Identifying Adverse Events Using International Classification of Diseases, Tenth Revision Y Codes in Korea: A Cross-sectional Study.

OBJECTIVES: The use of administrative data is an affordable alternative to conducting a difficult large-scale medical-record review to estimate the scale of adverse events. We identified adverse events from 2002 to 2013 on the national level in Korea, using International Classification of Diseases, tenth revision (ICD-10) Y codes. METHODS: We used data from the National Health Insurance Service-National Sample Cohort (NHIS-NSC). We relied on medical treatment databases to extract information on ICD-10 Y codes from each participant in the NHIS-NSC. We classified adverse events in the ICD-10 Y codes into 6 types: those related to drugs, transfusions, and fluids; those related to vaccines and immunoglobulin; those related to surgery and procedures; those related to infections; those related to devices; and others. RESULTS: Over 12 years, a total of 20 817 adverse events were identified using ICD-10 Y codes, and the estimated total adverse event rate was 0.20%. Between 2002 and 2013, the total number of such events increased by 131.3%, from 1366 in 2002 to 3159 in 2013. The total rate increased by 103.9%, from 0.17% in 2002 to 0.35% in 2013. Events related to drugs, transfusions, and fluids were the most common (19 446, 93.4%), followed by those related to surgery and procedures (1209, 5.8%) and those related to vaccines and immunoglobulin (72, 0.3%). CONCLUSIONS: Based on a comparison with the results of other studies, the total adverse event rate in this study was significantly underestimated. Improving coding practices for ICD-10 Y codes is necessary to precisely monitor the scale of adverse events in Korea.

Evaluation of the learning curve for external cephalic version using cumulative sum analysis.

OBJECTIVE: We evaluated the learning curve for external cephalic version (ECV) using learning curve-cumulative sum (LC-CUSUM) analysis. METHODS: This was a retrospective study involving 290 consecutive cases between October 2013 and March 2017. We evaluated the learning curve for ECV on nulli and over para 1 group using LC-CUSUM analysis on the assumption that 50% and 70% of ECV procedures succeeded by description a trend-line of quadratic function with reliable R2 values. RESULTS: The overall success rate for ECV was 64.8% (188/290), while the success rate for nullipara and over para 1 groups was 56.2% (100/178) and 78.6% (88/112), respectively. 'H' value, that the actual failure rate does not differ from the acceptable failure rate, was -3.27 and -1.635 when considering ECV success rates of 50% and 70%, respectively. Consequently, in order to obtain a consistent 50% success rate, we would require 57 nullipara cases, and in order to obtain a consistent 70% success rate, we would require 130 nullipara cases. In contrast, 8 to 10 over para 1 cases would be required for an expected success rate of 50% and 70% on over para 1 group. CONCLUSION: Even a relatively inexperienced physician can experience success with multipara and after accumulating experience, they will manage nullipara cases. Further research is required for LC-CUSUM involving several practitioners instead of a single practitioner. This will lead to the gradual implementation of standard learning curve guidelines for ECV.

Gene expression analysis of primary normal human hepatocytes infected with human hepatitis B virus.

AIM: To find the relationship between hepatitis B virus (HBV) and hepatocytes during the initial state of infection by cDNA microarray. METHODS: Primary normal human hepatocytes (PNHHs) were isolated and infected with HBV. From the PNHHs, RNA was isolated and inverted into complement DNA (cDNA) with Cy3- or Cy5- labeled dUTP for microarray analysis. The labeled cDNA was hybridized with microarray chip, including 4224 cDNAs. From the image of the microarray, expression profiles were produced and some of them were confirmed by RT-PCR, immunoblot analysis, and NF-kappaB luciferase reporter assay. RESULTS: From the cDNA microarray, we obtained 98 differentially regulated genes. Of the 98 genes, 53 were up regulated and 45 down regulated. Interestingly, in the up regulated genes, we found the TNF signaling pathway-related genes: LT-alpha, TRAF2, and NIK. By using RT-PCR, we confirmed the up-regulation of these genes in HepG2, Huh7, and Chang liver cells, which were transfected with pHBV1.2x, a plasmid encoding all HBV messages. Moreover, these three genes participated in HBV-mediated NF-kappaB activation. CONCLUSION: During the initial state of HBV infection, hepatocytes facilitate the activation of NF-kappaB through up regulation of LT-alpha, TRAF2, and NIK.

Interferon-gamma inhibits hepatitis B virus-induced NF-kappaB activation through nuclear localization of NF-kappaB-inducing kinase.

BACKGROUND & AIMS: Nuclear factor-kappaB (NF-kappaB) signaling pathway is an important regulating pathway in liver diseases, including hepatocellular carcinoma. In our study, immunohistochemical analysis showed that NF-kappaB-inducing kinase (NIK), an upstream kinase of IkappaB kinases, nuclear localization occurs only in liver tissues obtained from hepatitis B surface antigen (HBsAg)(+) patients but not in tissues from HBsAg(-) patients. The aim of the present study was to identify the inducer of NIK nuclear localization and determine whether the NIK nuclear localization affects the hepatitis B virus (HBV)-mediated NF-kappaB activation. METHODS: The experiments were performed on HepG2.2.15 cells and on HepG2 cells transfected with pHBV1.2x, a plasmid encoding all HBV messages, using NF-kappaB-dependent luciferase reporter gene assay, electrophoretic mobility shift assay, immunoblot analysis, and fluorescent microscopy analysis. RESULTS: HBV induced NIK-dependent NF-kappaB activation. However, interferon (IFN)-gamma induced NIK nuclear localization and inhibited NF-kappaB activation in HepG2.2.15 cells and in HepG2 cells transfected with pHBV1.2x. When NIK nuclear localization was inhibited by deletion of nuclear localization signal on NIK, IFN-gamma did not induce the NIK nuclear localization and did not inhibit NF-kappaB activation. CONCLUSIONS: IFN-gamma selectively inhibits HBV-mediated NF-kappaB activation. This inhibition is accomplished by NIK nuclear localization, which is a novel mechanism of NF-kappaB inhibition.

Prenatal diagnosis of trisomy 18: report of 30 cases.

OBJECTIVES: To review the detection rate of the prenatal screening tests used for the diagnosis of the trisomy 18. METHODS: From 1 October 1998 to 31 December 2001, we reviewed the database and medical records of 30 cases of trisomy 18. All were singletons and trisomy 18 was confirmed by amniocentesis in 19 cases, by cordocentesis in 6 cases, by chorionic villi sampling in 2 cases and by skin biopsy in 3 cases. RESULTS: Of the 30 study cases, 23 cases (77%) were offered genetic study due to abnormal ultrasound (US) findings. Twelve (40%) out of the 23 cases were due to abnormal US findings detected before the triple test and 11 (37%) were due to abnormal US findings after the normal triple test. Six cases (20%) were offered genetic study because of an abnormal triple test, and one case was offered genetic study due to advanced maternal age only. Including the second targeted ultrasonogram, one or more abnormal US findings were found in all 30 fetuses. CONCLUSIONS: Abnormal US finding is the most sensitive screening test for trisomy 18. The most sensitive ultrasonographic finding for trisomy 18 at under 16 weeks of gestation is increased nuchal translucency (75%) and, after 16 weeks, is cardiac defect (83%).

Fidelity of hepatitis B virus polymerase.

Although efficient vaccines are available, chronic hepatitis B (HBV) infection poses a major health problem worldwide, and prolonged treatment of chronically infected HBV patients with nucleoside analogs often results in drug-resistant HBV variants. Therefore, it is critical to evaluate the contribution of the HBV polymerase to mutations. FLAG-tagged wild-type (FPolE) and mutant (FPolE/D551A) HBV polymerases have been expressed in insect cells and purified. The purified FPolE showed DNA polymerase activity, but FPolE/D551A did not, implying that the activity was derived from FPolE. No 3'-->5'exonuclease activity was detected in FPolE. The fidelity of FPolE was investigated and compared with that of HIV-1 RT, which is highly error-prone. The fidelity of HBV polymerase seems to be achieved by increasing the Km for the dNTP being misinserted. The nucleotide misinsertion efficiency of FPolE and HIV-1 RT ranged from 3.59 x 10-4 (C : T) to 1.51 x 10-3 (G : T) and from 1.75 x 10-4 (C : T) to 1.62 x 10-3 (G : T), respectively, and the overall misinsertion efficiency of HIV-1 RT was just 1.04-fold higher than that of FPolE, implying that HBV polymerase is fairly error-prone. Though HBV genetic mutation rate in replication is thought to be between those in RNA and DNA viruses, our data shows that the rate of mutation by HBV polymerase is higher than the rate of genetic mutation in vivo. This may be a result from more overlapping HBV genes in the HBV genome than that of other retroviruses.