Impact of narcotics information management system on inappropriate benzodiazepine receptor agonist prescriptions: A quasi-experimental analysis in South Korea.

AIMS: The South Korean government implemented the narcotics information management system (NIMS) on 18 May 2018 to manage benzodiazepine receptor agonists (BzRAs) and narcotics effectively and establish a reporting mechanism for these drugs. This study assessed the effects of NIMS on inappropriate use of BzRAs. METHODS: Using national patient sample data from 2016 to 2020, we analysed adult outpatients who were prescribed oral BzRAs. We conducted a time series and segmented regression analysis using selected indicators to analyse the monthly variations related to the inappropriate use of these medications. RESULTS: The study revealed no significant changes in the indicators of inappropriate BzRA use following the NIMS implementation. Contrary to expectations, there was a significant increase in the proportion of patients exceeding defined daily dose (DDD) and in those receiving concurrent prescriptions of multiple BzRAs, following the implementation of NIMS. The immediate impact of the COVID-19 pandemic was an increase in DDD exceedance; however, overall, this did not significantly affect BzRA use. CONCLUSIONS: The introduction of NIMS did not significantly enhance the management of BzRA misuse. Additional measures, including continuous monitoring, system improvements and comprehensive education for prescribers and patients, are recommended to ensure the appropriate use of psychotropic medications.

Temporal trends in use of antisecretory agents among patients administered clopidogrel-based dual antiplatelet therapy after percutaneous coronary intervention.

BACKGROUND: Antisecretory drugs are commonly prescribed with clopidogrel-based dual antiplatelet therapy (DAPT) to prevent gastrointestinal bleeding in high-risk patients after percutaneous coronary intervention (PCI). However, omeprazole and esomeprazole (inhibiting proton pump inhibitors [PPIs]) may increase cardiovascular event rates on co-administration with clopidogrel. This study aimed to examine trends in the use of antisecretory agents in patients administered clopidogrel-based DAPT and the concomitant use of clopidogrel and inhibiting PPIs. METHODS: We used National Inpatient Sample data compiled by the Health Insurance Review & Assessment Service from 2009 to 2020. Further, we identified patients who were prescribed clopidogrel-based DAPT after PCI and investigated the concomitant use of antisecretory agents with clopidogrel. To verify the annual trend of drug utilization, we used the Cochran-Armitage trend test. RESULTS: From 2009 to 2020, the percentage of H2 receptor antagonist users decreased steadily (from 82.5% in 2009 to 25.3% in 2020); instead, the percentage of PPI users increased (from 23.7% in 2009 to 82.0% in 2020). The use of inhibiting PPI also increased (from 4.2% in 2009 to 30.7% in 2020). Potassium competitive acid blockers (P-CABs) were rarely used before 2019; however, in 2020, it accounted for 7.8% of the antisecretory users. CONCLUSIONS: Our study demonstrates that the use of inhibiting PPIs increased steadily in patients administered clopidogrel-based DAPT therapy. This is a major concern since the concomitant use of inhibiting PPIs with clopidogrel could increase the risk of cardiovascular events.

Adherence to antiemetic guidelines in solid cancer patients receiving highly emetogenic chemotherapy in Korea.

BACKGROUND: Highly emetogenic chemotherapy (HEC) is known to induce nausea and vomiting (CINV) in approximately 90% of cancer patients undergoing this regimen unless proper prophylactic antiemetics are administered. This study aimed to analyze the use of a three-drug prophylactic antiemetic regimen during the first cycle of chemotherapy and assess the compliance rate with the National Comprehensive Cancer Network (NCCN) guidelines. METHODS: This retrospective study utilized data from the National Inpatient Sample database from 2016 to 2020 provided by the Health Insurance Review and Assessment Service. The claims data encompassed 10 to 13% of inpatients admitted at least once each year. Patients with solid cancers treated with two HEC regimens, namely anthracycline + cyclophosphamide (AC) and cisplatin-based regimens, were selected as the study population. We evaluated the use of a three-drug prophylactic antiemetic regimen, including a neurokinin-1 receptor antagonist, a 5-hydroxytryptamine-3 receptor antagonist, and dexamethasone and compliance with the NCCN guidelines. Multiple logistic regression was conducted to estimate the influence of variables on guideline adherence. RESULTS: A total of 3119 patients were included in the analysis. The overall compliance rate with the NCCN guidelines for prophylactic antiemetics was 74.3%, with higher rates observed in the AC group (87.9%) and lower rates in the cisplatin group (60.4%). The AC group had a 6.37 times higher likelihood of receiving guideline-adherent antiemetics than the cisplatin group. Further analysis revealed that, compared to 2016, the probability of complying with the guidelines in 2019 and 2020 was 0.72 times and 0.76 times lower, respectively. CONCLUSION: This study showed that a considerable proportion of HEC-treated patients received guideline-adherent antiemetic therapies. However, given the variations in adherence rates between different chemotherapy regimens (AC vs. cisplatin), efforts to improve adherence and optimize antiemetic treatment remain essential for providing the best possible care for patients experiencing CINV.

Impact of the Narcotics Information Management System on Opioid Use Among Outpatients With Musculoskeletal and Connective Tissue Disorders: Quasi-Experimental Study Using Interrupted Time Series.

BACKGROUND: Opioids have traditionally been used to manage acute or terminal pain. However, their prolonged use has the potential for abuse, misuse, and addiction. South Korea introduced a new health care IT system named the Narcotics Information Management System (NIMS) with the objective of managing all aspects of opioid use, including manufacturing, distribution, sales, disposal, etc. OBJECTIVE: This study aimed to assess the impact of NIMS on opioid use. METHODS: We conducted an analysis using national claims data from 45,582 patients diagnosed with musculoskeletal and connective tissue disorders between 2016 and 2020. Our approach included using an interrupted time-series analysis and constructing segmented regression models. Within these models, we considered the primary intervention to be the implementation of NIMS, while we treated the COVID-19 outbreak as the secondary event. To comprehensively assess inappropriate opioid use, we examined 4 key indicators, as established in previous studies: (1) the proportion of patients on high-dose opioid treatment, (2) the proportion of patients receiving opioid prescriptions from multiple providers, (3) the overlap rate of opioid prescriptions per patient, and (4) the naloxone use rate among opioid users. RESULTS: During the study period, there was a general trend of increasing opioid use. After the implementation of NIMS, significant increases were observed in the trend of the proportion of patients on high-dose opioid treatment (coefficient=0.0271; P=.01) and in the level of the proportion of patients receiving opioid prescriptions from multiple providers (coefficient=0.6252; P=.004). An abrupt decline was seen in the level of the naloxone use rate among opioid users (coefficient=-0.2968; P=.04). While these changes were statistically significant, their clinical significance appears to be minor. No significant changes were observed after both the implementation of NIMS and the COVID-19 outbreak. CONCLUSIONS: This study suggests that, in its current form, the NIMS may not have brought significant improvements to the identified indicators of opioid overuse and misuse. Additionally, the COVID-19 outbreak exhibited no significant influence on opioid use patterns. The absence of real-time monitoring feature within the NIMS could be a key contributing factor. Further exploration and enhancements are needed to maximize the NIMS' impact on curbing inappropriate opioid use.

Exploring the prescribing trends and factors affecting initial anti-parkinsonian drug selection in Korea: A nationwide population-based cohort study.

BACKGROUND: Parkinson's disease (PD) is a common neurodegenerative disorder typically treated with dopamine replacement therapy and dopamine agonists (DAs) to alleviate symptoms and minimize dyskinesia. Optimal treatment strategies for patients newly diagnosed with PD have been a topic of debate for many years. METHODS: We conducted a 10-year descriptive study of drug prescription trends and factors affecting prescription choices for newly diagnosed drug-naïve PD patients using data from the National Health Insurance program in Korea. To identify statistically significant differences in yearly trends, we employed the Cochran-Armitage trend test. Additionally, we utilized multiple logistic regression analysis to investigate the factors associated with the selection of levodopa and DAs as initial anti-parkinsonian drugs. RESULTS: A total of 99,118 patients with PD who were prescribed levodopa or DAs alone as initial anti-parkinsonian drugs between 2011 and 2020 were eligible for inclusion in the analysis. The prescription rate of DAs increased until 2012, and then steadily decreased annually. The likelihood of levodopa prescription increased with age and at higher-level hospitals. In terms of comorbidities, patients with Alzheimer's disease and cerebrovascular diseases were more likely to be prescribed levodopa than those with peptic ulcer disease and dyslipidemia. CONCLUSION: The decline in levodopa prescriptions was reversed in 2012, and the prescription rate has continued to increase until recently. The odds ratio of levodopa prescription increased in elderly patients with Alzheimer's disease and decreased in patients with Medical aid insurance and peptic ulcer disease.

Long-term effectiveness and safety of cilostazol versus clopidogrel in secondary prevention of noncardioembolic ischemic stroke.

PURPOSE: Cilostazol is a widely used antiplatelet drug for secondary stroke prevention in Asia, but its comparison with clopidogrel is not well understood. This study aims to investigate the effectiveness and safety of cilostazol compared to clopidogrel for the secondary prevention of noncardioembolic ischemic stroke. METHODS: This retrospective comparative effectiveness research analyzed 1:1 propensity scorematched data from insured individuals between 2012 and 2019, using administrative claims data in Health Insurance Review and Assessment in Korea. Patients with diagnosis codes for ischemic stroke without cardiac disease were included and divided into two groups, those receiving cilostazol and those receiving clopidogrel. The primary outcome was a recurrent ischemic stroke. Secondary outcomes included all-cause death, myocardial infarction, hemorrhagic stroke, and a composite of these outcomes. The safety outcome was major gastrointestinal bleeding. RESULTS: The study analyzed 4,754 patients in the propensity scorematched population and found no statistically significant difference in recurrent ischemic stroke (cilostazol group vs clopidogrel group, 2.7% vs 3.2%; 95% CI, 0.62-1.21), the composite outcome of recurrent ischemic stroke, all-cause death, myocardial infarction, and hemorrhagic stroke (5.1% vs 5.5%; 0.75-1.22), and major gastrointestinal bleeding (1.3% vs 1.5%; 0.57-1.47) between patients receiving cilostazol and those receiving clopidogrel. In subgroup analysis, cilostazol was associated with a lower incidence of recurrent ischemic stroke compared to clopidogrel in hypertensive patients (2.5% vs 3.9%; interaction P = 0.041). CONCLUSIONS: This real-world study suggests that cilostazol is effective and safe for noncardioembolic ischemic stroke and may be associated with better effectiveness in hypertensive patients compared to clopidogrel.

Real world co-prescribing contraindicated drugs with fluconazole and itraconazole.

PURPOSE: This study aimed to investigate co-prescribing of contraindicated drugs with fluconazole and itraconazole using real-world nationwide data. METHODS: This retrospective cross-sectional study was performed using claims data collected by the Health Insurance Review and Assessment Service (HIRA) of Korea during 2019-2020. To determine the drugs that should be avoided in patients taking fluconazole or itraconazole, Lexicomp® and Micromedex® were used. The co-prescribed medications, co-prescription rates, and potential clinical consequences of the contraindicated drug-drug interactions (DDIs) were investigated. RESULTS: Of the 197 118 prescriptions of fluconazole, 2847 co-prescriptions with drugs classified as contraindicated DDI by either Micromedex® or Lexicomp® were identified. Further, of the 74 618 prescriptions of itraconazole, 984 co-prescriptions with contraindicated DDI were identified. Solifenacin (34.9%), clarithromycin (18.1%), alfuzosin (15.1%), and donepezil (10.4%) were frequently found in the co-prescriptions of fluconazole, whereas tamsulosin (40.4%), solifenacin (21.3%), rupatadine (17.8%), and fluconazole (8.8%) were frequently found in the co-prescriptions of itraconazole. In 1105 and 95 co-prescriptions of fluconazole and itraconazole, accounting for 31.3% of all co-prescriptions, potential DDIs were associated with a risk of corrected QT interval (QTc) prolongation. Of the total 3831 co-prescriptions, 2959 (77.2%) and 785 (20.5%) were classified as contraindicated DDI by Micromedex® alone and by Lexicomp® alone, respectively, whereas 87 (2.3%) were classified as contraindicated DDI by both Micromedex® and Lexicomp®. CONCLUSIONS: Many co-prescriptions were associated with the risk of DDI-related QTc prolongation, warranting the attention of healthcare providers. Narrowing the discrepancy between databases that provide information on DDIs is required for optimized medicine usage and patient safety.

Utilization of triple antithrombotic therapy in patients with atrial fibrillation undergoing percutaneous coronary intervention.

BACKGROUND: Triple antithrombotic therapy (TAT), a combination of an oral anticoagulant and dual antiplatelet therapy (DAPT), is a key treatment for prevention of ischemic events in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI). However, TAT is not extensively used because of the risk of bleeding. This study aimed to determine the utilization and influencing factors of TAT using real-world data in the non-vitamin K antagonist oral anticoagulants (NOACs) era. METHODS: We analyzed National Inpatient Sample data compiled by the Health Insurance Review & Assessment Service (HIRA-NIS) from 2011 to 2020. Patients with AF who underwent PCI with stent implantation and with an increased stroke risk were selected as candidates for TAT therapy. Demographic and clinical factors associated with TAT use were investigated using the chi-squared test and the Student t-test, and influencing factors were identified using multiple logistic regression. RESULTS: The TAT utilization rate steadily increased from 30.3% in 2011 to 65.4% in 2020 (Cochran-Armitage trend test: p < 0.001) with an average of 45.9%. Positive influencing factors for TAT use were identified as congestive heart failure, history of previous stroke/transient ischemic attack/thromboembolism, valvular heart disease, and year. Negative influencing factors included insurance type (medical aid or Patriots & Veterans Insurance), type of medical institution (general hospitals or primary medical institutions), and comorbidities such as renal disease, liver disease, and history of the previous hemorrhage. CONCLUSIONS: The utilization of TAT following PCI among high-stroke risk AF patients steadily increased from 2011 to 2020, reaching 65.4% by the end of the study period. However, in 2020, a significant proportion of 29.4% of patients still received DAPT, indicating that many AF patients undergoing PCI did not receive adequate antithrombotic therapy.

Prescription changes in patients with gastrointestinal disorders after withdrawal of ranitidine: a nationwide population-based cohort study.

OBJECTIVE: Ranitidine products contain unacceptable levels of N-nitrosodimethylamine. This study aimed to investigate changes in the treatment regimen and their influencing factors after the ranitidine recall. METHODS: This retrospective study used data from nationwide Korean claims from 2019. Patients with gastrointestinal disorders treated with ranitidine for at least a month on 25 September 2019, were selected for this study. Other histamine-2 receptor antagonists (H2RAs), proton pump inhibitors (PPIs), potassium-competitive acid blockers (PCABs), and prostaglandin E1 analogs were administered as alternatives to ranitidine. Kaplan-Meier survival and Cox proportional hazards regression analyses were performed to gauge the time until switching to alternative drugs and assess the influencing factors. RESULTS: In total, 7502 patients were included in this study, among which 5164 (68.8%) switched from ranitidine to an alternative drug. The most prescribed alternative drugs were H2RAs, followed by PPIs, PCABs, and prostaglandin E1 analogs. Increasing age; Medical Aid insurance (MedAid); and a history of hypertension, diabetes mellitus, asthma, and osteoarthritis were associated with a higher probability of switching treatments. Patients with concomitant gastroesophageal reflux disease and peptic ulcers were more likely to switch to alternative drugs than patients with gastritis. CONCLUSIONS: Approximately two-thirds of patients with gastrointestinal disorders switched from ranitidine to alternative drugs within 3 months after ranitidine withdrawal. The Cox regression analysis showed that age (>55 years); insurance type (MedAid); comorbidities, such as hypertension, diabetes mellitus, asthma, and osteoarthritis, and gastrointestinal disorder severity influenced the switch from ranitidine to alternative drugs.

Efficacy of melatonin for chronic insomnia: Systematic reviews and meta-analyses.

We conducted systematic reviews and meta-analyses to evaluate the efficacy of melatonin versus placebo or other hypnotic agents in improving sleep quality and quantity in patients with chronic insomnia. A literature search on Ovid-MEDLINE, EMBASE, and the Cochrane Library was performed up to November 2020. Sleep onset latency, total sleep time, sleep efficiency, sleep quality and quality of life were examined as outcomes. We identified 24 randomized controlled trials of chronic insomnia including four studies of patients with comorbid insomnia. All studies were compared with placebo. Due to heterogeneity, we conducted subgroup analyses by age group. In non-comorbid insomnia, melatonin was only significantly effective in sleep onset latency and total sleep time in children and adolescents. In adults group, melatonin was not significantly effective in improving sleep onset latency, total sleep time, and sleep efficiency. In comorbid insomnia, melatonin significantly improved sleep onset latency in all age groups, but there was only one study in adults group. In conclusion, melatonin did not appear to be effective in adults but might be effective in children and adolescents with chronic insomnia for both comorbid insomnia and non-comorbid insomnia. Further studies are needed to establish the efficacy and safety of melatonin by age groups.

Association between cost-sharing and drug prescribing in Korean elderly veterans with chronic diseases: A real-world claims data study.

This study aimed to investigate the relationship between cost-sharing and drug prescribing and its appropriateness in Korean elderly veterans with chronic conditions. This is a cross-sectional study using real-world claims data. Veterans with primary hypertension or dyslipidemia were compared with two controls with higher levels of cost-sharing. Study subjects (age ≥65 years) were selected through stratified random sampling and matching the individual attributes. The primary outcome was the annual amount of drugs prescribed per patient, and the secondary outcomes included several other measures investigating multifaceted aspects of drug prescribing, medical institution utilization behavior, and prescribing appropriateness. Gamma regression models or logistic regression models were employed. Veterans were prescribed 59%~74% more drugs (exp (ß) = 1.59 [95% confidence interval [CI] = 1.55-1.64] ~ 1.74 [1.70-1.79]) compared to the National Health Insurance (NHI) patients. This was attributed mainly to longer prescribing days (44%) and slightly more prescriptions (6%~7%) than NHI patients. Veterans spent 14%~15% higher medication costs. Veterans were less likely to visit multiple medical institutions by estimates of 0.77 (0.76-0.79) ~ 0.80 (0.79-0.82). Similar but smaller differences were observed between veterans and medical aid (MedAid) patients. The veteran patients showed a more than 50% increased risk of therapeutic duplication than the other two controls (adjusted odds ratio [ORs] = 1.47 [1.37-1.57] ~ 1.61 [1.50-1.72]). Inappropriate drug prescribing was also more common in veterans than the two controls (adjusted ORs = 1.20 [1.11-1.31] ~ 1.32 [1.22-1.43]). In Korean elderly veterans with chronic illnesses, a level of cost-sharing was associated with having more prescribed medicines, and increased inappropriate prescribing.

Effectiveness and Safety of Regdanvimab in Patients With Mild-To-Moderate COVID-19: A Retrospective Cohort Study.

BACKGROUND: Regdanvimab has decreased the time to clinical recovery from coronavirus disease 2019 (COVID-19) and lowered the rate of oxygen therapy according to the results from phase 2/3 randomized controlled trial. More information is needed about the effects and safety of regdanvimab. METHODS: We analyzed data for patients with high-risk mild or moderate COVID-19 being admitted to Busan Medical Center between December 1, 2020 and April 16, 2021. A propensity score (PS) matched analysis was conducted to compare patients treated with and without regdanvimab. The primary outcome was in-hospital death or disease aggravation which means the need for oxygen therapy (low- or high-flow oxygen therapy and mechanical ventilation) and secondary outcomes comprised the length of hospital stay and adverse reactions. RESULTS: Among 1,617 selected patients, 970 (60.0%) were indicated for regdanvimab. Of these, 377 (38.9%) were administered with regdanvimab. Among a 1:1 PS-matched cohort of 377 patients each treated with and without regdanvimab, 19 (5%) and 81 (21.5%) reached the composite outcome of death, or disease aggravation, respectively (absolute risk difference, -16.4%; 95% confidence interval [CI], -21.1, -11.7; relative risk difference, 76.5%; P < 0.001). Regdanvimab significantly reduced the composite outcome of death, or disease aggravation in univariate (odds ratio [OR], 0.194; 95% CI, 0.112-0.320; P < 0.001) and multivariable-adjusted analyses (OR, 0.169; 95% CI, 0.095-0.289; P < 0.001). The hospital stay was shorter for the group with than without regdanvimab. Some hematological adverse reactions were more frequent in the group without regdanvimab, but other adverse reactions did not significantly differ between the groups. CONCLUSION: Regdanvimab was associated with a significantly lower risk of disease aggravation without increasing adverse reactions.

Underutilisation of prophylactic G-CSF in breast cancer patients receiving adjuvant docetaxel/cyclophosphamide chemotherapy.

Docetaxel/cyclophosphamide (TC) is a widely used adjuvant chemotherapy regimen, especially in patients with node-negative or low-risk node-positive breast cancer. Guidelines recommend the use of prophylactic granulocyte colony-stimulating factor (G-CSF) to prevent febrile neutropenia. In this study, we aimed to explore the use of G-CSF as a primary prophylactic and determine the factors influencing its use. This retrospective study used nationwide claims data from the National Inpatient Sample compiled by the Health Insurance Review and Assessment Service in South Korea from 2018. The claims data included 10% of inpatients admitted at least once in 2018 and 1% of outpatients who were not admitted. Female patients with breast cancer who received an adjuvant TC regimen after surgery were selected. Primary prophylactic G-CSF was defined as G-CSF prescribed within two days of the first cycle of TC. The factors influencing its utilisation were investigated using the chi-square test and a multiple logistic regression model. A total of 229 patients were included in the analysis. The proportion of patients who received primary prophylactic G-CSF treatment after the first cycle of TC was 55.5%. The factors positively influencing G-CSF utilization were patients' age ≥65 years, location (i.e. metropolitan areas), and the type of healthcare facility (i.e. non-tertiary hospitals). The use of prophylactic G-CSF in patients with breast cancer who received the adjuvant TC regimen was insufficient. The use of primary G-CSF prophylaxis should be emphasised to reduce the risk of febrile neutropenia among patients receiving a myelosuppressive TC regimen.

Factors Influencing the Selection of Non-Vitamin K Antagonist Oral Anticoagulants for Stroke Prevention in Patients With Non-Valvular Atrial Fibrillation.

BACKGROUND: Major atrial fibrillation (AF) guidelines recommend non-vitamin K antagonist oral anticoagulants (NOACs) over warfarin, except in rare clinical circumstances based on 4 randomized controlled trials comparing each NOAC with warfarin. We aimed to investigate the current NOAC prescription behaviors in alignment with the recent clinical evidence available. METHOD: We conducted a cross-sectional analysis of NOAC-using patients with non-valvular atrial fibrillation (NVAF) who were aged ≥65 years on the index date (July 1, 2018) based on nationwide claims data. The types of NOACs being taken were analyzed using chi-squared tests, and factors influencing NOAC selection were identified using multinomial logistic regression analysis. RESULTS: A total of 6,061 patients were included. Among the 4 NOACs, rivaroxaban was the most used NOAC. Patients aged ≥75 years (odds ratio [OR] = 1.270, confidence interval [CI] = 1.089-1.450) and women (OR = 1.148, CI = 1.011-1.284) were more likely to use apixaban relative to rivaroxaban. Patients with prior stroke/transient ischemic attack/thromboembolism had higher odds of using dabigatran (OR = 1.508, CI = 1.312-1.704) and apixaban (OR = 1.186, CI = 1.026-1.346). Patients with renal disease had higher odds of using apixaban (OR = 1.466, 95% CI = 1.238-1.693). These findings are consistent with the efficacy and safety profiles reported in pivotal trials and observational studies comparing individual NOACs. CONCLUSION: Among the 4 NOACs, rivaroxaban was the most commonly used NOAC. Apixaban was preferred for patients aged ≥75 years, females, and patients with renal disease.

Effect of nationwide concurrent drug utilization review program on drug-drug interactions and related health outcome.

BACKGROUND: A computerized drug utilization review (DUR) program has provided physicians and pharmacists with alerts on drug-drug interactions (DDIs), drug-age precautions and therapeutic duplication in Korea since 2010. OBJECTIVE: The purpose of this study was to evaluate the impact of the DUR program on health outcomes associated with DDIs. METHODS: An uncontrolled before-after study was performed to investigate the impact of the nationwide DUR program on DDIs and related health outcomes. The study population consisted of people who used two types of DDI pairs before DUR implementation (from January 2009 to December 2010) and post-DUR implementation (from January 2012 to December 2013); (i) benzodiazepines with concurrent use of metabolic enzyme inhibitors and (ii) QTc (heart-rate corrected QT interval) prolongation agents. The main outcome measures were all-cause and cause-specific hospitalization admissions or emergency department (ED) visits. RESULTS: This study included 107 874 people who used benzodiazepines with enzyme inhibitors and 8489 who received co-medication of QTc prolongation agents. For patients receiving a combination of benzodiazepines and enzyme inhibitors, both all-cause hospitalization and cause-specific hospitalization decreased after DUR implementation, from 43.2% to 41.7% and from 4.6% to 4.5% (adjusted odds ratio [OR] = 0.96; 95% confidence interval (CI), 0.93-0.98; OR = 0.89, 95% CI = 0.84-0.99, respectively). For patients receiving co-medication of QTc prolongation agents, all-cause hospitalization (54.2%) was lower than before (54.9%) (OR = 0.87, 95% CI = 0.79-0.96), but no significant change was found for cause-specific hospitalization and ED visits. CONCLUSION: Implementation of a DUR program may reduce the adverse health outcomes posed by DDIs in patients on combination of benzodiazepines and enzyme inhibitors potentially QTc-prolongation agents.

Medication utilization among adult patients with attention-deficit/hyperactivity disorder after reimbursement criteria change.

This study analyzed the pattern of attention-deficit/hyperactivity disorder (ADHD) medication initiation in adult patients with ADHD after the reimbursement criteria change and identified the influencing factors associated with it using the claim data. We identified 243 adult patients with ADHD who had not been prescribed ADHD drugs before 1 September 2016. We conducted Kaplan-Meier survival analysis to calculate the time to initial prescription of ADHD medications, and Cox proportional hazard regression analysis to estimate the influencing factors. Approximately one-third of the patients (n = 76, 31.3%) were first prescribed ADHD medications after reimbursement approval, and 40 of them (16.5%) started treatment with osmotic release oral system methylphenidate. The patient's age group (30-39 years) and the status of diagnosis before the index date were associated with early initiation of pharmacotherapy. The odds of starting ADHD medications increased approximately 2.7-fold in the 30-39 age group and 0.2-fold in the case of patients who were diagnosed before the approval. Our findings show that both diagnosis and treatment of adult ADHD remains inadequate despite the change in reimbursement criteria. Improving awareness of adult ADHD among both the public and the professionals is essential to increase its chances of diagnosis and treatment.

Zolpidem overutilisation among Korean patients with insomnia.

This study aimed to investigate zolpidem overutilisation among Korean patients with insomnia. We analysed the National Patient Sample (NPS) data compiled by the Health Insurance Review & Assessment Service (HIRA-NPS) in 2016. Zolpidem overutilisation was defined as when a patient used zolpidem for longer than 30 consecutive days and prescriptions overlapped with more than 10% of total prescription periods. Demographic and clinical factors associated with the overutilisation of zolpidem were investigated using a logistic regression model. The proportion of zolpidem overutilisers was estimated at 5.0%. Factors such as age (0-39 years), consuming controlled-release dosage formulations of zolpidem, presence of psychiatric disorders (depression, bipolar disorder, schizophrenia and anxiety disorder) and other medical conditions (hypertension, diabetes mellitus and arthritis) were observed to be risk predictors for zolpidem overutilisation. The formulation was selected owing to the absence of a quantity restriction for zolpidem CR in Korea during the study period. Possible approaches to prevention and control of zolpidem overutilisation include regulatory or legal provisions promoting rational drug use, management of psychiatric and medical co-morbid disorders, and widespread implementation of cognitive behavioural therapy for insomnia as a first-line treatment option.

Factors That Affect Time to Switch From Warfarin to a Direct Oral Anticoagulant After Change in the Reimbursement Criteria in Patients With Atrial Fibrillation.

BACKGROUND: Anticoagulation therapy is recommended for stroke prevention in high-risk patients with atrial fibrillation (AF). This study aimed to estimate the time to switch from warfarin to a direct oral anticoagulant (DOAC) and identify the factors associated with it. METHODS: By using claims data, we studied 7111 warfarin-using patients with nonvalvular AF who were aged ≥65 years. The Kaplan-Meier analysis was performed to estimate the time to switch from warfarin to a DOAC, and Cox proportional hazard regression analysis was used to estimate the influencing factors. RESULTS: Approximately one-third of the patients (2403, 33.8%) switched from warfarin to a DOAC during the study period. Female sex, aged between 75 and 79 years, having a Medical Aid or Patriots and Veterans Insurance, hypertension, and history of prior stroke, and transient ischemic attack or thromboembolism (prior stroke/TIA/TE) were associated with a significantly shorter time to switch. The odds of switching to a DOAC were increased by approximately 1.2-fold in the women and 1.4-fold in the patients with prior stroke/TIA/TE. CONCLUSIONS: Approximately one-third of the warfarin-using patients switched from warfarin to a DOAC within 6 months after the change in the DOAC reimbursement criteria. In the Cox proportional hazard regression analysis, the factors that affected anticoagulant switching from warfarin to a DOAC were female sex and history of prior stroke/TIA/TE.

National trends in metformin-based combination therapy of oral hypoglycaemic agents for type 2 diabetes mellitus.

BACKGROUND: The American Diabetes Association guidelines recommend metformin monotherapy for type 2 diabetes mellitus as an initial agent due to its effectiveness and safety. If the target glycosylated haemoglobin level is not attained within 3 months, add-on therapy is recommended. This study aimed to investigate the prescribing trends of add-on therapy to metformin focusing on factors affecting the selection of second agents using real-world data. METHODS: Patients who were undergoing metformin monotherapy for at least 3 months and switched to metformin-based combination therapy were selected. The oral antidiabetic drugs used as add-on therapy were classified into 4 classes: dipeptidyl peptidase-4 inhibitors (DPP4I), sodium glucose cotransporter-2 inhibitors (SGLT2I), sulphonylureas (SU), and thiazolidinediones (TZD). The drug regimen was also classified as older and newer agents. Chi-square test and logistic regression analysis were performed to estimate the influencing factors. RESULTS: In 2014-2016, the use of DPP4I and SGLT2I increased, whereas the use of SU and TZD decreased. Our results show that the prescription pattern was influenced by the type and location of the institution, specialty of physicians, some comorbidities, and patient characteristics such as age and sex. Newer agents were more commonly used in younger patients. SGLT2I were more preferred in women than in men. Patients with dyslipidaemia showed increased odds of utilising newer agents. CONCLUSION: DPP4I were the most commonly utilised agents in metformin-based combination therapy and SGLT2I use is expected to increase more due to their cardioprotective effects. Proper selection of add-on therapy, based on drug-specific effects and patient factors, is necessary.

Service design oriented multidisciplinary collaborative team care service model development for resolving drug related problems.

Our goal was to help prevent drug-related morbidity and mortality by developing a collaborative multidisciplinary team care (MTC) service model using a service design framework that addressed the unmet needs and perspectives of diverse stakeholders. Our service model was based on a "4D" framework that included Discover, Define, Design, and Develop phases. In the "discover" phase, we conducted desk research and field research of stakeholders to identify the unmet needs in existing patient care services. We used service design tools, including service safaris, user shadowing, and customer journey maps to identify pain and opportunity points in the current services. We also performed focus group discussions and in-depth interviews with stakeholders to explore the needs for improved services. In the "define" phase, we generated the service concept by mind mapping and brainstorming about the needs of stakeholders. The service concept was defined to be a Patient-oriented, Collaborative, Advanced, Renovated, and Excellent (P-CARE) service. We named the service "DrugTEAM" (Drug Therapy Evaluation And Management). In the "design" phase, we designed and refined four prototypes based on results from validation tests for their application towards following services: 1) medication reconciliation, 2) medication evaluation and management, 3) evidence-based drug information, and 4) pharmaceutical care transition services. During the "develop" phase, we implemented four services in a longitudinal chronic care model, considering the time spent by patients for each inpatient and outpatient setting. In conclusion, this is a study to develop a collaborative MTC service model using service design framework, focused on managing the unmet needs of patients and healthcare providers. As a result of implementing this service model, we expect to strengthen the professional relationship between pharmacists and stakeholders to ultimately create better patient outcomes.