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Mee Yeon Lee,1 Suhyun Lee,1 Kyu-Nam Heo,1 Woo-Youn Kim,1 Sun Hoi Jung,2 Young-Mi Ah,3 Ju-Yeun Lee1 1College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea; 2Department of Pharmacy, Seoul National University Boramae Medical Center, Seoul, Republic of Korea; 3College of Pharmacy, Yeungnam University, Gyeongsan-si, Republic of KoreaCorrespondence: Ju-Yeun Lee, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, Republic of Korea, Tel +82-2-3668-7472, Email jypharm@snu.ac.krPurpose: The use of proton pump inhibitors (PPI) is recommended to prevent nonsteroidal anti-inflammatory drug (NSAID)-induced gastrointestinal (GI) complications. The incidence of several adverse effects during the long-term use of PPI prompts the search for other alternatives. Limited studies have evaluated the efficacy of rebamipide, a widely used mucoprotective drug, as a gastroprotective agent (GPA) compared to PPI, focusing on the elderly chronic NSAID users, nor with GI risk stratification. We aimed to determine the population who would get benefit from the use of rebamipide as an alternative to PPI to prevent traditional nonsteroidal anti-inflammatory drug (tNSAID)-associated GI complications.Patients and Methods: We identified 41,889 and 35,708 elderly chronic tNSAID users with PPI and rebamipide co-therapy, respectively, from the national claims database. Outcome was defined as hospitalization or emergency department visits due to serious GI complications. Propensity score-matched cohorts were constructed and compared within risk strata.Results: In high and moderate risk groups with two risk factors, rebamipide showed a higher risk of serious GI complication compared to PPI (aHR 2.63, 95% CI 1.24– 5.59 and aHR 2.42, 95% CI 1.21– 4.83, respectively). However, in elderly patients without risk factors, there was no significant difference in the risk of serious GI complications between PPI and rebamipide (aHR 0.69, 95% CI 0.27– 1.76).Conclusion: This study suggested that rebamipide can be considered as an alternative to PPI in elderly chronic tNSAID users without risk factors. However, elderly patients with other risk factors should use PPI rather than rebamipide. Therefore, the presence of GI risk factors needs to be evaluated in elderly chronic tNSAID users to prescribe the most suitable GPA in clinical practice.Keywords: aged, gastroprotective agent, nonsteroidal anti-inflammatory drug, rebamipide, risk group

Young-Mi Ah,1 Jaekyu Shin,2 Ju-Yeun Lee3 1College of Pharmacy, Yeungnam University, Gyeongsangbuk-do, Republic of Korea; 2Department of Clinical Pharmacy, School of Pharmacy, University of California San Francisco, San Francisco, CA, USA; 3College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea Purpose: We compared treatment adherence and persistence during treatment with an angiotensin receptor blocker (ARB)-based single pill combination (SPC) and free equivalent combination (FEC) and between SPCs of an ARB with a thiazide diuretic (TD) and an ARB with a calcium channel blocker (CCB) as initial treatment in uncomplicated hypertensive patients who received pre-packaged medications from the pharmacy. Patients and methods: Uncomplicated hypertensive patients who started combination treatment consisting of ARB and either TD or CCB were identified from a Korean national claims database. We used propensity score matching to construct two pairs of cohorts: SPC and FEC cohorts (20,175 patients per cohort) and SPC cohorts of ARB + TD and ARB + CCB (45,253 patients per cohort). We compared adherence measured via the medication possession ratio as well as overall 1-year and initial treatment persistence. Results: Compared with the FEC cohort, the SPC cohort had significantly higher medication adherence (OR 1.31, 95% CI 1.25–1.37), overall persistence (HR 1.33, 95% CI 1.28–1.38), and initial treatment persistence (HR 1.61, 95% CI 1.56–1.64). Neither the rate of medication adherence nor the rate of treatment persistence differed significantly between the ARB + TD and ARB + CCB cohorts. However, the ARB + CCB cohort had a significantly higher rate of initial treatment persistence than did the ARB + TD cohort (HR 1.12, 95% CI 1.10–1.14). Conclusion: Our data suggest that, compared with FEC therapy, initiating an ARB-based SPC therapy may increase adherence and persistence in patients with uncomplicated hypertension who also receive pre-packaged medication from the pharmacy. Although using an ARB + CCB SPC may improve initial treatment persistence, it does not increase adherence or overall persistence when compared with an ARB + TD SPC. Keywords: single pill combination, persistence, adherence, hypertension, angiotensin receptor blocker

Background: To prevent the recurrence of Adverse Drug Events (ADEs), particularly drug allergies, it is essential to avoid re-exposure to causative drugs. Awareness of previous ADEs is crucial for patients because they can share accurate information with healthcare providers (HCPs). This study aims to assess users' willingness to share ADE information and evaluate the factors related to this willingness by utilizing a prospective ADE information-sharing system currently under consideration in South Korea., Methods: In September 2023, a self-administered questionnaire was collected from a sex-, age-, and regionally stratified nationwide convenience sample of adults recruited through a commercial panel in South Korea. Factors contributing to the willingness to share ADE information and create electronic ADE cards (e-ADE cards) were investigated using multivariate logistic regression analysis., Results: Among the 1,000 respondents, 458 (45.8%) were willing to share ADE information, and 521 (52.1%) were willing to create e-ADE cards. The willingness to share personal ADE information and create e-ADE cards was positively associated with the perceived benefits of sharing ADE, trust in HCPs and positive experiences. Notably, older adult patients demonstrated a higher willingness to share information and use e-ADE cards, with rates of 56% and 62%, respectively., Conclusions: Our findings indicate that the approach to sharing personal ADE information should be distinct from that of sharing comprehensive health information. Notably, users are likely to willingly disclose their personal information even if they are not anonymized, owing to the significant perceived benefits of sharing. The findings of this study can enhance awareness about sharing personal ADE information and contribute to the successful establishment of an ADE information-sharing system, thereby improving the patient safety environment., (© 2024. The Author(s).)

Background: Oral anticoagulants (OACs) are essential for the prevention and treatment of thromboembolic disorders, but bleeding, a major complication, can have a fatal impact on the patient's treatment., Objectives: We aimed to estimate the nationwide, real-world incidence rate of bleeding in patients taking OACs and confirm the incidence by indications and risk factors., Methods: This cross-sectional study identified OAC users from April 1 to December 31, in both 2019 and 2020, using the HIRA-NPS database. The primary outcome variables were the incidence rate of major bleeding events during OAC treatment and within 30 days of treatment discontinuation. We estimated the adjusted incidence rate ratio (aIRR) in subpopulations., Results: Among 18,822 OAC users, the incidence rate of major bleeding was 27.9 (95% CI: 24.6-31.5) per 1,000 person-years. The incidence rate of major bleeding was higher in patients with a bleeding history, with an aIRR of 11.51; those at high bleeding risk (HAS-BLED score ≥3), with an aIRR of 1.51; those with high CCI scores ≥3, with an aIRR of 1.88; and those with liver disease, with an aIRR of 1.41. For indications, compared to patients with nonvalvular atrial fibrillation (NVAF), the aIRR of major bleeding was significantly higher at an aIRR of 2.35 in patients undergoing VTE treatment. Patients with ischemic stroke showed a higher incidence of major bleeding with an aIRR of 2.13 than NVAF patients. The aIRR of major bleeding in the oral anticoagulant group, compared to the matched control group, was 2.25 (95% CI: 1.93-2.63)., Conclusion: These findings may be useful for implementing strategies to improve the evaluation and management of anticoagulation-related bleeding., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Jeong, Heo, Lee, Ah, Min, Han and Lee.)

Background: The rising global incidence of cancer has increased the demand for chemotherapy, which is a crucial treatment modality. Recent advancements in cancer treatment, including targeted agents and immunotherapy, have introduced complications owing to their specific mechanisms. However, comprehensive studies of the combined complications of these approaches are lacking., Objectives: This study aimed to comprehensively assess and analyze the overall incidence of anticancer drug-related complications in a nationwide patient cohort, utilizing a customized National Health Insurance Sharing Service database in Korea., Design: Retrospective cohort study., Methods: We included patients who were prescribed anticancer drugs (excluding endocrine agents) and diagnosed with cancer. For the type of cancer classification, the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) was used and anticancer drugs were classified based on the Anatomical Therapeutic Chemical code. We classified cancer into 18 types based on the ICD-10 code and delineated cancer-related complications into 12 categories. Complications included hematological, gastrointestinal, infectious, cardiovascular, major bleeding, endocrine, neurotoxic, nephrotoxic, dermatological, pulmonary, musculoskeletal, and hepatotoxic effects., Result: We included 294,544 patients diagnosed with cancer and administered anticancer drugs between 2016 and 2018, with follow-up continuing until 2021. We identified 486,929 anticancer drug-related complications, with an incidence of 1843.6 per 1000 person-years (PY). Anemia was the most common complication, with a rate of 763.7 per 1000 PY, followed by febrile neutropenia (295.7) and nausea/vomiting (246.9). Several complications peaked during the first months following the initiation of anticancer drug therapy; however, herpes, skin infection, heart failure, and peripheral neuropathy peaked at 6-12 months. Among major cancers, breast cancer had the lowest overall incidence of complications. Targeted therapies revealed lower complication rates than cytotoxic chemotherapy; however, they also required careful monitoring of rash., Conclusion: This study highlights the importance of the proactive management of anticancer drug-related complications for patient care improvement., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2024.)

Purpose: This study aimed to perform a nationwide analysis of medication errors (MEs) from hospitals using national reporting system data and to compare the ME patterns among different age groups., Methods: We analyzed medication-related incidents in acute care hospitals reported to the Korean Patient Safety Reporting and Learning System (KOPS), which is a patient safety reporting system, from July 2016 to December 2020. The stages of the medication use process, type of errors, medication class involved in MEs, and degree of harm were analyzed., Results: Among a total of 5071 medication-related incidents, 37.7% (1911 cases) were incidents that caused patient harm and 1.2% caused long-term, permanent, and fatal harm. The proportion of medication-related incidents that resulted in harm was the highest among the <1-year-old age group (67 cases, 51.5%), followed by the elderly (≥ 65 years) (828 cases, 40.9%). The cases leading to patient death were most frequently reported in patients aged ≥65 years. Medication-related incidents occurred mainly in the administration stage (2954 cases, 58.3%), and wrong dose was the most frequently reported ME type. The most prevalent medication class occurring in the 20-64-year age group (256 cases, 11.7%) was 'antibacterials for systemic use', whereas 'contrast media' (236 cases, 11.6%) and 'blood substitutes and perfusion solutions' (98 cases, 19.3%) were the most prevalent drug classes in the ≥65- and <20-year-old age groups, respectively., Conclusions: It is necessary to establish guidelines for the prevention of medication-related incidents according to the medication use process and patient age group., (© 2024 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

Background: Older adults are at an increased risk of acute kidney injury (AKI), particularly in community settings, often due to medications. Effective prevention hinges on identifying high-risk patients, yet existing models for predicting AKI risk in older outpatients are scarce, particularly those incorporating medication variables. We aimed to develop an AKI risk prediction model that included medication-related variables for older outpatients., Methods: We constructed a cohort of 2,272,257 outpatients aged ≥65 years using a national claims database. This cohort was split into a development (70%) and validation (30%) groups. Our primary goal was to identify newly diagnosed AKI within one month of cohort entry in an outpatient context. We screened 170 variables and developed a risk prediction model using logistic regression., Results: The final model integrated 12 variables: 2 demographic, 4 comorbid, and 6 medication-related. It showed good performance with acceptable calibration. In the validation cohort, the area under the receiver operating characteristic curve value was 0.720 (95% confidence interval, 0.692-0.748). Sensitivity and specificity were 69.9% and 61.9%, respectively. Notably, the model identified high-risk patients as having a 27-fold increased AKI risk compared with low-risk individuals., Conclusion: We have developed a new AKI risk prediction model for older outpatients, incorporating critical medication-related variables with good discrimination. This tool may be useful in identifying and targeting patients who may require interventions to prevent AKI in an outpatient setting., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

This systematic review and meta-analysis aimed to determine the association between the use of sodium-glucose cotransporter 2 (SGLT-2) inhibitors and dementia onset as well as cognitive function in patients with diabetes mellitus. We comprehensively searched the MEDLINE, Embase, and CENTRAL databases to select relevant studies published up to August 2023. The use of SGLT-2 inhibitors significantly lowers dementia risk compared to SGLT-2i non-users (Hazard ratio: 0.68, 95 % CI: 0.50-0.92). Furthermore, our findings indicated a positive effect of SGLT-2 inhibitor use on cognitive function score improvement, as demonstrated by the standardized mean difference of 0.88 (95 % CI: 0.32-1.44), particularly among populations with mild cognitive impairment or dementia. This systematic review and meta-analysis indicate a potential role of SGLT-2 inhibitors in reducing the risk of dementia in patients with diabetes mellitus. These findings underscore the need for well-controlled large clinical trials and future research in this field., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Polypharmacy and the use of potentially inappropriate medications are common among nursing home residents and are associated with negative outcomes. Although deprescribing has been proposed as a way to curtail these problems, the best way to implement multidisciplinary comprehensive medication review and deprescribing and its real impact in specific high-risk populations, such as nursing home residents, is still unclear. This multicenter randomized controlled clinical trial aims to assess the effects of a multidisciplinary mediation management program on medication use and health problems., Methods: A total of 1,672 residents aged ≥ 65 years from 22 nursing homes in South Korea who meet the targeted criteria, such as the use of ≥ 10 medications, are eligible to participate. The experimental group will receive a comprehensive medication review, deprescription, and multidisciplinary case conference with the help of platform. Outcomes will be measured at baseline, at the end of the intervention, as well as at 3, 6, 9, and 12 months after the end of the intervention. The primary endpoints will be the rate of adverse drug events, number of potentially inappropriate medications/potentially inappropriate medication users/two or more central nervous system drug/ central nervous system drug users, delirium, emergency department visits, hospitalization, and falls. The secondary endpoint will be the number of medications taken and polypharmacy users., Discussion: Our trial design is unique in that it aims to introduce a structured operationalized clinical program focused on reducing polypharmacy and potentially inappropriate medications in a nursing home setting with large samples., Trial Registration: Ethical approval was granted by the public institutional review board of the Ministry of Health and Welfare (2022-1092-009). The study is also registered with the Clinical Research Information Service (Identifier: KCT0008157, Development and evaluation of a multidisciplinary medication management program in long-term care facility residents Status: Approved First Submitted Date: 2023/01/18 Registered Date: 2023/02/03 Last Updated Date: 2023/01/18 (nih.go.kr) https://cris.nih.go.kr/ ), which includes all items from the World Health Organization Trial Registration Dataset., (© 2024. The Author(s).)

Background: Chronic opioid use is associated with problematic opioid use, such as opioid abuse. It is important to develop a prediction model for safe opioid use. In this study, we aimed to develop and validate a risk score model for chronic opioid use in opioid-naïve, noncancer patients, using data from a nationwide database., Methods: Data from the National Health Insurance Claims Database in the Republic of Korea from 2016 to 2018 were used, and adult, noncancer patients who were started on non-injectable opioid analgesics (NIOAs) were included. The risk score model was developed using the β coefficient of each variable in the multivariable logistic regression analysis., Results: Overall, 676,676 noncancer patients were started on NIOAs, of which 65,877 (9.7%) were prescribed NIOAs chronically. Age, baseline healthcare utilization, comorbidities, co-medications, and pattern of first NIOA prescription were identified as risk factors for chronic opioid use. The c-static for the performance of our risk score model was 0.754 (95% confidence interval, 0.750-0.758)., Conclusion: To our knowledge, this is the first tool that can predict chronic opioid use in the Korean population. The model can help physicians examine the risk of chronic opioid use by patients who are started on NIOA., (© 2023 World Institute of Pain.)

This study developed and validated a risk-scoring model, with a particular emphasis on medication-related factors, to predict emergency department (ED) visits among older Korean adults (aged 65 and older) undergoing anti-neoplastic therapy. Utilizing national claims data, we constructed two cohorts: the development cohort (2016-2018) with 34,642 patients and validation cohort (2019) with 10,902 patients. The model included a comprehensive set of predictors: demographics, cancer type, comorbid conditions, ED visit history, and medication use variables. We employed the least absolute shrinkage and selection operator (LASSO) regression to refine and select the most relevant predictors. Out of 120 predictor variables, 12 were integral to the final model, including seven related to medication use. The model demonstrated acceptable predictive performance in the validation cohort with a C-statistic of 0.76 (95% CI 0.74-0.77), indicating reasonable calibration. This risk-scoring model, after further clinical validation, has the potential to assist healthcare providers in the effective management and care of older patients receiving anti-neoplastic therapy., (© 2024. The Author(s).)

Introduction: The efficacy of intracoronary (IC) antithrombotic therapy, which may best prevent the no-reflow phenomenon during percutaneous coronary intervention (PCI), remains unclear. Therefore, we compared the efficacy and safety of different IC antithrombotic agents., Materials and Methods: This systematic review and network meta-analysis of randomized controlled trials (RCTs) compared IC fibrinolytic agents (recombinant tissue plasminogen activators [rtPAs] and non-rtPAs) or glycoprotein IIb/IIIa inhibitors (small molecules and monoclonal antibodies) with placebo by searching the relevant studies published before September 21, 2022. Bayesian network meta-analyses were performed using random-effects models., Results: Twenty-five RCTs with 4546 patients were included. Non-rtPAs and small molecules were significantly more effective in achieving thrombolysis in myocardial infarction (TIMI) grade 3 flow than placebo (odds ratio [OR] 2.28, 95 % credible intervals [CrI] 1.24-4.13; OR 2.06, 95 % CrI 1.17-3.46). Moreover, these agents' efficacy was observed in other microcirculation-related outcomes, including TIMI myocardial perfusion grade 3, complete ST-segment resolution, and corrected TIMI frame counts. Within 6 months, small molecules were associated with both an improved left ventricular ejection fraction (MD 3.90, 95 % CrI 0.48-7.46) and major adverse cardiac events (MACE) reduction (OR 0.36, 95 % CrI 0.20-0.61). Non-rtPAs demonstrated a reduced MACE incidence within 6 months (OR 0.51, 95 % CrI 0.31-0.81). The results were consistent in the subgroup with a total ischemic time > 6 h. No significant differences in mortality or bleeding events were observed., Conclusions: IC non-rtPAs and small molecules may be effective for adjunctive therapy to PCI, particularly in patients with longer ischemia periods., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Falls impact over 25% of older adults annually, making fall prevention a critical public health focus. We aimed to develop and validate a machine learning-based prediction model for serious fall-related injuries (FRIs) among community-dwelling older adults, incorporating various medication factors., Methods: Utilizing annual national patient sample data, we segmented outpatient older adults without FRIs in the preceding three months into development and validation cohorts based on data from 2018 and 2019, respectively. The outcome of interest was serious FRIs, which we defined operationally as incidents necessitating an emergency department visit or hospital admission, identified by the diagnostic codes of injuries that are likely associated with falls. We developed four machine-learning models (light gradient boosting machine, Catboost, eXtreme Gradient Boosting, and Random forest), along with a logistic regression model as a reference., Results: In both cohorts, FRIs leading to hospitalization/emergency department visits occurred in approximately 2% of patients. After selecting features from initial set of 187, we retained 26, with 15 of them being medication-related. Catboost emerged as the top model, with area under the receiver operating characteristic of 0.700, along with sensitivity and specificity rates around 65%. The high-risk group showed more than threefold greater risk of FRIs than the low-risk group, and model interpretations aligned with clinical intuition., Conclusion: We developed and validated an explainable machine-learning model for predicting serious FRIs in community-dwelling older adults. With prospective validation, this model could facilitate targeted fall prevention strategies in primary care or community-pharmacy settings., (© 2023. The Author(s).)

Background: With the aging population, older adults are more likely to receive outpatient care. Therefore, it is necessary to identify drug-related problems (DRPs) and potentially inappropriate medications (PIMs) associated with adverse clinical outcomes in community-dwelling older adults. This study aimed to develop a medication review tool for community-dwelling older adults in Korea., Methods: We developed the tool using three steps: (i) establishment of a preliminary list by reviewing 21 existing tools, (ii) a two-round Delphi survey to evaluate clinical appropriateness and (iii) a two-round Delphi survey to evaluate applicability. The list was categorized into 23 diseases/conditions with five types of DRPs. The interventions for each item have been described., Results: The preliminary list contained 100 items. The final list contained 81 items, including 17 general PIMs, 26 PIMs under specific disease/conditions, 16 potential drug interactions, 20 potential omissions and 2 PIMs requiring dose adjustment., Conclusion: We developed a disease-based explicit medication review tool that can be used in primary care. This tool would assist primary care healthcare providers in identifying inappropriate medication use, which may help reduce adverse clinical consequences in older adults. Further studies are required to validate the clinical efficacy of this tool., (© The Author(s) 2023. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Hospitalization of nursing home (NH) residents impose a significant healthcare burden. However, there is still a lack of information regarding the risk of hospitalization from inappropriate prescribing in NH residents. We aimed to estimate the nationwide prevalence of potentially inappropriate medication (PIM) use among NH residents using the Korean tool and 2019 Beers criteria and to assess their associations with hospitalization or emergency department (ED) visits., Methods: We included older adults aged 65 years or above who were admitted to NHs between July 2008 and December 2018 using national senior cohort database. The prevalence of PIM use based on the Korean medication review tool and Beers criteria on the date of admission to NH was estimated. And the adjusted hazard ratios (aHRs) of polypharmacy, numbers of PIM, each PIM category for hospitalization/ED visits within 30 days of admission to NH was calculated using Cox proportional hazard model to show the association., Results: Among 20,306 NH residents, the average number of medications per person was 7.5 ± 4.7. A total of 89.3% and 67.9% of the NH residents had at least one PIM based on the Korean tool and 2019 Beers criteria, respectively. The risk of ED visits or hospitalization significantly increased with the number of PIMs based on the Korean tool (1-3: aHR = 1.24, CI 1.03-1.49; ≥4: aHR = 1.46, CI 1.20-1.79). Having four or more PIMs based on the Beers criteria increased the risk significantly (aHR = 1.30, CI 1.06-1.53) while using 1-3 PIMs was not significantly associated (aHR = 1.07, CI 0.97-1.19). Residents with any potential medication omission according to the Korean criteria, were at 23% higher risk of hospitalization or ED visits (aHR = 1.23, CI 1.07-1.40)., Conclusions: This study demonstrated that PIMs, based on the Korean tool and Beers criteria, were prevalent among older adults living in NHs and the use of PIMs were associated with hospitalization or ED visits. The number of PIMs based on the Korean tool showed dose-response increase in the risk of hospitalization or ED visits., (© 2023. The Author(s).)

Background: Intracoronary (IC) administration of glycoprotein IIb/IIIa inhibitors (GPIs) has been studied as an adjunctive therapy to improve outcomes in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention. In this systematic review and meta-analysis, we aimed to evaluate the efficacy and safety of IC administration of GPIs compared with those of intravenous (IV) administration in patients with STEMI., Methods: We searched the MEDLINE, Embase, and Cochrane CENTRAL databases for relevant studies published before September 21, 2022. In total, 22 randomized controlled trials involving 7,699 patients were included., Results: The proportions of patients achieving thrombolysis in myocardial infarction grade 3 flow, myocardial blush grade 2/3, and complete ST-segment resolution were significantly higher in the IC group than in the IV group. Major adverse cardiac events (MACE) (RR: 0.54, 95% CI: 0.37-0.80) and heart failure (RR: 0.48, 95% CI: 0.25-0.91) within 1 month were significantly lower in the IC group than in the IV group; however, after 6 months, no difference was observed in MACE risk. Additionally, the risks of death and bleeding did not differ between the two routes of administration., Conclusions: When considering adjunctive GPI administration for patients with STEMI, the IC route may offer greater benefits than the IV route in terms of myocardial reperfusion and reduced occurrence of MACE and heart failure within 1 month. Nonetheless, when making decisions for IC administration of GPIs, the absence of a benefit for bleeding risk and difficulty accessing the administration route should be considered., (© 2023. The Author(s).)

Aims: Few studies have quantified the impact of risk factors on GI complications in elderly nonsteroidal anti-inflammatory drug (NSAID) users. This study aimed to develop and validate a risk prediction score for severe GI complications to identify high-risk elderly patients using NSAID., Methods: We used the following two Korean claims datasets: customized data with an enrolment period 2016-2017 for model development, and the sample data in 2019 for external validation. We conducted a nested case-control study for model development and validation. NSAID users were identified as the elderly (≥65 years) who received NSAIDs for more than 30 days. Serious GI complications were defined as hospitalizations or emergency department visits, with a main diagnosis of GI bleeding or perforation. We applied the logistic least absolute shrinkage and selection operator (LASSO) regression model for variable selection and model fitting., Results: We identified 8176 cases and 81 760 controls with a 1:10 matched follow-up period in the derivation cohort. In the external validation cohort, we identified 372 cases from 254 551 patients. The risk predictors were high-dose NSAIDs, nonselective NSAID, complicated GI ulcer history, male sex, concomitant gastroprotective agents, relevant co-medications, severe renal disease and cirrhosis. Area under the receiver operating characteristic curve was 0.79 (95% confidence interval, 0.77-0.81) in the external validation dataset., Conclusions: The prediction model may be a useful tool for reducing the risk of serious GI complications by identifying high-risk elderly patients., (© 2023 British Pharmacological Society.)

Background: In older adults, depression is associated with several other clinical problems such as cognitive impairment and low quality of life. Several studies have evaluated the relationship between vitamin D and depression in older adults; however, the results have been controversial thus far., Objective: This study aimed to investigate the effects of vitamin D supplementation on depressive symptom improvement among individuals aged ≥60 years with or without a diagnosis of depression or depressive symptoms based on a meta-analysis of randomized controlled trials (RCTs)., Methods: RCTs were identified to analyze the relationship between vitamin D supplementation and depressive symptoms. MEDLINE, CENTRAL, Embase, and PsycINFO were systematically searched for relevant articles published from inception to November 2022. RCTs that evaluated the effect of vitamin D supplementation in participants aged ≥60 years compared to placebo were included. A random effects model was used in this meta-analysis because of the differences between the included RCTs. The quality of the RCTs was assessed using Risk of Bias 2., Results: Seven trials were included in the analyses. The primary outcome of pre-post score changes included five trials with a total of 752 participants. The secondary outcome of post-intervention score included all seven trials with a total of 4,385 participants. No significant improvement in depressive symptoms in either pre-post score changes [standardized mean difference (SMD) = -0.49; 95% confidence interval (CI) -1.07-0.09; p = 0.10] or post-intervention score (SMD = -0.10; 95% CI -0.28-0.07; p = 0.25) was found., Conclusion: Vitamin D supplementation in older adults was not associated with an improvement in depressive symptoms. More studies in older adults are needed to evaluate the association between vitamin D supplementation and depression., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Park, Ah and Yu.)

Despite an increase in the use of targeted anticancer drugs and immunotherapy, cytotoxic anticancer drugs such as docetaxel continue to play a clinically important role. The aim of this study was to evaluate drug-drug interactions between docetaxel and coadministered medicines in patients with breast cancer a claims database. The Health Insurance Review and Assessment Service (HIRA) database (2017 to 2019) was used in this study. We evaluated the risk of neutropenia (defined using receipt of granulocyte colony-stimulating factor (G-CSF) prescriptions) under docetaxel administration or the coadministration of docetaxel and an interacting anticancer drug (predefined based on approval information obtained from the Korean Ministry of Food and Drug Safety and the Lexicomp electronic database). The propensity score matching method was applied to balance covariates in the case (patients with G-CSF prescriptions) and control (patients without G-CSF prescriptions) groups. We identified 947 female patients with breast cancer prescribed with docetaxel and excluded 321 patients based on inclusion criteria. Of the remaining 626 patients, 280 were assigned to the case group and 346 to the control group. Predefined drugs were coadministered to 71 (11.3%) patients during the 7-day period before and after the administration of docetaxel. Adjusted odds ratios (ORs) calculated using the logistic regression model applied to the propensity score matching showed no significant difference between the administration of docetaxel alone and docetaxel coadministration (adjusted OR, 2.010; 95% confidence interval, 0.906, 4.459). In conclusion, we suggest that coadministration of docetaxel and a predefined interacting drug are not associated with G-CSF prescription., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Shin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background and Objectives : Opioid use in Korea is lower than in other developed countries. However, recent studies have reported an increase in opioid prescriptions and the number of chronic opioid users. The current status of adverse events (AEs) associated with opioid analgesics in Korea is unclear. This nested case-control study aimed to evaluate the influence of opioid analgesic use patterns on all emergency department (ED) visits and opioid-related ED visits after opioid analgesic initiation using the national claims database. Materials and Methods: Adult non-cancer patients who initiated non-injectable opioid analgesics (NIOA) between January 2017 and June 2018 were included. We defined the case group as patients who visited the ED within six months of opioid initiation, and the control group was selected in a 1:1 ratio using an exact matching method. Results: A total of 97,735 patients (13.58%) visited the ED within six months of NIOA initiation. Nearly 32% of cases were linked to opioid-related AEs. The most frequent AEs were falls and fractures (61.27%). After adjusting for covariates, opioid initiation at the ED was associated with all-cause or opioid-related ED visits (adjusted odds ratio (aOR) = 3.19, 95% confidence interval (CI) = 3.09-3.29; aOR = 3.82, 95% CI = 3.62-4.04, respectively). Chronic NIOA use was associated with all-cause and opioid-related ED visits (aOR = 1.32, 95% CI = 1.23-1.40; aOR = 1.56, 95% CI = 1.39-1.76, respectively). Conclusion: This study found that 13% of non-cancer patients visited the ED within six months of NIOA initiation. In addition, the NIOA use pattern was significantly associated with all-cause and opioid-related ED visits.

Background: the identification and minimization of hyponatraemia-inducing medication (HIM) usage is among the effective strategies for preventing hyponatraemia. However, the differential risk of severe hyponatraemia is unknown., Objective: to evaluate the differential risk of severe hyponatraemia associated with newly started and concurrently used HIMs in older people., Design and Setting: a case-control study using national claims databases., Methods: we identified patients aged >65 years with severe hyponatraemia as those hospitalised with a primary diagnosis of hyponatraemia or who had received tolvaptan or 3% NaCl. A 1:20 matched control with the same visit date was constructed. Multivariable logistic regression was performed to assess the association of newly started or concurrently used HIMs comprising 11 medication/classes with severe hyponatraemia after covariate adjustment., Results: among 47,766,420 older patients, we identified 9,218 with severe hyponatraemia. After adjusting for covariates, all HIM classes were found to be significantly associated with severe hyponatraemia. Compared with persistently used HIMs, newly started HIMs increased the likelihood of severe hyponatraemia for eight classes of HIMs, with the highest increase being observed for desmopressin (adjusted odds ratio: 3.82, 95% confidence interval: 3.01-4.85). Concurrent use increased the risk of severe hyponatraemia compared to that with individually administered HIMs: thiazide-desmopressin (4.86, 3.90-6.07), medications causing the syndrome of inappropriate anti-diuretic hormone secretion (SIADH)-desmopressin (2.65, 2.25-3.11), medications causing SIADH-thiazides (1.87, 1.75-1.98) and combination among medications causing SIADH (1.36, 1.28-1.45)., Conclusions: in older adults, newly started and concurrently used HIMs increased the risk of severe hyponatraemia compared with persistently and singly used HIMs., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: To evaluate the prevalence of medication-related admissions (MRAs) and their association with potentially inappropriate medications (PIMs) used by nursing home residents admitted to the geriatric center of a tertiary hospital., Design: Cross-sectional study., Setting and Participants: Older patients admitted from nursing homes to the geriatric center of the Seoul National University Bundang Hospital who had undergone comprehensive geriatric assessment from January 1, 2016, to December 31, 2020., Methods: MRAs were determined and verified using a previously described MRA adjudication guide. The PIMs in the preadmission medication lists were identified according to each of the following criteria (as well as the combined criteria), the Beers, NORGEP-NH, STOPP/START-NH, and STOPPFrail criteria. Medication use factors associated with MRAs were analyzed using multivariate logistic regression., Results: Among the 304 acute care admissions, 32.2% were MRAs. The main cause of MRAs was acute kidney injury related with use of renin-angiotensin system inhibitors. Approximately 81% of the patients used at least 1 PIM according to the combined criteria. The use of 1 or more PIMs, renin-angiotensin system inhibitors, diuretics, nonsteroidal anti-inflammatory drugs, and benzodiazepines was significantly associated with MRAs. The combined criteria were able to predict MRAs better than the individual criteria., Conclusions and Implications: Approximately one-third of acute admissions of nursing home residents may be MRAs. Interventions for the optimal use of medication among nursing home residents are needed., (Copyright © 2022 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Background and objectives : We aimed to describe medication-related incidents or medication errors (MEs) reported by community pharmacists and analyze the prevalent medications involved. Materials and Methods : We extracted ME reports from databases comprising patient safety incidents reported to the Korean Pharmaceutical Association between January 2013 and June 2021. Medications were analyzed according to the second (therapeutic subgroup) and fifth (chemical substance) levels of the Anatomical Therapeutic Chemical classification. Results : A total of 9046 MEs were identified, most of which were near miss reports (88.3%). Among the errors that reached the patients (521 cases), harmful incidents accounted for 76.8%. Most MEs occurred during prescription (89.5%), while harmful MEs occurred mainly during dispensing (73.3%). In the prescription step, wrong drugs (44.8%), dosing errors (27.0%), and wrong durations (14.0%) were common. Anti-inflammatory and anti-rheumatic products (M01), drugs for acid-related disorders (A02), and antihistamines for systemic use (R06) were the most frequently reported medication classes involved. Harmful incidents were most common for dosing errors (31.0%) and wrong drugs (26.8%) and were common with warfarin, levothyroxine, and glimepiride. Conclusions : The MEs reported by community pharmacists were mainly prescribing errors, most of which were rectified before reaching patients. The prevalent medications involved in harmful errors include anti-diabetic, anti-thrombotic, and anti-inflammatory agents.

Background: Residents in long-term care (LTC) facilities (LTCFs) may have multimorbidity and be unable to self-administer medication. Thus, due to the risk of potentially inappropriate medications (PIMs), epidemiological studies on PIM use and its associated factors should be conducted to ensure safe medication use for residents in LTCFs. Objective: We evaluated PIM use among residents of LTCF and the associated factors in residents of LTCFs in Korea using a nationwide database. Methods: This cross-sectional study used the Korea National Health Insurance Service Senior Cohort (KNHIS-SC) database 2.0 of the National Health Insurance Service (NHIS), a single public insurer in Korea. We analyzed older adults aged ≥65 years who were residents of LTCFs in 2018, using the KNHIS-SC database. The 2019 American Geriatrics Society (AGS) Beers criteria was used for PIM identification. The prevalence of PIM use was defined as the proportion of LTCF residents who received PIM prescriptions at least once. We evaluated the frequency of prescriptions, including PIMs, and determined the most frequently used PIMs. We also conducted a multivariable logistic regression analysis to identify the factors associated with PIM use. Results: The prevalence of PIM among the LTCF residents was 81.6%. The prevalence of PIM was 74.9% for LTC grades 1 or 2 (high dependence) and 85.2% for LTC grades 3-5 (low dependence). Quetiapine was the most frequently prescribed PIM, followed by chlorpheniramine. The low dependence level was significantly associated with PIM use (odds ratio of LTC grades 3-5: 1.49, 95% confidence interval 1.32-1.68, reference: LTC grades 1 or 2); moreover, the number of medical institutions visited, and medications emerged as primary influencing factors. Conclusion: Most LTCF residents were vulnerable to PIM exposure. Furthermore, exposure to PIMs is associated with LTC grade. This result highlights the need for comprehensive medication management of LTCF residents., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Jang, Ah, Jang, Kim, Lee and Kim.)

Objectives: Older adults are more likely to experience drug-related problems (DRP), which could lead to medication-related emergency department visits (MRED). To properly evaluate MRED, the entire history of drug use should be evaluated in a structured manner. However, limited studies have identified MRED with complete prescription records. We aimed to evaluate the prevalence and risk factors of MRED among community-dwelling older patients by linking national claims data and electronic medical records using a standardized medication related admission identification method. Methods: We included older patients who visited the emergency departments of four participating hospitals in 2019. Among the 54,034 emergency department (ED) visitors, we randomly selected 6,000 patients and structurally reviewed their medical records using a standardized MRED identification method after linking national claims data and electronic medical records. We defined and categorized MRED as ED visits associated with adverse drug events and those caused by the underuse of medication, including treatment omission and noncompliance and assessed as having probable or higher causality. We assessed preventability using Schumock and Thornton criteria. Results: MRED was observed in 14.3% of ED visits, of which 76% were preventable. In addition, 32.5% of MRED cases were related to underuse or noncompliance, and the rest were related to adverse drug events. Use of antipsychotics, benzodiazepines, anticoagulants, traditional nonsteroidal anti-inflammatory drugs without the use of proton pump inhibitors, P2Y12 inhibitors, insulin, diuretics, and multiple strong anticholinergic drugs were identified as predictors of MRED. Conclusion: One in seven cases of ED visits by older adults were medication related and over three-quarters of them were preventable. These findings suggest that DRPs need to be systemically screened and intervened in older adults who visit ED., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Park, Kim, Ah, Lee, Lee, Chae, Rho, Kim and Lee.)

Background: The use of opioid-gabapentinoid combinations has increased, raising several safety concerns. However, meta-analysis studies focusing on this issue are limited. Objective: To evaluate the risk of central nervous system (CNS) depression, gastrointestinal (GI) adverse events, and mortality of combination therapy compared with those of opioid therapy and to explore the differences in the results according to study design and indications. Methods: Relevant studies were selected (published before 30 January 2022) by searching the MEDLINE, Embase, and CENTRAL databases. The pooled odds ratios (OR) with 95% confidence intervals (CI) of the outcomes were estimated using the Mantel-Haenszel method. Subgroup and meta-regression analyses were performed according to study characteristics. Quality assessment was conducted using the Risk of Bias 2 tool for randomized controlled trials (RCTs) and Cochrane Collaboration's Risk of Bias in non-RCTs tool for non-randomized trials. Results: Adverse events were reported in 26 RCTs and 7 non-RCTs, and mortality was reported in 10 non-RCTs. Compared to opioid therapy, dizziness, cognitive dysfunction, and respiratory depression in combination therapy significantly increased in non-RCTs (OR 3.26, 95% CI 1.82-5.85; OR 3.13, 95% CI 1.51-6.50; OR 1.71, 95% CI 1.31-2.24, respectively), and a similar trend for dizziness and cognitive dysfunction was also identified in the RCT analysis, although the difference was not significant. Combination therapy for cancer pain was associated with the highest risk of sedation in subgroup analysis. Combination therapy significantly decreased the risk of GI adverse events, including nausea, vomiting, and constipation. The mortality risk associated with combination therapy was higher than that associated with opioid therapy (OR 2.76, 95% CI 1.26-6.05). Conclusion: Opioid-gabapentinoid combination therapy could be associated with an increased risk of CNS depression and mortality, despite tolerable GI adverse events. These data suggest that combination therapy requires close monitoring of CNS depression, especially in cancer patients. Caution is needed in interpreting the clinical meanings owing to the lack of risk difference in respiratory depression in the RCT-only analysis and the absence of RCT or prospective studies investigating mortality., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hahn, Jo, Yoo, Shin, Yu and Ah.)

Introduction: Residents in long-term care facilities (LTCFs) are likely to suffer from drug-related problems, such as inappropriate polypharmacy and potential prescribing omissions due to multimorbidity and high-level frailty. Medication reviews are thus necessary to identify and resolve drug-related problems in LTCF residents. In this study, we aimed to develop a medication review tool for older adults in LTCFs in Korea., Methods: We did a systematic review to identify previously developed explicit criteria and devised preliminary potentially inappropriate medications (PIMs) list for the LTCF elderly from previous tools. Each item on this list was categorized into 23 underlying diseases/conditions, and the interventions necessary for each PIM were included. A two-round modified Delphi survey was performed sequentially for consensus evaluation of clinical appropriateness and feasibility of the list items by 12 experts (seven physicians in different specialties and five pharmacists specialized in geriatrics) and seven pharmacists, respectively., Results: We identified 22 existing tools and devised a preliminary PIM list including 100 items. Ninety-one items were derived from the two-round Delphi survey for clinical appropriateness. In the feasibility test, 77 items were integrated into the final medication review tool for the LTCF elderly. The final list was composed of items relating to PIMs in general (18), potential drug interactions (14), PIMs under specific diseases/conditions (26), a need for dose adjustment (2), and potential omissions (17)., Conclusions: We developed a disease-category-based explicit medication review tool for detecting PIM use for LTCF residents. This tool may be helpful in implementing medication review practices to assist pharmacists or physicians for the elderly in LTCFs. Further research is required to validate the effectiveness of our tool in clinical practice., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), 2022.)

Introduction: The aim of this study was to investigate trends in the prevalence of potentially inappropriate opioid prescribing (PIOP) and identify potential risk factors among Korean noncancer patients., Methods: We conducted a cross-sectional study of annual national patient sample data from the Korean Health Insurance Review and Assessment Service (HIRA-NPS) for the period 2012-2018. Noncancer patients who were prescribed non-injectable opioid analgesics (NIOAs) at least once were included. The proportion of patients with at least one PIOP in terms of concurrent use of benzodiazepines or gabapentinoids, substance use disorder, treatment duration, and dosage was evaluated. Multivariable logistic regression was performed to identify the risk factors associated with PIOP., Results: Of the 9,772,503 noncancer patients, 1,583,444 (16.2%) were prescribed NIOAs at least once. Among them, 15.7% were exposed to PIOP, and the prevalence was much higher (31.6%) in the elderly group (age: ⩾65 years). The prevalence of PIOP increased 1.1-fold over 7 years (14.8-16.8%) among the total NIOA users and was more pronounced in non-tramadol NIOA users (a 1.5-fold increase, from 13.2% to 19.4%). Multivariable logistic regression indicated that older age, beneficiaries of medical aid or national meritorious service, exposure to polypharmacy, psychological disorder, chronic pain indication, and concomitant sedative use were independently associated with higher odds of PIOP., Discussion and Conclusion: We found that the prevalence of PIOP was 15.7% among Korean noncancer patients, and it increased over the 7-year study period. This increasing trend is alarming because it was more drastic with non-tramadol NIOAs compared with that with tramadol. Several patient-level risk factors associated with PIOP would be useful in targeted management strategies for the safe use of opioids., Plain Language Summary: Potentially inappropriate opioid prescribing and related risk factors among noncancer patients prescribed non-injectable opioids in Korea In Korea, the prevalence of non-injectable opioid analgesic (NIOA) use in noncancer patients steadily increased from 15.3% in 2012 to 17.1% in 2018.Also, the prevalence of potentially inappropriate opioid prescribing (PIOP) increased from 14.8% in 2012 to 16.8% in 2018.The following factors were associated with a markedly increased risk of PIOP: age, beneficiaries of medical aid or national meritorious service, polypharmacy, psychological disorder, chronic pain, and concomitant medications., Competing Interests: Conflict of interest statement: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), 2022.)

Purpose: Although clinically driven low-dose (CDLD) treatment with direct oral anticoagulants (DOACs) is frequently administered to Asian patients with atrial fibrillation, clinical evidence confirming its efficacy remains insufficient. We evaluated the clinical efficacy and safety of CDLD treatment with DOACs compared to on-label dose treatment in Asian patients with atrial fibrillation and assessed the differences in the baseline characteristics between patients receiving these treatments., Methods: We searched the MEDLINE, CENTRAL, EMBASE, Web of Science, and Scopus databases for articles from inception through July 2020., Results: Thirteen studies were included in this meta-analysis. The baseline characteristics of the CDLD group were significantly different from those of the standard dose (STD) and standard low-dose (SLD) groups. The incidences of thromboembolic events (risk ratio [RR] 0.46, 95% confidence interval [CI] 0.29-0.73, p < 0.001) and major bleeding (RR 0.55, 95% CI 0.35-0.87, p = 0.01) in the CDLD group were lower than those in the SLD group; however, they were comparable with those in the STD group. The incidence of a composite endpoint in the CDLD group was not significantly different from that in the STD group but was significantly lower than that in the SLD group (RR 0.50, 95% CI 0.38-0.65, p < 0.001)., Conclusion: The clinical outcomes of CDLD treatment showed no difference compared to those of the STD treatment despite the vulnerable baseline characteristics of the CDLD group for thromboembolic and major bleeding events., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

Opioid overdose can be serious adverse effects of opioid analgesics. Thus, several strategies to mitigate risk and reduce the harm of opioid overdose have been developed. However, despite a marked increase in opioid analgesic consumption in Korea, there have been no tools predicting the risk of opioid overdose in the Korean population. Using the national claims database of the Korean population, we identified patients who were incidentally prescribed non-injectable opioid analgesic (NIOA) at least once from 2017 to 2018 (N = 1,752,380). Among them, 866 cases of opioid overdose occurred, and per case, four controls were selected. Patients were randomly allocated to the development (80%) and validation (20%) cohort. Thirteen predictive variables were selected via logistic regression modelling, and a risk-score was assigned for each predictor. Our model showed good performance with c-statistics of 0.84 in the validation cohort. The developed risk score model is the first tool to identify high-risk patients for opioid overdose in Korea. It is expected to be applicable in the clinical setting and useful as a national level surveillance tool due to the easily calculable and identifiable predictors available from the claims database., (© 2022. The Author(s).)

Statin is highly recommended for dyslipidemia to prevent atherosclerosis-related cardiovascular diseases and death. The aim of this study was to compare the efficacies and safeties of low/moderate-intensity statin plus ezetimibe combination therapy vs. high-intensity statin monotherapy. Meta-analysis was conducted on data included in published studies performed to compare the effects of the two treatments on lipid parameters and hs-CRP. Safety-related parameters were also evaluated. Eighteen articles were included in the meta-analysis. In terms of efficacy, low/moderate-intensity statin plus ezetimibe reduced LDL-C (SE = 0.307; 95% CI 0.153-0.463), TC (SE = 0.217; 95% CI 0.098-0.337), triglyceride (SE = 0.307; 95% CI 0.153-0.463), and hs-CRP (SE = 0.190; 95% CI 0.018-0.362) significantly more than high-intensity statin therapy. In terms of safety, the two treatments were not significantly different in terms of ALT elevation, but high-intensity statin increased AST and CK significantly more than combination therapy. This analysis indicates that low/moderate-intensity statin plus ezetimibe combined therapy is more effective and safer than high-intensity statin monotherapy, which suggests the addition of ezetimibe to statin should be preferred over increasing statin dose and that high-intensity statin should be used more carefully, especially in patients with related risks., Competing Interests: The authors declare that they have no competing interests.

Introduction: Despite growing evidence showing an increased risk of concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs) and anticoagulants, few studies have investigated whether proton pump inhibitors can prevent gastrointestinal (GI) complications in patients receiving both NSAIDs and anticoagulants., Objective: We aimed to evaluate the risk of serious GI complications and the impact of GI preventive strategies on the concomitant use of NSAIDs and anticoagulants., Methods: Our nationwide cohort study using Korea's claims data included elderly patients (aged ≥ 65 years) who started anticoagulants and NSAIDs from 2016 to 2017. The outcome was serious GI complications defined as hospitalization or emergency department visits with GI bleeding or perforation. A Cox regression analysis was performed using time-dependent variables and propensity score matching., Results: In total, 92,379 patients were identified. Compared with non-prophylaxis, proton pump inhibitors and selective cyclooxygenase-2 inhibitors were associated with a 64% [adjusted hazard ratio, 0.36 (95% confidence interval 0.25-0.53)] and 74% [adjusted hazard ratio, 0.26 (95% confidence interval 0.19-0.36)] lower risk of serious GI complications, respectively. Cyclooxygenase-2 inhibitor use was not different from the use of non-selective NSAIDs with proton pump inhibitors for the prevention of serious GI complications. H2-receptor antagonists did not reduce the risk of serious GI complications compared with non-prophylaxis during concomitant non-selective NSAID and anticoagulant therapy., Conclusions: Proton pump inhibitors or cyclooxygenase-2 inhibitors used as GI preventive strategies did not completely eliminate but lowered the risk of serious GI complications among elderly patients receiving both NSAIDs and anticoagulants., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Surgery is an indication for opioid prescription in noncancer patients, and chronic use of opioids is associated with overdose and abuse., Objectives: We aimed to evaluate the prevalence and risk factors associated with chronic opioid use (COU) following surgery among noncancer patients., Design: A nationwide case-control study., Setting: Retrospective analysis of the annual national patient sample data from 2012 to 2018 in South Korea., Patients: Adults without cancer who had undergone surgery and received noninjectable opioids during hospital stay., Main Outcome Measures: COU during 3 months following surgery., Results: A total of 15 543 participants were included, and the prevalence overall and in opioid-naïve users was 8.1 and 5.7%, respectively. Prior exposure patterns of opioids [intermittent user, adjusted odds ratio (aOR) 2.35; 95% CI, 2.00 to 2.77, and continuous user, aOR 8.58; 95% CI, 6.54 to 11.24] and concomitant use of benzodiazepine (in continuous user, aOR 18.60; 95% CI 11.70 to 29.55) were strongly associated with COU compared with naïve users. Morphine milligram equivalent, type of opioid strength at discharge and prescription of nonopioid analgesics at discharge were also associated with COU. Compared with minor surgery, knee (aOR 1.49; 95% CI 1.17 to 1.89), spine (aOR 1.65; 95% CI 1.33 to 2.06) and shoulder (aOR 2.54; 95% CI 1.97 to 3.27) procedures showed a significantly positive association with COU. Sensitivity analysis in opioid-naïve patients showed similar results., Conclusion: About 8.1% of noncancer patients who had undergone surgery and were prescribed noninjectable opioids became chronic opioid users in Korea. Identified risk factors could be used to derive strategies for safe opioid use in noncancer patients in the future., (Copyright © 2021 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.)

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.

This study aimed to investigate the age- and sex-specific risk of urogenital infections in patients with type 2 diabetes mellitus (T2DM) treated with sodium-glucose co-transporter 2 (SGLT2) inhibitors. A self-controlled case series was conducted using annual national patient sample datasets from 2016 and 2017. Patients who were treated with SGLT2 inhibitors and who received antimicrobials for urogenital infections were included in the study. The incidence rate ratio (IRR) of urogenital infections during SGLT2 inhibitor exposure were compared with those in the non-exposure period. A total of 2,949 patients were included in the analysis, and 71.2% of the patients were women aged ≥ 50 years. Stratified analysis by age and sex showed that only women ≥ 50 years showed a significant increase in the risk of urinary tract infections (UTIs) (IRR 1.25, 95% CI 1.14-1.37) and genital infections (IRR 1.44, 95% CI 1.28-1.62). The highest risk of UTI risk was observed 8-14 days after initiating SGLT2 inhibitor therapy (IRR 1.49, 95% CI 1.07-2.08), and after 15-28 days for genital infections (IRR 2.11, 95% CI 1.66-2.67) in women ≥ 50. SGLT2 inhibitors increase the risk of urogenital infections in T2DM patients, especially in women aged ≥ 50 years. Monitoring of urogenital infections in women aged ≥ 50 years, especially during the first month after starting SGLT2 inhibitors, is recommended., (Copyright © 2021 Elsevier B.V. All rights reserved.)

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 < 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.

Background: Cautious use or avoidance of hyponatraemia-inducing medications (HIMs) is recommended in older patients with hyponatraemia., Objective: To evaluate the use of HIMs after treatment for symptomatic or severe hyponatraemia and to investigate the impact of HIMs on the recurrence of symptomatic or severe hyponatraemia in older patients., Design and Settings: A cross-sectional and nested case-control study using data obtained from national insurance claims databases., Methods: The rate of prescribing HIMs during the 3 months before and after the established index date was analysed in a cross-sectional analysis. Multivariable logistic regression was performed to investigate the association between HIM use and recurrence of symptomatic or severe hyponatraemia after adjusting for covariates in a case-control study., Results: The cross-sectional study included 1,072 patients treated for symptomatic or severe hyponatraemia. The proportion of patients prescribed any HIMs after hyponatraemia treatment decreased from 76.9 to 70.1%. The prescription rates significantly decreased for thiazide diuretics (from 41.9 to 20.8%) and desmopressin (from 8.6 to 4.0%), but the proportion of patients prescribed antipsychotics increased from 9.2 to 17.1%. Of 32,717 patients diagnosed with hyponatraemia, 913 (2.8%) showed recurrent hyponatraemia. After adjusting for comorbid conditions, the use of any HIMs including proton pump inhibitors [adjusted odds ratio (aOR) 1.34, 95% confidence interval (CI) 1.15-1.57] and two or more HIMs (aOR 1.48, 95% CI 1.22-1.78) especially in combination with thiazide diuretics increased the likelihood of severe hyponatraemia recurrence., Conclusions: Prevalent use of HIMs after treatment for symptomatic or severe hyponatraemia and multiple HIM use increase the risk of recurrent hyponatraemia in geriatric patients., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background The increasing use of antithrombotic therapies in older patients has led to an increased risk of gastrointestinal (GI) bleeding in chronic nonsteroidal anti-inflammatory drug (NSAID) users. Therefore, there is a pressing need for GI prophylaxis in these high-risk patients. Objective To analyze prescribing patterns and factors associated with the use of gastroprotective agents (GPAs) among high-risk, chronic NSAID users. Setting National claims database including 20% of the total Korean population aged ≥ 65 years. Method In this cross-sectional study, we identified older adults prescribed traditional NSAIDs for > 90 days and classified them into high- and ultra-high-risk groups if they had one or two or more GI risk factors, respectively. Proton pump inhibitors or misoprostol prescribed for more than 80% of traditional NSAID treatment days was regarded as appropriate GI prophylaxis. Main outcome measure Prevalence and associated factors with appropriate GI prophylaxis. Results Among 69,992 chronic traditional NSAID users, 38.8% and 9.4% belonged to the high and ultra-high-risk groups; 13.2% and 19.9% received appropriate GI prophylaxis, respectively. The most frequently used GPA was histamine H 2 antagonists. Multiple NSAID use, concomitant antiplatelets and anticoagulants, and prior GI ulcer history increased the likelihood of receiving appropriate GI prophylaxis. Advanced age (≥ 85 years), indications other than arthritis, and neurology specialists negatively affected appropriate GI prophylaxis use. Conclusion Approximately one in five chronic NSAID users, considered ultra-high risk, are prescribed appropriate GI prophylaxis in Korea. Advanced age, indications, and specialties of the prescriber all need to be considered when selecting target populations for interventions.

Purpose: We aimed to investigate the prevalence and predicting factors of inappropriate polypharmacy including potentially inappropriate medications (PIMs) and drug-drug interactions (DDIs) and their associations with emergency department (ED) visits in older Korean patients receiving anti-neoplastic therapy., Methods: We identified older patients receiving anti-neoplastic therapy in 2016 from the National Health Claims database. We investigated the prevalence of inappropriate polypharmacy comprising PIMs and DDIs in geriatric patients according to the 2019 American Geriatrics Society Beers Criteria ® and chemotherapeutic DDIs using Lexicomp Online TM and Micromedex ® . A nested case-control study was conducted to evaluate the associations between inappropriate polypharmacy and ED visits during anti-neoplastic therapy. Multivariate logistic regressions were performed after adjusting for age, sex, cancer diagnosis, prior ED visits, Charlson Comorbidity Index, and type of anti-neoplastic therapy., Results: Inappropriate polypharmacy, its subtype PIMs, geriatric, and chemotherapeutic DDIs were observed in 85.4%, 80.4%, 17.3%, and 37.9% of the 21,956 patients receiving anti-neoplastic therapy, respectively. After adjusting for confounding factors, the presence of inappropriate polypharmacy (adjusted odds ratio (aOR) 2.15, 95% confidence interval (CI) 1.97-2.35), 2 or more PIMs (aOR 1.85, 95% CI 1.68-2.02), 2 or more chemotherapeutic DDIs (aOR 2.88, 95% CI 2.54-3.28), and geriatric DDIs (aOR 1.61, 95% CI 1.43-1.80) increased the likelihood of ED visits during anti-neoplastic therapy., Conclusion: This nationwide study showed that inappropriate polypharmacy was prevalent and increased the risk of ED visits in older patients receiving anti-neoplastic therapy. Study findings suggested a need to implement deprescribing strategies in this population.

Media has become a major source of information on health and plays a role in the decision-making process on health topics. We aimed to evaluate the association between zolpidem use and media broadcasts that reported the suicide risk. We obtained the data of adult outpatients who have been prescribed zolpidem or other hypnotics from the National Patient Sample database (2015-2017). We evaluated the change in zolpidem or other hypnotic prescription trends based on the prescription rate and average daily prescribed dose before and after July 2016, using interrupted time series analysis. A total of 129,787 adult patients had at least one zolpidem prescription in 3 years. The prescription rate of zolpidem after the broadcast decreased significantly by 0.178% (95% confidence interval (CI): -0.214, -0.142), whereas that of other hypnotic users did not differ from that before the broadcast (-0.020%, 95% CI: -0.088, 0.047). However, the trends in the prescription rate before and after the broadcast did not differ for zolpidem and other hypnotics. Broadcasting medication safety through major public media could have an effect on medication use. After broadcasting about the suicide risk of zolpidem, its overall prescription rate decreased immediately, but the trend was not changed.

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.

Purpose: We aimed to gain insight into the real-world prevalence of potentially significant drug-drug interactions (DDIs) involving oral antineoplastic agents using nationwide data in Korea., Methods: The data from the 2016 and 2017 Health Insurance Review and Assessment Service-National Patients Sample (HIRA-NPS) of South Korea were used. The drugs prescribed concomitantly with oral anticancer drugs were screened for the potential DDIs by using two international DDI databases: Lexicomp TM and Micromedex®. Potentially significant DDIs were defined as DDIs with a severity rating of "major" or higher from at least one reference. The DDIs were classified into category 1 if the severity ratings were major or higher using both references., Results: Overall 5657 cases of DDIs in 2925 patients (26.4%) and 1640 cases of category 1 DDIs in 997 patients (9.0%) were identified among 11,076 patients receiving oral anticancer drugs. The prevalence was highest among the targeted agents (63.2%) followed by traditional (21.2%) and endocrine agents (19.3%). The common potential clinical consequences were increased risk of corrected QT interval prolongation (36.7%), reduced efficacy of antineoplastic agents (30.4%), and increased toxicities of antineoplastic agents (8.0%). Polypharmacy and the duration of oral cancer treatment increased the likelihood of potential DDIs in addition to individual antineoplastic agents., Conclusions: This study showed that potentially significant DDIs with oral antineoplastic agents were prevalent in real-world practice. Recognizing the high prevalence of DDIs among patients taking oral antineoplastic agents is a necessary step toward improving the clinical outcome.

Background: The dose response relationship of nine-year cumulative anticholinergic exposure and dementia onset was investigated using the Korean version anticholinergic burden scale (KABS) in comparison with the Anticholinergic Cognitive Burden Scale (ACB). We also examined the effect of weak anticholinergics in the prediction of dementia., Methods: A retrospective case-control study was conducted comprising 86,576 patients after 1:2 propensity score matching using the longitudinal national claims database. For cumulative anticholinergic burden estimation, average daily anticholinergic burden score during the 9 years prior to dementia onset was calculated using KABS and ACB and categorized as minimal, < 0.25; low, 0.25-1; intermediate, 1-2; and high, ≥ 2. Adjusted odds ratio (aOR) between cumulative anticholinergic burden and incident dementia was estimated., Results: Patients with high exposure according to KABS and ACB comprised 3.2 and 3.4% of the dementia cohort and 2.1 and 2.8% of the non-dementia cohort, respectively. Dose-response relationships were observed between anticholinergic burden and incident dementia. After adjusting covariates, compared with minimal exposure, patients with high exposure according to KABS and ACB had a significantly higher risk for incident dementia with aOR of 1.71 (95% confidence interval (CI) 1.55-1.87) and 1.22 (CI 1.12-1.33), respectively. With the exclusion of weak anticholinergics, the association became stronger, i.e., 1.41 (CI 1.14-1.75) with ACB whereas the association became slightly weaker with KABS, i.e., 1.60 (CI 1.38-1.86)., Conclusion: This study confirmed the dose response relationship for cumulative anticholinergic burden measured using the Korean specific anticholinergic burden scale with incident dementia.

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 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., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Considering the concerns about topical corticosteroid (TC) phobia that prevents necessary use of patients from using the necessary TCs, estimating the incidence and characteristics of adverse drug events (ADEs) related to TCs in the real world is warranted. However, limited study investigated them. This prospective observational study aimed to assess the utility patterns and safety data related to TC use and predisposing factors among community-dwelling population. We included and prospectively observed the TC users through nationwide multi-centre observational cohort based on community pharmacies and dermatologic clinic. Among the enrolled 1175 over-the-counter and prescription TC users, a total of 1103 participants were included for the analysis. Inappropriate TC use was observed in 6.3%. The cumulative incidence and prevalence of overall ADE for 6 months were 3.5% and 7.2%, respectively, and the incidence rate was 0.3 cases per 1000 person-days of TC use. Most ADEs were local reactions, mainly skin atrophy and hyperpigmentation. Exposure to TCs for >12 weeks (adjusted odds ratio [aOR] 4.38, 95% confidence interval [CI] 2.23-8.63) and past experience of ADE (aOR 36.70, 95% CI 16.74-80.44) were identified as significant predictors of TC-related ADEs. The ADE incidence related to TCs was relatively low, and the real-world safety of using TCs in the general population might not be greatly concerning. However, some populations who are highly at a risk of ADEs should be closely monitored and made aware regarding the risk., (© 2019 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Background: Sedative agents are avoided in older adults because of potential risks including cognitive impairment, fall, frailty, and mortality. However, no studies addressing both prediagnostic and postdiagnostic period of dementia have evaluated sedative agent usage over an extended period., Objectives: To describe a longitudinal change in sedative medication use before and after the diagnosis with dementia over 10 years compared to patients without dementia., Methods: We conducted a retrospective cohort study using longitudinal claims data for senior national health insurance beneficiaries. After 1:4 propensity score matching, 54,165 older patients (≥60 years) were included. Difference-in-difference (DID) of sedative burden and use of sedative agents pre- and post-dementia diagnosis were estimated, and compared to those of patients without dementia. The yearly average daily sedative load (adSL) for each individual was calculated after applying duration, dose, and sedative score of medications from the sedative load model. The medication use for each sedative category was calculated using the defined daily dose (DDD) per 1000 patient-days., Results: The adSL in patients with dementia was consistently high before and after diagnosis and significantly increased after diagnosis, compared to those of patients without dementia (DID 0.123 unit/day, 95% confidence interval 0.117-0.129). DID of medication use was the highest for antidepressants (64.764 DDD/1000 patient-days) followed by Z-drugs and antipsychotics. Atypical antipsychotic and antidepressant usage steeply increased after dementia diagnosis., Conclusion: Sedative burden in patients with dementia before and after dementia diagnosis was higher than that in patients without dementia, and was further increased after dementia diagnosis., Competing Interests: The authors have declared that no competing interests exist.

Aim: The aim of this study was to develop the Korean Anticholinergic Burden Scale through assessment of previously developed tools, a literature review and a modified Delphi process., Methods: We carried out a systematic review to identify previously published anticholinergic burden tools. A composite medication list was made by extracting medications and their quantitative grading from the existing tools, after excluding the medications not distributed in Korea and topical agents. We also added medications available in Korea that had not been rated. For medications with conflicting anticholinergic scores or no anticholinergic score, we determined the final score from 0 ("no anticholinergic effect") to 3 ("strong anticholinergic effect") with a literature review and expert consensus through a two-round Delphi process., Results: A composite list of 655 medications with anticholinergic scores was extracted from 10 existing tools. A total of 38 medications available in Korea were added to the list. A total of 494 medications were deemed suitable for a Korean-specific scale. We confirmed the anticholinergic scores of 352 medications from existing scales, and 142 underwent the Delphi process. The final scores graded by experts showed high reliability among experts with an intra-class correlation of 0.98 (95% confidence interval 0.97-0.98). Finally, 56 medications were categorized as strong anticholinergics, 23 as moderate, 59 as weak and 356 as having no anticholinergic activity., Conclusions: This newly created consensus-driven anticholinergic burden scale designed specifically for the Korean healthcare system might be a practical tool for assessing anticholinergic burden in older adults with polypharmacy in routine medication reviews and in research. Geriatr Gerontol Int 2019; 19: 628-634., (© 2019 Japan Geriatrics Society.)

Few studies have evaluated the association between anticholinergic burden and treatment modification after starting a cholinesterase inhibitor in clinical practice. We aimed to evaluate the effect of anticholinergic burden on anti-dementia treatment modification, delirium and mortality. We retrospectively analysed older adults (n = 25 825) who started a cholinesterase inhibitor during 2003-2011 from Korean National Health Insurance Service Senior Cohort Database. High anticholinergic burden was defined as an average daily Anticholinergic Cognitive Burden (ACB) score of >3 during the first 3 months. We investigated the impact of high anticholinergic burden on the rate of treatment modification, delirium and mortality in comparison with minimal ACB (ACB score ≤1) in propensity-matched cohorts (N = 7438). Approximately 6.0% of patients with dementia were exposed to a high anticholinergic burden within the first three months of treatment. In high anticholinergic burden cohorts, significantly more patients experienced treatment modification (34.9% vs. 32.1%) or delirium (5.6% vs. 3.6%) and the mortality rate was also higher (16.8% vs. 14.1%) than controls. A multivariate Cox proportional hazard regression analysis showed that an average ACB score >3 within the first three months significantly increased the risk of treatment modification (hazard ratio (HR): 1.12, 95% confidence interval (CI): 1.02-1.24), delirium (HR: 1.52, CI: 1.17-1.96) and mortality (HR: 1.23, CI: 1.06-1.41). This study showed that high anticholinergic burden negatively affected the treatment response to cholinesterase inhibitors and that an average ACB score >3 was an independent prognostic factor for delirium or mortality in dementia patients., (© 2018 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Background: Limited studies have evaluated the medication-taking behavior in very elderly hypertensive patients. The aim of this study was to evaluate the persistence and adherence with antihypertensive agents in treatment-naïve patients, along with other related factors, according to age., Methods: Adult (19-64 years), elderly (65-79 years), and very elderly (≥80 years) uncomplicated hypertensive patients starting antihypertensive monotherapy were identified from the National Health Insurance claims database. The first-year treatment persistence and adherence rates measured using the medication possession ratio were assessed and compared in these three age cohorts., Results: After propensity score matching, three age cohorts with 6689 patients each were assembled from 228,925 uncomplicated hypertensive patients who began antihypertensive monotherapy in 2012. The treatment persistence and adherence rates over the first year were the lowest in the very elderly (59.5% and 62.8%, respectively) and highest in the elderly (65.2% and 67.9%, respectively) patients among the three age cohorts (p < 0.001). The adjusted risk for treatment non-persistence was significantly higher in the very elderly (adjusted hazard ratio, 1.20; 95% confidence interval, 1.13-1.27) compared with the elderly. Having more comorbidities, being a beneficiary of medical aid, and having a diagnosis of dementia were unique positive predictors for treatment persistence in the very elderly, along with common predictors such as female sex, dyslipidemia, and an initially chosen antihypertensive therapeutic class other than beta blockers and thiazide diuretics., Conclusions: Very elderly patients were less likely to continue antihypertensive therapy over the first year compared with their younger counterparts. Our findings suggest that a low comorbidity index and lack of medical aid support negatively affect the treatment persistence in this population.