• 한국임상약학회지
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• 제32권1호
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• pp.1-7
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• 2022

Objective: The purpose of this study was to detect signals of Adverse Events (AEs) after varenicline treatment using spontaneous AEs reporting system in Korea. Methods: This study was conducted by Korea Institute of Drug Safety and Risk Management-Korea Adverse Event Reporting System Database (KIDS-KD) reported from January 2013 to December 2017 through Korea Adverse Event Reporting System. Signals of varenicline that satisfied the data-mining indices, proportional reporting ratio, reporting odds ratio and information component were defined. The detected signals were checked whether they included in drug labels in South Korea and United States of America (USA). Results: A total number of drug AE reports associated with all drugs in the KIDS-KD reported between January 2013 and December 2017 was 2,665,429. Among them, the number of AE reports associated with varenicline was 1,398. Eighteen meaningful signals of varenicline were detected that satisfied with the criteria of data-mining indices. Finally, two signals such as hypotonia, incorrected dose administered were not included in the drug labels. Conclusion: New AE signals of varenicline that were not listed on the drug labels in South Korea and USA were detected. However, further pharmacoepidemiological studies such as randomized controlled trial are needed to evaluate the causality of the signals of varenicline.

• 한국임상약학회지
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• 제33권2호
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• pp.122-127
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• 2023

Background: This study was aimed to identify the safety signals of metoclopramide in Korea Adverse Event Reporting System (KAERS) database by proportionality analysis methods. Methods: The study was conducted using Korea Institute of Drug Safety and Risk Management-Korea Adverse Event Reporting System Database (KIDS-KD) reported from January 2013 to December 2017 through KAERS. Signals of metoclopramide that satisfied the data-mining indices of proportional reporting ratio (PRR), reporting odds ratio (ROR) and information component (IC) were defined. The detected signals were checked whether they included in drug labels in the Ministry of Food and Drug Safety (MFDS), U.S. Food and Drug Administration (FDA) and Micromedex^®. Results: A total number of drug AE reports associated with all drugs of data in this study was 2,665,429. Among them, the number of AE reports associated with metoclopramide was 22,583. Forty-two meaningful signals of metoclopramide were detected that satisfied with the criteria of data-mining indicies. Especially neurological signals including extrapyramidal reactions, represented in the safety letter of regulatory agencies were identified in this study. Conclusion: Neurological signals of metoclopramide including extrapyramidal reactions were detected. It is believed that this search for signals can contribute to ensuring safety in the use of metoclopramide.

• 한국임상약학회지
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• 제33권2호
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• pp.86-96
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• 2023

Background: Using KIDS-KAERS database (KIDS-KD) from 2016 to 2020, the aim is to investigate signals of adverse events of alpha-adrenoceptor antagonists and to present adverse events that are not included in the precautions for use when marketing approval. Methods: This study was conducted by disproportionality analysis. Data mining analysis was performed to detect signals of alpha-adrenoceptor antagonists, such as terazosin, doxazosin, alfuzosin, silodosin, and tamsulosin. The signal was defined by three criteria as proportional reporting ratio (PRR), reporting odds ratio (ROR), and information component (IC). Detected signals were compared with product labeling and the European Medicines Agency-Important Medical Events list. Results: Out of the total number of 408,077 reports for adverse events, 6,750 cases were reported as adverse events of alpha-adrenoceptor antagonists. Dizziness, mouth dryness, hypotension postural, and oedema peripheral are identified as common adverse events of five alpha-adrenoceptor antagonists and are typically listed on drug labels. However, new signals were detected for pneumonia, chronic obstructive airway disease, eye diseases such as glaucoma and cataracts, fracture, and ileus of tamsulosin that were not previously listed on the drug labels in Korea. Conclusions: This study identified signals related to adverse drug reactions of alpha-adrenoceptor antagonists and presented serious adverse events, suggesting new adverse reactions to be aware of when using alpha-adrenoceptor antagonists.

• Korean Journal of Radiology
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• 제24권7호
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• pp.626-639
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• 2023

Objective: To investigate the association of clinical, pathologic, and magnetic resonance imaging (MRI) variables with progressive disease (PD) during neoadjuvant chemotherapy (NAC) and distant metastasis-free survival (DMFS) in patients with triple-negative breast cancer (TNBC). Materials and Methods: This single-center retrospective study included 252 women with TNBC who underwent NAC between 2010 and 2019. Clinical, pathologic, and treatment data were collected. Two radiologists analyzed the pre-NAC MRI. After random allocation to the development and validation sets in a 2:1 ratio, we developed models to predict PD and DMFS using logistic regression and Cox proportional hazard regression, respectively, and validated them. Results: Among the 252 patients (age, 48.3 ± 10.7 years; 168 in the development set; 84 in the validation set), PD was occurred in 17 patients and 9 patients in the development and validation sets, respectively. In the clinical-pathologic-MRI model, the metaplastic histology (odds ratio [OR], 8.0; P = 0.032), Ki-67 index (OR, 1.02; P = 0.044), and subcutaneous edema (OR, 30.6; P = 0.004) were independently associated with PD in the development set. The clinical-pathologic-MRI model showed a higher area under the receiver-operating characteristic curve (AUC) than the clinical-pathologic model (AUC: 0.69 vs. 0.54; P = 0.017) for predicting PD in the validation set. Distant metastases occurred in 49 patients and 18 patients in the development and validation sets, respectively. Residual disease in both the breast and lymph nodes (hazard ratio [HR], 6.0; P = 0.005) and the presence of lymphovascular invasion (HR, 3.3; P < 0.001) were independently associated with DMFS. The model consisting of these pathologic variables showed a Harrell's C-index of 0.86 in the validation set. Conclusion: The clinical-pathologic-MRI model, which considered subcutaneous edema observed using MRI, performed better than the clinical-pathologic model for predicting PD. However, MRI did not independently contribute to the prediction of DMFS.

• Journal of Hospice and Palliative Care
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• 제18권2호
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• pp.120-127
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• 2015

목적: 국내 말기암환자를 대상으로 혈중 vitamin D 농도를 측정하고, 생존기간과의 관련성에 대하여 확인해 본다. 방법: 2012년 5월부터 15개월 동안, 국내 일개 병원의 말기암환자 96명을 대상으로 후향적 의무기록 조사를 시행하였다. Vitamin D 결핍에 영향을 미치는 요인들을 파악하기 위해 단순 로지스틱 회귀분석과 다중 로지스틱 회귀분석을 실시하였고, vitamin D가 생존기간에 미치는 영향을 파악하기 위해 다변수 분석으로 Cox's proportional hazard regression analysis를 실시하였다. 결과: 대상자의 평균 연령은 $67.06{\pm}13.77$세였고, 모든 대상자가 ECOG PS 3점 이상이었으며 혈중25(OH)D 농도는 평균 $8.60{\pm}7.16ng/ml$였다. 3명(3.1%)만이 vitamin D 충분상태(혈중 25(OH)D 농도${\geq}30ng/ml$)였으며, 5명은 vitamin D 상대적결핍상태(혈중 25(OH) 농도 20~30 ng/ml)였고, 13명(13.5%)은 vitamin D 결핍(혈중 25(OH)D 농도 10~20 ng/ml), 75명(78.1%)은 vitamin D 중증결핍상태(혈중 25(OH)D<10 ng/ml) 였다. 혈중 빌리루빈 농도가 1.2 mg/dl 이상인 경우 vitamin D 중증결핍과 관련이 있었다(Odds ratio, OR=5.041; P=0.039). 혈중 빌리루빈 농도가 높을수록 혈중 vitamin D 농도가 낮았으며, 고빌리루빈혈증인 환자는 vitamin D 중증결핍에 속할 위험이 더 크고(OR=18.476, P<0.05), 중앙생존기간도 유의하게 짧았다. Vitamin D 중증결핍인 경우 추정된 중앙생존기간은 짧았으나 통계적 유의성은 없었다. 다변량 분석결과에서 vitamin D 중증결핍은 사망의 위험인자가 아니었다. 결론: 말기암환자에서 혈중 vitamin D 결핍은 매우 심각하였으나, vitamin D 중증결핍이 생존기간에 영향을 미치지는 않았다.

• 한국임상수의학회지
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• 제28권4호
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• pp.339-343
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• 2011

젖소에서 쌍태분만이 이후의 산후질병 발생, 도태, 번식능력에 대한 영향과 쌍태분만에 대한 위험요인을 조사하였다. 9개 목장 1,717 분만축의 번식, 위생 및 분만관련 상세 자료가 분석에 이용되었다. 쌍태 분만율은 3.4%였으며, 임신기간은 쌍태분만 시에 단태분만 시에 비해 9일 단축되었다($270.6{\pm}2.0$ vs. $279.5{\pm}0.2$일, P < 0.01). 쌍태분만 시가 후산정체(47.5 vs. 16.0%), 대사성질병(18.6 vs. 3.8%) 및 자궁내막염의 발생(62.7 vs. 28.2%)뿐만 아니라 도태율(32.2 vs. 16.5%)이 단태분만 시에 비해 현저하게 증가되었다(P < 0.01). 쌍태분만은 분만으로부터 임신까지의 간격에 유의적인 영향을 미치지 않았으나, 분만계절이 영향을 미쳤는데, 즉 봄에 분만 시가 겨울에 분만 시에 비해 임신율이 감소되었으며(AHR = 0.80; P = 0.01), 또한 자궁내막염의 발생이 임신율의 감소를 초래하였다(AHR = 0.46, P < 0.01). 로지스틱 분석은 산차의 증가(P < 0.01)와 수태 전 번식호르몬의 사용(OR = 1.84, P < 0.05)이 쌍태분만의 위험요인임을 나타내었다. 결론적으로, 젖소에서 쌍태분만은 산후질병 발생과 도태의 증가에 의한 심한 경제적 손실을 초래하므로, 쌍태분만에 대한 적절한 관리 및 고산차 소 및 번식호르몬 사용에 대한 적절한 통제를 통한 위험요인을 감소시키는 것이 요구된다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권23호
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• pp.10209-10215
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• 2015

To assess the contribution of tumor necrosis factor $(TNF){\beta}$ +252 polymorphisms to risk and prognosis of hepatocellular carcinoma (HCC), we enrolled 150 pairs of sex- and age-matched patients with HCC, patients with cirrhosis alone, and unrelated healthy controls. $TNF{\beta}$ +252 genotypes were determined by polymerase chain reaction with restriction fragment length polymorphism. Multivariate analysis indicated that $TNF{\beta}$ G/G genotype [odds ratio (OR), 3.64; 95%CI, 1.49-8.91], hepatitis B surface antigen (OR, 16.38; 95%CI, 8.30-32.33), and antibodies to hepatitis C virus (HCV) (OR, 39.11; 95%CI, 14.83-103.14) were independent risk factors for HCC. There was an additive interaction between $TNF{\beta}$ G/G genotype and chronic hepatitis B virus (HBV)/HCV infection (synergy index=1.15). Multivariate analysis indicated that factors associated with $TNF{\beta}$ G/G genotype included cirrhosis with Child-Pugh C (OR, 4.06; 95%CI, 1.34-12.29), thrombocytopenia (OR, 6.55; 95%CI, 1.46-29.43), and higher serum ${\alpha}$-fetoprotein concentration (OR, 2.53; 95%CI, 1.14-5.62). Patients with $TNF{\beta}$ G/G genotype had poor cumulative survival (p=0.005). Cox proportional hazard model indicated that $TNF{\beta}$ G/G genotype was a biomarker for poor HCC survival (hazard ratio, 1.70; 95%CI, 1.07-2.69). In conclusion, there are independent and additive effects between $TNF{\beta}$ G/G genotype and chronic HBV/HCV infection on risk for HCC. It is a biomarker for poor HCC survival. Carriage of this genotype correlates with disease severity and advanced hepatic fibrosis, which may contribute to a higher risk and poor survival of HCC. Chronic HBV/HCV infected subjects with this genotype should receive more intensive surveillance for early detection of HCC.

• Tuberculosis and Respiratory Diseases
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• 제75권1호
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• pp.18-24
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• 2013

Background: We investigated the prevalence of latent tuberculosis infection (LTBI) among the health care workers (HCWs) and analyzed its risk factors in South Korea. Methods: A standard questionnaire regarding the baseline demographics and risk factors for LTBI was given to each participant and tuberculin skin test (TST), QuantiFERON-TB GOLD In-Tube (QFT-GIT) assay, and chest radiography were performed. Results: A total of 493 participants, 152 (30.8%) doctors and 341 (69.2%) nurses were enrolled in eight tertiary referral hospitals. The mean age of the subjects was 30.6 years old, and 383 (77.7%) were female. Of the 152 doctors, 63 (41.4%) and 36 (23.7%) were positive by TST and by QTF-GIT, respectively, and among the 341 nurses, 119 (34.9%) and 49 (14.4%) had positive TST and QFT-GIT results, respectively. Overall, the agreement between the two tests was 0.22 by the chance corrected proportional agreement rate (kappa coefficient) in 493 subjects. Experience of working in tuberculosis (TB)-related departments was significantly associated with positive LTBI test results by QFT-GIT assay, not by TST. In multivariate analysis, only age was independently associated with increased risk of a positive TST result, while age and experience of working in TB-related departments (odds ratio, 2.29; 95% confidence interval, 1.01-5.12) were independently associated with increased risk of a positive QFT-GIT result. Conclusion: A high prevalence of LTBI was found among South Korean HCWs. Considering the association between the experience of working in TB-related departments and high risk of LTBI, QFT-GIT may be a better diagnostic test for LTBI than TST in HCWs.

• 한국임상약학회지
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• 제24권1호
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• pp.39-44
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• 2014

Purpose: To investigate adverse drug reactions (ADR) and causative drugs in the elderly 65 years of age or older, using Korean spontaneous reporting adverse events reporting database from June 2009 to December 2010. Methods: We estimated the association between ADRs and implicated medications by calculating a proportional reporting ratio (PRR), reporting odds ratio (ROR), and information component (IC). We reexamined the most frequently implicated medications and ADRs, and the seriousness of ADRs. Then, we assessed reports and concordant rate of ADRs due to medications designated as "high-risk" in elderly by 2012 healthcare effectiveness data and information set (HEDIS) or "potentially inappropriate" by 2012 American Geriatrics Society updated Beers criteria for potentially inappropriate medications (PIMs). Results: Among 15,484 elderly reports, data-mining analysis by PRR, ROR and IC showed that 421 drug-ADR pairs were detected as signals (3,189). The most frequently reported ADR and causative drug were urticaria (470) and contrast media agents (647), respectively. One hundred eighty nine ADR cases were graded as serious. Twenty-two kinds of high-risk medications were shown to be implicated in only 0.9% of ADRs. Only thirty-nine cases were consistent with 2012 Beers criteria or HEDIS. Conclusion: These results suggest that management of the other medications including contrast media agents as well as close monitoring of PIMs are necessary for reducing ADRs in the elderly.

• Asian Pacific Journal of Cancer Prevention
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• 제13권3호
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• pp.851-856
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• 2012

Objective: NBS1 plays a key role in the repair of DNA double-strand break (DSB). We conducted this study to investigate the effect of two critical polymorphisms (rs1805794 and rs13312840) in NBS1 on treatment response and prognosis of advanced non-small cell lung cancer (NSCLC) patients with platinum-based chemotherapy. Methods: Using TaqMan methods, we genotyped the two polymorphisms in 147 NSCLC patients. Odds ratios (ORs) and their 95% confidential intervals (CIs) were calculated as a measure of difference in the response rate of platinum-based chemotherapy using logistic regression analysis. The Kaplan-Meier and log-rank tests were used to assess the differences in progression-free survival (PFS) and overall survival (OS). Cox proportional hazards model was applied to assess the hazard ratios (HRs) for PFS and OS. Results: Neither of the two polymorphisms was significantly associated with treatment response of platinum-based chemotherapy. However, patients carrying the rs1805794 CC variant genotype had a significantly improved PFS compared to those with GG genotype (16.0 vs. 8.0 months, P = 0.040). Multivariable cox regression analysis further showed that rs1805974 was a significantly favorable prognostic factor for PFS [CC/CG vs. GG: Adjusted HR = 0.62, 95% CI: 0.39-0.99; CC vs. CG/GG: Adjusted HR = 0.56, 95% CI: 0.32-0.97). Similarly, rs13312840 with a small sample size also showed a significant association with PFS (CC vs. CT/TT: Adjusted HR = 25.62, 95% CI: 1.53-428.39). Conclusions: Our findings suggest that NBS1 polymorphisms may be genetic biomarkers for NSCLC prognosis especially PFS with platinum-based chemotherapy in the Chinese population.