Risk of non-thyroidal autoimmune diseases in patients with Graves' disease: a nationwide retrospective cohort study.

OBJECTIVE: Graves' disease (GD) is a major autoimmune thyroid disorder and associated with non-thyroidal autoimmune disease (NTAD). We aimed to investigate the risk of NTAD in patients with GD compared with age- and sex-matched controls and to evaluate whether the risk differs between individuals with or without Graves' ophthalmopathy (GO). METHODS: This was a retrospective cohort study using data from the Korean National Health Claims database. We included 77 401 patients with GD (2,310 with GO) and 77 401 age- and sex-matched controls. Risk of NTAD were compared between the entire cohort and within the GD cohort. RESULTS: During a mean follow-up period of 9 years, NTAD developed in 12 341 (16.1%) patients in the GD cohort. Risk for systemic lupus erythematosus (SLE) [adjusted hazard ratio (aHR):1.15, 95% confidence interval (CI): 1.02-1.29], vitiligo (aHR: 1.24, 95% CI: 1.10-1.40), and alopecia areata (aHR: 1.11, 95% CI: 1.10-1.40) were higher in the GD cohort than in the control cohort. In the GD cohort, risk for SLE (aHR: 1.60, 95% CI: 1.11-2.33), Sjogren's syndrome (aHR: 1.89, 95% CI: 1.30-2.74), and ankylosing spondylitis (aHR: 1.53, 95% CI: 1.08-2.17) were higher in the GO group than in the non-GO group. CONCLUSION: This study demonstrated an increased risk of SLE, vitiligo and alopecia areata in patient with GD. In the GD cohort, patients with GO had an increased risk of SLE, Sjogren's syndrome and ankylosing spondylitis. These findings suggest that importance of implementing a strategy for early detection of NTAD based on the presence of GO.

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.

Inconsistency in steroid use as antiemetics in clinical trial protocols involving immune checkpoint inhibitors combined with chemotherapy.

OBJECTIVES: This study aims to investigate the use of steroids as antiemetics in clinical trials involving immune checkpoint inhibitors with chemotherapy. METHODS: Focusing on phase III trials registered before August 2023, it evaluated the consistency of steroid use guidelines. RESULTS: Out of 3452 trials screened, 44 were selected for in-depth review. The findings indicate a considerable variation: 13 trials did not specify the use of antiemetics, while 31 provided criteria for antiemetics, with 13 conforming to local standards, six to international guidelines, and five allowing either. Seven trials recommended effective antiemetics without detailed criteria. This inconsistency led to a range of steroid dosages, with only 11 trials advocating for minimizing or avoiding steroids for antiemetic purposes. CONCLUSION: The research highlights the lack of uniformity in antiemetic steroid use in trials, reflecting diverse clinical practices and underscoring the need for further research to understand the implications on treatment outcomes.

Increased Risk of Optic Neuritis in Patients With Fibromyalgia: Nationwide Population-Based Cohort Study in South Korea.

PURPOSE: To estimate the risk of incidence of optic neuritis and identify the high-risk group among patients with fibromyalgia (FM). DESIGN: Population-based cohort study. METHODS: A nationwide, population-based study was conducted using data from the Korean National Health Claims database from 2012 to 2021. This study included all the patients with FM from the entire South Korean population aged 20-79 years (FM group). Moreover, those with pain but not diagnosed with FM were considered as the non-FM group. A cohort was established by classifying it into the FM and non-FM groups during the recruitment period. A log-rank analysis was used to compare the risk of optic neuritis incidence between the FM group and non-FM group. Cox proportional hazards regression analysis was performed to calculate the adjusted hazard ratio (HR). The cohort was analyzed by stratifying according to age and sex. RESULTS: The FM and non-FM groups included 479,892 and 479,892 participants, respectively. The incidence rate of optic neuritis was 35.65/100,000 person-years in the FM group; the HR was significantly higher in the FM group than in the non-FM group (HR 2.11, 95% CI 1.84-2.41; P < .001). The mean interval between the onset of FM and incident optic neuritis was 2.4 ± 1.8 years. The risk increased significantly in men aged 60-79 years (HR 3.37, 95% CI 2.54-4.48) and in women aged 20-39 years (HR 2.07, 95% CI 1.38-3.22). CONCLUSION: We quantified the risk of optic neuritis through a long-term follow-up, which could contribute to understanding the pathophysiology and estimating the general health care burden associated with FM in a practical setting. Great attention should be paid to its risk in older men and younger women.

Contemporary Patterns and Underlying Causes of Vitrectomy in Pediatric and Adolescent Patients: A Nationwide, Population-Based Analysis.

PURPOSE: We determined the incidence, etiology, and longitudinal trends of vitreoretinal diseases necessitating pars plana vitrectomy (PPV) in the pediatric and adolescent population. DESIGN: Nationwide, population-based cohort study. METHODS: This study utilized data extracted from the Korean National Health Claims database spanning from 2009 to 2020. All pediatric and adolescent patients (under 20 years of age) who underwent PPV across the Korean population were included. The cumulative incidence of PPV was estimated from 2009 to 2020, with 2009 to 2011 as the washout period. The annual trends of PPV incidence, the proportion of each etiology, and comorbidity were estimated based on sex and specific age groups. RESULTS: In total, 1913 patients, including 83 infants, 746 pediatric patients, and 1084 adolescents, were newly identified as having undergone PPV surgery. The cumulative incidence of PPV surgery per 100,000 individuals was 21.42 (95% CI, 21.41-21.43). The rate of PPV was 2.4 times higher for males than females, and the rate of trauma as a comorbidity was also higher for males than females (13.1% vs 4.8%). Among males aged 5 years and older, the incidence of PPV nearly halved from 2011 to 2020. Among the primary etiologies, ROP had the highest rate (72%) in infants (under 1 year), while RD was most common (63%) in individuals aged 5 to 19 years. Myopia was present in 30.3% of patients, and atopic dermatitis was present in 31.8% of all patients. CONCLUSION: The primary etiologies underlying the need for PPV in the pediatric and adolescent populations vary by sex and age group. The incidence of PPV continues to decline in the adolescent population. Therefore, tailored patient education and age-specific etiological examination are recommended.

Real-world incidence and risk factors of bortezomib-related cardiovascular adverse events in patients with multiple myeloma.

BACKGROUND: Although most studies on the cardiovascular toxicity of proteasome inhibitors have focused on carfilzomib, the risk of cardiotoxicity associated with bortezomib remains controversial. This study aimed to evaluate the incidence and risk factors of cardiovascular adverse events (CVAEs) associated with bortezomib in patients with multiple myeloma in a real-world setting. METHODS: This cross-sectional study included patients who were treated with bortezomib at a tertiary hospital in South Korea. CVAEs, defined as hypertension, arrhythmia, heart failure, myocardial infarction, pulmonary arterial hypertension, angina, and venous thromboembolism, were detected using cardiac markers, ECG, echocardiography, medications, or documentation by clinicians. The patients were observed for at least 6 months and up to 2 years after starting bortezomib administration. RESULTS: Among the 395 patients, 20.8% experienced CVAEs of any grade, and 14.7% experienced severe adverse events. The median onset time for any CVAE was 101.5 days (IQR, 42-182 days), and new-onset/worsened hypertension was the most prevalent CVAE. The risk of CVAEs increased in patients with a body mass index lower than 18.5 (adjusted HR (aHR) 3.50, 95% confidence interval (CI) 1.05-11.72), light chain (1.80, 1.04-3.13), and IgD (4.63, 1.06-20.20) as the multiple myeloma subtype, baseline stroke (4.52, 1.59-12.80), and hypertension (1.99, 1.23-3.23). However, CVAEs did not significantly affect the 2-year overall survival and progression-free survival. CONCLUSION: Approximately 15% of the Korean patients treated with bortezomib experienced severe CVAEs. Thus, patients, especially those with identified risk factors, should be closely monitored for CVAE symptoms during bortezomib treatment.

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.

Development of machine learning algorithms for scaling-up antibiotic stewardship.

BACKGROUND: Antibiotic stewardship programs (ASP) aim to reduce inappropriate use of antibiotics, but their labor-intensive nature impedes their wide adoption. The present study introduces explainable machine learning (ML) models designed to prioritize inpatients who would benefit most from stewardship interventions. METHODS: A cohort of inpatients who received systemic antibiotics and were monitored by a multidisciplinary ASP team at a tertiary hospital in the Republic of Korea was assembled. Data encompassing over 130,000 patient-days and comprising more than 160 features from multiple domains, including prescription records, laboratory, microbiology results, and patient conditions was collected.Outcome labels were generated using medication administration history: discontinuation, switching from intravenous to oral medication (IV to PO), and early or late de-escalation. The models were trained using Extreme Gradient Boosting (XGB) and light Gradient Boosting Machine (LGBM), with SHapley Additive exPlanations (SHAP) analysis used to explain the model's predictions. RESULTS: The models demonstrated strong discrimination when evaluated on a hold-out test set(AUROC - IV to PO: 0.81, Early de-escalation: 0.78, Late de-escalation: 0.72, Discontinue: 0.80). The models identified 41%, 16%, 22%, and 17% more cases requiring discontinuation, IV to PO, early and late de-escalation, respectively, compared to the conventional length of therapy strategy, given that the same number of patients were reviewed by the ASP team. The SHAP results explain how each model makes their predictions, highlighting a unique set of important features that are well-aligned with the clinical intuitions of the ASP team. CONCLUSIONS: The models are expected to improve the efficiency of ASP activities by prioritizing cases that would benefit from different types of ASP interventions along with detailed explanations.

The Impact of Real-Time Documentation of In-Hospital Medication Changes on Preventing Undocumented Discrepancies at Discharge and Improving Physician-Pharmacist Communication: A Retrospective Cohort Study and Survey.

Background: Transitional medication safety is crucial, as miscommunication about medication changes can lead to significant risks. Unclear or incomplete documentation during care transitions can result in outdated or incorrect medication lists at discharge, potentially causing medication errors, adverse drug events, and inadequate patient education. These issues are exacerbated by extended hospital stays and multiple care events, making accurate medication recall challenging at discharge. Objective: Thus, we aimed to investigate how real-time documentation of in-hospital medication changes prevents undocumented medication changes at discharge and improves physician-pharmacist communication. Methods: We conducted a retrospective cohort study in a tertiary hospital. Two pharmacists reviewed medical records of patients admitted to the acute medical unit from April to June 2020. In-hospital medication discrepancies were determined by comparing preadmission and hospitalization medication lists and it was verified whether the physician's intent of medication changes was clarified by documentation. By a documentation rate of medication changes of 100% and <100%, respectively, fully documented (FD) and partially documented (PD) groups were defined. Any undocumented medication changes at discharge were considered a "documentation error at discharge". Pharmacists' survey was conducted to assess the impact of appropriate documentation on the pharmacists. Results: After reviewing 400 medication records, patients were categorized into FD (61.3%) and PD (38.8%) groups. Documentation errors at discharge were significantly higher in the PD than in the FD group. Factors associated with documentation errors at discharge included belonging to the PD group, discharge from a non-hospitalist-managed ward, and having three or more intentional discrepancies. Pharmacists showed favorable attitudes towards physician's documentation. Conclusion: Appropriate documentation of in-hospital medication changes, facilitated by free-text communication, significantly decreased documentation errors at discharge. This analysis underlines the importance of communication between pharmacists and hospitalists in improving patient safety during transitions of care.

During transitions of care, communication failures among healthcare professionals can lead to medication errors. Therefore, effective sharing of information is essential, especially when intentional changes in prescription orders are made. Documenting medication changes facilitates real-time communication, potentially improving medication reconciliation and reducing discrepancies. However, inadequate documentation of medication changes is common in clinical practice. This retrospective cohort study underlines the importance of real-time documentation of in-hospital medication changes. There was a significant reduction in documentation errors at discharge in fully documented group, where real-time documentation of medication changes was more prevalent. Pharmacists showed favorable attitudes toward the physician's real-time documenting of medication changes because it provided valuable information on understanding the physician's intent and improving communication and also saved time for pharmacists. This study concludes that physicians' documentation on medication changes may reduce documentation errors at discharge, meaning that proper documentation of medication changes could enhance patient safety through effective communication.