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.

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.

Development and validation of a medication-based risk prediction model for acute kidney injury in older outpatients.

BACKGROUND: Older adults are at an increased risk of acute kidney injury (AKI), particularly in community settings, often due to medications. Effective prevention hinges on identifying high-risk patients, yet existing models for predicting AKI risk in older outpatients are scarce, particularly those incorporating medication variables. We aimed to develop an AKI risk prediction model that included medication-related variables for older outpatients. METHODS: We constructed a cohort of 2,272,257 outpatients aged ≥65 years using a national claims database. This cohort was split into a development (70%) and validation (30%) groups. Our primary goal was to identify newly diagnosed AKI within one month of cohort entry in an outpatient context. We screened 170 variables and developed a risk prediction model using logistic regression. RESULTS: The final model integrated 12 variables: 2 demographic, 4 comorbid, and 6 medication-related. It showed good performance with acceptable calibration. In the validation cohort, the area under the receiver operating characteristic curve value was 0.720 (95% confidence interval, 0.692-0.748). Sensitivity and specificity were 69.9% and 61.9%, respectively. Notably, the model identified high-risk patients as having a 27-fold increased AKI risk compared with low-risk individuals. CONCLUSION: We have developed a new AKI risk prediction model for older outpatients, incorporating critical medication-related variables with good discrimination. This tool may be useful in identifying and targeting patients who may require interventions to prevent AKI in an outpatient setting.

Development of a claims-based risk-scoring model to predict emergency department visits in older patients receiving anti-neoplastic therapy.

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

Intracoronary antithrombotic therapy during primary percutaneous coronary intervention in patients with STEMI: A systematic review and network meta-analysis.

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

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.

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.

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.

Vitamin D supplementation for depression in older adults: a meta-analysis of randomized controlled trials.

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

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.

Drug-Drug interactions of docetaxel in patients with breast cancer based on insurance claims data.

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

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.

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.

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.

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.

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.

Medication-Related Acute Care Admission and Inappropriate Polypharmacy of Nursing Home Residents.

OBJECTIVES: To evaluate the prevalence of medication-related admissions (MRAs) and their association with potentially inappropriate medications (PIMs) used by nursing home residents admitted to the geriatric center of a tertiary hospital. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: Older patients admitted from nursing homes to the geriatric center of the Seoul National University Bundang Hospital who had undergone comprehensive geriatric assessment from January 1, 2016, to December 31, 2020. METHODS: MRAs were determined and verified using a previously described MRA adjudication guide. The PIMs in the preadmission medication lists were identified according to each of the following criteria (as well as the combined criteria), the Beers, NORGEP-NH, STOPP/START-NH, and STOPPFrail criteria. Medication use factors associated with MRAs were analyzed using multivariate logistic regression. RESULTS: Among the 304 acute care admissions, 32.2% were MRAs. The main cause of MRAs was acute kidney injury related with use of renin-angiotensin system inhibitors. Approximately 81% of the patients used at least 1 PIM according to the combined criteria. The use of 1 or more PIMs, renin-angiotensin system inhibitors, diuretics, nonsteroidal anti-inflammatory drugs, and benzodiazepines was significantly associated with MRAs. The combined criteria were able to predict MRAs better than the individual criteria. CONCLUSIONS AND IMPLICATIONS: Approximately one-third of acute admissions of nursing home residents may be MRAs. Interventions for the optimal use of medication among nursing home residents are needed.

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.

Risk of major adverse events associated with gabapentinoid and opioid combination therapy: A systematic review and meta-analysis.

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

Prevalence and predictors of medication-related emergency department visit in older adults: A multicenter study linking national claim database and hospital medical records.

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