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.

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 residents in Korean long-term care facilities.

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.

Development and Validation of a Trigger Tool for Identifying Drug-Related Emergency Department Visits.

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.

Comparative associations between anticholinergic burden and emergency department visits for anticholinergic adverse events in older Korean adults: a nested case-control study using national claims data for validation of a novel country-specific scale.

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.

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.

Underutilization of gastrointestinal prophylaxis in high-risk chronic nonsteroidal anti-inflammatory drug users in Korea.

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 H2 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.

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.

Prevalence of anticholinergic burden and risk factors amongst the older population: analysis of insurance claims data of Korean patients.

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.

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.

Impact of anticholinergic burden on emergency department visits among older adults in Korea: A national population cohort study.

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 ±â€¯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.

Change in sedative burden after dementia onset using difference-in-difference estimations.

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.

Development of an Anticholinergic Burden Scale specific for Korean older adults.

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.

Real-world safety evaluation of topical corticosteroid use: A community pharmacy-based, prospective, observational study.

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.

Effect of anticholinergic burden on treatment modification, delirium and mortality in newly diagnosed dementia patients starting a cholinesterase inhibitor: A population-based study.

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.