A national pharmacoepidemiological study of antibiotic use in Korean paediatric outpatients.

BACKGROUND: Information on the use of antibiotics in Eastern Asian children is limited. The objectives of this study were to evaluate in Korean paediatric outpatients (1) the nationwide pattern of prescribing antibiotics according to age group and medical institution and (2) the adherence of antibiotic use for acute respiratory tract infections to both national guidelines and European antibiotic prescribing quality indicators. METHOD: This population-based study used the national insurance reimbursement database for 2011. The study subjects were outpatients younger than 18 years old prescribed systemic antibiotics. Patterns of antibiotic prescription were compared according to diagnostic conditions, age group and medical institution. The disease-specific proportion of recommended antibiotic or quinolone use for acute respiratory tract infections was evaluated on the basis of clinical practice guidelines and European quality indicators. RESULTS: The data consisted of 70.7 million prescription records for 7.9 million paediatric outpatients, which means that 79.3% of the whole paediatric population used antibiotics. Broad-spectrum antibiotics made up 78.5% of the prescriptions, with broad-spectrum penicillins such as amoxicillin/clavulanate being the most commonly prescribed (50.2%). They were prescribed more commonly in younger paediatric patients (∼80%) than in adolescents (66.6%). The leading diagnosis accounting for antibiotic prescription was bronchitis (35.9%). The prescription proportion of recommended antibiotics in the European quality indicators was extremely low compared with the national guidelines: <0.1% for pharyngotonsillitis and 13.4% for acute otitis media. CONCLUSIONS: Antibiotic use in children in Korea is inappropriately high. In addition, broad-spectrum antibiotics are used excessively.

Ethnic variability in the allelic distribution of pharmacogenes between Korean and other populations.

OBJECTIVE: We examined the differences in allele frequencies for pharmacogenes among the Korean (KOR), Chinese (CHB), Japanese (JPT), Caucasian (CEU), and Nigerian (YRI) populations. METHODS: Fifty-seven pharmacogenes were selected from the imputed Korean Association REsource and HapMap databases. Minor allele frequencies were analyzed using the sample size-modified single nucleotide polymorphism-specific fixation index (FST) and the χ-test with Bonferroni's correction. Geneset analysis was also carried out to identify pharmacogenes that have significantly different allele frequencies among the various populations tested. RESULTS: The KOR population was the most divergent group from the YRI population (FST: 0.079) but very similar to the CHB and JPT populations (FST: 0.003). VKORC1 showed a large population divergence in the KOR-YRI (0.439) comparison. CYP3A4 was also highly divergent in the KOR-YRI (FST: 0.361) comparison. The calcium signaling pathway gene set was divergent in all pairwise population comparisons. CONCLUSION: In terms of the 57 pharmacogenes studied, there were no significant differences among the KOR, CHB, and JPT populations. However, the YRI and CEU populations were significantly differentiated from the three Eastern Asian groups. Future pharmacogenomics studies can utilize the polymorphisms identified in this study, as these variants may have important implications for the selection of highly informative single nucleotide polymorphisms for future clinical trials.

Gamma-irradiation enhances RECK protein levels in Panc-1 pancreatic cancer cells.

Radiotherapy is an important treatment for many malignant tumors, but there are recent reports that radiation may increase the malignancy of cancer cells by stimulating expression of type IV collagenases. In this study, we examined changes in matrix metalloproteinase (MMP) inhibitors, such as the tissue inhibitors of metalloproteinase (TIMP)-1, TIMP-2 and RECK, in response to irradiation in Panc-1 pancreatic cancer cells. Irradiation increased RECK protein levels but not mRNA levels, whereas no significant changes were found in TIMP-1 and TIMP-2. The enhanced RECK protein levels were associated with an increase in MMP inhibitory activity. However, irradiation slightly but reproducibly increased the invasiveness of the Panc-1 cells. Like irradiation, treatment of Panc-1 cells with transforming growth factor (TGF)-Beta1 led to a 2-fold increase in RECK protein levels. Transient transfection with Smad3 also increased RECK protein levels, but transfection with Smad7 markedly reduced them. Stable expression of Smad7 and treatment with SB431542, an inhibitor of TGF-Beta receptor I kinase, abolished TGF-Beta1- and radiation-mediated effects on RECK. Furthermore, irradiation increased levels of phosphorylated Smad3. We conclude that radiation post-transciptionally enhances RECK protein levels in Panc-1 cells, at least in part, via TGF-Beta signaling, and that irradiation increases Panc-1 invasiveness via a mechanism that may not be linked to MMP-2 activity.