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Volume 2(2); September 2011
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Editorial
A Tale of Two Fields: Mathematical and Statistical Modeling of Infectious Diseases
Hae-Wol Cho, Chaeshin Chu
Osong Public Health Res Perspect. 2011;2(2):73-74.   Published online June 30, 2011
DOI: https://doi.org/10.1016/j.phrp.2011.08.005
  • 1,167 View
  • 17 Download
  • 3 Citations
PDF
Original Articles
Development of a Predictive Model for Type 2 Diabetes Mellitus Using Genetic and Clinical Data
Juyoung Lee, Bhumsuk Keam, Eun Jung Jang, Mi Sun Park, Ji Young Lee, Dan Bi Kim, Chang-Hoon Lee, Tak Kim, Bermseok Oh, Heon Jin Park, Kyu-Bum Kwack, Chaeshin Chu, Hyung-Lae Kim
Osong Public Health Res Perspect. 2011;2(2):75-82.   Published online June 30, 2011
DOI: https://doi.org/10.1016/j.phrp.2011.07.005
  • 1,317 View
  • 12 Download
  • 9 Citations
AbstractAbstract PDFSupplementary Material
Objectives
Recent genetic association studies have provided convincing evidence that several novel loci and single nucleotide polymorphisms (SNPs) are associated with the risk of developing type 2 diabetes mellitus (T2DM). The aims of this study were: 1) to develop a predictive model of T2DM using genetic and clinical data; and 2) to compare misclassification rates of different models.
Methods
We selected 212 individuals with newly diagnosed T2DM and 472 controls aged in their 60s from the Korean Genome and Epidemiology Study. A total of 499 known SNPs from 87 T2DM-related genes were genotyped using germline DNA. SNPs were analyzed for significant association with T2DM using various classification algorithms including Quest (Quick, Unbiased, Efficient, Statistical tree), Support Vector Machine, C4.5, logistic regression, and K-nearest neighbor.
Results
We tested these models using the complete Korean Genome and Epidemiology Study cohort (n = 10,038) and computed the T2DM misclassification rates for each model. Average misclassification rates ranged at 28.2–52.7%. The misclassification rates for the logistic and machine-learning algorithms were lower than the statistical tree algorithms. Using 1-to-1 matched data, the misclassification rate of the statistical tree QUEST algorithm using body mass index and SNP variables was the lowest, but overall the logistic regression performed best.
Conclusions
The K-nearest neighbor method exhibited more robust results than other algorithms. For clinical and genetic data, our “multistage adjustment” model outperformed other models in yielding lower rates of misclassification. To improve the performance of these models, further studies using warranted, strategies to estimate better classifiers for the quantification of SNPs need to be developed.
Plasma Calcium and Risk of Hypertension: Propensity Score Analysis Using Data From the Korean Genome and Epidemiology Study
Jong Wook Kim, Kwang-Pil Ko, Hee Jo Koo, Younjhin Ahn, Seon-Joo Park, Hyo-Mi Kim, Yeonjung Kim, Sung Soo Kim
Osong Public Health Res Perspect. 2011;2(2):83-88.   Published online June 30, 2011
DOI: https://doi.org/10.1016/j.phrp.2011.07.004
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  • 3 Citations
AbstractAbstract PDFSupplementary Material
Objective To investigate associations between plasma calcium and future incidence of hypertension in a healthy population.
Methods
We used prospective data from Ansung and Ansan cohorts (n = 10,038) of the Korean Genome and Epidemiology Study. Data from baseline (2001–02) to the fourth study (2007–08) were used. After excluding hypertensive cases at baseline, missing data, and outliers, 5560 participants were analyzed. Propensity scores for having higher plasma calcium (≥2.37 mmol/L) were created for each participant. After propensity score matching (1:1 nearest neighbor matching within caliper), 2153 pairs were left for analysis. Factors that were significantly different between the lower and higher plasma calcium groups before matching either became nonsignificant or the difference decreased in size.
Results
Using multivariable Cox proportional hazard models with robust standard errors accounting for clustering of matched pairs, higher plasma calcium was associated with higher incidence of hypertension (adjusted HR, 1.24; robust 95%CI, 1.07–1.43). Among those with higher plasma calcium, low dietary calcium intake increased the development of hypertension, but the effect was not significant. Sensitivity analysis showed that our results were robust to hidden bias.
Conclusions
Plasma calcium was positively associated with incidence of hypertension. These results expand on cross-sectional associations between hypercalcemia and the metabolic syndrome, and extend the link to future risk of hypertension.
Modeling for Estimating Influenza Patients from ILI Surveillance Data in Korea
Joo-Sun Lee, Sun-Hee Park, Jin-Woong Moon, Jacob Lee, Yong Gyu Park, Yong Kyun Roh
Osong Public Health Res Perspect. 2011;2(2):89-93.   Published online June 30, 2011
DOI: https://doi.org/10.1016/j.phrp.2011.08.001
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  • 7 Citations
AbstractAbstract PDF
Objective Prediction of influenza incidence among outpatients from an influenza surveillance system is important for public influenza strategy.
Methods
We developed two influenza prediction models through influenza surveillance data of the Korea Centers for Disease Control and Prevention (each year, each province and metropolitan city; total reported patients with influenza-like illness stratified by age) for 6 years from 2005 to 2010 and disease-specific data (influenza code J09-J11, monthly number of influenza patients, total number of outpatients and hospital visits) from the Health Insurance Review and Assessment service.
Results
Incidence of influenza in each area, year, and month was estimated from our prediction models, which were validated by simulation processes. For example, in November 2009, Seoul and Joenbuk, the final number of influenza patients calculated by prediction models A and B underestimated actual reported cases by 64 and 833 patients, respectively, in Seoul and 6 and 9 patients, respectively, in Joenbuk. R-square demonstrated that prediction model A was more suitable than model B for estimating the number of influenza patients.
Conclusion
Our prediction models from the influenza surveillance system could estimate the nationwide incidence of influenza. This prediction will provide important basic data for national quarantine activities and distributing medical resources in future pandemics.
Increased Prevalence of low High-density Lipoprotein Cholesterol (HDL-C) Levels in Korean Adults: Analysis of the Three Korean National Health and Nutrition Examination Surveys (KNHANES 1998–2005)
Sun-Ja Choi, Sung-Hee Park, Hyun-Young Park
Osong Public Health Res Perspect. 2011;2(2):94-103.   Published online June 30, 2011
DOI: https://doi.org/10.1016/j.phrp.2011.07.006
  • 1,396 View
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  • 7 Citations
AbstractAbstract PDF
Objectives
High-density lipoprotein cholesterol (HDL-C) is an independent risk factor for cardiovascular diseases that has shown a remarkable increase, but little is known about the prevalence of low HDL-C in Korea. This study aimed to evaluate changing trends of low HDL-C prevalence, and indicate other risk factors associated with low HDL-C.
Methods
We selected subjects aged ≥20 years from the Korean National Health and Nutrition Examination Survey (KNHANES) 1998, 2001, and 2005 (n = 7962, 6436, and 6412). The mean level of HDL-C and the prevalence of low HDL-C was calculated, and cardiovascular risk factors associated with low HDL-C, as well as demographic, anthropometric, lifestyle, and nutrition factors, were assessed using the KNHANES 2005 data.
Results
Mean HDL-C levels in men and women between KNHANES 1998 and 2005 decreased significantly, from 48.1 to 42.3 and from 51.6 to 47.1 mg/dL, respectively (both p < 0.001). The decrease was slightly less for women compared with men for the same period, and women had higher HDL-C levels at all periods. Covariate-adjusted OR revealed that body mass index, waist circumference, and non-alcohol drinker in both men and women were associated with low HDL-C levels by KNHANES 2005, as were employed and light physical activity in men and low fat intake in women.
Conclusion
The prevalence of low HDL-C increased significantly from KNHANES 1998 to 2001 and 2005 (p < 0.001) in both men and women. body mass index, waist circumference, and non-alcohol drinker were identified as associated with low HDL-C in Korean adults.
Estimation of HIV Seroprevalence in Colorectal Hospitals by Questionnaire Survey in Korea, 2002–2007
Mee-Kyung Kee, Do Yeon Hwang, Jong Kyun Lee, Seung Hyun Kim, Chaeshin Chu, Jin-Hee Lee, Sung Soon Kim
Osong Public Health Res Perspect. 2011;2(2):104-108.   Published online June 30, 2011
DOI: https://doi.org/10.1016/j.phrp.2011.08.002
  • 1,485 View
  • 15 Download
  • 4 Citations
AbstractAbstract PDF
Objectives
The incidence of anal disease is higher among persons with human immunodeficiency virus (HIV) infection than among the general population. We surveyed the status of seroprevalence in colorectal hospitals in Korea.
Methods
The survey was conducted in colorectal hospitals in Korea from November to December 2008. The questionnaire was comprised of six topics about the status of HIV testing in colorectal hospitals. We gathered the data by website (http://hivqa.nih.go.kr/risk) or fax.
Results
Among 774 colorectal hospitals contacted, 109 (14%) hospitals participated in the survey. Among these, 48 hospitals (44%) performed HIV tests in their own hospitals and 11 (23%) took HIV testing by rapid method. The main reason for recommending an HIV test was surgical operation (54%) followed by endoscope (11%) and health checkup (9%). The annual number of HIV tests increased from 58,647 (at 21 hospitals) in 2002 to 246,709 (at 58 hospitals) in 2007. HIV seroprevalence was >3.0 per 10,000 individuals during 2002–2005, decreased to 2.2 per 10,000 individuals in 2006 and rose to 2.8 per 10,000 individuals in 2007.
Conclusions
HIV seroprevalence of colorectal hospitals was more than twice that of general hospitals in Korea. HIV surveillance systems based on colorectal hospitals for HIV/AIDS transmission prevention by early HIV diagnosis are needed.
Ingenol Protects Human T Cells From HIV-1 Infection
Kee-Jong Hong, Hak Sung Lee, Yeong-shik Kim, Sung Soon Kim
Osong Public Health Res Perspect. 2011;2(2):109-114.   Published online June 30, 2011
DOI: https://doi.org/10.1016/j.phrp.2011.07.001
  • 1,267 View
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  • 10 Citations
AbstractAbstract PDF
Objectives
Many natural compounds have been investigated as drug candidates to prevent human immunodeficiency virus (HIV) with low cytotoxicity. We tested whether ingenol from Euphorbia ingens exerts anti-HIV effects in human T cell lines.
Methods
and Results Ingenol effectively maintained high cell viability (CD50, >1 mM) in H9 and MT4 T cells. The efficacy of ingenol to inhibit HIV-1 infection was dose dependent. ED50 for 100 and 200 TCID50 of HIV-1 was 5.06 and 16.87 μM, respectively. Gag p24 antigen production in ingenol-treated MT4 cells was reduced by 24.5% on day 6 post-infection. While p24 antigen was reduced in ingenol-treated cells, levels of cytokines such as TNF-α and IL-6 and chemokines such as RANTES and MCP-1 were increased. dUTP level related to late apoptotic events was increased on day 2 post-infection of HIV by ingenol treatment, whereas expression of annexin V was unchanged. Reduced levels of iNOS and ZAP-70 after HIV infection were recovered by ingenol treatment.
Conclusion
Ingenol helps T cells to survive longer against viremia after HIV-1 infection, without exerting cytotoxic effects. Ingenol can be considered a safe and efficacious candidate for immune-boosting therapy for AIDS patients.
Multilocus Sequence Analysis of Housekeeping Genes and Antigenic Determinant Genes in Bordetella pertussis Strains Isolated in Korea
Sang-Oun Jung, Yu Mi Moon, So-Hyeon Kim, Hwa Young Sung, Seung-Jik Kwon, Yeon Ho Kang, Jae Yon Yu
Osong Public Health Res Perspect. 2011;2(2):115-126.   Published online June 30, 2011
DOI: https://doi.org/10.1016/j.phrp.2011.08.003
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  • 2 Citations
AbstractAbstract PDF
Objectives
To confirm genotype diversities of clinical isolates of Bordetella pertussis and to evaluate the risk of pertussis outbreak in Korea.
Methods
Seven housekeeping genes and 10 antigenic determinant genes from clinical B. pertussis isolates were analyzed by Multilocus sequence typing (MLST).
Results
More variant pattern was observed in antigenic determinant genes. Especially, PtxS1 gene was the most variant gene; five genotypes were observed from eight global genotypes. In the bacterial type, the number of observed sequence types in the isolates was seven and the most frequent form was type 1 (79.6%). This major sequence type also showed a time-dependent transition pattern. Older isolates (1968 and 1975) showed type 1 and 6 in housekeeping genes and antigenic determinant genes, respectively. However, these were changed to type 2 and 1 in isolates 1999–2008. This transition was mainly attributed to genotype change of PtxS1 and Fim3 gene; the tendency of genotype change was to avoid vaccine-derived genotype. In addition, there was second transition in 2009. In this period, only the sequence type of antigenic determinant genes was changed to type 2. Based Upon Related Sequence Types (BURST) analysis confirmed that there were two clonal complexes (ACCI and ACCII) in the Korean isolates. Moreover, the recently increased sequence type was revealed as AST2 derived from AST 3 in ACCI.
Conclusions
Genotype changes in Korean distributing strains are still progressing and there was a specific driving force in antigenic determinant genes. Therefore continuous surveillance of genotype change of the distributing strains should be performed to confirm interrelationship of genotype change with vaccine immunity.
Improved HPLC Method Using 2,3-naphthalenedicarboxaldehyde as Fluorescent Labeling Agent for Quantification of Histamine in Human Immunoglobulin Preparations
Jung-Hwan Kim, In Soo Shin, Yoo Kyoung Lee, Ho Jung Oh, Sang Ja Ban
Osong Public Health Res Perspect. 2011;2(2):127-134.   Published online June 30, 2011
DOI: https://doi.org/10.1016/j.phrp.2011.07.003
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  • 14 Citations
AbstractAbstract PDF
Objectives
To develop and optimize quantitative HPLC method using 2,3-naphthalenedicarboxaldehyde (NDA) after simple and efficient solid phase extraction to determine the histamine in a biopharmaceutical (Histobulin™).
Methods
The HPLC method was established using NDA-induced Histobulin and compared with the recently reported HPLC method using o-phthaldehyde (OPA). The validated NDA-applied HPLC method was adjusted to 15 lots of Histobulin and compared by the current lot-release-test method using fluorimetry in recovery of histamine and reproducibility.
Results
Analyses of six HPLC chromatograms using NDA and OPA each were compared. NDA produced a more stable chromatogram baseline than OPA, and showed better stability. The HPLC analysis was validated in accuracy (91–103%), precision (interday/intraday assay CV ≤2.30%), and linearity of dose–response curve (R2 ≥ 0.9919). The detection limit was 0.0076 μg/mL and the quantitative limit was 0.0229 μg/mL. The amount of histamine per 12 mg of immunoglobulin was determined to be 0.17 ± 0.016 μg by the HPLC and 0.025 ± 0.013 μg by the current lot-release-test method using fluorimetry.
Conclusion
NDA derivatization showed better stability compared with the OPA method. Therefore the newly established NDA-derivatizated HPLC method may be more suitable than the fluorimetric method in lot-release-tests of biopharmaceuticals.
A Note on Obesity as Epidemic in Korea
Mun Seok Kim, Chaeshin Chu, Yongkuk Kim
Osong Public Health Res Perspect. 2011;2(2):135-140.   Published online June 30, 2011
DOI: https://doi.org/10.1016/j.phrp.2011.08.004
  • 1,285 View
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  • 9 Citations
AbstractAbstract PDF
Objective To analyze the incidence of obesity in adults aged 19–59 years in Korea and predict its trend in the future.
Methods
We considered a two-compartmental deterministic mathematical model Susceptible-Infected-Susceptible (SIS), a system of difference equations, to predict the evolution of obesity in the population and to propose strategies to reduce its incidence.
Results
The prevention strategy on normal-weight individuals produced a greater improvement than that produced by treatment strategies.
Conclusions
Mathematical model sensitivity analysis suggests that obesity prevention strategies are more effective than obesity treatment strategies in controlling the increase of adult obesity in Korea.
Brief Report
Registration of Human Embryonic Stem Cell Lines: Korea, 2010
Ji-Yoon Lee, Dae-Yeon Lee, Young-Sil Choi, Kyoung-Jae Lee, Yong-Ou Kim
Osong Public Health Res Perspect. 2011;2(2):141-147.   Published online June 30, 2011
DOI: https://doi.org/10.1016/j.phrp.2011.07.002
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  • 3 Citations
AbstractAbstract PDF
In an effort to increase the credibility of human embryonic stem cell (hESC) lines established in Korea, obligatory registration was introduced by the Bioethics and Safety Act 2008, effective as of January 1, 2010.The DNA fingerprint, chromosome stability, expression of pluripotency markers, and contamination of mycoplasma of the submitted lines were analyzed by Korea Centers for Disease Control and Prevention (KCDC). The characterization data and ethical aspects, such as informed consent for donation of surplus embryos, were reviewed by a 10-member advisory review committee for stem cell registry.A total of 55 domestic hESC lines were submitted for registration in 2010; among them 51 were registered. Among these submitted lines, 26 were additionally characterized by KCDC, while 25 lines previously characterized by the Ministry of Education, Science and Technology were not additionally analyzed by KCDC.Registration completed an oversight system for embryo research by registering the products of licensed embryo research projects, making embryo research more transparent in Korea. Information about hESC lines is available at the website of the Korea Stem Cell Registry (kscr.nih.go.kr).

PHRP : Osong Public Health and Research Perspectives