BACKGROUND: The protective effect of metformin against breast cancer is inconclusive. OBJECTIVE: To evaluate the effect of metformin on breast cancer risk and mortality in patients with type 2 diabetes. METHOD: A comprehensive literature search was performed for pertinent articles published prior to June 30, 2014, using PubMed and EMBASE. Study heterogeneity was estimated with I2 statistic. The data from the included studies were pooled and weighted by random-effects model. The quality of each included study was assessed on the basis of the 9-star Newcastle-Ottawa Scale and publication bias was evaluated by visual inspection of a funnel plot. RESULTS: Ten studies were included in the meta-analysis of the association of metformin and breast cancer risk. By synthesizing the data from the studies, the pooled odds ratio (OR) was 0.72 (95% CI: 0.59, 0.87) (p = 0.0005). Three cohort studies were included for meta-analysis of the association between metformin and breast cancer-related mortality. Metformin was associated with a significant decrease in mortality (Risk ratio: 0.68; 95% CI: 0.51, 0.90, p = 0.007). CONCLUSION: The present meta-analysis suggests that metformin appears to be associated with a lower risk of breast cancer incidence and mortality in patients with type 2 diabetes.
Breast Neoplasms* ; Breast* ; Cohort Studies ; Diabetes Mellitus ; Diabetes Mellitus, Type 2* ; Humans ; Incidence ; Metformin* ; Mortality* ; Odds Ratio ; Population Characteristics ; Publication Bias

OBJECTIVE: A meta-analysis was performed to determine effect of ginseng on blood pressure. METHODS: The databases of PubMed, Embase, Cochrane Library, RISS, DBpia, KISS, and Koreamed were searched for all published studies from inception to January 2016. The following terms were used: "ginseng", "hypertension", and "blood pressure". Using the Review Manager 5, mean differences (MDs) were pooled to measure the effect of ginseng on blood pressure compared to that of placebo. RESULTS: Eleven randomized controlled trials were included. In this meta-analysis, ginseng treatment significantly lowered systolic blood pressure (SBP) in a dose-independent way (MD: -1.99, p = 0.04). In subgroup analysis, 8-12 week consumption of ginseng achieved significantly greater reduction in SBP (MD: -3.14, p = 0.03), while single administration of ginseng failed to show BP-lowering effect. When ingested over 8-12 weeks, ginseng significantly lowered diastolic blood pressure (DBP) (MD: -1.96, p = 0.03). No significant association was found between ginseng dose and the magnitude of BP-lowering effect. However, a significant positive relationship was observed between baseline SBP level and the magnitude of SBP reduction (r = 0.848, p = 0.033). Such a relationship was not seen in DBP. CONCLUSION: Consumption of ginseng for 8-12 weeks achieved significant reductions in SBP and DBP in a dose-independent way. There was a significant positive relationship between baseline SBP level and the magnitude of SBP reduction.
Blood Pressure* ; Panax*

OBJECTIVE: To estimate the association between ABCG2 C421A polymorphism and response to imatinib in chronic myeloid leukemia. METHODS: A systematic review was conducted to evaluate the effect of ABCG2 C421A polymorphism on imatinib response. The databases of PubMed, Embase, Web of science, CINAHL with FullText, and Cochrane Library were searched for all published studies from inception to December 2015. The following terms were used with functions of 'AND' and 'OR': 'chronic myeloid leukemia', 'CML', 'drug transporter', 'ABCG2', 'BCRP', 'polymorphisms', 'SNPs', and 'imatinib'. The studies reporting the association between ABCG2 polymorphism and imatinib response were evaluated. RESULTS: A total of 7 studies were included in the present meta-analysis. The pooled analysis showed that ABCG2 c.421CC genotype was significantly associated with poor response to imatinib under the dominant model (CC vs CA+AA; OR: 0.56; 95% CI: 0.41, 0.77; p = 0.0004). The subgroup analysis of Asian studies demonstrated a significantly lower response in c.421CC genotype than in c.421CA or c.421AA genotype (OR: 0.52; 95% CI: 0.37, 0.73; p = 0.0002). In subgroup analyses of 5 studies, the patients with the c.421CC genotype exhibited higher risk for worse response than the patients with c.421CA or c.421AA genotype (heterozygote codominant model: CC vs. AC; OR: 0.49, 95% CI: 0.33, 0.73; p = 0.0006; homozygote codominant model: CC vs AA; OR: 0.43; 95% CI: 0.25, 0.75, p = 0.003). CONCLUSION: The ABCG2 c.421CC genotype was significantly associated with poor response to imatinib compared to the c.421CA and c.421AA genotypes in chronic myeloid leukemia, especially in Asian patients.
Asian Continental Ancestry Group ; Genotype ; Homozygote ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive* ; Imatinib Mesylate

OBJECTIVE: Clinical practice guidelines (CPGs) are systematically developed statements aimed at helping optimal care of the patient in a given clinical circumstance. Because of the increasing evidence that active implementation of CPGs improve health outcomes, there is a growing awareness of the importance of guideline development and dissemination. The objective of this study was to investigate the status of CPG development and availability of the CPGs in Korea. METHOD: We searched in the Web sites of 180 organizations to identify CPGs which were developed and/or published in Korea until 1 July 2014. The data of titles, published year, publisher, distributer, and accessibility at the internet web of all CPGs were collected and analyzed. RESULTS: A total of 172 CPGs were developed and 80% had been released since 2009. Most (51.2%) were developed for management of 4 diseases: 28 for digestive system disease; 27 for infectious disease; 18 for endocrine and metabolic diseases; and 15 for neoplasms. Of the 172 CPGs, 150 CPGs were publicly available. Among the 150 CPGs, 78.7% (118/150) were developed by only one organization. CONCLUSION: To ensure the production of high-quality CPGs, it is necessary to collaborate with other relevant professional societies in guideline development process. In addition, stronger efforts on wider dissemination of CPGs must be employed at the country levels to promote implementation of CPGs in clinical settings.
Communicable Diseases ; Digestive System Diseases ; Evidence-Based Medicine ; Humans ; Internet ; Korea* ; Metabolic Diseases

BACKGROUND: In this systematic review and meta-analysis, the effect of metformin on weight loss was assessed to determine whether metformin should be recommended for the prevention or treatment of weight gain in patients receiving antipsychotic medication for the treatment of schizophrenia or schizoaffective disorder. METHODS: The PubMed, Embase, and Cochrane Library databases were searched for all published randomized controlled trials (RCTs) from inception to June 2018. In addition, the references of relevant articles were also examined. Using Review Manager 5, the pooled estimates of the weighted mean difference (WMD) of the changes in body weight and body mass index (BMI) and the corresponding 95 % confidence intervals (CIs) were calculated. RESULTS: The meta-analysis included 15 RCTs. The pooled analysis showed that compared with placebo, metformin led to significant reductions in body weight (WMD: −2.09, 95% CI: −2.59, −1.60; p<0.00001) and BMI (WMD: −0.90, 95% CI: −1.08, −0.72; p<0.00001). The effect of metformin on weight loss was greater in patients receiving olanzapine than in patients receiving clozapine (body weight, WMD: −2.39, 95% CI: −3.76, −1.02; p=0.0006 for olanzapine; −1.99, 95% C: −3.47, −0.51; p=0.009 for clozapine; BMI, WMD: −1.15, 95% CI: −1.74, −0.57, p=0.0001 for olanzapine; WMD: 0.76, 95% CI: −1.23, −0.28; p=0.002 for clozapine). CONCLUSION: Metformin can be recommended to manage olanzapine-induced weight gain in patients with schizophrenia or schizoaffective disorder. The magnitude of the reductionss in body weight and BMI implieds that the use of metformin to attenuate olanzapine-induced weight gain can minimize the risk of coronary heart disease.
Body Mass Index ; Body Weight ; Clozapine ; Coronary Disease ; Humans ; Metformin* ; Psychotic Disorders* ; Schizophrenia* ; Weight Gain* ; Weight Loss

BACKGROUND: This study was performed to clarify the effect of SLCO1B1 T521C on statin-induced myotoxicity. METHODS: The PubMed, Embase, Ovid, and Cochrane Library databases were searched for all published studies between database inception and April 2018. Using Review Manager 5, the pooled odds ratio (OR) and corresponding 95% confidence interval (CI) were determined to assess the effect of SLCO1B1 T521C on statin-induced myotoxicity by using different genetic models. RESULTS: Eleven observational studies and one randomized controlled trial were included in the meta-analysis. The pooled analysis showed that the incidence of statin-induced myotoxicity was significantly associated with the SLCO1B1 521C variant allele. Among patients using statins, the incidence of myotoxicity was higher in those carrying the 521TC or 521CC variant than in those carrying the 521TT variant in the dominant model (TC + CC vs TT, OR: 1.57; 95% CI: 1.20, 2.05; p = 0.001). The 521TC genotype was associated with a higher risk of myotoxicity than the 521TT genotype (OR: 1.42; 95% CI: 1.09, 1.86; p = 0.009). Furthermore, the incidence of myotoxicity was higher in 521CC carriers than in 521TC carriers (OR: 1.40; 95% CI: 1.06, 1.83; p = 0.02) and noticeably higher in 521CC carriers than in 521TT carriers (OR: 2.26; 95% CI: 1.23, 4.17; p = 0.009). CONCLUSION: The identification of individuals with the SLCO1B1 521C variant allele prior to the initiation of statin therapy might be useful to predict the risk of toxicity development, determine the individual dose, and prevent myotoxicity.
Alleles ; Genotype ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Incidence ; Models, Genetic ; Odds Ratio

OBJECTIVE: As the demands of healthcare environment change, it is necessary to advance human health care by improving students' essential competencies including knowledge, skills, abilities, inter-professional collaboration and patient centered care. This study identified long term accomplishment and improvement of the essential competencies in clinical pharmacy practice education (CPPE) at Korean hospitals over time. METHODS: This study was conducted for pharmacy students who completed CPPE evaluation related to tertiary hospitals and secondary hospitals located in Seoul and Gyeonggi-do regional area from 2014 to 2018. RESULTS: Over the past 5 years, overall results of student evaluation on the essential competencies in CPPE at both tertiary and secondary hospitals showed a decreasing trend or did not change. Essential competency in CPPE at tertiary hospitals had been identified as superior on ‘Learn clinical knowledge in the treatment of diseases’ to secondary hospitals [average number of students (%): 210 (72.9%) vs 68 (68.0%)]. On the other hand, essential competencies in CPPE at secondary hospitals had been identified as better at ‘inter-professionals collaborative teamwork and direct patient care’ than tertiary hospitals [average number of students (%): 64 (64.0%) and 56 (56.0%) vs 121 (42.0%) and 90 (31.3%)]. A total of 176 (61.1%) students in tertiary hospitals and 66 (66.0%) in secondary hospitals evaluated that ‘patient-centered care’ education was good. CONCLUSION: In tertiary hospitals, all six essential competency outcomes have not been improved, whereas four essential competency outcomes showed an increasing trend in secondary hospitals. It will be necessary to develop outcome-based CPPE education program to better reflect the essential competencies.
Cooperative Behavior ; Delivery of Health Care ; Education ; Gyeonggi-do* ; Hand ; Humans ; Patient-Centered Care ; Pharmacy* ; Seoul* ; Students, Pharmacy ; Tertiary Care Centers

BACKGROUND: Clinical Pharmacy Practice Experience (CPPE) is an important curriculum that offers students patient-centered disease prevention and treatment with evidence-based optimal pharmacotherapy for better clinical outcomes. However, few studies have evaluated the perception of pharmacy students regarding CPPE in tertiary and secondary hospitals. This study aimed to evaluate the perception of pharmacy students regarding the learning program of CPPE. METHODS: The survey questionnaire consisted of 15 self-administered questions regarding pharmacy practices, barriers, and improvement of practical training. Fourteen institutional pharmacies located in seven regions responded to a survey questionnaire from March 1 to June 30, 2017. The participants were pharmacy students doing clerkship in a hospital setting. RESULTS: The response rate was 73.6%. Thirty-five participants (22.4%) had used a hospital library, but 121 (77.6%) had never used the library for drug information resources. Eighty-one (50.0%) responded that clinical knowledge and drug information was the most beneficial practice. Thirty-seven (31.1%) respondents in the tertiary hospitals and 19 (46.3%) in the secondary hospitals answered that they were filling prescriptions during the daily break. On the other hand, 72 respondents (60.5%) in the tertiary hospitals and 17 (41.5%) in the secondary hospitals did literature research to prepare for presentation. CONCLUSION: More students in secondary hospitals continue to fill prescriptions during the daily break, as compared to those in tertiary hospitals. Therefore, the authors suggest self-directed learning to improve clinical performance and each institution considers offering onsite or online library service to improve evidence-based CPPE for pharmacy school students.

Objective: This study aimed to investigate the occurrence and types of the adverse events (AEs) associated with oral fluconazole and itraconazole and factors associated with specific types of AEs. Methods: We analyzed AEs reported by community pharmacies nationwide over 10 years using the Korea Adverse Event Reporting System database. Various AE terms were categorized into 18 types, and concomitant medications were classified by drug-drug interaction (DDI) severity. The relationship between the specific type of AE and age, sex, and number of concomitant medications was investigated using multiple logistic regression analysis. Results: A total of 879 AE reports of fluconazole and 401 reports of itraconazole were analyzed; of these reports, 321 and 83 reports of fluconazole and itraconazole, respectively, described concomitant drug administration categorized as DDI severity of contraindicated or major. Women had a higher risk of psychiatric AEs associated with fluconazole use (OR, 1.587; p=0.042). Polypharmacy increased the risk for psychiatric AEs (OR, 3.598; p<0.001 for fluconazole and OR, 2.308; p=0.046 for itraconazole).In dermatologic AEs, the mean age of patients who received itraconazole was lower than that of patients who received fluconazole (46.3±16.8 vs. 54.9±15.4; p<0.001). Co-administration of fluconazole with 1-3 drugs increased the risk of neurological AEs (OR, 1.764; p=0.028). Conclusion When using fluconazole and itraconazole, psychiatric AEs should be noted, particularly in women and in case of polypharmacy; moreover, when fluconazole is co-administered with other drugs, attention should be paid to the occurrence of neurological AEs.

Background: Globally, the number of patients with aspergillosis is increasing, and the mortality rate remains high. This study aimed to investigate prescribing patterns of antifungal drugs for patients with aspergillosis in South Korea using real-world data. Methods: This retrospective cross-sectional study was performed using National Patient Sample (NPS) data collected by the Health Insurance Review and Assessment Service (HIRA) during 2011-2020. The use of antifungal drugs in patients with aspergillosis was investigated. Results: A total of 1374 patients were identified: 333 patients with invasive pulmonary aspergillosis (IPA) (24.2%), 436 patients with other PA (31.7%), 73 patients with other forms of aspergillosis (5.3%), and 532 patients with unspecified aspergillosis (38.7%). The odds of receiving an antifungal prescription were higher for IPA than for other PA (aOR, 0.233; p<0.001), and higher for hematologic malignancies than for respiratory disorders other than cancer or infections (aOR, 10.018; p<0.001). During each hospitalization period, 56.1% (97/173) and 6.4% (11/173) of IPA hospitalizations received voriconazole and itraconazole monotherapy, respectively, whereas 44.3% (27/61) and 27.9% (17/61) of other PA hospitalizations received itraconazole and voriconazole monotherapy, respectively. Among outpatients with IPA, 67.5% (85/126) and 26.2% (33/126) received voriconazole and itraconazole alone, respectively, whereas among outpatients with other PA, 86.1% (68/79) and 12.7% (10/79) received itraconazole and voriconazole alone, respectively, during the year. Conclusion In Korea, voriconazole monotherapy was preferred in IPA inpatients, and itraconazole monotherapy was preferred in other PA inpatients. In the ambulatory care settings for IPA and other PA, itraconazole monotherapy was preferred.