Sodium-glucose cotransporter-2 inhibitors and their potential role in dementia onset and cognitive function in patients with diabetes mellitus: a systematic review and meta-analysis.

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.

Medication-related incidents in acute care hospitals among different age groups: An analysis of national patient safety report data.

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.

Development of a multidisciplinary medication management program in nursing homes: protocol for a randomized controlled trial : Multidisciplinary medication management in nursing homes.

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.

Development and validation of a predictive model for persistent opioid use in new opioid analgesic users via a nationwide claims database.

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 ß 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.

Derivation and validation of a risk prediction score for nonsteroidal anti-inflammatory drug-related serious gastrointestinal complications in the elderly.

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.

Intracoronary versus intravenous glycoprotein IIb/IIIa inhibitors during primary percutaneous coronary intervention in patients with STEMI: a systematic review and meta-analysis.

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.

The differential risk of severe hyponatraemia based on the use patterns of hyponatraemia-inducing medications in older adults.

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.

Development of a medication review tool for community-dwelling older adults in Korea.

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.

Potentially inappropriate medication use as predictors of hospitalization for residents in nursing home.

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.

Development and validation of a machine learning-based fall-related injury risk prediction model using nationwide claims database in Korean community-dwelling older population.

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.

Risk Factors for Emergency Department Presentations after the Initiation of Opioid Analgesics in Non-Cancer Patients in Korea: A Nationwide Study.

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.

Analysis of Medication Errors Reported by Community Pharmacists in the Republic of Korea: A Cross-Sectional Study.

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.

Efficacy and Safety of Clinically Driven Low-Dose Treatment with Direct Oral Anticoagulants in Asians with Atrial Fibrillation: a Systematic Review and Meta-analysis.

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.

Risk factors of chronic opioid use after surgical procedures in noncancer patients: A nationwide case-control study.

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.

Association of inappropriate polypharmacy with emergency department visits in older patients receiving anti-neoplastic therapy: a population-based study.

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 OnlineTM 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.

Awareness of the use of hyponatraemia-inducing medications in older adults with hyponatraemia: a study of their prevalent use and association with recurrent symptomatic or severe hyponatraemia.

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.

Real-world prevalence of potential drug-drug interactions involving oral antineoplastic agents: a population-based study.

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: LexicompTM 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.

Dose response relationship of cumulative anticholinergic exposure with incident dementia: validation study of Korean anticholinergic burden scale.

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.

Persistence with antihypertensives in uncomplicated treatment-naïve very elderly patients: a nationwide population-based study.

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.

Clinical and economic evaluation of pharmacists' contribution to patient care on a multi-disciplinary liver transplant team.

OBJECTIVES: We aimed to describe and to evaluate the clinical and economic implications of pharmacists' interventions as members of the liver transplant team for hospitalized liver recipients. METHODS: Retrospective descriptive and cost-benefit analysis of documented pharmacist interventions for hospitalized patients from January 2010 to June 2012 was conducted. The type of drug-related problems (DRPs) was categorized. The clinical significance of pharmacist interventions was rated using five scales by two professionals. The cost avoidance was estimated based on the probability that an adverse drug event (ADE) would have occurred without intervention using previously reported additional costs for ADE treatment. RESULTS: A total of 1,880 interventions were documented for 420 liver transplant recipients. The most common DRP was "need additional drug therapy" (42.6%), followed by "dosage problems" (23.5%). The most common drug class addressed by intervention was antimicrobials (51.4%). Most interventions were rated as more than clinically "significant". Analysis showed that pharmacist activities related to potential ADE prevention had a clear cost-benefit with a net cost-benefit € 94,009 and a cost-benefit ratio of 3.8. CONCLUSION: This study demonstrated the positive impact of clinical pharmacists on the care of hospitalized liver transplant patients in terms of both clinical and economic outcomes.