Cardiovascular risk in rheumatoid arthritis patients treated with targeted synthetic and biological disease-modifying antirheumatic drugs: A multi-centre cohort study.

BACKGROUND: This study aimed to compare the cardiovascular safety of interleukin-6 inhibitors (IL-6i) and Janus Kinase inhibitors (JAKi) to tumour necrosis factor inhibitors (TNFi). METHODS: We conducted a retrospective cohort study using population-based electronic databases from Hong Kong, Taiwan and Korea. We identified newly diagnosed patients with rheumatoid arthritis (RA) who received b/tsDMARDs first time. We followed patients from b/tsDMARD initiation to the earliest outcome (acute coronary heart disease, stroke, heart failure, venous thromboembolism and systemic embolism) or censoring events (death, transformation of b/tsDMARDs on different targets, discontinuation and study end). Using TNFi as reference, we applied generalized linear regression for the incidence rate ratio estimation adjusted by age, sex, disease duration and comorbidities. Random effects meta-analysis was used for pooled analysis. RESULTS: We identified 8689 participants for this study. Median (interquartile range) follow-up years were 1.45 (2.77) in Hong Kong, 1.72 (2.39) in Taiwan and 1.45 (2.46) in Korea. Compared to TNFi, the adjusted incidence rate ratios (aIRRs) (95% confidence interval [CI]) of IL-6i in Hong Kong, Taiwan and Korea are 0.99 (0.25, 3.95), 1.06 (0.57, 1.98) and 1.05 (0.59, 1.86) and corresponding aIRR of JAKi are 1.50 (0.42, 5.41), 0.60 (0.26, 1.41), and 0.81 (0.38, 1.74), respectively. Pooled aIRRs showed no significant risk of cardiovascular events (CVEs) associated with IL-6i (1.05 [0.70, 1.57]) nor JAKi (0.80 [0.48, 1.35]) compared to TNFi. CONCLUSION: There was no difference in the risk of CVE among RA patients initiated with IL-6i, or JAKi compared to TNFi. The finding is consistent in Hong Kong, Taiwan and Korea.

A Nationwide Survey of mRNA COVID-19 Vaccinee's Experiences on Adverse Events and Its Associated Factors.

BACKGROUND: Although coronavirus disease 2019 (COVID-19) vaccines have been distributed worldwide under emergency use authorization, the real-world safety profiles of mRNA vaccines still need to be clearly defined. We aimed to identify the overall incidence and factors associated with adverse events (AEs) following mRNA COVID-19 vaccination. METHODS: We conducted web-based survey from December 2 to 10 in 2021 with a 2,849 nationwide sampled panel. Study participants were individuals who had elapsed at least two-weeks after completing two dosing schedules of COVID-19 vaccination aged between 18-49 years. We weighted the participants to represent the Korean population. The outcome was the overall incidence of AEs following mRNA COVID-19 vaccination and associated factors. We estimated the weighted odds ratios (ORs) using multivariable logistic regression models to identify the factors associated with AEs. RESULTS: Of the 2,849 participants (median [interquartile range] age, 35 [27-42] years; 51.6% male), 90.8% (n = 2,582) for the first dose and 88.7% (n = 2,849) for the second dose reported AEs, and 3.3% and 4.3% reported severe AEs, respectively. Occurrence of AEs was more prevalent in mRNA-1273 (OR, 2.06; 95% confidence interval [CI], 1.59-2.67 vs. BNT162b2), female sex (1.88; 1.52-2.32), and those with dermatologic diseases (2.51; 1.32-4.77). History of serious allergic reactions (1.96; 1.06-3.64) and anticoagulant medication use (4.72; 1.92-11.6) were associated with severe AEs. CONCLUSION: Approximately 90% of participants reported AEs following mRNA COVID-19 vaccination. Substantial factors, including vaccine type (mRNA-1273), female sex, and dermatologic diseases were associated with AEs. Our findings could aid policymakers in establishing vaccination strategies tailored to those potentially susceptible to AEs.

Association between tramadol use and seizures: A nationwide case-case-time-control study.

PURPOSE: Tramadol may lower the seizure threshold; however, there is no conclusive evidence to confirm this. This study aimed to determine whether the use of tramadol is associated with the occurrence of seizures. METHODS: We conducted a case-case-time-control (CCTC) study by identifying patients who had received tramadol and seizure diagnosis in a nationwide healthcare database in South Korea between 2003 and 2015. Each case was matched for age and sex to one future case to adjust for time trends in exposure without selection bias from the use of an external control group. The use of tramadol was assessed during a risk period of 1-30 days, and two reference periods, 61-90 days and 91-120 days, preceding the first diagnosis of seizures. We calculated the adjusted odds ratio (aOR) by dividing the OR in cases (case-crossover) by the OR in future cases (control-crossover). We performed a dose-response analysis using the average daily dose. RESULTS: We identified 2523 incident cases with matched future cases (mean age, 45.4 years; 50% men). The aOR for seizure with tramadol use was 0.94 (95% confidence interval [CI], 0.98-1.43) in the CCTC analysis, with a case-crossover OR of 1.19 (0.98-1.43) and control-crossover OR of 1.27 (1.03-1.56). The dose-response analysis showed a similar trend in the main analysis: a low-dose aOR of 0.80 (0.50-1.28) and a high-dose aOR of 0.92 (0.41-2.11). CONCLUSION: We could not identify a significant association between transient use of tramadol and incidence of seizures in clinical practice.

Association of mental disorders with SARS-CoV-2 infection and severe health outcomes: nationwide cohort study.

BACKGROUND: Epidemiological data on the association between mental disorders and the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) severity are limited. AIMS: To evaluate the association between mental disorders and the risk of SARS-CoV-2 infection and severe outcomes following COVID-19. METHOD: We performed a cohort study using the Korean COVID-19 patient database based on national health insurance data. Each person with a mental or behavioural disorder (diagnosed during the 6 months prior to their first SARS-CoV-2 test) was matched by age, gender and Charlson Comorbidity Index with up to four people without mental disorders. SARS-CoV-2-positivity risk and the risk of death or severe events (intensive care unit admission, use of mechanical ventilation and acute respiratory distress syndrome) post-infection were calculated using conditional logistic regression analysis. RESULTS: Among 230 565 people tested for SARS-CoV-2, 33 653 (14.6%) had mental disorders; 928/33 653 (2.76%) tested SARS-CoV-2 positive and 56/928 (6.03%) died. In multivariable analysis using the matched cohort, there was no association between mental disorders and SARS-CoV-2-positivity risk (odds ratio OR = 0.95; 95% CI 0.87-1.04); however, a higher risk was associated with schizophrenia-related disorders (OR = 1.50; 95% CI 1.14-1.99). Among confirmed COVID-19 patients, the mortality risk was significantly higher in patients with than in those without mental disorders (OR = 1.99, 95% CI 1.15-3.43). CONCLUSIONS: Mental disorders are likely contributing factors to mortality following COVID-19. Although the infection risk was not higher for people with mental disorders overall, those with schizophrenia-related disorders were more vulnerable to infection.

Utilization of targeted disease-modifying anti-rheumatic drugs (DMARDs) for managing rheumatoid arthritis in the last decade: A two-country comparison.

OBJECTIVE: To compare trends in the use of targeted disease-modifying anti-rheumatic drugs (DMARDs) for rheumatoid arthritis (RA), between Korea and Australia. MATERIALS AND METHODS: Using sampled claims databases in Korea and Australia (2010 - 2018), we analyzed the trends in the use of individual targeted DMARDs (biologic and targeted synthetic) for RA in both countries. RESULTS: The use of targeted DMARDs for the management of RA showed an increase of over 200 and 300% in Australia and Korea, respectively. The tumor necrosis factor inhibitors (TNFis) etanercept and adalimumab were the most commonly prescribed drugs in 2010 in both countries, with non-TNFi use increasing over the study period. The introduction of tofacitinib in 2015 led to 10 and 15% market share uptake in Korea and Australia, respectively. CONCLUSION: Trends in the use of targeted DMARDs for RA were similar in Korea and Australia, and the use of non-TNFis, including tofacitinib, increased in both countries.

Risk of mortality associated with concomitant antidepressant and benzodiazepine therapy among patients with depression: a population-based cohort study.

BACKGROUND: With antidepressants (ADs) having minimal therapeutic effects during the initial weeks of treatment, benzodiazepines (BZDs) are concomitantly used to alleviate depressive symptoms of insomnia or anxiety. However, with mortality risks associated with this concomitant use yet to be examined, it remains unclear as to whether this concomitant therapy offers any benefits in treating depression. METHODS: We conducted a population-based cohort study using South Korea's nationwide healthcare database from 2002 to 2017. Of 2.6 million patients with depression, we identified 612,729 patients with incident depression and newly prescribed ADs or BZDs, by excluding those with a record of diagnosis or prescription within the 2 years prior to their incident diagnosis. We classified our study cohort into two discrete groups depending on the type of AD treatment received within 6 months of incident diagnosis-AD monotherapy and AD plus BZD (AD+BZD) therapy. We matched our study cohort in a 1:1 ratio using propensity scores to balance baseline characteristics and obtain comparability among groups. The primary outcome was all-cause mortality, and patients were followed until the earliest of outcome occurrence or end of the study period. We conducted multivariable Cox proportional hazards regression analysis to estimate adjusted hazards ratios (HRs) with 95% confidence intervals (CIs) for the risk of mortality associated with AD+BZD therapy versus AD monotherapy. RESULTS: The propensity score-matched cohort had 519,780 patients with 259,890 patients in each group, where all baseline characteristics were well-balanced between the two groups. Compared to AD monotherapy, AD+BZD therapy was associated with an increased risk of all-cause mortality (adjusted HR, 1.04; 95% CI, 1.02 to 1.06). CONCLUSIONS: Concomitantly initiating BZDs with ADs was associated with a moderately increased risk of mortality. Clinicians should therefore exercise caution when deciding to co-prescribe BZDs with ADs in treating depression, as associated risks were observed.

Zoledronic acid and skeletal-related events in patients with bone metastatic cancer or multiple myeloma.

INTRODUCTION: Investigations of ZA effectiveness using large, real-world databases are rare. We examined whether zoledronic acid (ZA) decreased the risk of skeletal-related events (SREs) among patients with bone metastases (BMs) from breast cancer (BC) or prostate cancer (PC), or multiple myeloma (MM) in routine clinical practice. MATERIALS AND METHODS: We conducted a propensity score-matched cohort study using the Korean National Health Insurance database. Our cohort included patients diagnosed with BM after BC or PC, or MM between 2004 and 2015. SRE was defined as having a record of pathologic fracture, spinal cord compression, radiation, or surgery to bone. The incidence of multiple SREs was calculated according to SRE history. We calculated the incidence rate ratio (IRR) to examine the relative difference in the risk of SREs of ZA users compared to those of ZA non-user. RESULTS: Among 111,679 patients, diagnosed with BM and one of the three cancer types, 5608 were included in the analysis after propensity score matching. A decreased risk of SREs was observed for the ZA use in patients with history of SRE in BC [IRR = 0.74, 95% confidence interval (CI) = 0.66-0.83], PC (IRR = 0.86, 95% CI = 0.73-1.02), and MM (IRR = 0.74, 95% CI = 0.59-0.93). For patients without SRE history, ZA use was not associated with decreased risks of SREs, but rather increased the risks (BC: IRR = 1.96, 95% CI 1.87-2.05; PC: IRR = 1.66, 95% CI 1.54-1.80; MM: IRR = 1.92, 95% CI 1.57-2.34). CONCLUSIONS: Our study suggests that the ZA use was associated with a decreased risk of SRE for patients with SRE history. However, no preventive effects of ZA were observed for patients without history.

Association between use of antiemetics, antipsychotics, or antidepressants and the risk of Parkinson's disease
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OBJECTIVE: Antipsychotics, antidepressants, and antiemetics are well-known causative agents of parkinsonism. However, it is not certain that the use of these medications increases the risk of Parkinson's disease (PD). We aim to define the risk of PD associated with use of antipsychotic, antidepressant, or antiemetic therapy. MATERIALS AND METHODS: We conducted a population-based nested case-control study using data from the South Korean health insurance database. For each PD case, we randomly selected sex, age group, cohort entry date, duration of follow-up, and Charlson comorbidity score-matched controls (up to 3). Exposure was categorized into six groups based on treatments received 1 - 90 days before the index date (separate use of either: antiemetics; antipsychotics; or antidepressants; combined use of antiemetics with either: antipsychotics; or antidepressants; and combined use of all three). We used conditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for PD. RESULTS: Final subjects included 31,428 cases and 94,284 matched controls. We observed an increased risk of PD with the separate use of antiemetics (adjusted OR, 1.08; 95% CI, 1.05 - 1.11) and that of antipsychotics (1.31; 1.12 - 1.52), and the combined use of antiemetics and antipsychotics (1.42; 1.15 - 1.75). Both antidepressants alone and with antipsychotics were not associated with higher risk of PD. CONCLUSIONS: Separate or concurrent use of antiemetics and antipsychotics showed increased risks of PD. Although statistical significance was observed, when taking into account that there still lie unmeasured, unconsidered confounders, there may be no clinical association present. Caution will be needed in prescribing these drugs in patients who have prognostic factors for PD. 
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Physician and pharmacist satisfaction and clinical needs for the real-time medication surveillance program in South Korea.

BACKGROUND: Since December 2010, a nationwide real-time medication surveillance program has been implemented in Korea to prevent potential adverse drug reactions. Our goal was to evaluate physicians' and pharmacists' satisfaction and clinical needs for the medication surveillance program in Korea. METHODS: Both web- and paper-based surveys were conducted using a structured questionnaire among 1164 physicians and pharmacists from May 23, 2014 to August 11, 2014. The survey consisted of questions about the participant's satisfaction with the medication surveillance program, clinical usefulness, clinical need for the medication surveillance program, and sociodemographic characteristics. Multivariate ordinal logistic regression was performed to investigate the factors influencing satisfaction levels with the medication surveillance program. RESULTS: We analyzed data from 1120 respondents, including 503 physicians and 617 pharmacists. Overall, 63.1% of the respondents were satisfied with the medication surveillance program. Pharmacists were more satisfied with the program than were physicians (69.1% vs. 55.6%; adjusted odds ratio, 2.13; 95% confidence interval, 1.65-2.76). Among the respondents, 77.8% cited a decrease in therapeutic duplication to be a major improvement resulting from the medication surveillance program, 82.6% considered the drug-drug interaction information useful, and 48.7% suggested that the program should include information on liver or kidney disease-drug interaction. CONCLUSIONS: Overall, 63.0% of physicians and pharmacists were satisfied, and a decrease in therapeutic duplication was regarded as the most beneficial component. Further improvements by considering clinical needs of physicians and pharmacists will be needed to increase satisfaction.

The risk profile of rhegmatogenous retinal detachment before and after using a fluoroquinolone: a 12 year nationwide self-controlled case series study.

Objectives: To determine whether or not fluoroquinolone use increases the incidence of retinal detachment. Design: Self-controlled case series analysis. Participants: Participants were identified using the South Korean National Health Insurance Database between 1 January 2004 and 31 December 2015. A total of 15 134 patients who experienced rhegmatogenous retinal detachment (RRD) with at least one prescription of a fluoroquinolone were included. Methods: Incidence rate ratios (IRRs) and their 95% CIs were calculated using conditional Poisson regression. The main outcome measure was a recorded diagnosis of RRD (ICD-10: H33.0) with a claim for the surgical code for RRD. Results: We found an increased risk of retinal detachment in the first 1-30 days following the initiation of fluoroquinolone therapy (IRR 1.85; 95% CI 1.71-1.95), which rose for the 31-60 days period (IRR 2.05; 95% CI 1.43-2.95) but remained constant after more than 60 days (IRR 1.25; 95% CI 0.75-2.10). However, the elevated risk was also found in the 1-30 day period prior to the initiation of fluoroquinolone therapy (IRR 1.58; 95% CI 1.49-1.68) and also 31-60 days before medication use (IRR 1.11; 95% CI 1.03-1.19). Conclusions: Our case-based study indicated that the risk after fluoroquinolone exposure doubled; however, the risk profile before and after fluoroquinolone use means that the association between fluoroquinolone use and retinal detachment might not be a causal relationship.

Potentially inappropriate medication and hospitalization/emergency department visits among the elderly in Korea.

OBJECTIVE: To investigate the association between potentially inappropriate medicine (PIM) use, defined using the American Geriatric Society (AGS) 2012 Beers criteria, and the risk of hospitalization or emergency department (ED) visits in elderly patients, and to examine the most frequently used PIMs among patients with adverse outcomes. DESIGN/SETTING: This was a retrospective study using National Health Insurance claims data from 2010 to 2012. INTERVENTION(S): Elderly patients who took PIMs are compared to those who were not taking PIMs. STUDY PARTICIPANTS: Elderly patients (n = 79 552) who visited medical institutions in Jeju Island during 2011. MAIN OUTCOME MEASURE: Hospitalization and ED visits were evaluated according to whether the patients took PIMs during the study period. The most frequent medications used by the PIM group were also investigated. RESULTS: The likelihood of hospitalization was higher in older patients who took at least one PIM than in those who were not taking PIMs during the study period (odds ratio 2.25, 95% confidence interval 2.09-2.44). Patients taking PIMs were more likely to visit EDs (odds ratio 1.59, 95% confidence interval 1.50-1.67). Among patients who were hospitalized or visited EDs, 45.5% had taken at least one PIM on that day. The most commonly used PIMs included chlorpheniramine maleate, diazepam, metoclopramide HCl and diclofenac sodium. CONCLUSION: Our findings indicate that PIM use can lead to negative health consequences, providing further evidence of the inappropriateness of these medications. Thus, pharmaceutical policies regarding PIM use may need to be implemented for elderly adults in Korea.

Physicians' and pharmacists' acceptance of online, real-time "drug combinations to avoid" messages.

UNLABELLED: Drug-induced prolongation of the electrocardiogram QT interval, a risk factor for ventricular arrhythmia and death, has been observed for some small drugs with masses < 1 kDa. Over the last two decades, patient exposure to large molecule monoclonal antibody drugs with masses > 40 kDa has increased dramatically; hence, the aim of this study was to systematically review the scientific literature for evidence of QT prolongation induced by these drugs. METHODS: The PubMed and Embase databases were searched for cases indicative of drug-induced QT prolongation for 28 pre-identified monoclonal antibody drugs authorized in Europe. Cases were identified by applying a standardized search string and a subsequent text search and manual review. In parallel, the public European Medicines Agency (EMA) database was searched for reported frequencies of adverse events indicative of QT prolongation. RESULTS: A valid case of drug-induced QT prolongation, caused indirectly by hypocalcaemia, could be identified for only 1 out of 28 monoclonal antibody drugs (denosumab) from the PubMed and Embase search. The EMA database showed no hits for denosumab. Considering that hypocalcaemia-mediated QT prolongation is an already-identified and labelled risk for denosumab, the current study did not identify any additional evidence of QT prolongation caused by monoclonal antibody drugs.

Comparative effectiveness of lazertinib in patients with EGFR T790M-positive non-small-cell lung cancer using a real-world external control.

Lazertinib is a recently developed third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors used for patients with advanced EGFR T790M-positive non-small-cell lung cancer. We evaluated the effectiveness of lazertinib compared with osimertinib using an external control. We obtained individual patient data for the lazertinib arm from the LASER201 trial and the osimertinib arm from registry data at the Samsung Medical Center. In total, 75 and 110 patients were included in the lazertinib and osimertinib groups, respectively. After propensity score matching, each group had 60 patients and all baseline characteristics were balanced. The median follow-up duration was 22.0 and 29.6 months in the lazertinib and osimertinib group, respectively. The objective response rate (ORR) were 76.7% and 86.7% for lazertinib and osimertinib, respectively (p = 0.08). The median progression-free survival (PFS) was 12.3 months (95% confidence interval [CI] 9.5-19.1) and 14.4 months (95% CI 11.8-18.1) for the lazertinib and osimertinib group, respectively (hazard ratio [HR] 0.97; 95% CI 0.64-1.45, p = 0.86). The median overall survival with lazertinib was not reached and that with osimertinib was 29.8 months (HR 0.44; 95% CI 0.25-0.77, p = 0.005). Our study suggests that lazertinib has an ORR and PFS comparable to those of osimertinib and has the potential for superior survival benefits.

Cardiovascular, Neurological, and Immunological Adverse Events and the 23-Valent Pneumococcal Polysaccharide Vaccine.

Importance: Despite widespread immunization with the 23-valent pneumococcal polysaccharide vaccine (PPSV23), safety concerns remain owing to a lack of statistical power and largely outdated evidence. Objective: To evaluate the association between cardiovascular, neurological, and immunological adverse events and PPSV23 vaccination in older adults. Design, Setting, and Participants: This population-based cohort study using a self-controlled risk interval design used a large linked database created by linking the Korea Immunization Registry Information System and the National Health Information Database (2018 to 2021). Participants included patients aged 65 years or older with a history of PPSV23 vaccination and incident cardiovascular, neurological, or immunological events during the risk and control intervals. Data were analyzed from November 2022 to April 2023. Exposure: 23-valent pneumococcal polysaccharide vaccine. Main Outcomes and Measures: The occurrence of 1 among 6 cardiovascular events (myocardial infarction, atrial fibrillation, cardiomyopathy, heart failure, hypotension, and myocarditis or pericarditis), 2 neurological events (Bell palsy and Guillain-Barré syndrome), and 3 immunological events (sepsis, thrombocytopenia, and anaphylaxis) during the risk and control periods. The risk and control intervals were defined as 1 to 28 and 57 to 112 days after PPSV23 vaccination, respectively. Conditional Poisson regression was used to estimate the incidence rate ratio (IRR) with a 95% CI. Results: Altogether, 4355 of the 1 802 739 individuals who received PPSV23 vaccination and experienced at least 1 outcome event were included (mean [SD] age, 72.4 [8.2] years; 2272 male participants [52.1%]). For cardiovascular events, there were no significant associations for myocardial infarction (IRR, 0.96; 95% CI, 0.81-1.15), heart failure (IRR, 0.85; 95% CI, 0.70-1.04), and stroke (IRR, 0.92; 95% CI, 0.84-1.02). Similarly, no increased risks were observed for neurological and immunological outcomes: Bell palsy (IRR, 0.95; 95% CI, 0.72-1.26), Guillain-Barré syndrome (IRR, 0.27; 95% CI, 0.06-1.17), sepsis (IRR, 0.99; 95% CI, 0.74-1.32), and thrombocytopenia (IRR, 1.18; 95% CI, 0.60-2.35). Conclusions and Relevance: In this self-controlled risk interval study, there was no appreciable increase in risk for most cardiovascular, neurological, or immunological adverse events following PPSV23. The updated safety profile of PPSV23 provides supportive evidence for the establishment of immunization strategies for older adults.

Factors Affecting Health-Related Quality of Life in Patients With Metastatic Breast Cancer.

PURPOSE: Improving survival and health-related quality of life (HRQOL), along with symptom relief, is important for the treatment of metastatic breast cancer (MBC). This study measured HRQOL and analyzed its influence on sociodemographic and clinical factors in patients with MBC. METHODS: We interviewed 298 patients with MBC to investigate their sociodemographic characteristics and HRQOL by using EuroQol-5D-5L (EQ-5D) between September and October 2014. We also reviewed medical records to examine the clinical condition of the patients, including disease progression, adverse events, treatments, chronic disease, and metastatic areas. The distribution of the EQ-5D index was compared between different clinical conditions by using the Kruskal-Wallis test. We also conducted multiple regression analyses to identify the factors affecting HRQOL in patients with MBC. RESULTS: The mean EQ-5D index was 0.79 for all patients surveyed. The mean EQ-5D index score was significantly lower in patients in the progressed state than in those in the progression-free survival state (0.73 vs. 0.80, p = 0.0002). The HRQOL of patients treated with chemotherapy alone was significantly lower than that of patients treated with hormonal or targeted therapy (0.76 vs. 0.82 or 0.85; p = 0.0020). Regression analysis revealed that the clinical factors associated with lower HRQOL were progressed state, chemotherapy, and adverse events, such as hair loss or stomatitis. Finally, young age, high income, and employment were the sociodemographic factors that were positively associated with better HRQOL. CONCLUSION: This study provides new information on the health utility of MBC patients on the basis of various patient characteristics and offers insights that can assist medical professionals in treating patients with MBC and help policymakers implement cancer strategies. Further research is needed to reflect the changing environment of cancer treatment and enrich available evidence.

A Propensity-Matched Retrospective Comparative Study with Historical Control to Determine the Real-World Effectiveness of Durvalumab after Concurrent Chemoradiotherapy in Unresectable Stage III Non-Small Cell Lung Cancer.

This study aimed to add real-world evidence to the literature regarding the effectiveness and safety of durvalumab consolidation (DC) after concurrent chemoradiotherapy (CCRT) in the treatment of unresectable stage III non-small cell lung cancer (NSCLC). Using a hospital-based NSCLC patient registry and propensity score matching in a 2:1 ratio, we conducted a retrospective cohort study of patients with unresectable stage III NSCLC who completed CCRT with and without DC. The co-primary endpoints were 2-year progression-free survival and overall survival. For the safety evaluation, we evaluated the risk of any adverse events requiring systemic antibiotics or steroids. Of 386 eligible patients, 222 patients-including 74 in the DC group-were included in the analysis after propensity score matching. Compared with CCRT alone, CCRT with DC was associated with increased progression-free survival (median: 13.3 vs. 7.6 months, hazard ratio[HR]: 0.63, 95% confidence interval[CI]: 0.42-0.96) and overall survival (HR: 0.47, 95% CI: 0.27-0.82) without an increased risk of adverse events requiring systemic antibiotics or steroids. While there were differences in patient characteristics between the present real-world study and the pivotal randomized controlled trial, we demonstrated significant survival benefits and tolerable safety with DC after the completion of CCRT.

Relationship between the early initiation of insulin treatment and diabetic complications in patients newly diagnosed with type 2 diabetes mellitus in Korea: A nationwide cohort study.

AIMS/INTRODUCTION: To evaluate the relationship between early insulin initiation within a year after type 2 diabetes mellitus diagnosis and the risk of diabetic complications. MATERIALS AND METHODS: We carried out a cohort study using the Korean National Health Insurance Service database. The study participants were newly diagnosed with type 2 diabetes mellitus between 2009 and 2013. After applying propensity score matching (1:1) to the cohort of patients who received two or more oral antidiabetic drugs (OADs) or insulin as the first prescription within 1 year after type 2 diabetes mellitus diagnosis, we computed hazard ratios (HRs) and 95% confidence intervals (CIs) using a Cox proportional hazards regression to compare the risk of diabetes-related microvascular and macrovascular complications and all-cause mortality in insulin versus OAD initiators. RESULTS: Within the cohort, 52,188 and 1,804 patients received OAD and insulin, respectively. After matching, each group contained 534 patients. Compared with the OAD group, the risk of overall microvascular complications was significantly higher for insulin (HR 1.48, 95% CI 1.28-1.71). No increased risks of overall macrovascular complications (HR 0.90, 95% CI 0.62-1.30) and all-cause mortality were observed (HR 1.06, 95% CI 0.67-1.68). CONCLUSIONS: In the present study, early insulin treatment was not associated with the risk of macrovascular complications and all-cause mortality compared with OAD treatment; however, the risk of microvascular complications was higher in the insulin group.

The Impact of Payment Scheme Changes on Medication Adherence and Persistence of Patients Diagnosed with Depression in Korea.

As of 1 July 2018, the Korean National Health Insurance Service (NHIS) changed the fee schedule for individual psychotherapy (IP). We sought to analyze the impact of the IP payment scheme changes on the medication adherence and persistence of patients diagnosed with depression in Korea. We utilized the NHIS claims database from 2017 to 2019. Patients who were newly diagnosed with depression and utilized IP and were prescribed antidepressants during the study period were included. Adherence was measured using the medication possession ratio (MPR), and persistence was measured using the length of therapy (LOT) during the follow-up period. Adherence and persistence during the pre-policy period (before the change of the payment scheme, from January 2018 until June 2018) and the post-policy period (after the change, from July 2018 until December 2019) were compared. During the study period, a total of 176,740 patients with depression were identified. The average MPR significantly increased from 0.20 to 0.33 in the pre- and post-policy periods, respectively (p < 0.001). The average LOT of the patients improved considerably from 36 to 56 days in the pre- and post-policy periods, respectively (p < 0.001). Poisson regression analysis showed that patients with depression who were female, 19-34 years of age (vs. 50-64 years or over 64 years), and in the post-policy period were significantly associated with greater adherence and persistence rates. Payment scheme changes were associated with an increased adherence and persistence of medication use among patients diagnosed with depression.

Clinical and Cost-Saving Effects of the Drug Utilization Review Modernization Project in Inpatient and Outpatient Settings in Korea.

OBJECTIVES: Korea's national health insurance authority introduced a drug utilization review modernization pilot project in which health professionals provided follow-up services to monitor adverse drug events. We aimed to evaluate the effects of the project on clinical and economic outcomes. METHODS: We conducted difference-in-differences analysis using National Health Insurance claims data from the Health Insurance Review and Assessment Service. We calculated the number of adverse drug events and allergic reactions as a clinical indicator and medical costs incurred to manage these events as an economic indicator. Absolute difference in each outcome measure was defined as the value after the project minus the value before the project. Difference-in-differences was defined as a difference in absolute differences between the intervention group and the control group. RESULTS: Overall, difference-in-differences were -43 and -826 for the number of drug-related adverse events and allergic reactions and -$198,700 and $53,318 for medical costs in the inpatient and outpatient settings, respectively. For outpatients, the monthly number of adverse drug events and allergic reactions has grown higher for the control group than for the intervention group after implementation of the pilot project. CONCLUSIONS: Implementation of the pilot project lowered the number of adverse drug events and allergic reactions in the inpatient and outpatient setting. The project also lowered medical costs incurred to manage these events in the inpatient setting only. Based on our findings, we recommend that the pilot project be expanded on a nationwide level at least in the inpatient setting.

Cancer risk associated with the use of valsartan in Korea: A nationwide cohort study.

BACKGROUND: Despite valsartan's widespread use, few studies have explored its potential carcinogenicity. We evaluated the association between valsartan and cancer. METHODS: We conducted a retrospective cohort study using data from 2002 to 2015 gathered from the National Health Insurance database. Patients with hypertension aged ≥ 30 who used valsartan or other angiotensin II receptor blockers (ARBs) were included. Eligible patients were those with no prior history of the use of any ARBs, diagnosis of cancer, or organ transplantation in the 4 years predating their first use of the drugs of interest. The primary and secondary outcomes included the occurrence of all cancers and site-specific solid cancers, respectively. After applying propensity score (PS) matching, Cox regression was used to calculate the hazard ratios (HRs) and 95 % confidence intervals (CIs). RESULTS: A total of 1,550,734 individuals were identified as new users of valsartan or other ARBs. Of the 153,047 valsartan users, 16,047 were diagnosed with cancer. No increased risk of overall cancer was observed in valsartan users as compared to other ARB users (aHR = 1.00; 95 % CI, 0.98-1.02). Valsartan was, however, associated with a slightly elevated risk of liver (aHR = 1.09; 95 % CI, 1.01-1.16) and kidney cancer (aHR = 1.11; 95 % CI, 1.02-1.22). CONCLUSION: Compared with other ARBs, valsartan did not increase the risk of overall cancer. A slightly increased risk for some solid cancers was associated with valsartan use, though the absolute rate difference was small.