Inhibitory co-receptor Lag3 supports Foxp3+ regulatory T cell function by restraining Myc-dependent metabolic programming.

Lymphocyte activation gene 3 (Lag3) is an inhibitory co-receptor expressed on activated T cells and has been proposed to regulate regulatory T (Treg) cell function. However, its precise modality and mechanisms remain elusive. We generated Treg cell-specific Lag3-mutant mouse models and found that Lag3 was essential for Treg cell control of autoimmunity. RNA sequencing analysis revealed that Lag3 mutation altered genes associated with metabolic processes, especially Myc target genes. Myc expression in Lag3-mutant Treg cells was increased to the level seen in conventional T helper (Th)1-type effector cells and directly correlated with their metabolic profiles and in vivo suppressive functions. The phosphatidylinositol 3-kinase (PI3K)-Akt-Rictor pathway was activated in Lag3-mutant Treg cells, and inhibiting PI3K, Rictor, or lactate dehydrogenase A (Ldha), a key Myc target enzyme converting pyruvate to lactate, was sufficient to restore normal metabolism and suppressive function in Lag3-mutant Treg cells. These findings indicate that Lag3 supports Treg cell suppression partly by tuning Myc-dependent metabolic programming.

Anti-inflammatory Roles of Glucocorticoids Are Mediated by Foxp3+ Regulatory T Cells via a miR-342-Dependent Mechanism.

Glucocorticoids (GC) are the mainstay treatment option for inflammatory conditions. Despite the broad usage of GC, the mechanisms by which GC exerts its effects remain elusive. Here, utilizing murine autoimmune and allergic inflammation models, we report that Foxp3+ regulatory T (Treg) cells are irreplaceable GC target cells in vivo. Dexamethasone (Dex) administered in the absence of Treg cells completely lost its ability to control inflammation, and the lack of glucocorticoid receptor in Treg cells alone resulted in the loss of therapeutic ability of Dex. Mechanistically, Dex induced miR-342-3p specifically in Treg cells and miR-342-3p directly targeted the mTORC2 component, Rictor. Altering miRNA-342-3p or Rictor expression in Treg cells dysregulated metabolic programming in Treg cells, controlling their regulatory functions in vivo. Our results uncover a previously unknown contribution of Treg cells during glucocorticoid-mediated treatment of inflammation and the underlying mechanisms operated via the Dex-miR-342-Rictor axis.

Stimulation Strength Determined by Superantigen Dose Controls Subcellular Localization of FOXP3 Isoforms and Suppressive Function of CD4+CD25+FOXP3+ T Cells.

Staphylococcal superantigens induce massive activation of T cells and inflammation, leading to toxic shock syndrome. Paradoxically, increasing evidence indicates that superantigens can also induce immunosuppression by promoting regulatory T cell (Treg) development. In this study, we demonstrate that stimulation strength plays a critical role in superantigen-mediated induction of immunosuppressive human CD4+CD25+FOXP3+ T cells. Suboptimal stimulation by a low dose (1 ng/ml) of staphylococcal enterotoxin C1 (SEC1) led to de novo generation of Treg-like CD4+CD25+FOXP3+ T cells with strong suppressive activity. In contrast, CD4+CD25+ T cells induced by optimal stimulation with high-dose SEC1 (1 µg/ml) were not immunosuppressive, despite high FOXP3 expression. Signal transduction pathway analysis revealed differential activation of the PI3K signaling pathway and expression of PTEN in optimal and suboptimal stimulation with SEC1. Additionally, we identified that FOXP3 isoforms in Treg-like cells from the suboptimal condition were located in the nucleus, whereas FOXP3 in nonsuppressive cells from the optimal condition localized in cytoplasm. Sequencing analysis of FOXP3 isoform transcripts identified five isoforms, including a FOXP3 isoform lacking partial exon 3. Overexpression of FOXP3 isoforms confirmed that both an exon 2-lacking isoform and a partial exon 3-lacking isoform confer suppressive activity. Furthermore, blockade of PI3K in optimal stimulation conditions led to induction of suppressive Treg-like cells with nuclear translocation of FOXP3, suggesting that PI3K signaling impairs induction of Tregs in a SEC1 dose-dependent manner. Taken together, these data demonstrate that the strength of activation signals determined by superantigen dose regulates subcellular localization of FOXP3 isoforms, which confers suppressive functionality.

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.

Increased risk of incident gout in patients with hyperthyroidism: a nationwide retrospective cohort study.

Previous studies have reported that thyroid dysfunction is associated with increased serum uric acid levels; however, the relationship between hyperthyroidism and incidence of clinical manifestations of gout has not been fully investigated. Therefore, this study aimed to longitudinally investigate the risk of gout in patients with hyperthyroidism. This nationwide retrospective cohort study used data from the Korean National Health Claims Database. We included 76,494 patients with hyperthyroidism and 76,542 age- and sex-matched controls. A Cox proportional hazard regression model was used to adjust for potential confounders and estimate the risk of incident gout in patients with hyperthyroidism. During a mean follow-up of 9 years, incident gout developed in 3,655 (4.8%) patients with hyperthyroidism and 3251 (4.2%) controls. Hyperthyroidism was significantly associated with increased risk of incident gout [adjusted hazard ratio (HR), 1.12; 95% confidence interval (CI) 1.07-1.18], independent of baseline metabolic profiles. The median time from the diagnosis of hyperthyroidism to the development of gout was 6 years. When stratified by age and sex, the risk of gout was still significant in the < 50-year age group (HR: 1.2, 95% CI 1.12-1.29) and males (HR: 1.21, 95% CI 1.12-1.30), but not in the older age group (> 50 years) and females. Hyperthyroidism is an important risk factor for incident gout, particularly in younger age groups (< 50 years) and males. Our results highlight the importance of continuous screening for gout in patients with hyperthyroidism.

A study on user willingness to participate in an adverse drug event information sharing system.

BACKGROUND: To prevent the recurrence of Adverse Drug Events (ADEs), particularly drug allergies, it is essential to avoid re-exposure to causative drugs. Awareness of previous ADEs is crucial for patients because they can share accurate information with healthcare providers (HCPs). This study aims to assess users' willingness to share ADE information and evaluate the factors related to this willingness by utilizing a prospective ADE information-sharing system currently under consideration in South Korea. METHODS: In September 2023, a self-administered questionnaire was collected from a sex-, age-, and regionally stratified nationwide convenience sample of adults recruited through a commercial panel in South Korea. Factors contributing to the willingness to share ADE information and create electronic ADE cards (e-ADE cards) were investigated using multivariate logistic regression analysis. RESULTS: Among the 1,000 respondents, 458 (45.8%) were willing to share ADE information, and 521 (52.1%) were willing to create e-ADE cards. The willingness to share personal ADE information and create e-ADE cards was positively associated with the perceived benefits of sharing ADE, trust in HCPs and positive experiences. Notably, older adult patients demonstrated a higher willingness to share information and use e-ADE cards, with rates of 56% and 62%, respectively. CONCLUSIONS: Our findings indicate that the approach to sharing personal ADE information should be distinct from that of sharing comprehensive health information. Notably, users are likely to willingly disclose their personal information even if they are not anonymized, owing to the significant perceived benefits of sharing. The findings of this study can enhance awareness about sharing personal ADE information and contribute to the successful establishment of an ADE information-sharing system, thereby improving the patient safety environment.

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.

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.

Nationwide-incidence and trends of fibromyalgia in South Korea: a population-based study.

Reports of the incidence of fibromyalgia (FM) in Asia are uncommon. Therefore, this study used nationwide representative data to investigate the age- and sex-specific incidence and annual trends of FM in South Korea. This nationwide population-based study used data from the Korean National Health Claims Database. From 2012 to 2021, patients with FM diagnosed according to the ACR 2010 criteria from the entire Korean population aged 20-70 years were included in the enrolment database. Age- and sex-specific cumulative and annual incidences were analyzed and incident cases from 2014 to 2021 were included, considering the 2-year washout period. Among the total cohort of 42 million in the entire Korean population, 270,160 had FM during the study period. The incidence in the general population aged 20-70 years was 751.25 (95% confidence interval [CI] 751.10-751.40) per 100,000 persons (men: 95% CI 608.45-608.98; women: 95% CI 898.02-898.69). The incidence of FM increased with advancing age, peaking at 50-54 years both in men and women. The annual incidence was 88.07 (95% CI 88.02-88.13) in 2014; it increased from 2014 to 2019 and peaked in 2019 (109.20; 95% CI 101.65-101.76). The incidence of FM in South Korea was about twice the global average, with a gradual increase over the study period. These detailed estimates can help with proper planning within the healthcare system.

Clinical and Economic Impact of Pharmacists' Intervention on Care of Pediatric Hematology and Oncology Patients.

INTRODUCTION: Children with cancer may be one of the most vulnerable groups to drug-related adverse events because they possess characteristics of patients with cancer as well as pediatric patients. To evaluate the clinical and economic impact of pharmacists' intervention on the care of pediatric hematology and oncology patients in the inpatient and outpatient settings of a children's hospital. METHODS: The pharmacist-intervention records from 2017 were retrospectively reviewed. Intervention rate, type of drug-related problems, acceptance rate, and frequently involved drugs in pharmacist interventions were analyzed. One physician and one pharmacist evaluated the clinical significance of each intervention. A cost-benefit analysis was conducted from hospital and patient perspective. The benefit from cost savings by reducing the number of prescribed drugs that are disposed was estimated as the benefit from hospital perspective. The benefit from cost avoidance based on the potential to avoid an adverse drug event (ADE) was estimated as the benefit from patient perspective. The cost of reviewing prescriptions was estimated based on the pharmacists' salary and the time involved. RESULTS: In 2017, 2361 interventions were performed in 381 pediatric patients with cancer. The acceptance rate was 97.2%. More than half of the interventions were regarded as clinically "significant" (58.8%) and "very significant" (14.6%). The cost-benefit of US$28,705 was determined from hospital perspective, with a cost-benefit ratio of 1.45:1. The cost-benefit of US$35,611 was calculated from patient perspective, with a cost-benefit ratio of 1.55:1. CONCLUSIONS: Pharmacists' intervention in the care of hematology and oncology pediatric patients was effective in preventing clinically significant ADEs and had a positive economic impact on the health-care budget from both hospital and patient perspective.

Adverse Drug Events Associated With Remdesivir in Real-World Hospitalized Patients With COVID-19, Including Vulnerable Populations: A Retrospective Multicenter Study.

BACKGROUND: Remdesivir is a US Food and Drug Administration-approved drug for coronavirus disease 2019 (COVID-19). Clinical trials were conducted under strictly controlled situations for a selected population, and their reported adverse events may not fully represent conditions in real-world patients. We aimed to estimate the incidence of adverse drug events (ADEs) associated with remdesivir in hospitalized patients with COVID-19, including vulnerable subpopulations, such as those with impaired renal or hepatic function and pregnant women. METHODS: This retrospective observational study included hospitalized patients with confirmed COVID-19 treated with remdesivir between January and December 2021 at ten hospitals. ADEs and severe ADEs (Common Toxicity Criteria for Adverse Events grade ≥ 3) were operationally defined and analyzed through laboratory investigations. The incidence of ADEs was compared with that of each matched control in subpopulations with renal or hepatic impairment and pregnant women. RESULTS: Among 2,140 patients, 1,416 (66.2%) and 295 (13.8%) experienced at least one ADE and severe ADE, respectively. The most frequent ADE was 'hepatic injury' (42.9%), followed by anemia (27.6%). The most common severe ADEs were 'hypokalemia' (5.3%), 'hepatic injury' (2.9%), and 'anemia' (3.6%). There was no significant difference in the incidence of ADEs in patients relative to their respective matched-control groups, including those with renal impairment (80.0% vs. control 71.8%, P = 0.063), hepatic impairment (70.4% vs. control 75.0%, P = 0.623) and pregnant women (78.6% vs. control 63.7%, P = 0.067). However, severe ADE incidence was significantly higher in patients with renal impairment (40.8% vs. 16.0%, P < 0.001). The most common severe ADEs in those were 'anemia' (15.3%), 'hypokalemia' (10.5%), and 'thrombocytopenia' (8.9%). There was no statistically significant difference in the incidence of severe ADEs in patients with hepatic impairment or in pregnancy (P = 0.230; P = 0.085). CONCLUSION: A significant proportion of patients with COVID-19 treated with remdesivir experienced ADEs and severe ADEs. Given the high incidence of severe ADEs, caution is required in patients with renal impairment. Further studies are needed to investigate ADEs in pregnant women and patients with hepatic impairment.

Novel innovative computer-based test (Inno-CBT) item types for national licensing examinations for health care professionals.

BACKGROUND: An effective test mechanism to evaluate clinical knowledge and skills of the entry-level healthcare professionals is important for providing clinical competency and improving patient care. This study aimed to develop novel, innovative computer-based test (Inno-CBT) item types for application in the national examination of Korean healthcare professionals. METHODS: This exploratory study was conducted from May 2021 to March 2022 by a team of faculty members from pharmacy schools in South Korea. A literature search using PubMed, Google Scholar, RISS, Web of Science, and KoreaMed was performed. Forum presentations, media articles, and previous reports by the Korea Health Personnel Licensing Examination Institute (KHPLEI) were included. Workshops were held, information and ideas were collected and conceptualized, and item types were designed, drafted, and refined. By repeating this process, the Inno-CBT item types were finalized. RESULTS: Forty-one Inno-CBT item types with 28 subtypes were developed. New digital technologies, such as a reactive responsive media interface, an animation insertion, multimedia embedding, and network surfing, were utilized in these novel types. It was anticipated that these Inno-CBT item types would effectively measure abilities in healthcare knowledge, problem-solving skills, and professional behaviors. Some potential barriers to implementing the Inno-CBT item types include item difficulty, operational unfamiliarity, complexity in scoring protocols, and network security. CONCLUSIONS: A variety of styles of novel Inno-CBT item types were developed to evaluate the multifaceted and in-depth professional abilities required for healthcare professionals. Prior to implementing these item types in the national examination, item validation and technical support should be conducted.

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.