Risk of encephalitis and meningitis after COVID-19 vaccination in South Korea: a self-controlled case series analysis.

BACKGROUND: Several neurological manifestations shortly after a receipt of coronavirus infectious disease 2019 (COVID-19) vaccine have been described in the recent case reports. Among those, we sought to evaluate the risk of encephalitis and meningitis after COVID-19 vaccination in the entire South Korean population. METHODS: We conducted self-controlled case series (SCCS) analysis using the COVID-19 immunization record data from the Korea Disease Control Agency between February 2021 and March 2022, linked with the National Health Insurance Database between January 2021 and October 2022. We retrieved all medical claims of adults aged 18 years or older who received at least one dose of COVID-19 vaccines (BNT162b2, mRNA-1273, ChAdOx1-S, or Ad26.COV2.S), and included only those who had a diagnosis record for encephalitis or meningitis within the 240-day post-vaccination period. With day 0 defined as the date of vaccination, risk window was defined as days 1-28 and the control window as the remainder period excluding the risk windows within the 240-day period. We used conditional Poisson regression to estimate the incidence rate ratios (IRR) with 95% confidence intervals (CI), stratified by dose and vaccine type. RESULTS: From 129,956,027 COVID-19 vaccine doses administered to 44,564,345 individuals, there were 251 and 398 cases of encephalitis and meningitis during the risk window, corresponding to 1.9 and 3.1 cases per 1 million doses, respectively. Overall, there was an increased risk of encephalitis in the first 28 days of COVID-19 vaccination (IRR 1.26; 95% CI 1.08-1.47), which was only significant after a receipt of ChAdOx1-S (1.49; 1.03-2.15). For meningitis, no increased risk was observed after any dose of COVID-19 vaccine (IRR 1.03; 95% CI 0.91-1.16). CONCLUSIONS: Our findings suggest an overall increased risk of encephalitis after COVID-19 vaccination. However, the absolute risk was small and should not impede COVID-19 vaccine confidence. No significant association was found between the risk of meningitis and COVID-19 vaccination.

Investigating the safety profiles of exogenous melatonin and associated adverse events: A pharmacovigilance study using WHO-VigiBase.

Melatonin, a pineal hormone that modulates circadian rhythms, sleep, and neurotransmitters, is widely used to treat sleep disorders. However, there are limited studies on the safety of melatonin. Therefore, we aimed to present the overall patterns of adverse events (AEs) following melatonin administration and identify potential safety signals associated with melatonin. Using VigiBase, a global individual case safety report (ICSRs) database managed by the World Health Organization (WHO), we conducted a retrospective, observational, pharmacovigilance study of melatonin between January 1996 and September 2022. Disproportionality analysis was conducted using two comparator settings: all other drugs and other sleep medications. We used multivariable logistic regression to estimate reporting odds ratios (RORs) with 95% confidence intervals (CIs) to compare the frequencies of AEs reporting between melatonin and each comparator setting. Furthermore, we assessed adverse events of special interests (AESIs) that could potentially be associated with melatonin. Signals were identified when the following criteria were met: cases ≥3, x2 ≥ 4, IC025 ≥ 0, and the lower end of the 95% CI of ROR > 2. These signals were then compared with the AE information on the drug labels provided by regulatory bodies. A total of 35 479 AE reports associated with melatonin were identified, with a higher proportion of reports from females (57.1%) and individuals aged 45-64 years (20.8%). We identified 21 AEs that were commonly detected as safety signals in the disproportionality analyses, including tic, educational problems, disturbance in social behavior, body temperature fluctuation, and growth retardation. In AESI analyses, accidents and injuries (adjusted ROR 2.97; 95% CI, 2.80-3.16), fall (2.24; 2.12-2.37), nightmare (4.90; 4.37-5.49), and abnormal dreams (3.68; 3.19-4.25) were detected as a signal of melatonin when compared to all other drugs, whereas those signals were not detected when compared to other sleep medications. In this pharmacovigilance study, exogenous melatonin showed safety profiles comparable to other sleep medications. However, several unexpected potential safety signals were identified, underscoring the need for further investigation at the population level.

Real-world data emulating randomized controlled trials of non-vitamin K antagonist oral anticoagulants in patients with venous thromboembolism.

BACKGROUND: Emulating randomized controlled trials (RCTs) by real-world evidence (RWE) studies would benefit future clinical and regulatory decision-making by balancing the limitations of RCT. We aimed to evaluate whether the findings from RWE studies can support regulatory decisions derived from RCTs of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with venous thromboembolism (VTE). METHODS: Five landmark trials (AMPLIFY, RE-COVER II, Hokusai-VTE, EINSTEIN-DVT, and EINSTEIN-PE) of NOACs were emulated using the South Korean nationwide claims database (January 2012 to August 2020). We applied an active comparator and new-user design to include patients who initiated oral anticoagulants within 28 days from their VTE diagnoses. The prespecified eligibility criteria, exposure (each NOAC, such as apixaban, rivaroxaban, dabigatran, and edoxaban), comparator (conventional therapy, defined as subcutaneous heparin followed by warfarin), and the definition of outcomes from RCTs were emulated as closely as possible in each separate emulation cohort. The primary outcome was identical to each trial, which was defined as recurrent VTE or VTE-related death. The safety outcome was major bleeding. Propensity score matching was conducted to balance 69 covariates between the exposure groups. Effect estimates for outcomes were estimated using the Mantel-Haenszel method and Cox proportional hazards model and subsequently compared with the corresponding RCT estimates. RESULTS: Compared to trial populations, real-world study populations were older (range: 63-69 years [RWE] vs. 54-59 years [RCT]), with more females (55-60.5% vs. 39-48.3%) and had a higher prevalence of active cancer (4.2-15.4% vs. 2.5-9.5%). The emulated estimates for effectiveness outcomes showed superior effectiveness of NOAC (AMPLIFY: relative risk 0.81, 95% confidence interval 0.70-0.94; RE-COVER II: hazard ratio [HR] 0.60, 0.37-0.96; Hokusai-VTE: 0.49, 0.31-0.78; EINSTEIN-DVT: 0.54, 0.33-0.89; EINSTEIN-PE: 0.50, 0.34-0.74), when contrasted with trials that showed non-inferiority. For safety outcomes, all emulations except for AMPLIFY and EINSTEIN-DVT yielded results consistent with their corresponding RCTs. CONCLUSIONS: This study revealed the feasibility of complementing RCTs with RWE studies by using claims data in patients with VTE. Future studies to consider the different demographic characteristics between RCT and RWE populations are needed.

Predictors of COVID-19 Vaccine Hesitancy Among Parents of Children Aged 5-11 Years in Korea.

This was a cross-sectional study using the data collected from a nationwide survey between November and December 2022 to explore factors associated with hesitancy towards coronavirus disease 2019 (COVID-19) vaccination for children. Among 3,011 participants with child aged 5-11 years, 82.5% demonstrated hesitancy towards vaccinating their child. This was more common among mothers (odds ratio 1.84 [95% confidence interval 1.46-2.31]), those residing outside metropolitan area (urban: 2.46 [1.89-3.20]; rural: 2.87 [2.09-3.93]) or with history of COVID-19 diagnosis (2.22 [1.78-2.76]). Parents were also hesitant if their child recently had COVID-19 (3.41 [2.67-4.37]). Conversely, they were less likely to be hesitant if they had three or more children (0.66 [0.46-0.94]) or if their child has underlying medical condition(s) (0.54 [0.41-0.71]). Our findings highlight high prevalence of parental hesitancy towards COVID-19 vaccination for children, and call for targeted outreach efforts from the stakeholders to facilitate the vaccine uptake in this pediatric population.

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.

Consistency of listed indications and contraindications between the U.S., the U.K., Japan, and Korea on prescription drug labels.

Inclusion of indications and contraindications in drug labeling is essential for drug approval. Little is known regarding how well new drug information labels agree across countries. To compare the number of indications and contraindications on the labels of drugs in the U.S., U.K., Japan, and Korea, we selected 81 new drugs approved in these countries between 2008 and 2016 and assessed the number of indications and contraindications on each label. Average and median numbers with standard deviations were presented for the 81-drug set, and for subsets grouped according to drug class. Correlation analyses were conducted to estimate Pearson and concordance correlation coefficients. No significant difference was observed across countries in the number of indications, the average being 1.69, 1.67, 1.54, and 1.51 in the U.S., the U.K., Korea, and Japan (p = 0.31), respectively. By contrast, substantial variation was observed in the number of contraindications, the average being 1.54, 2.42, 3.53, and 3.00 in the U.S., the U.K., Korea, and Japan (p < 0.001), respectively. Pearson correlation coefficients comparing contraindications were 0.40, 0.48, and 0.47 for U.S.-U.K., U.S.-Korea, and U.S.-Japan, but 0.83, 0.73, and 0.71 for U.K.-Korea, U.K.-Japan, and Korea-Japan, respectively (p < 0.01). There is consistency in the number of indications, but a substantial discrepancy in contraindications listed in drug labeling across countries. Further study is warranted to improve global harmonization of contraindication listings.

Dynamic Patterns and Persistence of Anticoagulation Therapy in Patients with Venous Thromboembolism in South Korea: A Nationwide Cohort Study.

BACKGROUND: Venous thromboembolism (VTE) is associated with increased morbidity, mortality, and health care expenditure. However, the comprehensive utilization of anticoagulation therapy in patients with VTE, especially regarding active cancer, in real-world practice remains unclear. OBJECTIVE: To describe the prescription, persistence, and patterns of anticoagulation therapy among patients with VTE stratified according to active cancer. METHODS: Using Korean nationwide claims data, we identified an incident, treatment-naïve cohort of patients with VTE from 2013 to 2019 and classified them according to the presence/absence of active cancer. We explored the secular trends, treatment patterns (e.g., discontinuation, interruption, and switch), and persistence of anticoagulation therapy. RESULTS: There were 48,504 and 7,255 patients without and with active cancer, respectively. Non-vitamin K antagonist oral anticoagulants (NOACs) were the most common anticoagulant in both groups (65.1 and 57.9%, respectively). The prescription of NOACs increased steeply over time, regardless of active cancer, whereas parenteral anticoagulants (PACs) plateaued and warfarin decreased sharply. A heterogeneous pattern was observed between the groups without and with active cancer (3-month persistence was 60.8, 62.9, 57.2, and 3.4%, respectively; 6-month persistence was 42.3, 33.5, 25.9, and 1.2% vs. 9.9%). Median durations of continuous anticoagulant therapy for warfarin, NOAC, and PAC were 183, 147, and 3 days in nonactive cancer patients, and 121, 117, and 44 days in active cancer patients. CONCLUSION: Our findings suggest that there were substantial differences in persistence, patterns, and patient characteristics of anticoagulant therapy based on index anticoagulant and active cancer.

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.

Neurological and immunological adverse events after pneumococcal conjugate vaccine in children using national immunization programme registry data.

BACKGROUND: Despite the general consensus on the safety of pneumococcal conjugate vaccine (PCV), safety concerns unveiled during post-licensure surveillance need to be addressed. We investigated whether there is a transient increased risk following a three-dose series of pneumococcal conjugate vaccine (PCV) administered at 2, 4 and 6 months of age. METHODS: This was a population-based cohort study using the Korea immunization registry data linked to nationwide administrative claims data. Self-controlled risk interval analysis was conducted for PCV recipients who had an outcome of interest within pre-defined risk and control intervals between 2018 and 2022. The outcomes were anaphylaxis, asthma, encephalopathy, febrile seizure, Kawasaki disease and thrombocytopenia. We used conditional Poisson regression model to estimate the incidence rate ratios (IRRs) and 95% confidence intervals (CIs) comparing the outcomes in the risk and control intervals. RESULTS: Of 1 114 096 PCV recipients, 8661 had outcomes either in the risk or control intervals. Their mean age at Dose 1 was 10.0 weeks, 58.3% were boys, and 85.3% received 13-valent PCV. PCV was not associated with an increased risk of any outcomes except for febrile seizure. There were 408 (56.0%) cases of febrile seizure in the risk interval, corresponding to an IRR of 1.27 (95% CI 1.10-1.47). CONCLUSIONS: It is reassuring to note that there was no increased risk of the potential safety concerns following PCV administration. Despite the transient increased risk of febrile seizure, absolute numbers of cases were small. Febrile seizure is generally self-limiting with a good prognosis, and should not discourage parents or caregivers from vaccinating their children.

Evaluation of the Regulatory Required Post-Authorization Safety Study for Propacetamol: Nested Case-Control and Case-Time-Control Studies.

PURPOSE: Following the withdrawal of propacetamol in Europe owing to safety issues, the regulatory authority of South Korea requested a post-marketing surveillance study to investigate its safety profile. MATERIALS AND METHODS: We conducted nested case-control and case-time-control (CTC) analyses of cases and controls identified for outcomes of interest, including anaphylaxis, thrombosis, and Stevens-Johnson syndrome (SJS), using the claims database of South Korea, 2010-2019. Risk-set sampling was used to match each case with up to 10 controls for age, sex, cohort entry date, and follow-up duration. Exposure to anaphylaxis, thrombosis, and SJS was assessed within 7, 90, and 30 days of the index date, respectively. We calculated odds ratios (OR) with 95% confidence intervals (CIs) using conditional logistic regression to assess the risk of outcomes associated with propacetamol. RESULTS: We identified cases of anaphylaxis (n=61), thrombosis (n=95), and SJS (n=1) and matched them to controls (173, 268, and 4, respectively). In the nested case-control analysis, the ORs for anaphylaxis and SJS were inestimable given the small number of propacetamol users during the risk period; meanwhile, the OR for thrombosis was 1.60 (95% CI 0.71-3.62). In the CTC design, the effect estimate was only estimated for thrombosis (OR 0.56, 95% CI 0.09-3.47). CONCLUSION: In both nested case-control and CTC analyses, propacetamol was not associated with an increased risk of anaphylaxis, thrombosis, or SJS. The findings from this study, which used routinely collected clinical data, provide reassuring real-world evidence regarding the safety of propacetamol in a nationwide population to support regulatory decision-making.

Lazertinib versus Platinum-Based Chemotherapy with Epidermal Growth Factor Receptor (EGFR)-Positive Non-Small-Cell Lung Cancer after Failing EGFR-Tyrosine Kinase Inhibitor: A Real-World External Comparator Study.

BACKGROUND: Lazertinib is a third-generation tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR-TKI) that selectively inhibit common EGFR mutation and T790M mutation in non-small-cell lung cancer (NSCLC) patients. No previous studies have compared lazertinib to platinum-based chemotherapy. We have compared lazertinib with platinum-based chemotherapy in EGFR-mutated NSCLC patients after previous EGFR-TKI therapy. METHODS: We retrospectively compared 200 patients from LASER201, LASER301, and LASER-PMS studies to 334 patients who were treated with platinum-based chemotherapy after previous EGFR-TKI from the Samsung Medical Center. After propensity score matching (PSM), we selected 156 patients from each group. The primary outcome was progression-free survival (PFS), with overall survival (OS), objective response rate (ORR), and time to treatment discontinuation (TTD) as secondary outcomes. RESULTS: The median follow-up of PFS was 15.61 months in the lazertinib group and 21.67 months in the external control group. The PFS was significantly longer in patients who were treated with lazertinib than those treated with platinum-based chemotherapy (10.97 months vs. 5.10 months; adjusted hazard ratio (HR) 0.40; 95% confidence interval (CI), 0.29-0.55; p < 0.01) after PSM. Lazertinib showed superior OS (32.23 months vs. 18.73 months; adjusted HR 0.45; 95% CI, 0.29-0.69; p < 0.001), ORR (64.1% vs. 47.4%), and TTD (11.66 months vs. 6.73 months; adjusted HR 0.54; 95% CI, 0.39-0.75; p < 0.001) compared to platinum-based chemotherapy. CONCLUSION: Based on this retrospective, external control study, lazertinib has demonstrated significantly better efficacy compared with platinum-based chemotherapy. The external controls provide important context to evaluate efficacy in single-arm studies.

Premature Mortality and Causes of Death Among People With Epilepsy: A Nationwide Population-Based Incident Cohort Study.

BACKGROUND AND OBJECTIVES: People with epilepsy (PWE) are at risk of premature death with considerable variability according to the study population. We aimed to estimate the risk and causes of death in PWE according to age, disease severity, disease course, comorbidities, and socioeconomic status in Korea. METHODS: We conducted a nationwide population-based retrospective cohort study using the National Health Insurance database linked with the national death register. Newly treated PWE from 2008 to 2016 who were identified by antiseizure medication (ASM) prescriptions and diagnostic codes for epilepsy/seizure were included and observed until 2017. We assessed all-cause and cause-specific crude mortality rates and standardized mortality ratios (SMRs). RESULTS: Among 138,998 PWE, 20,095 deaths were identified, and the mean follow-up period was 4.79 years. The SMR was 2.25 in the overall group of PWE, with a higher value in the younger age group at diagnosis and a shorter time interval after diagnosis. The SMR in the monotherapy group was 1.56, while that in the group with 4 or more ASMs was 4.93. PWE without any comorbidities had an SMR of 1.61. PWE who were rural residents had a higher SMR than those who were urban residents (2.47 vs 2.03, respectively). The causes of death among PWE were cerebrovascular disease (18.9%, SMR 4.50), malignant neoplasms outside the CNS (15.7%, SMR 1.37), malignant neoplasms of the CNS (6.7%, SMR 46.95), pneumonia (6.0%, SMR 2.08), and external causes (7.2%, SMR 2.17), including suicide (2.6%, SMR 2.07). Epilepsy itself and status epilepticus accounted for 1.9% of the overall death. The excess mortality associated with pneumonia and external causes was persistently high, whereas the excess mortality associated with malignancy and cerebrovascular diseases tended to decrease with increasing time since diagnosis. DISCUSSION: This study showed excess mortality in PWE, even in those without comorbidities and those receiving monotherapy. Regional disparities and sustained risks of deaths from external causes over 10 years imply potential points of intervention. In addition to active control of seizures, education about injury prevention, monitoring for suicidal ideation, and efforts to improve accessibility to epilepsy care are all required to reduce mortality.

Heterogeneous distributions in clinical events preceding anticoagulant treatment nonpersistence in patients with venous thromboembolism stratified by active cancer: A nationwide cohort study.

BACKGROUND: Nonpersistence in anticoagulation therapy is common and associated with undesirable clinical outcomes in patients with venous thromboembolism (VTE). METHODS: We investigated preceding clinical events of treatment nonpersistence (e.g., switching, discontinuing, or restarting) in VTE patients with and without active cancer using Korean claims database. RESULTS: Clinically significant events including thromboembolic events, hepatic function change and surgery preceded treatment nonpersistence, but heterogeneous distributions of clinical events were observed in the presence of active cancer. Patients with active cancer had a low rate of clinical events preceding treatment nonpersistence, and new active cancer diagnosis in the nonactive cancer group was most common before the switch to parenteral anticoagulants from warfarin or non-vitamin K antagonist oral anticoagulants (NOACs). CONCLUSION: These findings suggest that clinically significant events can precede treatment nonpersistence and largely paralleled current guidelines for patients with VTE, whereas heterogeneous distributions of clinical events were observed in the presence of active cancer.

Barriers to COVID-19 vaccine surveillance: the issue of under-reporting adverse events.

OBJECTIVES: This study investigated the reporting rates of adverse events following immunization (AEFIs) to the spontaneous reporting system (SRS) and its predictors among individuals with AEFIs after coronavirus disease 2019 (COVID-19) vaccination. METHODS: A cross-sectional, web-based survey was conducted from December 2, 2021 to December 20, 2021, recruiting participants >14 days after completion of a primary COVID-19 vaccination series. Reporting rates were calculated by dividing the number of participants who reported AEFIs to the SRS by the total number of participants who experienced AEFIs. We estimated adjusted odds ratios (aORs) using multivariate logistic regression to determine factors associated with spontaneous AEFIs reporting. RESULTS: Among 2,993 participants, 90.9% and 88.7% experienced AEFIs after the first and second vaccine doses, respectively (reporting rates, 11.6 and 12.7%). Furthermore, 3.3% and 4.2% suffered moderate to severe AEFIs, respectively (reporting rates, 50.5 and 50.0%). Spontaneous reporting was more prevalent in female (aOR, 1.54; 95% confidence interval [CI], 1.31 to 1.81); those with moderate to severe AEFIs (aOR, 5.47; 95% CI, 4.45 to 6.73), comorbidities (aOR, 1.31; 95% CI, 1.09 to 1.57), a history of severe allergic reactions (aOR, 2.02; 95% CI, 1.47 to 2.77); and those who had received mRNA-1273 (aOR, 1.25; 95% CI, 1.05 to 1.49) or ChAdOx1 (aOR, 1.62; 95% CI, 1.15 to 2.30) vaccines versus BNT162b2. Reporting was less likely in older individuals (aOR, 0.98; 95% CI, 0.98 to 0.99 per 1-year age increment). CONCLUSIONS: Spontaneous reporting of AEFIs after COVID-19 vaccination was associated with younger age, female sex, moderate to severe AEFIs, comorbidities, history of allergic reactions, and vaccine type. AEFIs under-reporting should be considered when delivering information to the community and in public health decision-making.

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.

A study of the regional differences in propacetamol-related adverse events using VigiBase data of the World Health Organization.

Upon withdrawal of propacetamol, an injectable formulation of the paracetamol prodrug, in Europe due to safety concerns, South Korea's regulatory body requested a post-marketing surveillance study exploring its safety profile. We characterized regional disparities in adverse events (AE) associated with propacetamol between Asia and Europe using the World Health Organization's pharmacovigilance database, VigiBase. We performed disproportionality analyses using reporting odds ratios (rOR) and information component (IC) to determine whether five AEs (anaphylaxis, Stevens-Johnson syndrome, thrombosis, contact dermatitis/eczema, injection site reaction [ISR]) were associated with propacetamol versus non-propacetamol injectable antipyretics in Asia and Europe, separately. In Asia, there was a high reporting ratio of propacetamol-related ISR (rOR 5.72, 95% CI 5.19-6.31; IC025 1.27), satisfying the signal criteria; there were no reports of thrombosis and contact dermatitis/eczema. Two signals were identified in Europe, with higher reporting ratios for thrombosis (rOR 7.45, 95% CI 5.19-10.71; IC025 1.92) and contact dermatitis/eczema (rOR 16.73, 95% CI 12.48-22.42; IC025 2.85). Reporting ratios of propacetamol-related anaphylaxis were low for Asia and Europe. While signals were found for thrombosis and contact dermatitis/eczema in Europe, these were not detected in Asia. These findings suggest potential ethnic differences in propacetamol-related AEs between Asia and Europe, which could serve as supportive data for future decision-making.

Predictors of COVID-19 booster vaccine hesitancy among fully vaccinated adults in Korea: a nationwide cross-sectional survey.

OBJECTIVES: This study explored predictors of coronavirus disease 2019 (COVID-19) booster hesitancy among fully vaccinated young adults and parental COVID-19 vaccine hesitancy for their children. METHODS: This cross-sectional study administered an online survey from December 2 to December 20, 2021. We enrolled participants aged 18-49 years, for whom ≥2 weeks had passed after their initial COVID-19 vaccination. We estimated odds ratios (ORs) with 95% confidence intervals (CIs) using multivariate logistic regression to evaluate factors associated with booster/vaccine hesitancy. RESULTS: Among the 2,993 participants, 48.8% showed hesitancy (wait and see: 40.2%; definitely not: 8.7%). Booster hesitancy was more common among women (OR, 1.25; 95% CI, 1.05 to 1.50), younger people (OR, 1.44; 95% CI, 1.17 to 1.77), those with a lower education level (OR, 2.05; 95% CI, 1.10 to 3.82), those who received the mRNA-1273 vaccine type (OR, 2.01; 95% CI, 1.65 to 2.45), and those who experienced serious adverse events following previous COVID-19 vaccination (OR, 2.03; 95% CI, 1.47 to 2.80). The main reasons for booster hesitancy were concerns about safety (54.1%) and doubts about efficacy (29.8%). Among the 1,020 respondents with children aged <18 years, 65.8% were hesitant to vaccinate their children against COVID-19; hesitancy was associated with younger parental age, education level, the type of vaccine the parent received, and a history of COVID-19 infection. CONCLUSIONS: Concerns about the efficacy and safety of COVID-19 vaccines were the major barrier to booster acceptance. The initial COVID-19 vaccine type (mRNA-1273), young age, gender (women), a low education level, and adverse events after the first COVID-19 vaccine were key predictors of booster hesitancy.

Differential Demographic and Clinical Characteristics between MMR Vaccinated and Unvaccinated Children in South Korea: A Nationwide Study.

In the context of recent measles outbreaks, substantial factors associated with measles-mumps-rubella (MMR) unvaccination need to be clarified. This study aimed to identify differential demographic and clinical characteristics between MMR vaccinated and unvaccinated groups. We used a large-linked database to identify children born between 2008 and 2016 by combining data from the Korea Immunization Registry Information System and National Health Information database. The MMR vaccination status was ascertained up to the age of 2 to define MMR vaccinated and unvaccinated groups. We conducted a multivariate logistic regression to estimate odds ratios (ORs) with 95% confidence intervals (CIs) to identify factors associated with MMR unvaccination. Of 3,973,253 children, 75,674 (1.9%) did not receive the MMR vaccine. Compared with the MMR vaccinated group, the underutilization of healthcare resources was more notable in the MMR unvaccinated group (number of outpatient visits (5.73 ± 12.1 vs. 25.8 ± 17.06); days hospitalized (1.69 ± 14.5 vs. 2.32 ± 6.90)). Children were less likely to receive the MMR vaccine if they were born with congenital anomaly (OR 2.12; 95% CI 1.90-2.36), were never admitted to an intensive care unit (1.88; 1.78-1.98), or never visited an emergency room (3.57; 3.53-3.72). There were substantial factors associated with MMR unvaccination, underscoring a need to optimize targeted interventions tailored to the subset of children in South Korea.

Association between human papillomavirus vaccination and serious adverse events in South Korean adolescent girls: nationwide cohort study.

OBJECTIVE: To evaluate the association between human papillomavirus (HPV) vaccination and serious adverse events in adolescent girls in South Korea. DESIGN: Cohort study. SETTING: A large linked database created by linking the Korea Immunization Registry Information System and the National Health Information Database, between January 2017 and December 2019. PARTICIPANTS: 441 399 girls aged 11-14 years who had been vaccinated in 2017: 382 020 had been vaccinated against HPV and 59 379 had not been vaccinated against HPV. MAIN OUTCOME MEASURES: Outcomes were 33 serious adverse events, including endocrine, gastrointestinal, cardiovascular, musculoskeletal, haematological, dermatological, and neurological diseases. A cohort design was used for the primary analysis and a self-controlled risk interval design for the secondary analysis; both analyses used a risk period of one year after HPV vaccination for each outcome. Incidence rate and adjusted rate ratios were estimated using Poisson regression in the primary analysis, comparing the HPV vaccinated group with the HPV unvaccinated group, and adjusted relative risks were estimated using conditional logistic regression in the secondary analysis. RESULTS: Among the 33 predefined serious adverse events, no associations were found with HPV vaccination in the cohort analysis, including Hashimoto's thyroiditis (incidence rate per 100 000 person years: 52.7 v 36.3 for the vaccinated and unvaccinated groups; adjusted rate ratio 1.24, 95% confidence interval 0.78 to 1.94) and rheumatoid arthritis (incidence rate per 100 000 person years: 168.1 v 145.4 for the vaccinated and unvaccinated groups; 0.99, 0.79 to 1.25), with the exception of an increased risk observed for migraine (incidence rate per 100 000 person years: 1235.0 v 920.9 for the vaccinated and unvaccinated groups; 1.11, 1.02 to 1.22). Secondary analysis using self-controlled risk intervals confirmed no associations between HPV vaccination and serious adverse events, including migraine (adjusted relative risk 0.67, 95% confidence interval 0.58 to 0.78). Results were robust to varying follow-up periods and for vaccine subtypes. CONCLUSIONS: In this nationwide cohort study, with more than 500 000 doses of HPV vaccines, no evidence was found to support an association between HPV vaccination and serious adverse events using both cohort analysis and self-controlled risk interval analysis. Inconsistent findings for migraine should be interpreted with caution considering its pathophysiology and the population of interest.