Biomedical subjects

Heejung Bang

Publications and source records attributed to Heejung Bang.

At least 19 recordsLinked to original sources

PubMed2007

On estimating treatment effects under non-compliance in randomized clinical trials: are intent-to-treat or instrumental variables analyses perfect solutions?

In this report, we compared four estimators (intent-to-treat, as treated, per protocol, and instrumental variables estimators) that are conventionally considered for treatment effect estimation by simulation under different non-compliance scenarios in typical clinical trial settings. We found that intent-to-treat and instrumental variables estimators are not perfect and can be problematic in some situations although these two estimators carry desirable properties as we assume.

Humans↗

PubMed2006

Do competence skills moderate the impact of social influences to drink and perceived social benefits of drinking on alcohol use among inner-city adolescents?

Only a few studies have found competence skills to be a protective factor against adolescent alcohol use; others did not find a direct effect on alcohol. A possible reason for this is that competence skills may moderate the effects of risk factors for alcohol use and that aspect has not been examined often or in a longitudinal design. This study tested whether several competence skills served either as direct protective factors against alcohol use or moderators of the impact of social risk factors on alcohol use. Participants (N = 1318) completed questionnaires that included measures of decision-making skills, refusal skill techniques, resisting media influences, friends' drinking and perceived social benefits of drinking, as well as current drinking amount and future drinking at baseline, one-year follow-up and two-year follow-up. Data analyses were conducted using multi-level mixed effects generalized linear models with random intercept. All the competence skills and the risk factors predicted current and future drinking. Several significant interactions were found between (1) perceived social benefits of drinking and decision-making skills, (2) perceived social benefits of drinking and refusal skill techniques and (3) friends' drinking and refusal skill techniques. Competence skills served as protective factors, as well as moderators. One possible reason that competence enhancement approaches to alcohol prevention are effective may be due to the inclusion of the competence skills component.

Adolescent↗

PubMed2006

Tutorial in biostatistics: Analyzing associations between total plasma homocysteine and B vitamins using optimal categorization and segmented regression.

Data analysts consider standard regression models (e.g., generalized linear model) or nonparametric smoothing techniques (e.g., loess or splines) when examining the association between two variables. Before this step, a quantile-based summarization is typically used for exploring the exposure-response relationship. Unfortunately, these exploratory approaches may not be optimal or efficient for guiding the formal analysis in many biological and nutritional data settings. We suggest a recently developed method for selection of cutpoints as a tool of data summary and segmented regression as a modeling approach in the analysis of plasma total homocysteine and related vitamins. These methods are often complementary in discovering the underlying complex pattern of association.

Algorithms↗

PubMed2006

Letrozole reduces estrogen and gonadotropin exposure in women with breast cancer undergoing ovarian stimulation before chemotherapy.

CONTEXT: Women with breast cancer are not typically offered embryo or oocyte cryopreservation to preserve their fertility before chemotherapy because of the potential risks associated with high estrogen levels arising from ovarian stimulation. OBJECTIVE: We aimed to determine whether the combination of an aromatase inhibitor with gonadotropin treatment in breast cancer patients produces comparable results to standard in vitro fertilization (IVF), without a significant increase in estradiol levels and delay in the initiation of chemotherapy. PATIENTS AND METHODS: Stages I-IIIA breast cancer patients (n = 47) received 5 mg/d letrozole and 150-300 IU FSH to cryopreserve embryos or oocytes. Age-matched retrospective controls (n = 56) were selected from women who underwent IVF for tubal disease. RESULTS: Whereas letrozole and FSH stimulation resulted in significantly lower peak estradiol levels (mean +/- sd 483.4 +/- 278.9 vs. 1464.6 +/- 644.9 pg/ml; P < 0.001) and 44% reduction in gonadotropin requirement, compared with controls, the length of stimulation, number of embryos obtained, and fertilization rates were similar. The human chorionic gonadotropin administration criteria had to be adjusted to 20 mm after letrozole stimulation, compared with 17-18 mm in the controls. The mean delay from surgery to cryopreservation was 38.6 d, with 81% of all patients completing their IVF cycles within 8 wk of surgery. CONCLUSION: Ovarian stimulation with letrozole and FSH appears to be a cost-effective alternative for fertility preservation in breast cancer patients with reduced estrogen exposure, compared with standard IVF. If patients are referred promptly, they may undergo embryo or oocyte cryopreservation without a delay in chemotherapy.

Adult↗

PubMed2006

Which psychosocial factors moderate or directly affect substance use among inner-city adolescents?

Past etiology of adolescent substance use research concentrated on the main effects of various risk factors. The purpose of this study was to also longitudinally predict interactions on poly-drug use intensity and future smoking among inner-city adolescents. A panel sample of baseline, 1-year and 2-year follow-ups (N=1459) from the control group of a longitudinal smoking prevention trial participated. We focused on the main effects, as well as, interaction effects between psychosocial protective factors and various risk factors, including perceived norms of friends, peers and adults to use drugs. Significant effects were identified for intensity of poly-drug use and future smoking. The analysis of the poly-drug use outcome indicated that refusal assertiveness undermined perceived friends' drug use and siblings' smoking, and that low risk-taking undermined perceived friends' drug use. There was a main effect for low psychological wellness. The significant interactions between perceived friends' drug use with refusal assertiveness and decision-making skills were observed for future smoking. Moreover, perceived peer smoking norms, siblings' smoking, and high risk-taking also showed significant main effects for increasing future smoking.

Adolescent↗

PubMed2006

Blood pressure usually considered normal is associated with an elevated risk of cardiovascular disease.

PURPOSE: Research on the risk of cardiovascular disease among individuals with prehypertension (blood pressure 120/80 to 139/89 mm Hg) is incomplete. Additional information among individuals with a high risk of cardiovascular disease complications may help to focus current and future efforts. SUBJECTS AND METHODS: We performed a prospective cohort analysis among 8960 middle-aged adults in the Atherosclerosis Risk in Communities (ARIC) study. The exposure variables were blood pressure levels: high normal blood pressure, systolic blood pressure 130-139 mm Hg or diastolic blood pressure 85-89 mm Hg; and normal blood pressure, systolic blood pressure 120-129 mm Hg or diastolic blood pressure 80-84 mm Hg. The outcome was incident cardiovascular disease defined as fatal/nonfatal coronary heart disease, cardiac procedure, silent myocardial infarction, or ischemic stroke. Subgroup analysis was performed among blacks, diabetics, individuals aged 55-64 years, individuals with renal insufficiency, and among individuals with varying levels of low-density lipoprotein (LDL) cholesterol and body mass index (BMI). RESULTS: Compared with optimal blood pressure (systolic blood pressure <120 mm Hg and diastolic blood pressure <80 mm Hg), the relative risk (RR) of cardiovascular disease for high normal blood pressure was 2.33 (95% confidence interval [CI], 1.85-2.92), and RR for normal blood pressure was 1.81 (1.47-2.22); among blacks: RR for high normal blood pressure was 3.29 (95% CI, 1.68-6.45); among diabetics: RR for high normal blood pressure 4.10 (95% CI, 2.26-7.46); age 55-64 years: RR for high normal blood pressure 2.41 (95% CI, 1.75-3.30) among individuals with renal insufficiency: RR for high normal blood pressure was 1.90 (95% CI, 1.34-2.70); among individuals with BMI >30 kg/m2: RR for high normal blood pressure was 3.56 (95% CI, 1.99-6.35); and among individuals with LDL >160 mg/dL, RR for high normal blood pressure was 1.85 (95% CI, 1.26-2.72). CONCLUSIONS: Individuals with prehypertensive levels of blood pressure have an increased risk of developing cardiovascular disease relative to those with optimal levels. The association is pronounced among blacks, among individuals with diabetes mellitus, and among those with high BMI.

Blood Pressure↗

PubMed2006

Efficiency of oocyte cryopreservation: a meta-analysis.

OBJECTIVE: To determine the efficiency of oocyte cryopreservation relative to IVF with unfrozen oocytes. DESIGN: Meta-analysis. SETTING: Academic assisted reproduction center. PATIENT(S): Results of all reports from January 1997 to June 2005 with the patients undergoing IVF-intracytoplasmic sperm injection (ICSI) with cryopreserved cycles between 1996 and 2004 were compared with those of patients who underwent IVF-ICSI with unfrozen oocytes in 2002 and 2003 in our program. INTERVENTION(S): Mean age and number of ET cycles originating from unfrozen oocytes was matched with those for thaw cycles originating from oocytes cryopreserved with a slow-freezing (SF) protocol. Vitrification (VF) reports were not included in the comparative analysis because of a small number of pregnancies (10) before June 2005. MAIN OUTCOME MEASURE(S): The comparison of fertilization rate, clinical pregnancy, and live-birth rates per injected oocyte, clinical pregnancy and live-birth rates per transfer, and implantation rate between IVF-ICSI cycles with frozen and unfrozen oocytes. RESULT(S): Live-birth rates per oocyte thawed were 1.9% and 2.0% for SF and VF, respectively, before June 2005. Live-birth rates per injected oocyte and ET, respectively, were 3.4% and 21.6% for SF and were 6.6% and 60.4% for IVF with unfrozen oocytes. Compared to women who underwent IVF after SF, IVF with unfrozen oocytes resulted in significantly better rates of fertilization (odds ratio [95% confidence interval]); 2.22 (1.80, 2.74), of live birth per injected oocyte; 1.5 (1.26, 1.79), and of implantation; 4.66 (3.93, 5.52). These odds ratios were lower when oocyte cryopreservation success rates from 2002-2004 were compared with those for IVF with unfrozen oocytes. When the reports after June 2005 were considered, this trend did not appear to continue. With the consideration of VF reports after June 2005, however, higher pregnancy rates were achieved. CONCLUSION(S): In vitro fertilization success rates with slow-frozen oocytes are significantly lower when compared with the case of IVF with unfrozen oocytes. Although oocyte cryopreservation with the SF method appears to be justified for preserving fertility when a medical indication exists, its value for elective applications remains to be determined. Pregnancy rates with VF appear to have improved, but further studies will be needed to determine the efficiency and safety of this technique.

Cryopreservation↗

PubMed2005

Lipoprotein-associated phospholipase A2, high-sensitivity C-reactive protein, and risk for incident ischemic stroke in middle-aged men and women in the Atherosclerosis Risk in Communities (ARIC) study.

BACKGROUND: Measurement of inflammatory markers has been reported to identify individuals at increased risk for ischemic stroke. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a proinflammatory enzyme secreted by macrophages. We assessed Lp-PLA2 and C-reactive protein (CRP) levels along with traditional risk factors to examine their relation to ischemic stroke. METHODS: A proportional hazards model was used in a prospective case-cohort study of 12,762 apparently healthy middle-aged men and women in the Atherosclerosis Risk in Communities (ARIC) study who were observed for about 6 years. RESULTS: Mean Lp-PLA2 and CRP levels adjusted for sex, race, and age were higher in the 194 stroke cases than the 766 noncases, whereas low-density lipoprotein cholesterol (LDL-C) level was not significantly different. Both Lp-PLA2 and CRP levels were associated with ischemic stroke after adjustment for age, sex, and race: hazard ratios were 2.23 for the highest vs the lowest tertile of Lp-PLA2 and 2.70 for CRP level higher than 3 vs lower than 1 mg/L. In a model that included smoking, systolic hypertension, lipid levels, and diabetes, Lp-PLA2 and CRP levels in the highest category were associated with hazard ratios of 1.91 (95% confidence interval, 1.15-3.18; P = .01) and 1.87 (95% confidence interval, 1.13-3.10; P = .02), respectively. Individuals with high levels of both CRP and Lp-PLA2 were at the highest risk after adjusting for traditional risk factors compared with individuals with low levels of both, whereas others were at intermediate risk. CONCLUSION: Levels of Lp-PLA2 and CRP may be complementary beyond traditional risk factors in identifying middle-aged individuals at increased risk for ischemic stroke.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

PubMed2005

Vitamin Intervention For Stroke Prevention trial: an efficacy analysis.

BACKGROUND AND PURPOSE: The Vitamin Intervention for Stroke Prevention trial (VISP) intention-to-treat analysis did not show efficacy of combined vitamin therapy for recurrent vascular events in patients with nondisabling stroke. Reasons for lack of efficacy may have included folate fortification of grain products, inclusion of the recommended daily intake for B12 in the low-dose arm, treatment with parenteral B12 in patients with low B12 levels in both study arms, a dose of B12 too low for patients with malabsorption, supplementation with nonstudy vitamins, and failure of patients with significant renal impairment to respond to vitamin therapy. We conducted an efficacy analysis limited to patients most likely to benefit from the treatment, based on hypotheses arising from evidence developed since VISP was initiated. The criteria for this subgroup were defined before any data analysis. METHODS: For this analysis, we excluded patients with low and very high B12 levels at baseline (<250 and >637 pmol/L, representing the 25th and 95th percentiles), to exclude those likely to have B12 malabsorption or to be taking B12 supplements outside the study and patients with significant renal impairment (glomerular filtration rate <46.18; the 10th percentile). RESULTS: This subgroup represents 2155 patients (37% female), with a mean age of 66+/-10.7 years. For the combined end point of ischemic stroke, coronary disease, or death, there was a 21% reduction in the risk of events in the high-dose group compared with the low-dose group (unadjusted P=0.049; adjusted for age, sex, blood pressure, smoking, and B12 level P=0.056). In Kaplan-Meier survival analysis comparing 4 groups, patients with a baseline B12 level at the median or higher randomized to high-dose vitamin had the best overall outcome, and those with B12 less than the median assigned to low-dose vitamin had the worst (P=0.02 for combined stroke, death, and coronary events; P=0.03 for stroke and coronary events). CONCLUSIONS: In the era of folate fortification, B12 plays a key role in vitamin therapy for total homocysteine. Higher doses of B12, and other treatments to lower total homocysteine may be needed for some patients.

Aged↗

PubMed2005

Medical cost analysis: application to colorectal cancer data from the SEER Medicare database.

Incompleteness is a key feature of most survival data. Numerous well established statistical methodologies and algorithms exist for analyzing life or failure time data. However, induced censorship invalidates the use of those standard analytic tools for some survival-type data such as medical costs. In this paper, some valid methods currently available for analyzing censored medical cost data are reviewed. Some cautionary findings under different assumptions are envisioned through application to medical costs from colorectal cancer patients. Cost analysis should be suitably planned and carefully interpreted under various meaningful scenarios even with judiciously selected statistical methods. This approach would be greatly helpful to policy makers who seek to prioritize health care expenditures and to assess the elements of resource use.

Aged↗

PubMed2005

The effect of cholesterol reduction with cholestyramine on renal function.

BACKGROUND: Epidemiological studies suggest that dyslipidemia is an independent risk factor for the development of renal insufficiency in otherwise healthy individuals. Yet, data on the effect of cholesterol reduction are lacking in this population. We performed a secondary analysis of a large existing cohort to determine whether treatment with cholestyramine improved renal function compared with placebo. METHODS: A total of 3,603 middle-aged men from the Lipid Research Clinics Coronary Primary Prevention Trial comprised the study group: 1,806 men were randomly assigned to treatment with cholestyramine, and 1,797 men, placebo. The primary outcome is difference in glomerular filtration rates between the 2 groups. RESULTS: A total of 1,806 men were randomly assigned to treatment with cholestyramine, and 1,797 men, placebo. For the entire group, the estimated mean difference in glomerular filtration rates between the cholestyramine and placebo groups was 0.39 mL/min/1.73 m2 (0.007 mL/s/1.73 m2; P = 0.28) during a follow-up period of more than 8 years. CONCLUSION: Cholesterol reduction with cholestyramine treatment did not meaningfully affect renal function compared with placebo in the present analysis. Prospective intervention trials are needed to determine whether decreasing serum cholesterol levels benefits kidney function in otherwise healthy individuals.

Adult↗

PubMed2005

Sample size calculation for simulation-based multiple-testing procedures.

In this article, we present a simple method to calculate sample size and power for a simulation-based multiple testing procedure which gives a sharper critical value than the standard Bonferroni method. The method is especially useful when several highly correlated test statistics are involved in a multiple-testing procedure. The formula for sample size calculation will be useful in designing clinical trials with multiple endpoints or correlated outcomes. We illustrate our method with a quality-of-life study for patients with early stage prostate cancer. Our method can also be used for comparing multiple independent groups.

Computer Simulation↗

PubMed2005

Sample size calculation for multiple testing in microarray data analysis.

Microarray technology is rapidly emerging for genome-wide screening of differentially expressed genes between clinical subtypes or different conditions of human diseases. Traditional statistical testing approaches, such as the two-sample t-test or Wilcoxon test, are frequently used for evaluating statistical significance of informative expressions but require adjustment for large-scale multiplicity. Due to its simplicity, Bonferroni adjustment has been widely used to circumvent this problem. It is well known, however, that the standard Bonferroni test is often very conservative. In the present paper, we compare three multiple testing procedures in the microarray context: the original Bonferroni method, a Bonferroni-type improved single-step method and a step-down method. The latter two methods are based on nonparametric resampling, by which the null distribution can be derived with the dependency structure among gene expressions preserved and the family-wise error rate accurately controlled at the desired level. We also present a sample size calculation method for designing microarray studies. Through simulations and data analyses, we find that the proposed methods for testing and sample size calculation are computationally fast and control error and power precisely.

Computer Simulation↗

PubMed2005

Doubly robust estimation in missing data and causal inference models.

The goal of this article is to construct doubly robust (DR) estimators in ignorable missing data and causal inference models. In a missing data model, an estimator is DR if it remains consistent when either (but not necessarily both) a model for the missingness mechanism or a model for the distribution of the complete data is correctly specified. Because with observational data one can never be sure that either a missingness model or a complete data model is correct, perhaps the best that can be hoped for is to find a DR estimator. DR estimators, in contrast to standard likelihood-based or (nonaugmented) inverse probability-weighted estimators, give the analyst two chances, instead of only one, to make a valid inference. In a causal inference model, an estimator is DR if it remains consistent when either a model for the treatment assignment mechanism or a model for the distribution of the counterfactual data is correctly specified. Because with observational data one can never be sure that a model for the treatment assignment mechanism or a model for the counterfactual data is correct, inference based on DR estimators should improve upon previous approaches. Indeed, we present the results of simulation studies which demonstrate that the finite sample performance of DR estimators is as impressive as theory would predict. The proposed method is applied to a cardiovascular clinical trial.

Antidepressive Agents↗

PubMed2005

Identifying individuals at high risk for diabetes: The Atherosclerosis Risk in Communities study.

OBJECTIVE: To develop and evaluate clinical rules to predict risk for diabetes in middle-aged adults. RESEARCH DESIGN AND METHODS: The Atherosclerosis Risk in Communities is a cohort study conducted from 1987-1989 to 1996-1998. We studied 7,915 participants 45-64 years of age, free of diabetes at baseline, and ascertained 1,292 incident cases of diabetes by clinical diagnosis or oral glucose tolerance testing. RESULTS: We derived risk functions to predict diabetes using logistic regression in a random half of the sample. Rules based on these risk functions were evaluated in the other half. A risk function based on waist, height, hypertension, blood pressure, family history of diabetes, ethnicity, and age was performed similarly to one based on fasting glucose (area under the receiver-operating characteristic curve [AUC] 0.71 and 0.74, respectively; P = 0.2). Risk functions composed of the clinical variables plus fasting glucose (AUC 0.78) and additionally including triglycerides and HDL cholesterol (AUC 0.80) performed better (P < 0.001). Evaluation of scores based on the metabolic syndrome as defined by the National Cholesterol Education Program or with slight variations showed AUCs of 0.75 and 0.78, respectively. Rules based on all these approaches, while identifying 20-56% of the sample as screen positive, achieved sensitivities of 40-87% and specificities of 50-86%. CONCLUSIONS: Rules derived from clinical information, alone or combined with simple laboratory measures, can characterize degrees of diabetes risk in middle-aged adults, permitting preventive actions of appropriate intensity. Rules based on the metabolic syndrome are reasonable alternatives to rules derived from risk functions.

Arteriosclerosis↗

PubMed2004

Lipoprotein-associated phospholipase A2, high-sensitivity C-reactive protein, and risk for incident coronary heart disease in middle-aged men and women in the Atherosclerosis Risk in Communities (ARIC) study.

BACKGROUND: Measuring C-reactive protein (CRP) has been recommended to identify patients at high risk for coronary heart disease (CHD) with low LDL cholesterol (LDL-C). Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a proinflammatory enzyme associated primarily with LDL. METHODS AND RESULTS: In a prospective, case cohort study in 12 819 apparently healthy middle-aged men and women in the Atherosclerosis Risk in Communities study, the relation between Lp-PLA2, CRP, traditional risk factors, and risk for CHD events over a period of approximately 6 years was examined in a proportional hazards model, stratified by LDL-C. Lp-PLA2 and CRP levels were higher in the 608 cases than the 740 noncases. Both Lp-PLA2 and CRP were associated with incident CHD after adjustment for age, sex, and race with a hazard ratio of 1.78 for the highest tertile of Lp-PLA2 and 2.53 for the highest category of CRP versus the lowest categories. Lp-PLA2 correlated positively with LDL-C (r=0.36) and negatively with HDL-C (r=-0.33) but not with CRP (r=-0.05). In a model adjusted for traditional risk factors including LDL-C, the association of Lp-PLA2 with CHD was attenuated and not statistically significant. For individuals with LDL-C below the median (130 mg/dL), Lp-PLA2 and CRP were both significantly and independently associated with CHD in fully adjusted models. For individuals with LDL-C <130 mg/dL, those with both Lp-PLA2 and CRP levels in the highest tertile were at the greatest risk for a CHD event. CONCLUSIONS: Lp-PLA2 and CRP may be complementary in identifying individuals at high CHD risk who have low LDL-C.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

PubMed2004

Assessment of blinding in clinical trials.

Success of blinding is a fundamental issue in many clinical trials. The validity of a trial may be questioned if this important assumption is violated. Although thousands of ostensibly double-blind trials are conducted annually and investigators acknowledge the importance of blinding, attempts to measure the effectiveness of blinding are rarely discussed. Several published papers proposed ways to evaluate the success of blinding, but none of the methods are commonly used or regarded as standard. This paper investigates a new approach to assess the success of blinding in clinical trials. The blinding index proposed is scaled to an interval of -1 to 1, 1 being complete lack of blinding, 0 being consistent with perfect blinding and -1 indicating opposite guessing which may be related to unblinding. It has the ability to detect a relatively low degree of blinding, response bias and different behaviors in two arms. The proposed method is applied to a clinical trial of cholesterol-lowering medication in a group of elderly people.

Aged↗

PubMed2004

Estimating treatment effects in studies of perinatal transmission of HIV.

Fetal loss often precludes the ascertainment of infection status in studies of perinatal transmission of HIV. The standard analysis based on liveborn babies can result in biased estimation and invalid inference in the presence of fetal death. This paper focuses on the problem of estimating treatment effects for mother-to-child transmission when infection status is unknown for some babies. Minimal data structures for identifiability of parameters are given. Methods using full likelihood and the inverse probability of selection-weighted estimators are suggested. Simulation studies are used to show that these estimators perform well in finite samples. Methods are applied to the data from a clinical trial in Dar es Salaam, Tanzania. To validly estimate the treatment effect using likelihood methods, investigators should make sure that the design includes a mini-study among uninfected mothers and that efforts are made to ascertain the infection status of as many babies lost as possible. The inverse probability weighting methods need precise estimation of the probability of observing infection status. We can further apply our methodology to the study of other vertically transmissible infections which are potentially fatal pre- and perinatally.

Female↗