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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.
Subject(s)
Acrylamides , Aniline Compounds , Carcinoma, Non-Small-Cell Lung , ErbB Receptors , Lung Neoplasms , Protein Kinase Inhibitors , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/mortality , ErbB Receptors/genetics , ErbB Receptors/antagonists & inhibitors , Male , Female , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/mortality , Aged , Middle Aged , Acrylamides/therapeutic use , Aniline Compounds/therapeutic use , Aniline Compounds/pharmacology , Protein Kinase Inhibitors/therapeutic use , Aged, 80 and over , Treatment Outcome , Progression-Free Survival , Mutation , Adult , Pyrimidines/therapeutic use , Indoles , Morpholines , PyrazolesABSTRACT
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pneumococcal polysaccharide vaccine (PPSV23), safety concerns remain owing to a lack of statistical power and largely outdated evidence.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 1â¯802â¯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.
Subject(s)
Bell Palsy , Guillain-Barre Syndrome , Heart Failure , Myocardial Infarction , Pneumococcal Vaccines , Sepsis , Thrombocytopenia , Aged , Humans , Male , Cohort Studies , Pneumococcal Vaccines/adverse effectsABSTRACT
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.
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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.
Subject(s)
Antirheumatic Agents , Arthritis, Rheumatoid , Cardiovascular Diseases , Humans , Cardiovascular Diseases/epidemiology , Retrospective Studies , Risk Factors , Arthritis, Rheumatoid/complications , Arthritis, Rheumatoid/drug therapy , Heart Disease Risk Factors , Antirheumatic Agents/adverse effects , Multicenter Studies as TopicABSTRACT
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.
Subject(s)
COVID-19 , Humans , Female , Male , Adolescent , Young Adult , Adult , Middle Aged , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , 2019-nCoV Vaccine mRNA-1273 , BNT162 Vaccine , RNA, Messenger , Vaccination/adverse effectsABSTRACT
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.
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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.
Subject(s)
Depression , Medication Adherence , Antidepressive Agents/therapeutic use , Databases, Factual , Depression/drug therapy , Female , Humans , Male , Retrospective StudiesABSTRACT
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.
Subject(s)
Angiotensin Receptor Antagonists , Neoplasms , Angiotensin Receptor Antagonists/adverse effects , Angiotensin-Converting Enzyme Inhibitors/adverse effects , Cohort Studies , Humans , Neoplasms/chemically induced , Neoplasms/epidemiology , Retrospective Studies , Valsartan/adverse effectsABSTRACT
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.
Subject(s)
Drug-Related Side Effects and Adverse Reactions , Hypersensitivity , Drug Utilization Review , Humans , Inpatients , Outpatients , Pilot ProjectsABSTRACT
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.
Subject(s)
Tramadol , Analgesics, Opioid/adverse effects , Case-Control Studies , Cross-Over Studies , Female , Humans , Male , Middle Aged , Odds Ratio , Seizures/chemically induced , Seizures/epidemiology , Tramadol/adverse effectsABSTRACT
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.
Subject(s)
Diabetes Complications , Diabetes Mellitus, Type 2 , Cohort Studies , Diabetes Complications/drug therapy , Diabetes Mellitus, Type 2/chemically induced , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Humans , Hypoglycemic Agents/adverse effects , InsulinABSTRACT
OBJECTIVES: To detect the signals for drospirenone-containing oral contraceptives (DCOCs) and describe the reporting pattern of adverse events (AEs) caused by DCOCs compared with levonorgestrel/desogestrel/gestodene-containing (second/third generation) oral contraceptives. DESIGN: A descriptive analysis of claims data. SETTING: The Korea Institute of Drug Safety & Risk Management-Korea Adverse Event Reporting System Database from 1 February 2008 to 31 December 2017. OUTCOME MEASURES: Signals for DCOCs were identified using three data mining indices. The characteristics, death cases, and the annual pattern of AE reports were compared between DCOCs and second/third generation oral contraceptives. RESULTS: Of the 242 DCOC-related AEs, 54 signals were detected and 10 were identified as new signals that were not included in Korea, US and UK label. The newly detected signals include deep vein thrombophlebitis and frequent urination. Serious AEs were more likely to be reported with DCOCs (7.85%) than with second/third generation oral contraceptives (2.92%). Five deaths after use of DCOCs were reported with vascular AEs, such as pulmonary embolism and thrombosis, whereas one death after use of second/third generation oral contraceptives was reported with the cardiac arrest. CONCLUSIONS: We identified 10 new signals related to DCOCs that were not included in the current label. Additionally, we found higher reports of the deaths and vascular AEs associated with DCOCs than with second/third generation oral contraceptives, which warrants careful monitoring to ensure the safe use of DCOCs.
Subject(s)
Contraceptives, Oral , Desogestrel , Androstenes/adverse effects , Contraceptives, Oral/adverse effects , Female , Humans , Republic of Korea , Risk FactorsABSTRACT
OBJECTIVES: To examine the risk of serious infections (SIs) among patients with rheumatoid arthritis (RA) treated with tocilizumab compared with tumor necrosis factor inhibitor (TNFi) in Korea. METHODS: We conducted a retrospective cohort study using the Korean National Health Insurance data. The study cohort included patients ≥18 years with RA who were initiated with tocilizumab or TNFi between January 2013 and June 2018. The primary outcome was a composite endpoint of SIs, defined as an infection resulting in intravenous antimicrobial therapy or hospitalization. Secondary outcomes were organ-specific SIs. To control for confounders, we used inverse probability of treatment weighting (IPTW) using propensity score. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using a multivariable Cox regression model. RESULTS: A total of 8794 patients were identified: 1395 and 7399 patients initiated with tocilizumab and TNFi, respectively. The mean follow-up durations were 1.2 years for tocilizumab initiators and 1.0 year for TNFi initiators. After IPTW and adjustment, no increased risk of SIs was observed in tocilizumab versus TNFi (HR, 1.00; 95%CI, 0.90-1.11). In the secondary analysis, tocilizumab was associated with a higher risk of skin and subcutaneous tissue infections (HR, 1.26; 95%CI, 1.02-1.54) and a lower risk of urological and gynecological infections (HR, 0.65; 95%CI, 0.49-0.87) compared to TNFi. CONCLUSION: In this population-based cohort of RA patients in Korea, tocilizumab was not associated with a higher risk of SI compared to TNFi. However, tocilizumab should be carefully used for patients at high risk for skin-related infections.
Subject(s)
Antibodies, Monoclonal, Humanized , Antirheumatic Agents , Arthritis, Rheumatoid , Infections , Antibodies, Monoclonal, Humanized/adverse effects , Antirheumatic Agents/adverse effects , Arthritis, Rheumatoid/drug therapy , Humans , Infections/chemically induced , Infections/epidemiology , Republic of Korea/epidemiology , Retrospective Studies , Tumor Necrosis Factor Inhibitors/adverse effectsABSTRACT
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.
Subject(s)
Antirheumatic Agents , Arthritis, Rheumatoid , Biological Products , Adalimumab/therapeutic use , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Biological Products/therapeutic use , Cost-Benefit Analysis , Etanercept/therapeutic use , HumansABSTRACT
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.
Subject(s)
COVID-19 , Mental Disorders , Cohort Studies , Disease Susceptibility , Humans , Mental Disorders/epidemiology , SARS-CoV-2ABSTRACT
AIMS: To identify the association between ranibizumab and risk of stroke and acute myocardial infarction (AMI) in patients with exudative age-related macular degeneration (AMD). METHODS: We identified patients aged ≥45 years who received ranibizumab for exudative AMD from the Korean National Health Insurance database. Of these, we selected patients suffering stroke or AMI for the self-controlled case series. We estimated incidence rate ratios (IRR) for stroke or AMI by comparing incidence rates of ranibizumab-exposed periods to that of baseline using conditional Poisson regression. The risks of haemorrhagic and ischaemic strokes were also calculated separately. RESULTS: Among 33 134 patients receiving ranibizumab, 2397 patients had stroke or AMI. The risk of stroke (IRR=0.83, 95% CI 0.75 to 0.91) was not increased during the overall exposed period; however, there was a marginally elevated risk in ≥57 days exposed period (IRR=1.14, 95% CI 1.001 to 1.31). When analysing by the types of stroke, no increased risks of haemorrhagic (IRR=1.01, 95% CI 0.80 to 1.26) and ischaemic stroke (IRR=0.78, 95% CI 0.71 to 0.86) were observed during the exposed period, although the risks of ischaemic and haemorrhagic stroke were slightly elevated during ≥57 days exposed period. We could not find an association between ranibizumab and AMI. CONCLUSIONS: Ranibizumab intravitreal injections did not increase the overall risk of stroke or AMI. Although the cardiovascular risk in patient receiving ranibizumab seems to be low, continuous monthly use of ranibizumab for high-risk patients should be judged carefully.
Subject(s)
Cardiovascular Diseases/etiology , Ranibizumab/adverse effects , Risk Assessment/methods , Wet Macular Degeneration/drug therapy , Aged , Aged, 80 and over , Angiogenesis Inhibitors/administration & dosage , Angiogenesis Inhibitors/adverse effects , Cardiovascular Diseases/epidemiology , Female , Humans , Incidence , Intravitreal Injections , Macula Lutea/pathology , Male , Ranibizumab/administration & dosage , Republic of Korea/epidemiology , Retrospective Studies , Risk Factors , Tomography, Optical Coherence/methods , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Wet Macular Degeneration/diagnosisABSTRACT
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.
Subject(s)
Antidepressive Agents/therapeutic use , Benzodiazepines/therapeutic use , Adult , Antidepressive Agents/pharmacology , Benzodiazepines/pharmacology , Cohort Studies , Female , Humans , Male , MortalityABSTRACT
OBJECTIVE: To examine healthcare resource utilisation (HRU) and direct medical costs for patients with diabetic macular oedema (DME) treated with antivascular endothelial growth factor (anti-VEGF) in Korea by comparing with those for (1) patients with diabetes mellitus (DM) without retinopathy and (2) patients with neovascular age-related macular degeneration (nAMD) treated with anti-VEGF. DESIGN: Retrospective cohort study. SETTING: The Korean National Health Insurance (NHI) database from 1 January 2014 to 31 December 2016. PARTICIPANTS: We identified 1398 patients older than 30 years of age who received anti-VEGF treatment for DME in 2015 after excluding patients who had a diagnosis of nAMD in 2015 and any cancer in the preceding year. MAIN OUTCOME MEASURES: One-year healthcare resource use and direct medical costs of patients with DME treated with anti-VEGF. RESULTS: In total, 1398 patients with DME receiving anti-VEGF, 12 813 patients with DM without retinopathy and 12 222 patients with nAMD receiving anti-VEGF were identified. Hospital admissions and outpatient visits were highest in patients with DME, while the number of licensed anti-VEGF injections in those with DME was about half that of those with nAMD (2.1 vs 3.9 per patient per year). Mean 1-year medical costs were also higher in patients with DME (US$6723) than in those with DM without retinopathy (US$2687) and nAMD (US$4980). In a multivariable analysis with matched cohorts, DME was associated with 66% higher medical costs for comorbid diseases (adjusted OR (aOR), 1.66; 95% CI 1.45 to 1.90) and 50% lower anti-VEGF injections (aOR, 0.50; 95% CI 0.46 to 0.54) compared with nAMD. CONCLUSIONS: The overall HRU and economic burden for DME treated with anti-VEGF were higher than for DM without retinopathy or for nAMD treated with anti-VEGF. Meanwhile, the lower number of licensed anti-VEGF injections compared with nAMD may reflect a potential lack of ophthalmological treatment for DME supported by the NHI in Korea.
Subject(s)
Diabetes Mellitus , Diabetic Retinopathy , Macular Edema , Angiogenesis Inhibitors/therapeutic use , Costs and Cost Analysis , Delivery of Health Care , Diabetes Mellitus/drug therapy , Diabetic Retinopathy/drug therapy , Endothelial Growth Factors/therapeutic use , Humans , Intravitreal Injections , Macular Edema/drug therapy , Ranibizumab/therapeutic use , Republic of Korea , Retrospective Studies , Vascular Endothelial Growth Factor AABSTRACT
OBJECTIVE: We aimed to investigate whether concomitant use of benzodiazepines and opioids is associated with an increased risk of death in a population-based case-crossover setting. METHODS: We conducted a case-crossover study using the National Sample Cohort database. We introduced a 30-day hazard period before the onset of death and three consecutive previous 30-day control periods with a 30-day washout period. The use of opioids and/or benzodiazepines during the hazard period was compared with that in the three control periods. We performed the conditional logistic regression analysis to estimate the adjusted odds ratios (aORs) and their 95% confidence intervals (CIs). RESULTS: A total of 13,161 individuals who previously used benzodiazepines or opioids and died were included in the study. The risk of death was higher in patients with concomitant use of benzodiazepines and opioids (aOR, 1.86; 95% CI, 1.71-2.02) than in those who used either benzodiazepines or opioids only. In the subgroup analysis among concomitant users, the mortality risks were highest in patients aged less than 20â¯years (aOR, 3.85; 95% CI, 1.65-8.99), male patients (aOR, 2.20; 95% CI, 1.93-2.51), and patients with renal disease (aOR, 2.42; 95% CI, 1.57-3.74). CONCLUSION: In this study, concomitant use of benzodiazepines and opioids was associated with a higher risk of death compared with use of a single drug. The risks and benefits of co-prescribing of benzodiazepines and opioids must be weighed carefully.
Subject(s)
Analgesics, Opioid/adverse effects , Benzodiazepines/adverse effects , Mortality , Adult , Aged , Cohort Studies , Cross-Over Studies , Drug Interactions , Female , Humans , Male , Middle Aged , Odds Ratio , Young AdultABSTRACT
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.