Various methodologies for the genetic analysis of longitudinal data have been proposed and applied to data from large-scale genome-wide association studies (GWAS) to identify single nucleotide polymorphisms (SNPs) associated with traits of interest and to detect SNP-time interactions. We recently proposed a grid-based Bayesian mixed model for longitudinal genetic data and showed that our Bayesian method increased the statistical power compared to the corresponding univariate method and well detected SNP-time interactions. In this paper, we further analyze longitudinal obesity-related traits such as body mass index, hip circumference, waist circumference, and waist-hip ratio from Korea Association Resource data to evaluate the proposed Bayesian method. We first conducted GWAS analyses of cross-sectional traits and combined the results of GWAS analyses through a meta-analysis based on a trajectory model and a random-effects model. We then applied our Bayesian method to a subset of SNPs selected by meta-analysis to further discover SNPs associated with traits of interest and SNP-time interactions. The proposed Bayesian method identified several novel SNPs associated with longitudinal obesity-related traits, and almost 25% of the identified SNPs had significant p-values for SNP-time interactions.

We investigated the usefulness of age-specific cutoffs for screening of urinary tract infections (UTIs) in Korean outpatients, using the automated urine analyzer UF-1000i (Sysmex, Kobe, Japan). We retrospectively reviewed outpatient medical records. Urine samples of 7,443 outpatients from January 2010 to December 2017 were analyzed using urine culture and UF-1000i. ROC curves were calculated for each UF-1000i parameter based on the culture results. There were 1,398 culture positive samples, 5,774 culture negative samples, and 271 contaminated samples. UF-1000i had an area under the curve of ≥0.9 in outpatients >15 years. The appropriate cutoffs, which are the sum of bacterial (B-A-C) and white blood cell (WBC) counts, were 297.10/µL (15–24 years), 395.65/µL (25–44 years), 135.65/µL (45–64 years), 67.95/µL (65–74 years), and 96.5/µL (≥75 years). B-A-C and WBC counts differed among the three most frequently identified bacteria (Escherichia coli, Klebsiella pneumoniae, and Enterococcus faecalis). The UF-1000i system is useful for applying age-specific cutoffs to screen for UTIs, thereby preventing antibiotic abuse and reducing antibiotic resistance. Future studies can explore how its B-A-C and WBC counts can facilitate selection of empirical antibiotics by distinguishing between gram-positive and gram-negative bacteria.
Anti-Bacterial Agents ; Bacteria ; Drug Resistance, Microbial ; Enterococcus ; Gram-Negative Bacteria ; Humans ; Klebsiella pneumoniae ; Leukocytes ; Mass Screening ; Medical Records ; Outpatients ; Retrospective Studies ; ROC Curve ; Urinary Tract Infections ; Urinary Tract

Mycophenolate mofetil (MMF) is an immunosuppressive agent used to treat severe lupus, including lupus nephritis. Common adverse effects of MMF include gastrointestinal and hematological manifestations; however, cardiac toxicity in association with MMF has not been reported. We present a 21-year-old woman with lupus nephritis who developed ventricular tachycardia 2 hours after an overdose of MMF (34 g). Ventricular bigeminy was documented 12 hours after the MMF overdose. Transthoracic echocardiography showed no evidence of structural heart disease. The ventricular arrhythmia was successfully treated with potassium replacement, hydration, and cholestyramine. This case suggests that an overdose of MMF can induce ventricular tachycardia, and electrocardiogram monitoring is critical to identify this rare cardiac complication of MMF.
Arrhythmias, Cardiac ; Cardiotoxicity ; Cholestyramine Resin ; Echocardiography ; Electrocardiography ; Female ; Heart Diseases ; Humans ; Lupus Erythematosus, Systemic ; Lupus Nephritis ; Mycophenolic Acid ; Potassium ; Tachycardia, Ventricular ; Young Adult

Background: Fixed-dose combinations have the advantage of improving patient compliance, but may increase the risk of duplicate prescriptions. As the use of fixed-dose combination antihypertensives increases, it is necessary to investigate the current status of class duplication prescriptions (CDP) in patients taking fixed-dose combination antihypertensives in Korea and to identify factors associated with CDP. Methods: We conducted a retrospective observational study using nationally representative claim data. Hypertensive patients aged 20 years or older taking fixed-dose combination antihypertensives were extracted. Among these patients, patients with CDP were identified. A chi-square test was applied to determine the differences between patients with CDP and nonCDP. The associated factors of CDP were identified through multiple logistic regression. Results: Of the 74,165 patients who were prescribed fixed-dose combination antihypertensives, 426 patients (0.6%) with CDP were identified. The most common antihypertensive class associated with CDP was calcium channel blockers (194 patients, 45.5%), followed by angiotensin II receptor blockers (136 patients, 31.9%). Patients aged 75 years or older (odds ratio [OR] 1.83, 95% confidence interval [CI] 1.02-3.52), chronic kidney disease (OR 4.45, 95% CI 2.15-8.25), chronic heart failure (OR 2.71, 95% CI 1.93-3.72), coronary artery disease (OR 2.22, 95% CI 1.60-3.03) and Medical Aid/Patriots and Veterans Insurance (OR 1.49, 95% CI 1.04-2.07) were significantly associated with increased CDP. Conclusions The factors associated with CDP were the elderly, comorbidities, and low socioeconomic status. Since CDP can result in negative clinical outcomes, active intervention by the pharmacist is warranted.

Mycophenolate mofetil (MMF) is an immunosuppressive agent used to treat severe lupus, including lupus nephritis. Common adverse effects of MMF include gastrointestinal and hematological manifestations; however, cardiac toxicity in association with MMF has not been reported. We present a 21-year-old woman with lupus nephritis who developed ventricular tachycardia 2 hours after an overdose of MMF (34 g). Ventricular bigeminy was documented 12 hours after the MMF overdose. Transthoracic echocardiography showed no evidence of structural heart disease. The ventricular arrhythmia was successfully treated with potassium replacement, hydration, and cholestyramine. This case suggests that an overdose of MMF can induce ventricular tachycardia, and electrocardiogram monitoring is critical to identify this rare cardiac complication of MMF.

Background/Aims: Intrahepatic cholangiocarcinoma (iCCA) is a subgroup of cholangiocarcinoma and is the second- most-common primary hepatic tumor. Several predictive and prognostic factors have been analyzed; however, in this study we focused on the influence of age. Our aim was to use real-world results to determine the influence of age in iCCA patients. Methods: A retrospective analysis of patients treated between 2005 and 2016 at Konkuk University Medical Center. In total, 133 patients with iCCA were identified. The mass-forming, periductal-infiltrating, and intraductal-growth types were included; patients with extrahepatic or hilar-type cholangiocarcinoma were excluded. We defined two groups: a younger group, age < 65 years, and an older group, age ≥ 65 years. Statistical analyses using univariate and multivariate Cox regression analyses, including the Kaplan-Meier method, were conducted. Results: In total, 114 patients were enrolled. The two groups differed with regard to treatment options such as surgery with adjuvant chemotherapy or palliative chemotherapy (p = 0.012, p < 0.001). The younger group had significantly longer survival than the older group (p = 0.017). In the younger group, patients who received therapy had longer survival than those who did not (hazard ratio, 3.942; 95% confidence interval, 2.053 to 7.569; p < 0.001). Multivariate analysis indicated that younger age, lower bilirubin, low CA 19-9, and no lymph-node involvement were independent factors for improved survival. Conclusions Younger patients and those who underwent surgery with adjuvant chemotherapy had longer survival. The younger the patient, the more treatments received, including palliative chemotherapy.

Background: & Objectives: Fixed-dose combinations (FDCs) offer advantages in adherence and cost-effectiveness compared to free combinations (FCs), but they can also complicate the prescribing process, potentially leading to therapeutic duplication (TD). This study aimed to identify the prescribing patterns of FDCs for dyslipidemia and investigate their associated risk of TD. Methods: This was a retrospective cohort study involving drugs that included statins, using Health Insurance Review & Assessment ServiceNational Patient Sample (HIRA-NPS) data from 2018. The unit of analysis was a prescription claim. The primary outcome was TD.The risk ratio of TD was calculated and adjusted for patient, prescriber, and the number of cardiovascular drugs prescribed using a multivariable Poisson model. Results: Our study included 252,797 FDC prescriptions and 515,666 FC prescriptions. Of the FDC group, 46.52% were male patients and 56.21% were aged 41 to 65. Ezetimibe was included in 71.61% of the FDC group, but only 0.25% of the FC group. TD occurred in 0.18% of the FDC group, and the adjusted risk ratio of TD in FDC prescriptions compared to FC was 6. 44 (95% CI 5. 30-7. 82). Conclusions Prescribing FDCs for dyslipidemia was associated with a higher risk of TD compared to free combinations. Despite the relatively low absolute prevalence of TD, the findings underline the necessity for strategies to mitigate this risk when prescribing FDCs for dyslipidemia. Our study suggests the potential utility of Clinical Decision Support Systems and standardizing nomenclature in reducing medication errors, providing valuable insights for clinical practice and future research.

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 alphaadrenoceptor 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.

Purpose: This study aimed to evaluate the feasibility of measuring liver fat using the volumetric measurement method (Fatvol) by comparing it with the conventional 27-regions of interest drawing method (Fatroi). Materials and Methods: This retrospective study included 67 patients who underwent liver magnetic resonance imaging with fat quantification in August or September 2020.Two experienced abdominal radiologists measured the proton density fat fraction (PDFF) of the liver using the mDIXON-Quant sequence for each of two methods. The PDFF was measured twice with each method at intervals of at least 4 weeks to avoid recall bias. Measurement times were recorded. The intra-class correlation coefficient (ICC) was calculated for intra-exam repeatability, inter-reviewer reproducibility, and inter-exam agreement. Results: Measurement times for Fatvol were significantly shorter than for Fatroi. Measurement times for Fatroi and Fatvol, respectively, for reviewer A were 209.4 ± 55.1 s and 137.2 ± 51.5 s in session 1, and 180.9 ± 37.3 s and 127.0 ± 46.1 s in session 2. For reviewer B, the times were 190.7 ± 30.1 s and 74.8 ± 27.4 s in session 1, and 174.6 ± 21.8 s and 64.1 ± 17.5 s in session 2. In all cases, p < 0.001. The mean PDFF values were 7.2% ± 6.4% and 7.2% ± 6.5% (sessions 1 and 2, respectively) for Fatroi and 7.4% ± 6.0% and 7.3% ± 6.1% for Fatvol for reviewer A. For reviewer B, they were 7.1% ± 6.6% and 7.1% ± 6.6% for Fatroi and 7.4% ± 5.8% and 7.4% ± 5.8% for Fatvol. The ICCs between measurement methods (0.998 and 0.995 for reviewers A and B, respectively), for Fatvol within each reviewer (0.999 and 1.000 in sessions 1 and 2, respectively), and between reviewers (0.999) were excellent. Conclusion The measurement time could be significantly reduced using Fatvol compared to Fatroi while maintaining the consistency of the liver fat measurement values.

Objective: Overcrowding in the emergency department (ED) has been a long-standing global problem, but has yet to be resolved. This study was undertaken to investigate whether expansion of the ED can affect overcrowding. Methods: This was a retrospective study comparing two 10-month periods: before (September 2015 to June 2016) and after (September 2017 to June 2018) the ED expansion in an urban tertiary hospital. The ED expansion included expansion of the ambulatory area and establishment of a 25-bedded emergency ward dedicated to patients admitted through the ED. Results: Comparing the two study periods, we noted an increase in the number of patients visiting the ED, from 77,078 to 87,027. Moreover, the proportion of patients who returned home untreated significantly decreased from 11.5% to 0.9% (P<0.001). The number of adult patients increased from 40,814 to 60,720; in particular, the number of ambulatory patients increased from 18,648 to 42,944. Conversely, waiting time for X-ray and computed tomography increased (10.0 to 17.0 minutes, and 35.0 to 48.0 minutes, respectively). Other areas with increased time duration include median ED length of stay of total patients (193.0 minutes to 205.8 minutes), and time from consultation to admission decision (122.3 to 161.4 minutes). However, the boarding time decreased from 239.2 to 190.9 minutes. Conclusion The ED expansion allowed more patients to be treated, and the boarding time of admitted patients was reduced through operation of the emergency ward. However, due to increase in the number of visiting patients, the time required for medical treatment increased concurrently.