Sung-Eun Choi

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 meta-analysis. 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 β71 and β74, not by β71 alone.

The association between normal alanine aminotransferase levels and the metabolic syndrome: 2005 Korean National Health and Nutrition Examination Survey

The metabolic syndrome is known to sometimes exist in the presence of normal aminotransferase levels. The purpose of this study was to determine the lowest sex-specific level of alanine aminotransferase associated with the metabolic syndrome in a nationwide, representative Korean population. We analyzed data from adults 20 years and older (n = 3405) assessed in the Third Korean National Health and Nutrition Examination Survey (2005). Participants were divided into 4 groups according to the quartiles of alanine aminotransferase levels for each sex. Logistic regression modeling was performed after adjustment for age, body mass index, waist circumference, smoking, ingested alcohol amount, and physical activity. Alanine aminotransferase level groups 3 and 4 in women (> or =15 IU/L) and group 4 in men (> or =27 IU/L) were significantly associated with the metabolic syndrome compared with the lowest alanine aminotransferase groups (<16 IU/L in men, <11 IU/L in women). In men, the odds ratio (95% confidence interval) of the metabolic syndrome was 2.71 (1.31-5.63) for alanine aminotransferase group 4 (> or =27 IU/L). In women, odds ratios were 1.69 (1.02-2.80) and 2.06 (1.23-3.43) for alanine aminotransferase groups 3 (15 < or = alanine aminotransferase < 19 IU/L) and 4 (> or =19 IU/L), respectively. High-normal alanine aminotransferase levels (> or =27 IU/L in men, > or =15 IU/L in women) were strongly associated with the metabolic syndrome in Korean adults.

Intravenous Vitamin C administration reduces fatigue in office workers: a double-blind randomized controlled trial

BackgroundStudies of the efficacy of vitamin C treatment for fatigue have yielded inconsistent results. One of the reasons for this inconsistency could be the difference in delivery routes. Therefore, we planned a clinical trial with intravenous vitamin C administration.MethodsWe evaluated the effect of intravenous vitamin C on fatigue in office workers. A group of 141 healthy volunteers, aged 20 to 49 years participated in this randomized, double-blind, controlled clinical trial. The trial group received 10 grams of vitamin C with normal saline intravenously, while the placebo group received normal saline only. Since vitamin C is a well-known antioxidant, oxidative stress was measured. Fatigue score, oxidative stress, and plasma vitamin C levels were measured before intervention, and again two hours and one day after intervention. Adverse events were monitored.ResultsThe fatigue scores measured at two hours after intervention and one day after intervention were significantly different between the two groups (p = 0.004); fatigue scores decreased in the vitamin C group after two hours and remained lower for one day. Trial also led to higher plasma vitamin C levels and lower oxidative stress compared to the placebo group (p < 0.001, p < 0.001, respectively). When data analysis was refined by dividing each group into high-baseline and low-baseline subgroups, it was observed that fatigue was reduced in the lower baseline vitamin C level group after two hours and after one day (p = 0.004). The same did not hold for the higher baseline group (p = 0.206).ConclusionThus, intravenous vitamin C reduced fatigue at two hours, and the effect persisted for one day. There were no significant differences in adverse events between two groups. High dose intravenous vitamin C proved to be safe and effective against fatigue in this study.Trial RegistrationThe clinical trial registration of this trial is http://ClinicalTrials.govNCT00633581.

Meta-Analysis for the Pooled Sensitivity and Specificity of Hepatitis B Surface Antigen Rapid Tests

BACKGROUND Although hepatitis B surface antigen (HBsAg) rapid test based on immunochromatographic assay (ICA) is now widely used, the test has not been evaluated sufficiently enough to validate its performance. Thus, it is important to summarize the clinical performance of the test kits. In this study, we performed meta-analysis for the performance of the HBsAg rapid tests. METHODS PubMed database was searched using keywords about the accuracy of diagnostic tests for hepatitis B virus (HBV) infection. Two investigators assessed methodological quality utilizing standards for reporting of diagnostic accuracy studies (STARD) checklist. After performing a heterogeneity test, we obtained pooled sensitivity and specificity. Positive and negative predictive values (PPV and NPV) were simulated according to HBV prevalence. RESULTS A total of 38 studies was selected from 10 papers. The quality scores ranged from 3 to 13 (median, 8). Kappa value was good (0.85). The performance of the 38 studies was heterogeneous. When 33 studies with better quality from 7 papers were re-selected, the pooled sensitivity and specificity were 98.07% (95% confidence interval, CI: 97.67-98.47%) and 99.56% (95% CI: 99.21-99.91%), respectively. With an HBV prevalence of 5%, PPV and NPV were predicted to be 92.14% and 99.90%, respectively. CONCLUSIONS In view of high HBV prevalence in Korea, it is thought that the HBsAg rapid test can be used for HBV screening in small-sized laboratories or for epidemiologic studies. This study should be helpful in establishing a guideline for the proper performance evaluation of the HBsAg rapid tests.

Number of daily antihypertensive drugs and the risk of osteoporotic fractures in older hypertensive adults: National health insurance service – Senior cohort

BACKGROUND Antihypertensive medication represents one of the most common prescriptions for senior individuals. Numerous studies have assessed the influence of antihypertensive treatment on the risk for osteoporotic fracture, yet much controversy remains. We analyzed the relationship between the incidence of osteoporotic fracture and the average number of daily antihypertensive drugs (NDAD) included in the prescription of elderly hypertensive patients. METHODS The study population was derived from the National Health Insurance Service-Senior Cohort (2002-2013), and consisted of elderly patients (≥60 years) diagnosed with hypertension in 2009, who did not have osteoporotic fractures in 2008, and underwent at least one national health check-up between 2009 and 2013, and had complete records after 2010. The outcome measured was the incidence of osteoporotic fractures between 2010 and 2013. The study population was stratified into the three groups (low, moderate, and high), in terms of NDAD. RESULTS A total of 137,304 hypertensive patients were included. A multivariate model corrected by age, gender, body mass index, systolic blood pressure, underlying disease, smoking status, and use of medicines showed that the groups with moderate and high NDAD exhibited, respectively, 12% and 16% lower risk of osteoporotic fracture compared to that in the group with low NDAD. In terms of the risk of osteoporotic fracture associated with the number of daily thiazide diuretics (NDTD), the adjusted odds ratios (aOR; 95%CI) were 0.89 (0.84-0.94) and 0.93 (0.84-1.02) in the groups with moderate and high NDTD, respectively compared to low NDTD as reference. As to NDADnotTD, the aOR (95%CI) were 0.90 (95%CI, 0.86-0.94) and 0.89 (95%CI, 0.84-0.95) in the groups with moderate and high NDADnotTD, respectively compared to low NDADnotTD as reference. CONCLUSION In elderly hypertensive patients, the incidence of osteoporotic fracture decreased as the NDAD increased. The incidence rate of osteoporotic fracture also decreased with the increase in the number of daily non-thiazide antihypertensive drugs.

Detecting primary drug-resistant mutations in Korean HIV patients using ultradeep pyrosequencing

HIV primary resistance, drug resistance in treatment-naïve patients, is an emerging public health issue. The prevalence of HIV primary resistance mutations down to the level of 1% minor variants was investigated using ultradeep pyrosequencing (UDPS) in HIV-positive Korean blood donors and in treatment naïve chronic patients for the comparison. The entire pol region was sequenced from 25 HIV-positive blood donors, and 18 treatment-naïve chronic HIV patients. UDPS was successful in 19 blood donors and 18 chronic patients. In total, 1,011,338 sequence reads were aligned, and 28,093 sequence reads were aligned on average per sample. The prevalence of HIV primary resistance mutations in the HIV-positive blood donors and chronic HIV patients were 63.2% and 44.4% according to UDPS, respectively. Protease inhibitor (PI) drugs demonstrated different patterns in HIV-positive blood donors and chronic HIV patients, whereas non-nucleoside reverse transcriptase inhibitors (NNRTI), nucleoside reverse transcriptase inhibitors (NRTI), and integrase inhibitor (INI) drugs showed similar patterns between the two groups. Higher level of primary resistance prevalence was observed mainly because UDPS method could detect mutations in minor variants with 1-10% frequency. The higher resistance prevalence was observed in HIV-positive blood donors than in chronic patients. Considering that treatments for HIV-infected patients were recently amended to start at an earlier stage, information about degree of drug resistance to each drug between the two groups would help to establish future policies, design additional clinical trials, assess HIV patient care in Korea.

Impact of amino acid substitution at residue 9 of HLA-A2 on the development of acute GVHD in Korean pediatric patients receiving unrelated hematopoietic stem cell transplantation

Incompatibility of human leukocyte antigen (HLA) alleles between donors and recipients of unrelated hematopoietic stem cell transplantation (UHSCT) increases the risk of acute graft‐versus‐host disease (GVHD). We evaluated the positional effect of amino acid substitutions in HLA molecules on severe acute GVHD in Korean pediatric recipients of UHSCT. All of 64 donor–recipient pairs were serologically matched for HLA‐A, ‐B, and ‐DR loci. Only substitution at residue 9 resulting from an HLA‐A*02 polymorphism was significantly associated with the risk of severe acute GVHD in patients (OR = 7.0, P = 0.033) on multivariate analysis. Recipients of this mismatched HLA also showed shortened overall survival (HR = 9.7, P < 0.001) and increased risk for transplant‐related mortality (HR = 9.1, P = 0.027). Structural modeling showed that the amino acid substitution could alter the peptide preference of the ligand‐binding pocket. A single amino acid substitution at position 9 was a major predictor of severe acute GVHD in Korean pediatric patients.

Performance Evaluation of Abbott RealTime HBV Quantification Kit for HBV Viral Load by Real-Time PCR

BACKGROUND Hepatitis B virus (HBV) DNA quantification is necessary for starting and monitoring of antiviral therapy in patients with chronic hepatitis B. This study was intended to assess the clinical performance of Abbott RealTime HBV Quantification kit (Abbott Laboratories, USA). METHODS The performance was evaluated in terms of precision, linearity, detection sensitivity, cross-reactivity, and carry-over. A correlation with the Real-Q HBV Quantification kit (BioSewoom Inc., Korea) was also examined using serum samples from 64 patients diagnosed with chronic hepatitis B and underwent lamivudine therapy in Asan Medical Center. We verified the trueness of the system by comparing the outputs with the assigned values of the BBI panel (BBI Diagnostics, USA). RESULTS Within-run and between-run coefficients of variation (CV) were 3.56-4.71% and 3.03-4.98%, respectively. Linearity was manifested ranging from 53 to 10(9)copies/mL and the detection sensitivity was verified to be 51 copies/mL. None of hepatitis C virus showed cross-reactivity. No cross-contamination occurred when negative and positive samples were alternatively placed in a row. It showed a good correlation with the Real-Q HBV (r(2)=0.9609) and the test results for the BBI panel were also well agreed to the assigned values (r(2)=0.9933). CONCLUSIONS The performance of Abbott RealTime HBV Quantification kit was excellent; thus, it should be widely used in starting and monitoring of antiviral therapy in Korean patients with chronic hepatitis B.

Palliative Performance Scale Score at 1 Week After Palliative Care Unit Admission is More Useful for Survival Prediction in Patients With Advanced Cancer in South Korea

Background: The Palliative Performance Scale (PPS) is a useful prognostic index in palliative care. Changes in PPS score over time may add useful prognostic information beyond a single measurement. Objective: To investigate the usefulness of repeated PPS measurement to predict survival time of inpatients with advanced cancer admitted to a palliative care unit (PCU) in South Korea. Design: Prospective observational cohort study. Setting/Patients: 138 patients with advanced cancer admitted to a PCU in a university hospital in South Korea from June 2015 to May 2016. Measurements: The PPS score was measured on enrollment and after 1 week. We used Cox regression analyses to calculate hazard ratios (HRs) to demonstrate the relationship between survival time and the groups categorized by PPS and changes in PPS score, after adjusting for clinical variables. Results: There were significant differences in survival time among 3 groups stratified by PPS (10-20, 30-50, and ≥60) after 1 week. A group with a PPS of 10 to 20 at 1 week had the highest risk (HR: 5.18 [95% confidence interval, 1.57-17.04]) for shortened survival. On the contrary, there were no significant differences among these groups by initial PPS alone. Similarly, change in PPS was prognostic; median survival was 13 (10.96-15.04) days for those whose PPS decreased after 1 week and 27 (10.18-43.82) days for those with stable or increased PPS (P < .001). Conclusions: Measuring PPS over time can be very helpful for predicting survival in terminally ill patients with cancer, beyond a single PPS measure at PCU admission.

Development of a System for Extracting the Information of Candidate Tumor Markers Reported in Biomedical Literatures

BACKGROUND Since the human genome project was completed in 2003, there have been numerous reports on cancer and related markers. This study was aimed to develop a system to extract automatically information regarding the relationship between cancer and tumor markers from biomedical literatures. METHODS Named entities of tumor markers were recognized by both a dictionary-based method and machine learning technology of the support vector machine. Named entities of cancers were recognized by the MeSH dictionary. RESULTS Relational and filtering keywords were selected after annotating 160 abstracts from PubMed. Relational information was extracted only when one of the relational keywords was in an appropriate position along the parse tree of a sentence with both tumor marker and disease entities. The performance of the system developed in this study was evaluated with another set of 77 abstracts. With the relational and filtering keyword used in the system, precision was 94.38% and recall was 66.14%, while without the expert knowledge precision was 49.16% and recall was 69.29%. CONCLUSIONS We developed a system that can extract relational information between a tumor and its markers by incorporating expert knowledge into the system. The system exploiting expert knowledge would serve as a reference when developing another information extraction system in various medical fields.