP-signaling system for endochondral ossification to form a normal skeleton.

Animals↗

PubMed1998

Estimation of the log-normal mean.

The most commonly used estimator for a log-normal mean is the sample mean. In this paper, we show that this estimator can have a large mean square error, even for large samples. Then, we study three main alternative estimators: (i) a uniformly minimum variance unbiased (UMVU) estimator; (ii) a maximum likelihood (ML) estimator; (iii) a conditionally minimal mean square error (MSE) estimator. We find that the conditionally minimal MSE estimator has the smallest mean square error among the four estimators considered here, regardless of the sample size and the skewness of the log-normal population. However, for large samples (n > or = 200), the UMVU estimator, the ML estimator, and the conditionally minimal MSE estimators have very similar mean square errors. Since the ML estimator is the easiest to compute among these three estimators, for large samples we recommend the use of the ML estimator. For small to moderate samples, we recommend the use of the conditionally minimal MSE estimator.

Bayes Theorem↗

PubMed1998

Effectiveness of computer-generated reminders for increasing discussions about advance directives and completion of advance directive forms. A randomized, controlled trial.

BACKGROUND: Physicians can increase the rate of completion of advance directive forms by discussing directives with their patients, but the means by which physicians can be induced to initiate these discussions are unclear. Computer-generated reminders have been shown to increase physician compliance with practice guidelines. OBJECTIVE: To determine the effects of computer-generated reminders to physicians on the frequency of advance directive discussions between patients and their primary caregivers and the frequency of consequent establishment of advance directives. DESIGN: Randomized, controlled trial with a 2 x 2 factorial design. SETTING: An outpatient general medicine practice associated with an urban public hospital. PARTICIPANTS: Participants were 1) 1009 patients who were at least 75 years of age or were at least 50 years of age with serious underlying disease and 2) 147 primary care physicians (108 housestaff and 39 faculty). INTERVENTION: Computer-generated reminders that recommended discussion of one or both of two types of advance directives compared with no reminders. MEASUREMENTS: Discussions about advance directives, determined by patient interviews after all scheduled patient-physician outpatient encounters, and completed advance directive forms. The study period was approximately 1 year. RESULTS: Physicians who did not receive reminders (controls) discussed advance directives with 4% of the study patients compared with 24% for physicians who received both types of reminders (adjusted odds ratio, 7.7 [95% CI, 3.4 to 18]; P < 0.001). Physicians who did not receive reminders completed advance directive forms with only 4% of their study patients compared with 15% for physicians who received both types of reminders (adjusted odds ratio, 7.0 [CI, 2.9 to 17]; P < 0.001). Overall, 45% of patients with whom advance directives were discussed completed at least one type of advance directive. CONCLUSIONS: Simple computer-generated reminders aimed at primary caregivers can increase the rates of discussion of advance directives and completion of advance directive forms among elderly outpatients with serious illnesses.

Advance Care Planning↗

PubMed1998

Macronodular multi-organs tuberculoma: CT and MR appearances.

The case of a 21-year-old woman presenting with macronodular multi-organs tuberculoma is reported. She was examined for pulmonary tuberculosis on a chest X-ray film in January, 1995, and admitted with a cough, anorexia, and abdominal pain in July, 1996. Computed tomography revealed multiple calcified nodules with peripheral hypodense areas in the brain, and calcified hypodense masses in the liver and spleen. Magnetic resonance (MR) imaging showed hypointense masses in the liver and spleen on T1-weighted spin echo images and a hypointense mass with a hyperintense area on T2-weighted spin echo images. On contrast-enhanced dynamic MR images, the liver and spleen masses were unenhanced and hypointense with slight rim enhancement. T2-weighted spin echo images showed a round hypointense nodule in the right kidney and hydronephrosis and enlargement in the left kidney. Antituberculous treatment was started with a gradual improvement in her signs and symptoms. Her temperature became normal. However, she was systemically treated with antituberculous chemotherapy 10 months later, her condition worsened again. She died from increased intracranial pressure in August, 1997.

Adult↗

PubMed1998

COMPROC and CHECKNORM: computer programs for comparing accuracies of diagnostic tests using ROC curves in the presence of verification bias.

To assess relative accuracies of two diagnostic tests, we often compare the areas under the receiver operating characteristic (ROC) curves of these two tests in a paired design. Standard methods for analyzing data from a paired design require that every patient tested has the known disease status. In practice, however, some of the patients with test results may not have verified disease status. Any analysis using only verified cases may result in verification bias. COMPROC is an easy to use program for comparing the effectiveness of two diagnostic tests based on the area under the ROC curve in the presence of verification bias. COMPROC compensates for verification bias by implementing the maximum likelihood (ML) estimation of the areas and covariance matrix of two ROC curves under the missing at random (MAR) assumption as described by Zhou (Biometrics 54 (1998) 349-366). This method assumes normality of the difference of the two ROC curve area estimators. We also describe a program CHECKNORM that does a bootstrap analysis to test this normality assumption (B. Efron, R.J. Tibshirani, An Introduction to the Bootstrap, Chapman and Hall, London, 1993). COMPROC allows for the inclusion of observed covariates that may influence the decision to verify the disease status of a patient. The program computes the estimates of the area under the ROC curve for the two diagnostic tests along with the variance of each area, the covariance between the two areas, a two-sided p-value, and a confidence interval for the difference of the areas. The programs COMPROC and CHECKNORM require the scripting language Perl and the statistical software SAS and can be run on both UNIX machines as well as PCs. The use of COMPROC and CHECKNORM is illustrated in a clinical study designed to compare relative accuracies of MRI and CT in detecting pancreatic cancer.

Area Under Curve↗

PubMed1998

Risk of major hemorrhage for outpatients treated with warfarin.

OBJECTIVE: To determine the incidence of major hemorrhage among outpatients started on warfarin therapy after the recommendation in 1986 for reduced-intensity anticoagulation therapy was made, and to identify baseline patient characteristics that predict those patients who will have a major hemorrhage. DESIGN: Retrospective cohort study. SETTING: A university-affiliated Veterans Affairs Medical Center. PATIENTS: Five hundred seventy-nine patients who were discharged from the hospital after being started on warfarin therapy. MEASUREMENTS AND MAIN RESULTS: The primary outcome variable was major hemorrhage. In our cohort of 579 patients, there were 40 first-time major hemorrhages with only one fatal bleed. The cumulative incidence was 7% at 1 year. The average monthly incidence of major hemorrhage was 0.82% during the first 3 months of treatment and decreased to 0.36% thereafter. Three independent predictors of major hemorrhage were identified: a history of alcohol abuse, chronic renal insufficiency, and a previous gastrointestinal bleed. Age, comorbidities, medications known to influence prothrombin levels, and baseline laboratory values were not associated with major hemorrhage. CONCLUSIONS: The incidence of major hemorrhage in this population of outpatients treated with warfarin was lower than previous estimates of major hemorrhage measured before the recommendation for reduced-intensity anticoagulation therapy was made, but still higher than estimates reported from clinical trials. Alcohol abuse, chronic renal insufficiency, and a previous gastrointestinal bleed were associated with increased risk of major hemorrhage.

Aged↗

PubMed1998

Estimating the mean value of occupational exposures.

It is very important to provide an accurate estimate for the mean value of lognormal distributed occupational exposures. Four commonly used methods for estimating a lognormal mean are the sample mean, the maximum likelihood estimate (MLE), a bias-corrected MLE, and the minimum variance unbiased estimator (MVUE). In this article the explicit expressions are given for the mean square errors of these four estimators, and performances of these four estimators are compared in terms of their mean square errors. This article reaffirms the conclusion of earlier researchers that the MVUE is uniformly superior to the other three estimators.

Analysis of Variance↗

PubMed1998

Correcting for verification bias in studies of a diagnostic test's accuracy.

Standard methods for assessing the accuracy of diagnostic tests require determination of true disease status for each study patient. In practice, some study patients might not have verified disease status. If the decision to verify a patient is influenced by the test result, analysis using only verified cases might lead to biased results, commonly known as verification bias. This paper reviews recent developments in bias-correction methods for studies on the accuracy of diagnostic tests.

Diagnostic Techniques and Procedures↗

PubMed1998

Evaluation of diagnostic tests without gold standards.

This paper reviews statistical methods developed to estimate the sensitivity and specificity of screening or diagnostic tests when the fallible tests are not evaluated against a gold standard. It gives a brief summary of the earlier historical developments and focuses on the more recent methods. It covers Bayesian approaches and longitudinal studies with repeated testing. In particular, it reviews the procedures that do not require the assumption of independence between tests conditional on the true disease status.

Bayes Theorem↗

PubMed1998

Comparing correlated areas under the ROC curves of two diagnostic tests in the presence of verification bias.

Area Under Curve↗

PubMed1997

Methods for comparison of cost data.

BACKGROUND: Researchers are increasingly interested in examining costs of care, and large administrative and clinical databases have made relevant data readily available. Because a few patients incur high costs relative to most patients, the distribution of cost data is often skewed. How robust are the usual methods of cost analysis against the skewed distribution of cost data? OBJECTIVE: To determine the methods commonly used for comparing cost data, describe their limitations, and provide an alternate method of analysis. DESIGN: Review of statistical methods used in studies of medical costs published in medical journals between January 1991 and January 1996. Description of a Z-score method appropriate for testing the equality of mean costs between two log-normal samples; and reanalysis of published two-sample comparison results done by using the Z-score method. RESULTS: For two-sample comparisons, three methods were commonly used: the Student t-test on untransformed costs, the Wilcoxon test on untransformed costs, and the Student t-test on log-transformed costs. The t-test on untransformed costs ignores the skewness in cost data, the Wilcoxon test ignores unequal variances, and the t-test on log-transformed costs tests the wrong null hypothesis unless variances in the log-scale are equal. Eleven articles included two-sample tests and had enough information to allow reanalysis of the data using the Z-score method. These articles described a total of 23 Wilcoxon tests and 24 t-tests on untransformed costs. Most results did not change on reanalysis, but six results changed enough to alter conclusions. Specifically, reanalysis of data for which one Wilcoxon test had shown statistically significant results showed nonsignificant results; reanalysis of data for which two Wilcoxon tests had shown nonsignificant results showed statistically significant results. In articles that used t-tests on untransformed costs, two statistically significant results became nonsignificant on reanalysis and one nonsignificant result became statistically significant on reanalysis. CONCLUSIONS: The methods commonly used to compare costs of two groups have limitations. Some limitations may change some conclusions, and the direction of the change cannot be predicted. The Z-score method is designed to adjust for skewness in cost data and is appropriate for comparing means of log-normally distributed cost data.

Costs and Cost Analysis↗

PubMed1997

An empirical comparison of two semi-parametric approaches for the estimation of covariate effects from multivariate failure time data.

We conducted a simulation study to compare two semi-parametric approaches for the estimation of covariate effects from multivariate failure time data. The first approach was developed by Wei, Lin and Weissfeld (WLW) and the second by Liang, Self and Chang (LSC). Based on the simulation results we recommend Wei, Lin and Weissfeld's method for the situations with identical covariates and high correlations between the failure times. When the covariates are independent, LSC produces smaller mean squared errors than WLW, although at the expense of larger bias. We also compared four computer programs for implementing Wei, Lin and Weissfeld's approach: a FORTRAN program, MULCOX2; a SAS macro; the coxph function in S-plus, and a specialized software package for complex survey data (SUDAAN). Our comparison indicates that for large data sets, the speeds of the SAS macro and coxph are comparable, while MULCOX2- and SUDAAN took longer to run. However, MULCOX2 and coxph function in S-plus have the advantage of allowing time-dependent covariates, and SUDAAN has the advantage of handling complex survey data.

Adult↗

PubMed1997

Confidence intervals for the log-normal mean .

In this paper we conduct a stimulation study to evaluate coverage error, interval width and relative bias of four main methods for the construction of confidence intervals of log-normal means: the naive method; Cox's method; a conservative method; and a parametric bootstrap method. The simulation study finds that the naive method is inappropriate, that Cox's method has the smallest coverage error for moderate and large sample sizes, and that the bootstrap method has the smallest coverage error for small sample sizes. In addition, Cox's method produces the smallest interval width among the three appropriate methods. We also apply the four methods to a real data set to contrast the differences.

Bias↗

PubMed1997

Examination of racial differences in management of cardiovascular disease.

OBJECTIVES: We sought to identify the clinical characteristics associated with, and to investigate the impact of cohort selection criteria on, interracial use of invasive cardiac procedures and to determine survival. BACKGROUND: Although interracial differences in the use of invasive cardiac procedures have been previously reported, the underlying reasons are not known. METHODS: A retrospective cohort study was conducted at a Veterans Affairs Medical Center. Study patients were evaluated for cardiovascular disease between January 1 and December 31, 1993. RESULTS: The study included 1,406 male patients (85% white, 58% married), with a mean age of 63.4 years. African Americans were less likely than whites to undergo procedures (cardiac catheterization: odds ratio [OR] 0.37, 95% confidence interval [CI] 0.24 to 0.58; coronary angioplasty: OR 0.60, 95% CI 0.25 to 1.49; coronary bypass surgery: OR 0.22, 95% CI 0.08 to 0.63; any procedure: OR 0.32, 95% CI 0.21 to 0.50). On bivariate analysis, patients who underwent cardiac procedures were more likely to be younger, married and reside nonlocally and less likely to have severe comorbid disease; however, African Americans were less likely to be married and to reside nonlocally and more likely to have severe comorbid disease. Cohorts adjusting for referral status and specified cardiac diagnoses reduced or reversed interracial treatment differences. Thirty-day and 1-year survival rates (96% and 87.6%, respectively) were equivalent. CONCLUSIONS: Racial disparity in invasive cardiac procedure use may be partially explained by clinical differences and cohort selection bias. Despite treatment differences, survival rates were equivalent in African Americans and whites.

Black or African American↗

PubMed1997

Preferences of physicians and their patients for end-of-life care.

OBJECTIVE: Both physicians and patients view advance directives as important, yet discussions occur infrequently. We assessed differences and correlations between physicians' and their patients' desires for end-of-life care for themselves. MEASUREMENTS AND MAIN RESULTS: Study physicians (n = 78) were residents and faculty practicing in an inner-city, academic primary care general internal medicine practice. Patients (n = 831) received primary care from these physicians and were either at least 75 or between 50 and 74 years of age, with selected morbid conditions. Physicians and patients completed identical questionnaires that included an assessment of their preferences for six specific treatments if they were terminally ill. There were significant differences between physicians' and patients' preferences for all six treatments (p < .0001), with physicians wanting less treatment than their patients for five of them. Patients desiring more care (p < .01) were more often male (odds ratio [OR] 1.7). African-American (OR 1.6), and older (OR 1.02 per year). There were no such correlates with physicians' preferences. A treatment preference score was calculated from respondents' desires to receive or refuse the six treatments. Physicians' scores were highly correlated with those of their enrolled primary care patients (r = .51, p < .0001). CONCLUSIONS: Although patients and physicians as groups differ substantially in their preferences for end-of-life care, there was significant correlation between individual academic physicians' preferences and those of their primary care patients. Reasons for this correlation are unknown.

Adult↗

PubMed1997

Detection of thyroid remnant/metastasis without stunning: an ongoing dilemma.

The use of 131I doses of several mCi for scans can stun the thyrocytes and thyroid cancer cells, whereas the usual dose (300 microCi) of 123I does not. We compared the diagnostic accuracy of the 123I (300 microCi) scans and that of 131I (3-10 mCi) scans in 155 patients. The diagnostic accuracy of a 123I scan in detecting functioning thyroid remnant/metastasis was 89.5% (77/86 scans) and that of a 131I scan was 92.9% (39/42) in 6 week-postoperative patients (p = 0.750). For radioablation therapy follow-up patients, the diagnostic accuracy of 123I in determining presence or absence of functioning remnant or metastasis was 69.4% (25/36) and that of 131I was 92.5% (49/53) with a p value of 0.079. The success rates for complete ablation of functioning tissue after radioiodine therapy administered after diagnostic 123I and after 131I were 72% (34/47) and 56% (24/43), respectively, with a p value of 0.125. Our study indicates the following: 1) for the first postoperative evaluation, the diagnostic accuracy of the 123I scan was essentially equal to that of the 131I scan, and the success rate of radioablation therapy appears to be better than 123I scan; and 2) for postablation follow-up surveys, the 131I scan appears to be better but carries the risk of stunning the functioning cells.

Adolescent↗