Study on Interpretation of Quantitative Results of Prostate-specific Antigen Using Information Theory / 대한진단검사의학회지

BACKGROUND: The prostate-specific antigen (PSA) is considered the most useful among tumor markers currently used. However, its quantitative results are interpreted only qualitatively for the diagnosis of prostate cancer. The recently introduced information theory enables the information of the quantitative results transformed into Shannon's entropy (S) that represents uncertainties and then "1-S" representing diagnostic certainty. METHODS: The 882 urological patients enrolled were categorized into 2 groups: a patient group comprising 233 patients with prostate cancer and a disease control group comprising 649 patients with benign prostate disease. The level of PSA in all the patients was tested and was found to be > or =2 ng/mL. The variables like PSA level and age were modeled on logistic regression analysis to predict the probability of prostate cancer and the diagnostic certainty. RESULTS: The mean (SD) of PSA levels in the patient group and the disease control group were 44.5 ng/mL (37.62 ng/mL) and 5.7 ng/mL (3.70 ng/mL), respectively. The logistic regression model fitted well when the age variable was dichotomized at the age of 55 yr. The diagnostic certainty was lowest at a PSA level of 18.90 ng/mL in the 55-yr age group. CONCLUSIONS: The diagnostic certainty (1-S) of whether to diagnose prostate cancer or not at a certain PSA level could be obtained using the information theory. The methodology used in this study may help interpret the results of other quantitative tests.

Meta-analysis of the Association between HLA-DRB1 Allele and Rheumatoid Arthritis Susceptibility in Asian Populations

The aims of this study were to summarize results on the association of HLA-DRB1 with rheumatoid arthritis (RA) in Asians and to determine if the shared epitope (SE) hypothesis could explain the meta-analysis results. Among the papers published between January 1987 and July 2006 on RA susceptibility in Asian-Mongoloid populations (Korean, Japanese, Chinese, and Thai), 12 were selected for the metaanalysis. Mongoloid-Asian patients with RA had significantly higher frequencies of HLA-DRB1*0101, *0401, *0410, and *1001 than controls (OR 1.5-2.1, p<0.05 for association). When analyses were restricted to more ethnically homogeneous populations, HLA-DRB1*0405 showed a significant susceptibility to RA in Koreans (OR 5.65, 95% CI 4.32-7.39), whereas the HLA-DRB1*0301, *0403, *0406, *0701, *1301, and *1405 alleles showed protective association with RA (OR 0.32-0.70, p<0.05 for association). In conclusion, it was found that HLA-DRB1 *0101, *0401, *0405, *0410, and *1001 are susceptible, while HLA-DRB1* 0301, *0403, *0406, *0701, *1301, and *1405 are protective in Asian-Mongoloids. All the RA-associated alleles except DRB1*0301 could be explained by the structural model supporting the SE hypothesis that RA susceptibility is determined by the combination of amino acid residues at HLA-DR beta71 and beta74, not by beta71 alone.

Development of a Web-based Program to Calculate Sample Size for Evaluating the Performance of In Vitro Diagnostic Kits / 대한진단검사의학회지

BACKGROUND: Many studies evaluating the performance of in vitro diagnostic kits have been criticized for the lack of reliability. To attain reliability those evaluation studies should be preceded by sample size calculation ensuring statistical power. This study was intended to develop a web-based system to estimate the sample size, which was often neglected because it would require expert knowledge in statistics. METHODS: For sample size calculation, we extracted essential parameters from the performance studies on the 3rd generation anti-hepatitis C virus (HCV) kits reported in the literature. We developed a system with PHP web-script language and MySQL. The statistical models used in this system were as follows; one sample without power consideration (model 1), one sample with power consideration (model 2), and two samples with power consideration (model 3). RESULTS: Among the articles published between 1989 and 2005, 13 articles that evaluated the performance of anti-HCV kits were identified by searching with Medical Subject Headings (MeSH). The diagnostic sensitivity was 83-100% with a median of 145 samples (range; 12-1,091) and the specificity was 97-100% with a median of 1,025 samples (range; 33-4,381). The estimated sample size would be 280 in the model 1, 817 in the model 2, and 1,510 in the model 3, when we set 2% prevalence of HCV infection, 95% sensitivity of a conventional kit, 97% sensitivity of a new kit , 95% significance level (two-sided test), 2% allowable error, and 80% power. CONCLUSIONS: Our study indicates that an insufficient sample size is still a problem in performance evaluation. Our system should be helpful in increasing the reliability of performance evaluation by providing an appropriate sample size.

Quality Evaluation of the Performance Study of Diagnostic Tests Using STARD Checklist and Meta-Analysis for the Pooled Sensitivity and Specificity of Third Generation Anti-HCV EIA Tests / 대한진단검사의학회지

BACKGROUND: The third generation anti-hepatitis C virus (HCV) enzyme immunoassay (EIA) is now in use for screening HCV infection. The aim of this study was to pool the data on the sensitivity and specificity of third generation anti-HCV EIA tests after evaluating the quality of the studies using Standards for Reporting of Diagnostic Accuracy studies (STARD) checklist. METHODS: We searched MEDLINE and PubMed databases using keywords about the accuracy of diagnostic tests for HCV infections. Methodological quality was assessed by two persons with a modified STARD checklist. A heterogeneity test was performed, and in case heterogeneity was present, a sub-group analysis was done. Fixed-effects model was used to obtain pool sensitivity and specificity with 95% confidence intervals (CI). RESULTS: A total of 41 studies from 16 papers were selected. The quality score ranged from 6 to 13 (median 10.5); Inter-observer agreement was 93.62% (k=0.69); and 41 studies revealed heterogeneity. We performed a sub-group analysis with only 28 studies from 13 papers that were evaluated to be of high quality. A subgroup using polymerase chain reaction as the reference test revealed homogeneity and was calculated the pooled sensitivity and specificity of 99.92% (CI 99.77-100.07%) and 99.66% (CI 99.45-99.86%) respectively. Studies on test kits with an increased reactivity to the core region also showed homogeneity in sensitivity and the pooled sensitivity was 99.78% (CI 99.53-100.03%). CONCLUSIONS: For the first time in Korea, the diagnostic accuracy of test kits was evaluated by meta-analysis using STARD checklist. The methodology shown in this study should help extending laboratory medicine to an evidence-based medicine.