Search

This study aimed to investigate the activity of a nutrition support team (NST) and the trends of multi-chamber bag (MCB) and customized parenteral nutrition (PN) with NST consultations in South Korea. Data were obtained from the National Inpatient Sample Cohort between 2015 and 2020. Three datasets were constructed for NST consultation, MCB-PN product prescriptions, and aseptic preparation of total PN. The intersections of the NST consultation and each PN dataset were compiled into MCB-PN with NST or customized PN with a NST sub-dataset, respectively. Using personal identifiers, the patients’ characteristics were evaluated in the NST cohort. A total of 91,384 reimbursements and 70,665 patients were included. The NST activity had increased by more than 50% over 6 years. Approximately 70% and 11%, respectively, of the NST cohort were classified into two subgroups: MCB-PN with NST (M-NST) and customized PN with NST (C-NST). M-NST had many elderly patients with cancer and showed a higher in-hospital mortality than C-NST (12.6% vs. 9.5%). C-NST included a larger number of patients under the age of 5 years, and the hospitalization period was more extended than M-NST (26.2 vs. 21.2 days). The present study showed that NST activities and the proportion of PN with NST consultation are gradually increasing in South Korea.

Background This study aimed to determine whether pre-operative medication use is associated with unplanned 30-day readmission in elderly people undergoing cancer surgery. Methods Patients aged 65 years or older who were scheduled for cancer surgery and presented for comprehensive geriatric assessment were included. Comparisons of variables between patients with readmission and those without readmission were performed by univariate and multivariate analyses. Results A total of 473 patients were included. Multivariate analysis showed that pre-operative discontinuation-requiring medications (PDRMs) and gastrointestinal/hepato-pancreato-biliary (GI/HPB) cancer were significant factors for 30-day readmission. PDRM increased the risk of readmission by about 2.2-fold. Attributable risk of PDRM to readmission was around 55%. The adjusted odds ratio and attributable risk for GI/HPB surgery was 3.4 (95% CI 1.0–11.5) and 70.8%, respectively. Conclusions Medication use has an impact on unplanned 30-day readmission in geriatric oncology patients, further highlighting the importance of medication optimization for elderly patients with cancer surgery.

Summary: Background: Management of antiplatelet agents and other chronic anticoagulation medications in patients scheduled for surgery can reduce intraoperative bleeding complications. However, few studies on the association of antithrombotics, relative to their duration of action, with intraoperative transfusion have been conducted. We aimed to determine the association of recent use of antithrombotics, relative to their duration of action, with intraoperative transfusion in elderly people undergoing cancer surgery. Methods: The study subjects were patients aged 65 years or older who were scheduled for cancer surgery and presented for comprehensive geriatric assessment. We reviewed the baseline patient characteristics obtained from electronic medical records and the patients' preoperative medication history, including anticoagulants, antiplatelet agents, and streptokinase/streptodornase. Results: A total of 475 cancer patients were included. Multivariate analysis showed that long-acting anticoagulant therapy before surgery was a significant risk factor for intraoperative transfusion. Long-acting anticoagulants increased the risk of transfusion approximately 15.9-fold (95% CI 1.9–136.2). The attributable risk of long-acting anticoagulants to transfusion was approximately 93.7%. Also, low body mass index (BMI) and hepato-pancreato-biliary (HPB) surgery were significantly associated with intraoperative transfusion. The adjusted odds ratios for low BMI (

There are various trigger tools for detecting adverse drug events (ADEs), however, a drug-related emergency department (ED) visit trigger tool (DrEDTT) has not yet been developed. We aimed to develop and validate a DrEDTT with a multi-center cohort. In this cross-sectional study, we developed the DrEDTT consisting of 28 triggers through a comprehensive literature review and three phase expert group discussion. Next, we evaluated the performance of the DrEDTT by applying it to relevant medical records retrieved from four hospitals from January 2016 to June 2016. Two experts performed an in-depth chart review of a 25% of random sample of trigger flagged and unflagged ED visits and a true ADE was determined through causality assessment. Among 66,564 patients who visited the ED for reasons other than traffic accident and trauma during the study period, at least one trigger was found in 21,268 (32.0%) patients. A total of 959 true ADE cases (5.8%) were identified from a randomly selected 25% of ED visit cases. The overall positive predictive value was 14.0% (range: 8.3–66.7%). Sensitivity and specificity of DrEDTT were 77.7% and 70.4%, respectively. In conclusion, this newly developed trigger tool might be helpful to detect ADE-related ED visits.

Purpose: This study aimed to examine OATP1B1 (SLCO1B1) and OATP1B3 (SLCO1B3) on the pharmacokinetics of valsartan. Twenty-five subjects were genotyped for 16 single-nucleotide polymorphisms of the SLCO1B1 and SLCO1B3 genes. Methods: After a single dose of 160 mg of valsartan was orally administered to healthy male volunteers, drug concentrations were assayed up to 48 h. The 25 subjects were genotyped for 16 single-nucleotide polymorphisms (SNPs) of the SLCO1B1 and SLCO1B3 genes. Subjects were classified into groups according to their SLCO1B1*1B haplotype, 23 subjects were carriers of SLCO1B1*1B and two subjects were included in the reference group with SLCO1B1*1A/*1A. Alternations of the splicing factor-binding site pattern caused by the given mutation were evaluated with the Human Splicing Finder (HSF) 3.1. Results: The subjects who carried SLCO1B1*1B showed a 2.3-fold higher clearance than those without the *1B haplotype. Mean Cmax and AUCinf were reduced by 45% and 54%, respectively, in the SLCO1B1*1B genotype group compared to the reference group with the *1A/*1A genotype (p &lt, 0.01). The carriers of the rs4149153 T allele of SLCO1B3 had a 27% lower mean Cmax and a 1.5-fold higher Vd compared to homozygotic CC carriers (p &lt, 0.05). In a combined analysis of SLCO1B1 and SLCO1B3, subjects not carrying SLCO1B1 *1B and carrying SLCO1B3 rs4149153 T allele showed a 1.6-fold higher clearance than those with the other genotypes, whereas mean Cmax and AUClast were reduced by 35% and 42%, respectively (p &lt, 0.05), in the subjects. HSF 3.1 analysis showed that rs4149153 could cause alterations of the acceptor splice site (TAAATACTAAAGAC to TAAATATTAAAGAC) with scoring change (from 72.57 to 71.92, difference = −0.9). Conclusion: It was found that plasma exposure to valsartan is significantly decreased in SLCO1B1*1B carriers and carriers of the rs4149153 T allele of SLCO1B3, possibly as a result of increased hepatic uptake.

This study aimed to determine the association between hepatocyte nuclear factor 4 alpha (HNF4A) polymorphisms and bleeding complications in patients on warfarin with international normalized ratios between 2.0 and 3.0 after cardiac valve replacement.Nineteen single nucleotide polymorphisms of HNF4A in addition to VKORC1 rs9934438 and CYP2C9 rs1057910 were analyzed. Univariate and multivariate analyses were conducted to evaluate associations between genetic polymorphisms and bleeding risk. Attributable risk and number needed to genotype (NNG) were calculated to assess clinical value of genotyping.Of 142 patients, 21 experienced bleeding complications. Multivariate logistic regression analysis was conducted using factors with P0.1 in univariate analysis. Multivariate analysis showed that patients with the CC genotype of rs6130615 had an 8.4-fold increased risk of bleeding, compared with patients with the T allele. Attributable risk and NNG were 88.1% and 32.2, respectively. Patients with the TT genotype of rs3212191 had a 3.8-fold increased risk of bleeding, compared with C allele carriers, while patients with variant-type homozygotes for rs1884613 showed an 8.7-fold higher bleeding complication than C allele carriers. The attributable risk/NNG of rs3212191 and rs1884613 were 73.4%/17.6 and 88.5%/22.8, respectively. Among comorbidities, atrial fibrillation was the only significant risk factor for bleeding complications.Bleeding complications during warfarin therapy in patients with mechanical heart valves were associated with HNF4A polymorphisms and atrial fibrillation.

The purpose of this study was to investigate influence of gene polymorphisms of APOB and APOE on risk of bleeding complications at therapeutic INR, during warfarin treatment in Korean patients with mechanical cardiac valves. The study included 142 patients from the EwhA-Severance Treatment Group (EAST) of Warfarin. A total of 12 SNPs was investigated. Five SNPs of APOB (c.13013G>A, c.1853C>T, c.1594C>T, c.293C>T, and c.7545C>T) and five SNPs of APOE (g.4798T>G, g.6406G>A, g.10413T>C, c.388T>C, and c.526C>T) were selected. In addition to selected SNPs, VKORC1 g.6399C>T, and CYP2C9 c.1075A>C, which were known to have significant effects on warfarin stable doses, were also included in the study. Two SNPs of APOB (c.293C>T and c.1853C>T) were associated with bleeding complications. T allele carriers of c.293C>T had 8.6 times (95% CI 2.9–25.5, p T had 6.4 times (95% CI 2.3–17.9, p T and c.293C>T were 0.771 and 0.802, respectively. Among demographic characteristics, age was the only significant factor. This study revealed that APOB was associated with bleeding complications in patients with warfarin treatment after mechanical cardiac valves.

Aim: This study was designed to identify the possible effects of VEGFA polymorphisms on the occurrence of bleeding complications in patients with mechanical heart valves who have achieved therapeutic international normalized ratio (INR). Materials & methods: 13 SNPs of VEGFA were analyzed. Uni- and multi-variate analyses were conducted to identify associations between polymorphisms and bleeding complications. Results & conclusion: Patients with the CC genotype of rs35410204 had an approximately tenfold higher bleeding complication than those with the T allele. For rs866236, patients who had wild-type homozygotes showed an approximately 2.9-fold higher bleeding complication than C allele carriers. This study demonstrated that bleeding complications during warfarin therapy are associated with VEGFA polymorphisms in patients with mechanical heart valves.

Purpose: GATA4 and GATA6 are known to have potential roles in vascular regulation by affecting vascular smooth muscle cell differentiation and atrial natriuretic peptide levels. The aim of this retrospective study was to investigate the associations between GATA4 and GATA6 polymorphisms and bleeding complication risk at a therapeutic international normalized ratio (INR) in patients with mechanical heart valves. Patients and methods: Study patients were included from the Ewha-Severance Treatment (EAST) Group of Warfarin. It consisted of 229 patients who received warfarin therapy after undergoing mechanical heart valve replacement and maintained a stable INR (INR of 2.0-3.0 for at least three consecutive times). Twenty single-nucleotide polymorphisms including VKORC1, CYP2C9, GATA4, and GATA6 were analyzed. Multivariate logistic regression analysis was employed to investigate the independent risk factors for bleeding complications. To evaluate the potential clinical value of genotyping for preventing bleeding complications in patients with high-risk genotype, the number needed to genotype (NNG) was also calculated. Results: One hundred forty-two patients were included in this study, 21 of whom had bleeding complications. After adjusting covariates, TT genotype carriers of rs13273672 in GATA4 and CC genotype carriers of rs10454095 in GATA6 showed 5.0- (95% CI, 1.6-15.7) and 3.1-fold (95% CI, 1.1-8.7) higher bleeding complications than carriers of C allele and T allele, respectively. NNG for preventing one patient from experiencing bleeding complications in patients with TT genotype of rs13273672 and CC genotype of rs10454095 was 22.2 and 17.5, respectively. Patients with both TT genotype in rs13273672 and CC genotype in rs10454095 showed 8.7-fold (95% CI, 1.7-46.1) higher bleeding complications than those with other genotypes. NNG in patients having both TT genotype in rs13273672 and CC genotype in rs10454095 was calculated to be 40.0. Conclusions: This study showed that GATA4 and GATA6 gene polymorphisms could affect bleeding complications during warfarin treatment in patients with mechanical heart valves.

Objective: This nested case–control study aimed to investigate the effects of VEGFA polymorphisms on the development of bisphosphonate-related osteonecrosis of the jaw (BRONJ) in women with osteoporosis. Methods: Eleven single nucleotide polymorphisms (SNPs) of the VEGFA were assessed in a total of 125 patients. Logistic regression was performed for multivariable analysis. Machine learning algorithms, namely, fivefold cross-validated multivariate logistic regression, elastic net, random forest, and support vector machine, were developed to predict risk factors for BRONJ occurrence. Area under the receiver-operating curve (AUROC) analysis was conducted to assess clinical performance. Results: The VEGFA rs881858 was significantly associated with BRONJ development. The odds of BRONJ development were 6.45 times (95% CI, 1.69–24.65) higher among carriers of the wild-type rs881858 allele compared with variant homozygote carriers after adjusting for covariates. Additionally, variant homozygote (GG) carriers of rs10434 had higher odds than those with wild-type allele (OR, 3.16). Age ≥ 65 years (OR, 16.05) and bisphosphonate exposure ≥ 36 months (OR, 3.67) were also significant risk factors for BRONJ occurrence. AUROC values were higher than 0.78 for all machine learning methods employed in this study. Conclusion: Our study showed that the BRONJ occurrence was associated with VEGFA polymorphisms in osteoporotic women.

Although specialized pharmacists have been suggested to be essential members of antimicrobial stewardship programs (ASPs), not all hospitals in Korea operate ASPs with pharmacists involved. We aimed to evaluate the association of involvement of clinical pharmacists as team members of multidisciplinary ASPs with the incidence of antimicrobial-related adverse drug events (ADEs). Five tertiary teaching hospitals participated in this retrospective cohort study. At each participating hospital, we randomly selected 1000 participants among patients who had received systemic antimicrobial agents for more than one day during the first quarter of 2017. We investigated five categories of antimicrobial-related ADEs: allergic reactions, hematologic toxicity, nephrotoxicity, hepatotoxicity, and antimicrobial-related diarrhea. Multivariate logistic regression analysis was used to evaluate the potential impact of pharmacist involvement in ASPs on the incidence of ADEs. A total of 1195 antimicrobial-related ADEs occurred in 618 (12.4%) of the 4995 patients included in the analysis. The overall rate of ADE occurrence was 17.4 per 1000 patient days. Hospitals operating ASPs with pharmacists showed significantly lower AE incidence proportions than other hospitals (8.9% vs. 14.7%, p &lt, 0.001). Multidisciplinary ASPs that included clinical pharmacists reduced the risk of antimicrobial-related ADEs by 38% (adjusted odds ratio 0.62, 95% confidence interval 0.50–0.77). Our results suggest that the active involvement of clinical pharmacists in multidisciplinary ASPs may contribute to reduce the incidence of antimicrobial-related ADEs in hospitalized patients.

s Background Considering the limited generalizability of previous anticholinergic burden scales, the Korean Anticholinergic Burden Scale (KABS) as a scale specific to the Korean population was developed. We aimed to validate the KABS by detecting the associations between high anticholinergic burden, measured with the KABS, and emergency department (ED) visits compared to the pre-existing validated scales in older Korean adults. Methods A nested case-control study was conducted using national claims data. The cases included the first anticholinergic ED visits between July 1 and December 31, 2016. Anticholinergic ED visits were defined as ED visits with a primary diagnosis of constipation, delirium, dizziness, fall, fracture, or urinary retention. Propensity score-matched controls were identified. Average daily AB scores during 30 days before the index date were measured. Multivariate logistic regression analyses were performed. Results In total, 461,034 were included. The highest proportion of those with high AB was identified with KABS (5.0%). Compared with those who had a KABS score of 0, older adults with a score ≥ 3 were at higher risk for overall anticholinergic ED visits (aOR, 1.62, 95% CI, 1.53–1.72), as well as visits for falls/fractures (aOR: 1.54, 95% CI: 1.40–1.69), dizziness (aOR: 1.44, 95% CI: 1.30–1.59), delirium (aOR: 2.96, 95% CI: 2.28–3.83), constipation (aOR: 1.84, 95% CI: 1.68–2.02), and urinary retention (aOR: 2.13, 95% CI: 1.79–2.55). High AB by KABS showed a stronger association with overall anticholinergic ED visits and visits due to delirium and urinary retention than those by other scales. Conclusions In conclusion, KABS is superior to pre-existing scales in identifying patients with high AB and predicting high AB-related ED visits in older Korean adults.

Introduction The aim of this study is to identify the association between Attention Deficit Hyperactivity Disorder (ADHD) proneness and aggressive propensity in adolescents. Methods A quantitative, large‐scale, cross‐sectional study was performed from April to May 2016 in Korea. The survey questionnaire included overall health behaviors, as well as scales for assessing ADHD proneness (revised short form of the Conners‐Wells Adolescent Self‐Report Scale; CASS[S]) and aggressive behavior (Buss‐Perry Aggression Questionnaire; BPAQ) in adolescents. Area under the receiver operator characteristic (AUROC) curves was constructed to determine the cut‐off value of total aggression score for discriminating ADHD proneness. Results A total of 2,432 students participated in the survey, and 1,872 of them completed the questionnaire, indicating a response rate of 77.0%. Based on CASS(S), 33 (1.8%) subjects were classified as the ADHD group. AUROC curve analysis showed that a score of 68.5 points had higher sensitivity (83.3%) and specificity (69.4%) to discriminate ADHD proneness. ADHD proneness was significantly associated with higher aggression subdomain scores (physical, verbal, anger, and hostility). Especially, anger and hostility had a stronger relationship with ADHD proneness than did physical and verbal aggression. A multivariable analysis demonstrated that ADHD proneness was significantly related to body mass index in the top 10% of the study population, alcohol consumption, gastrointestinal trouble, daytime sleepiness, and total aggression score of 68.5 points or higher. Adolescents who had total aggression scores of 68.5 points or higher showed a 9.8‐fold (95% confidence interval [CI] 3.3–28.8) higher risk of ADHD compared with those who had scores less than 68.5 points. Conclusions Our results demonstrated that ADHD proneness was significantly associated with aggression propensity. In particular, anger and hostility were more closely associated with ADHD proneness than were other aggression subdomains., This large‐scale cross‐sectional study showed that ADHD proneness was associated with aggression propensity in adolescents. In subdomains of aggression, anger and hostility, which are inconspicuous behaviors, showed stronger association with ADHD tendency than did other aggression subdomains.

Although an elevated INR is highly associated with an increased risk of warfarin-associated bleeding, it has been reported that some patients also experience bleeding complications at therapeutic INRs. TGF-β1 polymorphisms has been reported to cause vascular malformations, resulting in bleeding complications, but there are few published genetic studies regarding bleeding complications in patients on warfarin therapy. This study aimed to determine if there is an association between transforming growth factor beta-1 (TGF-β1) polymorphisms and bleeding complications in patients who maintain international normalized ratios (INRs) of 2.0–3.0 with warfarin therapy after cardiac valve replacement. Eleven single nucleotide polymorphis (SNPs) of TGF-β1 (rs1800469, rs2241718, rs4803455, rs2241717, rs2241716, rs2241715, rs2241714, rs11083616, rs2317130, rs747857, and rs1982073) were analyzed. Univariate and multivariable analyses were conducted to evaluate the associations between genetic polymorphisms and bleeding risk. Attributable risk and the number needed to genotype (NNG) were calculated to identify the potential clinical value of genotyping. A discrimination of model was assessed via an analysis of the area under the receiver operating curve (AUROC). To test the model’s goodness of fit, a Hosmer–Lemeshow test was performed. Of 142 patients, 21 experienced bleeding complications. Among analyzed single nucleotide polymorphis (SNPs) of TGF-β1 (rs1800469, rs2241718, rs4803455, rs2241717, rs2241716, rs2241715, rs2241714, rs11083616, rs2317130, rs747857, and rs1982073), AA genotype carriers in rs2241718 had about 5.5 times more bleeding complications than those with the G allele after adjusting for other confounders. The attributable risk and NNG for rs2241718 were 81.9% and 57.8, respectively. The presence of atrial fibrillation and myocardial infarction increased bleeding complications 3.9- and 9.8-fold, compared with those without atrial fibrillation and myocardial infarction, respectively. Bleeding complications during warfarin therapy in patients with mechanical heart valves were associated with TGF-β1 polymorphisms as well as atrial fibrillation and myocardial infarction.

Objective The present prospective follow-up study aimed to evaluate the effects of KCNMB2 gene polymorphisms on ritodrine efficacy and adverse drug events (ADEs) in patients with preterm labor. Methods A total of 163 preterm labor patients were included in this single-center study. Nine single nucleotide polymorphisms (SNPs) in the KCNMB2 gene (rs10936979, rs7624046, rs7429015, rs7625907, rs6443559, rs9839376, rs9637454, rs11918114, and rs1382045) were assessed. The primary endpoint was time to delivery, and the secondary endpoint was ritodrine-induced ADEs. Results Patients with variant homozygotes of two SNPs (rs7624046 and rs9839376), which were in linkage disequilibrium, showed 2.06 [95% confidence interval (CI), 1.14-3.73] and 2.68 (95% CI, 1.16-6.20) times the hazard of time to delivery compared to wild-type allele carriers, respectively. Among demographic characteristics, gestational age at start of drug therapy and modified Bishop score were significant factors for time to delivery. Regarding safety outcomes, patients with variant homozygotes of rs7625907 had fewer ADEs compared to those with other genotypes (odds ratio, 0.32; 95% CI, 0.13-0.83). Conclusion This pharmacogenomic study suggests that ritodrine efficacy and ADEs are associated with KCNMB2 gene polymorphisms in patients with preterm labor.

This prospective, single-blind, randomized study was designed to evaluate the effect of genotype-based warfarin dosing compared with standard warfarin dosing in Korean patients with mechanical cardiac valves. Patients were assigned to either the genotype-based dosing group or the standard dosing group using stratified block randomization. The genotype-based dosing equation was adopted from a previous study which included VKORC1 rs9934438, CYP2C9 rs1057910, CYP4F2 rs2108622, and age. Primary outcomes included the percentage of time in the therapeutic range (pTTR): (i) during the first week following initiation of warfarin therapy, (ii) during hospitalization and (iii) until the first outpatient visit. A total of 91 patients were included in the analysis, 42 treated with genotype-based warfarin dosing and 49 treated with standard warfarin dosing. The genotype frequency differences of the three SNPs included in this study (ie, VKORC1, CYP2C9, CYP4F2), between the genotype-based dosing and standard dosing groups were not different. The genotype-based dosing group trended toward higher pTTR when compared with the standard dosing group, although this difference was not statistically significant. In patients with aortic valve replacement, TTRTraditional and TTRRosendaal were significantly higher in the genotype-based dosing group when compared with the standard dosing group during the first week following treatment initiation [ie, 58.5% vs. 38.1% (p = 0.009) and 64.0% vs. 44.6% (p = 0.012), respectively]. Based on the results, the genotype-guided dosing did not offer a significant clinical advantage, but a possible benefit in patients with aortic valve replacement has been suggested.

Objectives: In this study, we identified the health-related behaviors associated with aggression and examined the trends in both aggression and health-related behaviors among adolescents in the Republic of Korea. Methods: We used 2 cross-sectional samples of adolescents collected from the same geographic region 10 years apart. We measured aggression using the Aggression Questionnaire. Subject characteristics of the questionnaire included age, sex, caffeine intake, alcohol consumption, smoking, regular exercise, use of medications, and unstable mood. Results: Data pertaining to 1316 and 894 students were extracted from 2006 and 2016 surveys, respectively. Based on the multivariate results, sex and smoking were associated with physical aggression in both surveys, whereas sex and unstable mood were linked to verbal aggression. Alcohol consumption, unstable mood, and use of pain medications were related to anger; indigestion and unstable mood were associated with hostility in both years. The total aggression score was significantly related to alcohol consumption and unstable mood in both years after adjusting for other confounders. Conclusions: Health-related behaviors such as alcohol consumption and unstable mood showed meaningful relations with aggression. Accordingly, we should increase public awareness of factors associated with aggression, and government agencies and schools should implement comprehensive prevention efforts.

The present prospective follow-up study aimed to evaluate the effects of GRK5 polymorphisms on ritodrine efficacy and adverse drug events (ADEs) in pregnant women undergoing preterm labor. A total of 162 women undergoing preterm labor were included in the study. Seven single nucleotide polymorphisms (SNPs) in the GRK5 gene (rs915120, rs2230345, rs2230349, rs7923896, rs1020672, rs4752308, and rs4752292) were assessed. Homozygous variant carriers of rs4752292 and rs1020672 had 0.6 times the hazard of delivery compared to wild-type allele carriers (95% confidence interval [CI], 0.41~0.99 and 0.38~0.99, respectively). In addition, homozygous variant carriers of rs4752292 and rs1020672 had 2.4-fold more (95% CI, 1.10~4.98) and 2.3-fold more (95% CI, 1.04~5.06) ADEs compared to those with the wild-type homozygotes, respectively. Among demographic variables, gestational age and modified Bishop score were significant factors associated with time to delivery, while body weight and maximum ritodrine infusion rate were significant factors associated with ADEs. In silico analysis showed that both rs4752292 and rs1020672 had the potential to affect mRNA splicing by alteration of splicing motifs. The present study shows that ritodrine efficacy and ADEs are associated with GRK5 gene polymorphisms in pregnant women undergoing preterm labor.

This prospective study aimed to evaluate the effects of genetic polymorphisms in sulindac-related metabolizing enzyme genes including FMO3 and AOX1 on the population pharmacokinetics of sulindac in 58 pregnant women with preterm labor. Plasma samples were collected at 1.5, 4, and 10 h after first oral administration of sulindac. Plasma concentrations of sulindac and its active metabolite (sulindac sulfide) were determined, and pharmacokinetic analysis was performed with NONMEM 7.3. The mean maternal and gestational ages at the time of dosing were 32.5 ± 4.4 (range, 20–41) years and 27.4 ± 4.4 (range, 16.4–33.4) weeks, respectively. In the population pharmacokinetic analysis, one depot compartment model of sulindac with absorption lag time best described the data. The metabolism of sulindac and sulindac sulfide was described using Michaelis-Menten kinetics. In stepwise modeling, gestational age impacted volume of distribution (Vc), and FMO3 rs2266782 was shown by the Michaelis constant to affect conversion of sulindac sulfide to sulindac (KM32); these were retained in the final model. Genetic polymorphisms of FMO3 and AOX1 could affect the pharmacokinetics of sulindac in women who undergo preterm labor. The results of this study could help clinicians develop individualized treatment plans for administering sulindac.

Aim Smartphone overuse can cause not only mobility problems in the wrists, fingers and neck but also interference with sleep habits. However, research on smartphone addiction and sleep disturbances is scarce. Therefore, we aimed to investigate daytime sleepiness in association with smartphone addiction risk in Korean adolescents. Methods A cross-sectional survey method was used in this study. The Pediatric Daytime Sleepiness Scale was used to assess daytime sleepiness, and the Korean Smartphone Addiction Proneness Scale index was used to evaluate the degree of risk for smartphone addiction. Results The analyses were performed in 1796 adolescents using smartphones, including 820 boys and 976 girls. The at-risk smartphone users made up 15.1% of boys and 23.9% of girls. Our multivariate analyses demonstrated that students who were female, consumed alcohol, had lower academic performance, did not feel refreshed in the morning and initiated sleep after 12 am were at a significantly higher risk of smartphone addiction. The at-risk smartphone user group was independently associated with the upper quartile Pediatric Daytime Sleepiness Scale score in students with the following factors: Female gender, alcohol consumption, poor self-perceived health level, initiating sleep after 12 am, longer time taken to fall asleep and duration of night sleep less than 6 h. Conclusions The quality of sleep in adolescence affects growth, emotional stability and learning skills. Therefore, the management of smartphone addiction seems to be essential for proper sleeping habits. There is a critical need to develop a means of preventing smartphone addiction on a social level.

Background Ritodrine, a tocolytic β2-agonist, has been used extensively in Europe and Asia despite its safety concerns. This study was designed to identify associations between β2-adrenergic receptor (ADRB2) polymorphisms and adverse drug events (ADEs) in patients with preterm labor treated with ritodrine. Results This follow-up study was prospectively conducted at Ewha Womans University Mokdong Hospital in Korea. Five single nucleotide polymorphisms (SNPs) of the ADRB2 gene (rs1042713, rs1042714, rs1042717, rs1042718, and rs1042719) were analyzed in 186 pregnant women with preterm labor. Patients with the AA genotype of rs1042717 had significantly lower incidence of ADEs compared to those with the G allele (p = 0.009). In multivariate analysis, one of the predictors of ADEs was the maximum infusion rate of ritodrine (AOR 4.47, 95% CI 1.31–15.25). Rs1042719 was also a significant factor for ritodrine-induced ADEs. The CC genotype carriers had 78% decreased risk of ADEs compared to those with other genotypes. Conclusions This study demonstrates that ADEs induced by ritodrine are associated with ADRB2 gene polymorphisms, as well as the infusion rate of ritodrine in pregnant women with preterm labor.

Aim The present study aimed to investigate whether preoperative medication use is associated with postoperative length of hospital stay in older adults undergoing cancer surgery. Methods Patients aged ≥65 years who were scheduled for cancer surgery and presented for preoperative comprehensive geriatric assessment were included in the present study. Cognitive function evaluation and preoperative medication review were carried out, as well as baseline characteristics of participants collected from electronic medical records. The primary efficacy variable was the postoperative length of stay (LOS) in hospital. Results A total of 475 cancer patients were included for the analysis. Baseline characteristics of participants including older age, lower body mass index (BMI) and male sex were associated with longer postoperative stay. Among the clinical variables, cancer type, number of medications, potentially inappropriate medication (PIM) and delirium-inducing medication were found as statistically significant factors for postoperative LOS. In multivariate analysis, variables independently associated with postoperative LOS were cancer type, PIM use, BMI, and the number of medications after controlling for age, BMI, sex, cancer type, the number of medications, PIM, and delirium-inducing medication. In subgroup analysis of gastrointestinal cancer, multiple linear regression analysis showed that PIM use and BMI were significantly associated with LOS after adjustment for age, sex, and number of medication. Conclusions The present study supports the impact of medication use on postoperative LOS in geriatric oncology patients. The results add a further aspect to medication optimization in older patients undergoing cancer surgery. Geriatr Gerontol Int 2017; ••: ••–••.

Objectives The aim of this study was to evaluate the associations between polymorphisms of VKORC1, CYP2C9, CYP4F2, NR3C1 and VDR genes and stable warfarin doses in Korean patients with mechanical heart valves. Methods Seventeen single-nucleotide polymorphisms (SNPs) in 204 patients with stable warfarin dose were analyzed: VKORC1 (rs9934438), CYP2C9 (rs1057910), CYP4F2 (rs2108622), NR3C1 (rs41423247, rs1800445, rs56149945, rs10052957, rs6198, rs33388, rs6196, and rs244465), and VDR (rs1544410, rs11568820, rs731236, rs757343, rs7975232, and rs2228570). Statistical analyses were conducted to evaluate the associations of gene variations with stable warfarin dose. Number needed to genotype was obtained by calculating the percentage of patients whose predicted dose was at least 20% higher or lower than the actual stable dose. Results The combined genotypes of rs7975232 and rs2228570 of the VDR gene revealed a significant association with stable warfarin dose, along with VKORC1 , CYP2C9 , and CYP4F2 polymorphisms. Patients with the genotype combination GT,TT/CT,CC of VDR rs7975232/rs2228570 required significantly higher stable warfarin dose (5.79±2.02mg) than those with the other genotypic combinations (5.19±1.78mg, p =0.034). Multivariate analysis showed that VDR rs7975232/rs2228570 explained 2.0% of the 47.5% variability in overall warfarin dose. Adding VDR SNP combinations to the base model including non-genetic variables (age, sex, and body weight) and genetic variables ( VKORC1 rs9934438, CYP2C9 rs1057910, and CYP4F2 rs2108622) gave a number needed to genotype of 41. Conclusions This study showed that stable warfarin dose is associated with VDR SNPs along with VKORC1 , CYP2C9 , and CYP4F2 SNPs.

As a tocolytic agent, ritodrine has been used in European and Asian countries but has lost popularity due to safety concerns. This study aimed to investigate the relationship between adverse drug events caused by ritodrine and the CACNA1C polymorphisms in preterm labor patients. Data were collected from medical records including maternal age, gestational age, body mass index, dilation score, effacement score, modified Bishop score, maximum infusion rate, and adverse drug events. Five single-nucleotide polymorphisms of the CACNA1C gene (rs10774053, rs215994, rs215976, rs2239128, and rs2041135) were analyzed. One hundred eighty-six patients were included, 33 of whom had adverse drug events. A allele carriers of rs10774053 showed about 0.293-fold lower adverse drug events than GG genotype carriers (p = 0.012, absolute risk reduction = 16.5%) after adjusting for other confounding variables; the number needed to genotype for preventing one patient with GG genotype from suffering higher incidence of adverse drug events was calculated to be 14.6. Increase in maximum infusion rate of 1 mL/h was associated with a 1.03-fold (95% CI 1.01~1.06, p = 0.005) increased risk of adverse drug events. None of the patients with a CC genotype of rs215994 had adverse drug events, whereas 22.1% of the T allele carriers had adverse drug events. This study showed that CACNA1C gene polymorphisms could alter the probability of adverse drug event risk when ritodrine is used in preterm labor.

Background Despite growing interest in the negative clinical outcomes of multiple anticholinergic use, limited studies have evaluated anticholinergic burden in the geriatric population nationally. Objective To evaluate the prevalence of high anticholinergic burden using the newly developed Korean Anticholinergic Burden Scale in comparison with previous tools and to identify associated factors. Setting National insurance data from a cross section (20%) of older Koreans (2016). Methods Anticholinergic burden was measured using the Korean scale in comparison to the Anticholinergic Drug Scale, Anticholinergic Cognitive Burden, and Anticholinergic Risk Scale. High anticholinergic burden was defined as a summed score of ≥ 3 for concurrent medications or a dose-standardized average daily score of ≥ 3, using each anticholinergic scale. Main outcomes measured Prevalence and predictors of high anticholinergic burden. Results Data of 1,292,323 patients were analyzed. According to the Korean scale, the prevalence of high anticholinergic burden was 25.5%. This result was similar to that from the Anticholinergic Drug Scale (24.9%) and Anticholinergic Cognitive Burden (22.2%). Factors associated with an increased likelihood of anticholinergic burden include: age, gender (female), high Charlson comorbidity index score, polypharmacy, medical aid beneficiary, co-morbidities (such as schizophrenia, depression, urinary incontinence, and Parkinson's disease), frequent healthcare visits, various healthcare facilities utilized, and predominantly visiting hospital-level facilities. According to the Korean Anticholinergic Burden Scale, the major drugs contributing to the anticholinergic burden were ranitidine, chlorpheniramine, tramadol, and dimenhydrinate. Conclusion This study showed that 1 in 4 older Koreans are exposed to high anticholinergic burden. The predictors identified in this research might assist pharmacists in early interventions for their patients.

Background The purpose of this study was to investigate the relationship between anxiety proneness and aggressive behavior in adolescents. Methods A quantitative, large scale cross-sectional study was conducted in Korea. The survey questionnaire included general health behavior and scales for assessing anxiety (Revised Children’s Manifest Anxiety Scale; RCMAS) and aggressive behavior (The Aggression Questionnaire; AQ) in adolescents. Results A total of 2432 students participated in the survey, and 1933 individuals completed the questionnaire, indicating a response rate of 79.5%. Based on RCMAS, 163 (8.4%) subjects were classified as the anxiety group. Aggressive behavior was significantly associated with higher anxiety scores. In particular, among four subdomains of aggression, anger and hostility had a stronger relationship with anxiety than did physical and verbal aggression. Multivariate analysis demonstrated that anxiety was independently associated with gender, age, headache, constipation, asthma, and aggression score. Adolescents with total aggression scores of 69 or higher showed a 9-fold (AOR = 9.00, CI = 6.33–13.51) higher risk of anxiety compared to those with under 69. Conclusion Aggression and anxiety are important aspects of mental health in adolescents. Our results demonstrated that higher risk of anxiety was associated with total aggression scores. In particular, indirect aggression (i.e. anger and hostility) was more closely associated with anxiety than direct aggression.

SummaryWhat is known and objective Various factors contribute to the high rate of readmission among patients hospitalized with heart failure (HF). Determination of these factors is fundamental to identify potential targets for intervention in hospitalized patients. Methods The retrospective cohort study used a large national insurance database to identify episodes of HF. Clinical information up to 12 months from the index hospitalization was obtained. Depending on their outcome, eligible patients were classified into a 30-day readmission group after discharge or a non-readmission group. Potential predictors of 30-day readmission were categorized by patient, drug therapy and health system utilization factors. Results and discussion Heart failure was identified in 19 128 inpatients. Of these, 27·6% were readmitted within 30 days after discharge. The mean Charlson comorbidity index (CCI) score was 5·2 ± 2·9 for the readmission group and 4·3 ± 2·5 for the non-readmission group. The strongest predictors included paralysis [adjusted odds ratio (AOR) 2·27, 95% confidence interval (CI) 1·97–2·62], followed by metastatic cancer (AOR 2·22, 95% CI 1·81–2·72) and loop diuretic therapy (AOR 1·52, 95% CI 1·29–1·79). A prescription of ACE inhibitor or angiotensin receptor blocker at discharge was associated with a 17% decreased risk (AOR 0·83, 95% CI 0·77–0·89). What is new and conclusions Hospitalized patients with HF have a 30-day all-cause readmission rate exceeding a quarter. Post-discharge care should focus on patients with advanced age, acuity of admission, enrolled medical aid, hospitalization exceeding 14 days, higher CCI score, more than 10 prescription drugs at discharge, presence of several comorbidities and loop diuretic therapy, which are independent predictors for 30-day readmission.

There have been no studies on the characteristics of parenteral nutrition (PN) supply for adult inpatients in South Korea. The aim of this retrospective multicenter cross sectional study was to investigate the current practice and characteristics of PN support in hospitalized adult patients in South Korea for the first time. This study was conducted retrospectively for the adult patients who were hospitalized and received PN in nine hospitals on August 1st, 2017 to October 30th, 2017. We evaluated the type of PN formulation, PN administration period, administration route, calories supplied, amount of protein supplied, and laboratory results. Among the 11,580 inpatient admissions on that day, 1,439 patients received PN (12.4%). The majority of enrolled patients (96.5%) used the commercial PN, of which 86.2% were multi-chamber. 71.2% of them received PN peripherally. The average in hospital PN duration was 17.8 ± 52.6 days. Patients received only 65.4 ± 25.4% calories of their target calories. The in-hospital mortality of enrolled patients was 22%. In South Korea, commercial PN was usually administered to hospitalized adult patients and in-hospital mortality in adult patients using PN was higher in South Korea compared to other countries. This study provides the characteristics and the PN support status of hospitalized adult patients receiving PN in South Korea.

Objective To examine the association between benzodiazepine use and the risk of dementia. Design, setting, and participants We conducted a retrospective cohort study, using a nationwide healthcare database of South Korea (2002–2016). The participants included new users of benzodiazepines aged ≥50 years, with no prior prescription record of benzodiazepines or a history of dementia within the previous 5 years (2002–2006). Methods Outcome was defined as an incident dementia with specified algorithms using diagnosis and prescription records, with the application of a 5-year lag-time following the index date during which outcomes were censored. We used a multivariable Cox proportional hazard model to estimate hazard ratio (HR) and the 95% confidence interval (CI). Comorbidities and comedications were treated as time-varying covariates in 90-day windows, and an active comparator was used to reduce potential bias from confounding by indication. Active comparators were defined as new-users of antidepressants. Results Our final participants included 616,256 patients, after propensity score estimation and matching on a 1:1 ratio. We observed a 23% increase in the risk of dementia in benzodiazepine users, compared with that in nonusers, over a mean follow-up period of 5.5 years (HR 1.23, 95% CI 1.14–1.32). A consistent finding was observed when the lag-time duration was extended to 7 years, revealing a close to null association (HR 1.17, 95% CI 1.04–1.30). When new-users of antidepressants were used as the active comparator, no increase in the risk of dementia with benzodiazepines was observed over 7 years (HR 1.01, 95% CI 0.81–1.27). Conclusions and implications A significant association was observed between benzodiazepine use and the risk of dementia, compared with nonusers. However, a null or negative association was observed with the use of the active comparator, suggesting the absence of a causal association between dementia and benzodiazepine use.