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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 (

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.

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.

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.

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.

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.

Objectives. This study aimed to identify the possible effects of Myc and 8q24 polymorphisms on bleeding complications in patients who maintained international normalized ratio (INR) of 2.0-3.0 with warfarin therapy after cardiac valve replacement. Methods. Twenty-five single nucleotide polymorphisms were analyzed, including VKORC1, CYP2C9, Myc, and 8q24. Univariate and multivariate analyses were conducted to evaluate the associations between genetic polymorphisms and bleeding complications. Attributable risk and the number needed to genotype (NNG) were also calculated to evaluate the potential clinical value of genotyping. Results. We included 142 patients, among whom 21 experienced bleeding complications. Multivariate models showed that patients carrying the CC genotype of rs6983561 and the A allele of rs13281615 at 8q24 had 27.6- and 10.0-fold higher bleeding complications, compared with patients with the A allele and the GG genotype, respectively. For rs6983561, the attributable risk and NNG were 96.4% and 36.8, respectively, whereas, for rs13281615, the attributable risk and NNG were 90.0% and 8.3, respectively. Atrial fibrillation was associated with a 5.5-fold increased risk of bleeding complications. The AUROC value was 0.761 (95% CI 0.659-0.863, pχ2=0.846; 3 degrees of freedom; p=0.838). Conclusions. Bleeding complications during warfarin therapy were associated with 8q24 polymorphisms and atrial fibrillation in patients with mechanical heart valves.

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.

PURPOSE: Talc slurry (TS) has been commonly used with high success rates in managing spontaneous pneumothroax (SP), but there were concerns of post-procedural complications. Alternatively, doxycycline solution (DS) was used successfully. This retrospective study aims to compare the effectiveness and safety between talc and doxycycline as a sclerosing agent and to investigate risk factors for recurrence in patients with SP. METHODS: The review of medical records between January 2011 and December 2014 was conducted on 83 patients with SP who underwent pleurodesis with either TS (n=16) or DS (n=67). Recurrence and complications were compared between the DS and TS groups. Associations between recurrence after DS treatment and various factors were analysed. RESULTS: Recurrence was significantly higher in the DS group than in the TS group (P=0.033), whereas complications were higher in the TS group than the DS group: fever was significantly higher in the TS group (P=0.001). Recurrences associated with doxycycline use were found significantly more often in patients with recurrent diagnosis of SP, height/weight ≥3.25 cm/kg and weight

The introduction of biologic agents opened a new era of treatment of juvenile idiopathic arthritis (JIA) over the past decade. From clinical experience, it appears that biological agents are well tolerated overall, and serious adverse events are rare. However, such clinical studies have not been conducted in Korea. Therefore, we examined the safety profile of JIA patients with biologics in a single center in Korea. All JIA outpatients treated from April 2004 to June 2013 were enrolled and retrospectively reviewed. Pharmacy-based surveillance of adverse drug events (ADEs) was identified by recording the patient's symptoms in the medical record and suspected ADEs were additionally explored by screening laboratory test values and observing changes in medication orders. Finally, 83 patients were enrolled and experienced 109 ADEs in 52 patients. Most ADEs (99.1%) were mild to moderate in severity assessment. The total follow-up time was 328 patient-treatment years and the overall rate of ADEs was 0.33 per patient-years for etanercept. Infection including upper respiratory tract was the most common ADE and concomitant corticosteroids contributed to the risk of infections. If the dose of prednisolone increases 0.34 mg/kg/day, the probability of developing infections increases 3.29 times. Also, all 11 patients who stopped etanercept with injection site reactions were receiving a single use prefilled syringe. In our study, etanercept appears well tolerated and safe. Children affected by JIA should be carefully monitoring so as to limit the risk of ADEs during etanercept as much as possible. To gain further knowledge about risk profiles, national collaboration for the accumulation of long-term data should be encouraged in Korea.

Background Bleeding complications have been frequently reported in East Asian patients on warfarin with a target international normalized ratio (INR) of 2.0–3.0. Objective This study aimed to identify the optimal therapeutic range of the INR in Korean patients with non-valvular atrial fibrillation (NVAF). Setting Cardiovascular department of a 1320 inpatient bed Korean hospital. Method Retrospective chart review was conducted on 1014 patients for a total follow-up period of 2249.2 patient years. Major thromboembolic and bleeding complications were evaluated. The INR incidence of complication curve was plotted, and the optimal therapeutic range of INR was determined from the intersection of curves to ensure the lowest incidences of both thromboembolic and bleeding complications. For subgroup analysis, all patients were stratified by the following factors: age (above 75), disease (presence of hypertension, diabetes, congestive heart failure, and a history of stroke or thromboembolism), rhythm control procedure, and concurrent aspirin therapy. Main outcome measure Optimal therapeutic ranges of INR according to the risk factors. Results A total of 41 thromboembolic and 91 bleeding events occurred during the follow-up period. The complication rates were the lowest at an INR of 1.9 and the optimal therapeutic range was estimated to be 1.7–2.2 for the overall patients. The optimal therapeutic ranges of INR in the stratified patients were determined as follows: 1.3–1.8 in the patients ≥75 years of age; 1.5–2.0 in patients with hypertension, diabetes and concurrent aspirin therapy; 1.8–2.3 in patients with congestive heart failure; 1.9–2.4 in patients with previous stroke or thromboembolism; 1.7–2.2 in patients who had undergone rhythm control procedures. It has been shown that, by keeping the INR within these ranges, complication risks could be significantly reduced by up to 81 %. Conclusion The intensity of anticoagulation therapy for Korean patients with NVAF is optimal when INR is between 1.7 and 2.2.

Comprehensive geriatric assessment (CGA) has become a predictor for elderly cancer patients in post-surgical complications, including post-discharge institutionalization and mortality. To determine whether pre-operative medication use is associated with post-operative morbidity and mortality in oncology patients receiving CGA. Patients aged 65 years or older who were scheduled for cancer surgery and presented for CGA were included in the present study. Baseline characteristics of patients were collected from electrical medical records, and pre-operative medication review was performed. The primary outcome was death within 30 days after surgery and post-discharge institutionalization. A total of 475 cancer patients were included. Among them, three patients died within 30 days after surgery and 14 patients were discharged to another institution. All patients who died within 30 days after surgery had polypharmacy with marginal significance (P = 0.087). Multivariate analysis models were constructed using significant factors for post-surgery institutionalization from univariate analysis: Model I (polypharmacy and transfusion), Model II (polypharmacy and infection), and Model III (polypharmacy, transfusion, and infection). Infection was the most significant factor. Its adjusted odds ratio was as large as 11.1 and attributable risk was almost 91%. In pre-surgery medication use, only polypharmacy showed significant association with post-discharge institutionalization. Attributable risk of polypharmacy was around 75%. It is possible that pre-operative medication use has impact on death and post-discharge institutionalization in geriatric oncology patients, further highlighting the importance of medication optimization for elderly patients with cancer surgery.

Objectives This study aimed to evaluate the impact of high anticholinergic burden on overall emergency department (ED) visits and ED visits related to adverse effects of anticholinergic drugs among older adults. Methods For this retrospective cohort study, we used claims data from older adults with high representativeness. The average daily Anticholinergic Risk Scale (ARS) score was calculated based on the dosage, treatment duration, and potency of anticholinergic drugs during three months. A high-exposure group (ARS ≥ 2) and a non-exposure group were included in this analysis. The primary outcome was the first ED visit during the follow-up period. Anticholinergic ED visits were defined as ED visits with a main diagnosis of a fall, fracture, dizziness, delirium, constipation, or urinary retention. Results In total, 118,750 subjects (43.6% male) were included in this study. The mean age was 75.4 ± 6.6 years. The adjusted hazard ratios (aHRs) for all-cause and anticholinergic ED visits among those with high ARS scores were 1.28 (95% CI: 1.20–1.36) and 1.55 (95% CI: 1.38–1.74), respectively. The high-exposure group was at higher risk than the non-exposure group for ED visits for falls or fractures (aHR: 1.31, 95% CI: 1.07–1.60), dizziness (aHR: 1.71, 95% CI: 1.36–2.14), delirium (aHR: 2.05, 95% CI: 1.13–3.73), constipation (aHR: 1.65, 95% CI: 1.35–2.02) and urinary retention (aHR: 1.66, 95% CI: 1.30–2.12). Conclusions This study demonstrated that a high anticholinergic burden in older adults increased the risk of all-cause ED visits, anticholinergic ED visits and specific-cause ED visits.

Background Older patients undergoing surgery tend to have a higher frequency of delirium. Delirium is strongly associated with poor surgical outcomes. This study evaluated the association between pre-operative medication use and post-operative delirium (POD) in surgical oncology patients receiving comprehensive geriatric assessment (CGA). Methods A total of 475 patients who were scheduled for cancer surgery and received CGA from January 2014 to June 2015 were included. Pre-operative medication review through CGA was conducted on polypharmacy (≥5 medications), delirium-inducing medications (DIMs), fall-inducing medications (FIMs), and potentially inappropriate medications (PIMs). POD was confirmed by psychiatric consultation, and DSM-V criteria were used for diagnosing delirium. The model fit of the prediction model was assessed by computing the Hosmer-Lemeshow goodness-of-fit test. Effect size was measured using the Nagelkerke R2. Discrimination of the model was assessed by an analysis of the area under receiver operating curve (AUROC). Results Two models were constructed for multivariate analysis based on univariate analysis; model I included dementia and DIM in addition to age and sex, and model II included PIM instead of DIM of model I. Every one year increase of age increased the risk of POD by about 1.1-fold. DIM was a significant factor for POD after adjusting for confounders (AOR 12.78, 95 % CI 2.83-57.74). PIM was also a significant factor for POD (AOR 5.53, 95 % CI 2.03-15.05). The Hosmer-Lemeshow test results revealed good fits for both models (χ2 = 3.842, p = 0.871 for model I and χ2 = 8.130, p = 0.421 for model II). The Nagelkerke R2 effect size and AUROC for model I was 0.215 and 0.833, respectively. Model II had the Nagelkerke R2effect size of 0.174 and AUROC of 0.819. Conclusions These results suggest that pharmacists’ comprehensive review for pre-operative medication use is critical for the post-operative outcomes like delirium in older patients. Electronic supplementary material The online version of this article (doi:10.1186/s12877-016-0311-5) contains supplementary material, which is available to authorized users.

Background Various complications lead to reoperation in patients who undergo prosthetic valve replacement where inflammatory process could be involved. The goals of this study were to identify risk factors that correlate with reoperation in patients with prosthetic heart valves and to investigate the relationship between reoperation and inflammatory gene polymorphisms. Results The study included 228 patients from the EwhA–Severance Treatment Group of Warfarin. Single nucleotide polymorphisms of c-reactive protein (CRP), interferon-gamma, interleukin 1 beta, interleukin 6, interleukin 10, transforming growth factor beta 1, and tumor necrosis factor genes were genotyped by means of SNaPshot and TaqMan assays. Thirty-nine patients (17.1 %) underwent more than one heart valve operation. A threefold increased risk for heart valve reoperation was evident in homozygous variant-type (TT) carriers as compared with ancestral allele carriers of CRP rs1205. Logistic regression analysis revealed that CRP rs1205 (OR 2.68, 95 % CI 1.22–5.90, p = 0.014), valve position (mitral valve OR 2.80, 95 % CI 1.01–7.80, p = 0.048; tricuspid valve OR 9.24, 95 % CI 2.46–34.70, p = 0.001; reference: aortic valve) and time after first operation (OR 1.13, 95 % CI 1.06–1.20, p

NAD(P)H dehydrogenase, encoded by NAD(P)H quinone oxidoreductase 1 (NQO1), is an enzyme that catalyzes the reduction of quinones, including vitamin K. Given its potential role in vitamin K metabolism, this study aimed to investigate the effects of NQO1 polymorphisms on stable warfarin doses. We tested a possible effect of gene polymorphisms on variability in warfarin response using 206 Korean patients with mechanical cardiac valves. Single nucleotide polymorphisms (SNPs) of NQO1 with a minor allele frequency of at least 15 % were included. Also, genotypes of vitamin K epoxide reductase complex subunit 1 (VKORC1), cytochrome P450 (CYP) 2C9, CYP4F2, gamma-glutamyl carboxylase (GGCX), and GATA4 were determined. NQO1 rs1800566 (C>T) and rs10517 (C>T) were significantly associated with stable warfarin doses. Variant homozygote carriers required lower stable warfarin doses than those with wild-type C allele in rs1800566 (4.85 ± 1.61 vs. 5.61 ± 1.94 mg; p = 0.033), whereas patients with wild homozygote required lower doses than those with T allele in rs10517 (5.11 ± 1.73 vs. 5.75 ± 1.98 mg; p = 0.017). Similar results were obtained from stratified analysis using VKORC1 variant homozygote carriers in both SNPs. Multivariate analysis showed that rs10517 (C>T) increased contribution of gene variations to the overall warfarin dose variability from 42.5 to 43.8 %. Our results demonstrate that NQO1 gene polymorphisms influence stable warfarin doses in Korean patients.