Current status and clinical outcomes of pharmacotherapies according to SARS-CoV-2 mutations in patients with mild-to-moderate COVID-19: a retrospective single center study.

BACKGROUND: During the pandemic period, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutated, leading to changes in the disease's severity and the therapeutic effect of drugs accordingly. This study aimed to present the actual use of therapeutics and clinical outcomes based on the prevalence of each variant using real-world data. METHODS: We analyzed the electronic medical records of adult patients admitted to Busan Medical Center after confirming coronavirus disease 2019 (COVID-19) from February 1, 2020, to June 30, 2022. Patients with mild-to-moderate COVID-19 who were at a high risk of disease progression were selected as study subjects, and the time period was classified according to the variants as ancestral strain, Delta variant, or Omicron variant. We compared drug use status and clinical outcomes by time period. RESULTS: Among all 3,091 patients, corticosteroids were the most commonly used therapy (56.0%), being used most frequently in the Delta variant (93.0%), followed by the Omicron variant (42.9%) and ancestral strain (21.2%). Regdanvimab accounted for the majority of therapeutic use in the Delta variant (82.9%) and ancestral strain (76.8%), whereas remdesivir was most frequently used during the Omicron variant period (68.9%). The composite outcomes of death or disease aggravation were ranked in the order of the Delta variant, Omicron variant, and ancestral strain (14.5, 11.9, and 6.0%, respectively, P < 0.001). CONCLUSION: Regdanvimab was primarily used during the ancestral strain period, regdanvimab plus corticosteroids during the Delta variant period, and remdesivir during the Omicron variant period. The rate of death or disease aggravation was highest in the Delta variant, followed by the Omicron variant and the ancestral strain.

Temporal trends in use of antisecretory agents among patients administered clopidogrel-based dual antiplatelet therapy after percutaneous coronary intervention.

BACKGROUND: Antisecretory drugs are commonly prescribed with clopidogrel-based dual antiplatelet therapy (DAPT) to prevent gastrointestinal bleeding in high-risk patients after percutaneous coronary intervention (PCI). However, omeprazole and esomeprazole (inhibiting proton pump inhibitors [PPIs]) may increase cardiovascular event rates on co-administration with clopidogrel. This study aimed to examine trends in the use of antisecretory agents in patients administered clopidogrel-based DAPT and the concomitant use of clopidogrel and inhibiting PPIs. METHODS: We used National Inpatient Sample data compiled by the Health Insurance Review & Assessment Service from 2009 to 2020. Further, we identified patients who were prescribed clopidogrel-based DAPT after PCI and investigated the concomitant use of antisecretory agents with clopidogrel. To verify the annual trend of drug utilization, we used the Cochran-Armitage trend test. RESULTS: From 2009 to 2020, the percentage of H2 receptor antagonist users decreased steadily (from 82.5% in 2009 to 25.3% in 2020); instead, the percentage of PPI users increased (from 23.7% in 2009 to 82.0% in 2020). The use of inhibiting PPI also increased (from 4.2% in 2009 to 30.7% in 2020). Potassium competitive acid blockers (P-CABs) were rarely used before 2019; however, in 2020, it accounted for 7.8% of the antisecretory users. CONCLUSIONS: Our study demonstrates that the use of inhibiting PPIs increased steadily in patients administered clopidogrel-based DAPT therapy. This is a major concern since the concomitant use of inhibiting PPIs with clopidogrel could increase the risk of cardiovascular events.

Impact of the Narcotics Information Management System on Opioid Use Among Outpatients With Musculoskeletal and Connective Tissue Disorders: Quasi-Experimental Study Using Interrupted Time Series.

BACKGROUND: Opioids have traditionally been used to manage acute or terminal pain. However, their prolonged use has the potential for abuse, misuse, and addiction. South Korea introduced a new health care IT system named the Narcotics Information Management System (NIMS) with the objective of managing all aspects of opioid use, including manufacturing, distribution, sales, disposal, etc. OBJECTIVE: This study aimed to assess the impact of NIMS on opioid use. METHODS: We conducted an analysis using national claims data from 45,582 patients diagnosed with musculoskeletal and connective tissue disorders between 2016 and 2020. Our approach included using an interrupted time-series analysis and constructing segmented regression models. Within these models, we considered the primary intervention to be the implementation of NIMS, while we treated the COVID-19 outbreak as the secondary event. To comprehensively assess inappropriate opioid use, we examined 4 key indicators, as established in previous studies: (1) the proportion of patients on high-dose opioid treatment, (2) the proportion of patients receiving opioid prescriptions from multiple providers, (3) the overlap rate of opioid prescriptions per patient, and (4) the naloxone use rate among opioid users. RESULTS: During the study period, there was a general trend of increasing opioid use. After the implementation of NIMS, significant increases were observed in the trend of the proportion of patients on high-dose opioid treatment (coefficient=0.0271; P=.01) and in the level of the proportion of patients receiving opioid prescriptions from multiple providers (coefficient=0.6252; P=.004). An abrupt decline was seen in the level of the naloxone use rate among opioid users (coefficient=-0.2968; P=.04). While these changes were statistically significant, their clinical significance appears to be minor. No significant changes were observed after both the implementation of NIMS and the COVID-19 outbreak. CONCLUSIONS: This study suggests that, in its current form, the NIMS may not have brought significant improvements to the identified indicators of opioid overuse and misuse. Additionally, the COVID-19 outbreak exhibited no significant influence on opioid use patterns. The absence of real-time monitoring feature within the NIMS could be a key contributing factor. Further exploration and enhancements are needed to maximize the NIMS' impact on curbing inappropriate opioid use.

Utilization of triple antithrombotic therapy in patients with atrial fibrillation undergoing percutaneous coronary intervention.

BACKGROUND: Triple antithrombotic therapy (TAT), a combination of an oral anticoagulant and dual antiplatelet therapy (DAPT), is a key treatment for prevention of ischemic events in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI). However, TAT is not extensively used because of the risk of bleeding. This study aimed to determine the utilization and influencing factors of TAT using real-world data in the non-vitamin K antagonist oral anticoagulants (NOACs) era. METHODS: We analyzed National Inpatient Sample data compiled by the Health Insurance Review & Assessment Service (HIRA-NIS) from 2011 to 2020. Patients with AF who underwent PCI with stent implantation and with an increased stroke risk were selected as candidates for TAT therapy. Demographic and clinical factors associated with TAT use were investigated using the chi-squared test and the Student t-test, and influencing factors were identified using multiple logistic regression. RESULTS: The TAT utilization rate steadily increased from 30.3% in 2011 to 65.4% in 2020 (Cochran-Armitage trend test: p < 0.001) with an average of 45.9%. Positive influencing factors for TAT use were identified as congestive heart failure, history of previous stroke/transient ischemic attack/thromboembolism, valvular heart disease, and year. Negative influencing factors included insurance type (medical aid or Patriots & Veterans Insurance), type of medical institution (general hospitals or primary medical institutions), and comorbidities such as renal disease, liver disease, and history of the previous hemorrhage. CONCLUSIONS: The utilization of TAT following PCI among high-stroke risk AF patients steadily increased from 2011 to 2020, reaching 65.4% by the end of the study period. However, in 2020, a significant proportion of 29.4% of patients still received DAPT, indicating that many AF patients undergoing PCI did not receive adequate antithrombotic therapy.

Effectiveness and Safety of Regdanvimab in Patients With Mild-To-Moderate COVID-19: A Retrospective Cohort Study.

BACKGROUND: Regdanvimab has decreased the time to clinical recovery from coronavirus disease 2019 (COVID-19) and lowered the rate of oxygen therapy according to the results from phase 2/3 randomized controlled trial. More information is needed about the effects and safety of regdanvimab. METHODS: We analyzed data for patients with high-risk mild or moderate COVID-19 being admitted to Busan Medical Center between December 1, 2020 and April 16, 2021. A propensity score (PS) matched analysis was conducted to compare patients treated with and without regdanvimab. The primary outcome was in-hospital death or disease aggravation which means the need for oxygen therapy (low- or high-flow oxygen therapy and mechanical ventilation) and secondary outcomes comprised the length of hospital stay and adverse reactions. RESULTS: Among 1,617 selected patients, 970 (60.0%) were indicated for regdanvimab. Of these, 377 (38.9%) were administered with regdanvimab. Among a 1:1 PS-matched cohort of 377 patients each treated with and without regdanvimab, 19 (5%) and 81 (21.5%) reached the composite outcome of death, or disease aggravation, respectively (absolute risk difference, -16.4%; 95% confidence interval [CI], -21.1, -11.7; relative risk difference, 76.5%; P < 0.001). Regdanvimab significantly reduced the composite outcome of death, or disease aggravation in univariate (odds ratio [OR], 0.194; 95% CI, 0.112-0.320; P < 0.001) and multivariable-adjusted analyses (OR, 0.169; 95% CI, 0.095-0.289; P < 0.001). The hospital stay was shorter for the group with than without regdanvimab. Some hematological adverse reactions were more frequent in the group without regdanvimab, but other adverse reactions did not significantly differ between the groups. CONCLUSION: Regdanvimab was associated with a significantly lower risk of disease aggravation without increasing adverse reactions.

Factors Influencing the Selection of Non-Vitamin K Antagonist Oral Anticoagulants for Stroke Prevention in Patients With Non-Valvular Atrial Fibrillation.

BACKGROUND: Major atrial fibrillation (AF) guidelines recommend non-vitamin K antagonist oral anticoagulants (NOACs) over warfarin, except in rare clinical circumstances based on 4 randomized controlled trials comparing each NOAC with warfarin. We aimed to investigate the current NOAC prescription behaviors in alignment with the recent clinical evidence available. METHOD: We conducted a cross-sectional analysis of NOAC-using patients with non-valvular atrial fibrillation (NVAF) who were aged ≥65 years on the index date (July 1, 2018) based on nationwide claims data. The types of NOACs being taken were analyzed using chi-squared tests, and factors influencing NOAC selection were identified using multinomial logistic regression analysis. RESULTS: A total of 6,061 patients were included. Among the 4 NOACs, rivaroxaban was the most used NOAC. Patients aged ≥75 years (odds ratio [OR] = 1.270, confidence interval [CI] = 1.089-1.450) and women (OR = 1.148, CI = 1.011-1.284) were more likely to use apixaban relative to rivaroxaban. Patients with prior stroke/transient ischemic attack/thromboembolism had higher odds of using dabigatran (OR = 1.508, CI = 1.312-1.704) and apixaban (OR = 1.186, CI = 1.026-1.346). Patients with renal disease had higher odds of using apixaban (OR = 1.466, 95% CI = 1.238-1.693). These findings are consistent with the efficacy and safety profiles reported in pivotal trials and observational studies comparing individual NOACs. CONCLUSION: Among the 4 NOACs, rivaroxaban was the most commonly used NOAC. Apixaban was preferred for patients aged ≥75 years, females, and patients with renal disease.

Medication utilization among adult patients with attention-deficit/hyperactivity disorder after reimbursement criteria change.

This study analyzed the pattern of attention-deficit/hyperactivity disorder (ADHD) medication initiation in adult patients with ADHD after the reimbursement criteria change and identified the influencing factors associated with it using the claim data. We identified 243 adult patients with ADHD who had not been prescribed ADHD drugs before 1 September 2016. We conducted Kaplan-Meier survival analysis to calculate the time to initial prescription of ADHD medications, and Cox proportional hazard regression analysis to estimate the influencing factors. Approximately one-third of the patients (n = 76, 31.3%) were first prescribed ADHD medications after reimbursement approval, and 40 of them (16.5%) started treatment with osmotic release oral system methylphenidate. The patient's age group (30-39 years) and the status of diagnosis before the index date were associated with early initiation of pharmacotherapy. The odds of starting ADHD medications increased approximately 2.7-fold in the 30-39 age group and 0.2-fold in the case of patients who were diagnosed before the approval. Our findings show that both diagnosis and treatment of adult ADHD remains inadequate despite the change in reimbursement criteria. Improving awareness of adult ADHD among both the public and the professionals is essential to increase its chances of diagnosis and treatment.

Zolpidem overutilisation among Korean patients with insomnia.

This study aimed to investigate zolpidem overutilisation among Korean patients with insomnia. We analysed the National Patient Sample (NPS) data compiled by the Health Insurance Review & Assessment Service (HIRA-NPS) in 2016. Zolpidem overutilisation was defined as when a patient used zolpidem for longer than 30 consecutive days and prescriptions overlapped with more than 10% of total prescription periods. Demographic and clinical factors associated with the overutilisation of zolpidem were investigated using a logistic regression model. The proportion of zolpidem overutilisers was estimated at 5.0%. Factors such as age (0-39 years), consuming controlled-release dosage formulations of zolpidem, presence of psychiatric disorders (depression, bipolar disorder, schizophrenia and anxiety disorder) and other medical conditions (hypertension, diabetes mellitus and arthritis) were observed to be risk predictors for zolpidem overutilisation. The formulation was selected owing to the absence of a quantity restriction for zolpidem CR in Korea during the study period. Possible approaches to prevention and control of zolpidem overutilisation include regulatory or legal provisions promoting rational drug use, management of psychiatric and medical co-morbid disorders, and widespread implementation of cognitive behavioural therapy for insomnia as a first-line treatment option.

Factors That Affect Time to Switch From Warfarin to a Direct Oral Anticoagulant After Change in the Reimbursement Criteria in Patients With Atrial Fibrillation.

BACKGROUND: Anticoagulation therapy is recommended for stroke prevention in high-risk patients with atrial fibrillation (AF). This study aimed to estimate the time to switch from warfarin to a direct oral anticoagulant (DOAC) and identify the factors associated with it. METHODS: By using claims data, we studied 7111 warfarin-using patients with nonvalvular AF who were aged ≥65 years. The Kaplan-Meier analysis was performed to estimate the time to switch from warfarin to a DOAC, and Cox proportional hazard regression analysis was used to estimate the influencing factors. RESULTS: Approximately one-third of the patients (2403, 33.8%) switched from warfarin to a DOAC during the study period. Female sex, aged between 75 and 79 years, having a Medical Aid or Patriots and Veterans Insurance, hypertension, and history of prior stroke, and transient ischemic attack or thromboembolism (prior stroke/TIA/TE) were associated with a significantly shorter time to switch. The odds of switching to a DOAC were increased by approximately 1.2-fold in the women and 1.4-fold in the patients with prior stroke/TIA/TE. CONCLUSIONS: Approximately one-third of the warfarin-using patients switched from warfarin to a DOAC within 6 months after the change in the DOAC reimbursement criteria. In the Cox proportional hazard regression analysis, the factors that affected anticoagulant switching from warfarin to a DOAC were female sex and history of prior stroke/TIA/TE.

National trends in metformin-based combination therapy of oral hypoglycaemic agents for type 2 diabetes mellitus.

BACKGROUND: The American Diabetes Association guidelines recommend metformin monotherapy for type 2 diabetes mellitus as an initial agent due to its effectiveness and safety. If the target glycosylated haemoglobin level is not attained within 3 months, add-on therapy is recommended. This study aimed to investigate the prescribing trends of add-on therapy to metformin focusing on factors affecting the selection of second agents using real-world data. METHODS: Patients who were undergoing metformin monotherapy for at least 3 months and switched to metformin-based combination therapy were selected. The oral antidiabetic drugs used as add-on therapy were classified into 4 classes: dipeptidyl peptidase-4 inhibitors (DPP4I), sodium glucose cotransporter-2 inhibitors (SGLT2I), sulphonylureas (SU), and thiazolidinediones (TZD). The drug regimen was also classified as older and newer agents. Chi-square test and logistic regression analysis were performed to estimate the influencing factors. RESULTS: In 2014-2016, the use of DPP4I and SGLT2I increased, whereas the use of SU and TZD decreased. Our results show that the prescription pattern was influenced by the type and location of the institution, specialty of physicians, some comorbidities, and patient characteristics such as age and sex. Newer agents were more commonly used in younger patients. SGLT2I were more preferred in women than in men. Patients with dyslipidaemia showed increased odds of utilising newer agents. CONCLUSION: DPP4I were the most commonly utilised agents in metformin-based combination therapy and SGLT2I use is expected to increase more due to their cardioprotective effects. Proper selection of add-on therapy, based on drug-specific effects and patient factors, is necessary.