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Biomedical subjects

Chul Ahn

Publications and source records attributed to Chul Ahn.

At least 19 recordsLinked to original sources
PubMed2024

The phosphatidylserine targeting antibody bavituximab plus pembrolizumab in unresectable hepatocellular carcinoma: a phase 2 trial.

Immune checkpoint inhibitors targeting PD-1/L1 have modest efficacy in hepatocellular carcinoma as single agents. Targeting membranous phosphatidylserine may induce pro-inflammatory and -immune stimulating effects that enhance immunotherapy activity. This hypothesis was tested in a single-arm phase 2 trial evaluating frontline bavituximab, a phosphatidylserine targeting antibody, plus pembrolizumab (anti-PD-1) in patients with unresectable hepatocellular carcinoma (NCT03519997). The primary endpoint was investigator-assessed objective response rate among evaluable patients, and secondary end points included progression-free survival, incidence of adverse events, overall survival, and duration of response. Among 28 evaluable patients, the confirmed response rate was 32.1%, which met the pre-specified endpoint, and the median progression-free survival was 6.3 months (95% CI, 1.3-11.3 months). Treatment related-adverse events of any grade occurred in 45.7% of patients, with grade 3 or greater adverse events in 14.3% of patients. Adverse events of any cause were observed in 33 patients (94.3%), with grade 3 or greater adverse events in 11 patients (31.4%). Prespecified exploratory analyses of baseline tumor specimens showed that a depletion of B cells, and the presence of fibrotic tissue and expression of immune checkpoints in stroma was associated with tumor response. These results suggest that targeting phosphatidylserine may lead to synergistic effects with PD-1 blockade without increasing toxicity rates, and future studies on this therapeutic strategy may be guided by biomarkers characterizing the pre-treatment tumor microenvironment.

Humans↗
PubMed2003

Effect of simvastatin versus placebo on treadmill exercise time until the onset of intermittent claudication in older patients with peripheral arterial disease at six months and at one year after treatment.

Simvastatin significantly increased treadmill exercise time until onset of intermittent claudication from baseline by 54 seconds (a 24% increase, p <0.0001) at 6 months after treatment and by 95 seconds (a 42% increase, p <0.0001) at 1 year after treatment. At 6 months and 1 year after treatment with placebo, treadmill exercise time until onset of intermittent claudication was not significantly different from baseline exercise time.

Aged↗
PubMed2003

Sample size estimation for GEE method for comparing slopes in repeated measurements data.

Sample size calculation is an important component at the design stage of clinical trials. Controlled clinical trials often use a repeated measurement design in which individuals are randomly assigned to treatment groups and followed-up for measurements at intervals across a treatment period of fixed duration. In studies with repeated measurements, one of the popular primary interests is the comparison of the rates of change in a response variable between groups. Statistical models for calculating sample sizes for repeated measurement designs often fail to take into account the impact of missing data correctly. In this paper we propose to use the generalized estimating equation (GEE) method in comparing the rates of change in repeated measurements and introduce closed form formulae for sample size and power that can be calculated using a scientific calculator. Since the sample size formula is based on asymptotic theory, we investigate the performance of the estimated sample size in practical settings through simulations.

Data Interpretation, Statistical↗
PubMed2003

Interaction between soluble thrombomodulin and intercellular adhesion molecule-1 in predicting risk of coronary heart disease.

BACKGROUND: Results from previous ARIC (Atherosclerosis Risk In Communities) analyses indicate that soluble intercellular adhesive molecule-1 (sICAM) and soluble thrombomodulin (sTM) levels are associated with risk of coronary heart disease (CHD) in an opposite direction. A high sICAM level increases the risk of CHD, whereas a high level of sTM has a lower risk of CHD. It was unclear whether there was an interaction between sTM and sICAM. METHODS AND RESULTS: Using a nested case-cohort design, we measured sTM and sICAM in 317 incident CHD cases and 726 non-cases from the ARIC participants. Consistent with our previous reports, sICAM values in the upper versus the lower tertile increased the risk of CHD event by approximately 2-fold (95% confidence interval [CI], 1.46 to 2.87) whereas sTM values in the lower versus the upper tertile increased CHD risk by approximately 4-fold (95% CI, 2.80 to 5.74). Interaction between these 2 parameters was determined by weighted Cox proportional hazard regression. A significant interaction (P=0.038) was noted. Combinatorial analysis shows a significant increase in CHD risk ratio (RR) (4.66, 95% CI, 1.89 to 11.46) of the lower sTM/upper sICAM group versus the upper sTM/lower sICAM group. Individuals whose sTM values were in the upper tertile had a RR below 1, even when sICAM were in the upper tertile. The RR of lower tertile sTM was increased by sICAM in a tertile-dependent manner. CONCLUSIONS: Weighted Cox proportional hazard analysis shows a significant interaction between sTM and sICAM in predicting risk of CHD event. Combinatorial analysis reveals that an upper tertile sICAM had a significant increase in the risk of a CHD event only when sTM was in the lower tertile.

Case-Control Studies↗
PubMed2003

Physician perspectives on the importance of facts men ought to know about prostate-specific antigen testing.

OBJECTIVE: To determine physicians' rating of the importance of key facts men ought to know about prostate-specific antigen (PSA) screening and whether there are differences by specialty. PARTICIPANTS: A nationwide random sample of internists, family physicians, and urologists stratified by physician specialty from The Official ABMS Directory of Board-Certified Medical Specialists 2000 Edition. MEASUREMENTS: Internists (N = 139), family physicians (N = 160), and urologists (N = 151) were asked to rate how important it is for men to know 17 facts about PSA screening using a 5-point Likert scale. MAIN RESULTS: Of 769 eligible physicians, 450 responded, for an overall response rate of 59%. Urologists and nonurologists differed in rating how important it was for men to know 9 of the 17 key facts. Eight of the nine statements that urologists and nonurologists disagreed upon concerned facts reflecting uncertainty. Nonurologists were more likely than urologists to rate facts reflecting uncertainty as highly important for men to know. These included statements about prostate cancer risk, screening with PSA, and treatment. CONCLUSIONS: Despite professional guidelines supporting informed decision making, the importance of facts men ought to know about PSA testing differ by physician specialty. Systematic differences may reflect differences in professional guidelines about PSA testing.

Adult↗
PubMed2003

Chi-square test for R x C contingency tables with clustered data.

In ophthalmologic or dental studies, observations are frequently taken from multiple sites (called units), such as eyes or teeth, of each subject. In this case, observations within each subject (called clusters) may be dependent, although those from different subjects are independent. When a categorical observation is made from each site, application of the usual Pearson chi-square tests is invalid since sites within the same subject tend to be dependent. We propose a modified chi2 statistic for testing no treatment effect in these cases. The proposed methods do not require correct specification of the dependence structure within cluster. Simulation studies are conducted to show the finite-sample performance of the new methods. The proposed methods are applied to real-life data.

Animals↗
PubMed2003

Elderly diabetics with peripheral arterial disease and no coronary artery disease have a higher incidence of new coronary events than elderly nondiabetics with peripheral arterial disease and prior myocardial infarction treated with statins and with no lipid-lowering drug.

BACKGROUND: We report data showing the incidence of new coronary events in diabetics with prior myocardial infarction (MI), nondiabetics with prior MI, diabetes with no coronary artery disease (CAD), and nondiabetics with no CAD who were treated with and without statins. METHODS: We investigated-in an observational prospective study of 274 diabetics and 386 nondiabetics with peripheral arterial disease, mean age years, and a serum low-density lipoprotein cholesterol level of >/=125 mg/dl-the incidence of new coronary events in diabetics with prior MI, nondiabetics with prior MI, diabetics with no CAD, and nondiabetics with no CAD who were treated with and without statins. Follow-up was months. RESULTS: In patients treated with statins, the incidence of new coronary events was 73% in diabetics with prior MI (group 1), 37% in nondiabetics with prior MI (group 2), 57% in diabetics with no CAD (group 3), and 27% in nondiabetics with no CAD (group 4). In patients treated with no lipid-lowering drug, the incidence of new coronary events was 91% in diabetics with prior MI (group 5), 72% in nondiabetics with prior MI (group 6), 86% in diabetics with no CAD (group 7), and 52% in nondiabetics with no CAD (group 8). Significant p values were p<.0001 for group 1 versus 2, group 7 versus 8, and group 2 versus 6; p=.0006 for group 3 versus 4; p=.0007 for group 3 versus 7; p=.001 for group 5 versus 6; p=.002 for group 4 versus 8; p=.003 for group 1 versus 5; p=.015 for group 2 versus 3; and p=.047 for group 6 versus 7. CONCLUSIONS: In patients treated with and without statins, diabetics with no CAD had a higher incidence of new coronary events than did nondiabetics with prior MI.

Aged↗
PubMed2003

Informed consent for cancer screening with prostate-specific antigen: how well are men getting the message?

OBJECTIVES: This study examined knowledge about prostate-specific antigen (PSA) screening among African Americans and Whites. Because PSA screening for prostate cancer is controversial, professional organizations recommend informed consent for screening. METHODS: Men (n = 304) attending outpatient clinics were surveyed for their knowledge about and experience with screening. RESULTS: Most men did not know the key facts about screening with PSA. African Americans appeared less knowledgeable than Whites, but these differences were mediated by differences in educational level and experience with prostate cancer screening. CONCLUSIONS: Public health efforts to improve informed consent for prostate cancer screening should focus on highlighting the key facts and developing different approaches for men at different levels of formal education and prior experience with screening.

Black or African American↗
PubMed2002

Factor XIIIA Val34Leu polymorphism does not predict risk of coronary heart disease: The Atherosclerosis Risk in Communities (ARIC) Study.

Factor XIII catalyzes the cross-linking of fibrin. Cross-sectional studies have suggested that a common polymorphism site at residue 34 of the A subunit of factor XIII (FXIIIA) with a substitution of Leu for Val (FXIIIA Val34Leu) was associated with reduced coronary heart disease (CHD). This association has not been examined in prospective studies. Healthy subjects (n=15 792) were recruited from 4 US communities into the Atherosclerosis Risk in Communities (ARIC) study from 1987 to 1989. They were followed, and incident CHD events were identified and verified. For the present study, we included 423 patients with CHD as cases and 479 noncases. FXIIIA Val34Leu polymorphism was determined by the single-strand conformational polymorphism method. There were no significant differences in the genotype frequencies between cases and noncases. The genotypes showed little association with known CHD risk factors. A weighted proportional hazards regression analysis adjusting for other risk factors confirmed no association of the genotypes with risk of CHD. This prospective study did not provide evidence of a reduced CHD risk for the FXIIIA 34Leu allele.

Case-Control Studies↗
PubMed2002

Association of novel polymorphisms with the expression of SPARC in normal fibroblasts and with susceptibility to scleroderma.

OBJECTIVE: Fibroblasts from patients with systemic sclerosis (SSc) have an activated phenotype characterized by increased synthesis of extracellular matrix (ECM) components. SPARC (secreted protein, acidic and rich in cysteine) regulates the deposition or assembly of ECM components. The aim of this study was to investigate the role of SPARC in SSc susceptibility by functional and genetic association studies. METHODS: Complementary DNA (cDNA) microarrays were used to obtain gene expression data on cultured dermal fibroblasts from SSc patients. SPARC protein levels were assessed by Western blotting. Five polymorphic microsatellite markers within 5 cM of the SPARC gene (chromosome 5q31-32) were genotyped in Choctaw Indians, a population previously shown to have a high prevalence of SSc. Discovery of single-nucleotide polymorphisms (SNPs) was accomplished by sequencing the SPARC cDNA. These SNPs were then genotyped in a multi-ethnic cohort of SSc patients to determine potential associations with disease susceptibility in a broader population of SSc patients, as well as with various clinical and immunologic features of SSc. The functional relevance of these SNPs with regard to transcript stability of SPARC was also assessed. RESULTS: Microarrays demonstrated increased expression of SPARC, along with other ECM genes, in SSc patients compared with normal controls. SSc fibroblasts also had increased SPARC protein levels. Three of 5 microsatellite markers near SPARC showed significant associations with SSc in the Choctaw SSc patients. Sequencing of SPARC cDNA revealed 3 novel SNPs in the 3'-untranslated region at +998 (C-->G), +1551 (C-->G), and +1922 (T-->G). Homozygosity for the C allele at SNP +998 was significantly increased in SSc patients across ethnic lines. SPARC SNPs +1551 and +1922 demonstrated correlations with Raynaud's phenomenon and pulmonary fibrosis, respectively. Functional studies of SPARC SNP +998 in normal fibroblast cultures suggested a correlation between the SNP +998 C allele polymorphism and an increased messenger RNA half-life. CONCLUSION: This study is the first to show that polymorphisms of the SPARC gene are associated with susceptibility to, and clinical manifestations of, SSc and that they may also be functionally important in influencing SPARC expression in skin fibroblasts.

Blotting, Western↗
PubMed2002

Application of an adjusted chi2 statistic to site-specific data in observational dental studies.

BACKGROUND: When a binary response is observed on teeth from each subject belonging to 2 or more exposure groups, application of the usual Pearson chi2 tests is invalid, since such responses within the same subject are not independent. Consequently, special statistical methods are needed to control for the correlation among teeth (sites) within the same subject. A simple adjustment to the Pearson chi2 statistic has been proposed for comparing proportions in site-specific data. However, the required assumptions for this statistic have not yet been thoroughly addressed. These assumptions are guaranteed to hold in experimental comparisons, but may be violated in some observational studies. METHOD: We investigate the conditions under which the adjusted chi2 statistic is valid and examine the performance of the adjusted chi2 statistic when these conditions are violated. RESULTS: Our simulation study shows that the adjusted chi2 statistic generally produces good empirical type I errors under the assumption of a common intracluster correlation coefficient. Even if the intracluster correlations are different, the adjusted statistic performs well when the groups have equal numbers of clusters (subjects). CONCLUSION: The discussion is illustrated using an observational study of caries on the roots of teeth.

Analysis of Variance↗
PubMed2002

Prevalence of and association between silent myocardial ischemia and new coronary events in older men and women with and without cardiovascular disease.

OBJECTIVES: To investigate the prevalence of silent ischemia (SI) in older men and women detected by 24-hour ambulatory electrocardiograms (AECGs) and the association between SI and new coronary events. DESIGN: In a prospective study, the prevalence of SI detected by 24-hour AECGs and the incidence of new coronary events in 915 older men and 1,874 older women with coronary artery disease (CAD); with hypertension, valvular disease, or cardiomyopathy without CAD; and with no cardiovascular disease were investigated. SETTING: Large long-term healthcare facility. PARTICIPANTS: Nine hundred fifteen men, mean age 80, and 1,874 women, mean age 81. MEASUREMENTS: The prevalence of SI and the incidence of new coronary events in older men and women. RESULTS: SI was present in 34% of men and 33% of women with CAD; 15% of men and 14% of women with hypertension, valvular disease, or cardiomyopathy without CAD; and 6% of men and 5% of women with no cardiovascular disease. At 45-month follow-up in men and 47-month follow-up in women, SI significantly increased the incidence of new coronary events by 2.0 times in men and women with CAD (P <.001); by 1.8 times in men and 1.7 times in women with hypertension, valvular disease, or cardiomyopathy without CAD (P <.001); and by 6.3 times in men (P =.018) and 4.4 times in women (P =.008) with no cardiovascular disease. CONCLUSIONS: SI increases the incidence of new coronary events in older men and women with CAD, with hypertension, valvular disease, or cardiomyopathy without CAD, and with no cardiovascular disease.

Aged↗
PubMed2002

Prevalence and incidence of cardiovascular disease in 1160 older men and 2464 older women in a long-term health care facility.

BACKGROUND: We report the prevalence and incidence of cardiovascular disease in older men and women in a long-term health care facility. METHODS: The prevalence of hypertension, chronic atrial fibrillation, pacemaker rhythm, coronary artery disease (CAD), thromboembolic stroke, and symptomatic peripheral arterial disease (PAD) and the incidence of new coronary events, thromboembolic stroke, and congestive heart failure (CHF) were investigated in 1160 men, mean age 80 +/- 8 years, and in 2464 women, mean age 81 +/- 8 years, in a long-term health care facility. Mean follow-up was 46 +/- 30 months. RESULTS: The prevalences of hypertension, pacemaker rhythm, CAD, and thromboembolic stroke were similar in men and women. The prevalence of atrial fibrillation was higher in men (16%) than in women (13%; p =.019). The prevalence of PAD was higher in men (32%) than in women (26%; p =.0001). At the 46-month follow-up, the incidences of new coronary events, thromboembolic stroke, and CHF were similar in men and women. CONCLUSIONS: Older men and women in a long-term health care facility have a high prevalence and incidence of cardiovascular disease. The prevalences of hypertension, pacemaker rhythm, CAD, and thromboembolic stroke and the incidences of new coronary events, thromboembolic stroke, and CHF were similar in men and women. However, the prevalences of atrial fibrillation and of PAD were higher in men than in women.

Aged↗
PubMed2002

Risk factors for new atherothrombotic brain infarction in older Hispanic men and women.

BACKGROUND: We report the prevalence and incidence of atherothrombotic brain infarction (ABI) in older Hispanic men and women in a long-term health care facility. METHODS: The prevalence and incidence of ABI and the association of risk factors with new ABI were investigated in 201 Hispanic men, mean age 79 +/- 8 years, and in 302 Hispanic women, mean age 80 +/- 9 years, in a long-term health care facility. Mean follow-up was 42 +/- 20 months in men and 47 +/- 26 months in women. RESULTS: The prevalence of prior ABI was 33% in Hispanic men and 30% in Hispanic women. The incidence of new ABI was 24% in Hispanic men and 23% in Hispanic women. Significant independent risk factors for new ABI were age (risk ratio = 1.09 in men and 1.08 in women for each increase of 1 year of age), current cigarette smoking (risk ratio = 2.8 in men and 2.7 in women), hypertension (risk ratio = 2.8 in men), diabetes mellitus (risk ratio = 3.5 in men and 5.0 in women), prior ABI (risk ratio = 5.6 in men and 5.5 in women), serum total cholesterol (risk ratio = 1.03 in men and 1.01 in women for each 1 mg/dl increase), and serum high-density lipoprotein (HDL) cholesterol (risk ratio = 1.06 in men and 1.06 in women for each 1 mg/dl decrease). CONCLUSIONS: Significant independent risk factors for new ABI were age, current cigarette smoking, diabetes mellitus, prior ABI, serum total cholesterol, and serum HDL cholesterol (inverse association) in older Hispanic men and women and hypertension in older Hispanic men.

Aged↗