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.

Effectiveness and Safety of COVID-19 Vaccination During Preconceptional and Preclinical Pregnancy Period: A National Population Study

Background@#We aimed to assess the risk of maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and early abortive outcomes after the association between coronavirus disease 2019 (COVID-19) vaccination during the preconceptional period and preclinical pregnancy, which are likely to be inadvertent vaccination. @*Methods@#We used data from the Korea Disease Control and Prevention Agency-COVID19-National Health Insurance Service cohort from December 2020 to December 2021. The vaccinated pregnant women were matched to unvaccinated pregnant controls at a 1:4 ratio.The risks of SARS-CoV-2 infection and intensive care unit (ICU) admission within 14 days of infection were analyzed to assess its effectiveness. For safety measures, the adjusted relative risks (aRRs) of early abortive outcomes for the first COVID-19 vaccination during the preconceptional and preclinical periods were calculated considering covariates. We compared the risk of early abortion between mRNA and viral vector vaccines. @*Results@#The overall COVID-19 vaccination rates during the preconceptional period and preclinical pregnancy were 3.1% (6,662/215,211) and 2.6% (5,702/215,211), respectively.The cumulative incidence of ICU admission within 14 days of SARS-CoV-2 infection was 6/100,000 in the unvaccinated group, whereas there were no ICU admissions in the vaccinated groups. The risks of early abortive outcomes were not significantly different between the preconceptional vaccination group and the unvaccinated group (aRR, 1.04; 95% confidence interval [CI],0.99–1.10) or between preclinical pregnancy vaccination and their matched controls (1.02; 95% CI, 0.96–1.08). mRNA and viral vector vaccines have shown similar risks for early abortive outcomes and miscarriages. @*Conclusion@#Our findings have provided compelling evidence regarding the effectiveness and safety of COVID-19 vaccination prior to and during early pregnancy. Further research is required to extend the safety and efficacy profiles of COVID-19 vaccines to pregnant women and their babies.

Short-term safety profile of COVID-19 vaccination in children and adolescents with underlying medical conditions: a prospective cohort study

Purpose@#This article was to collect data on the safety of coronavirus disease 2019 (COVID-19) vaccines in children with underlying medical conditions. @*Methods@#We constructed a prospective cohort of children and adolescents aged 5 to 19 years who had received at least one dose of COVID-19 vaccine. Patients diagnosed with and treated for chronic kidney disease, autoimmune disease, or other chronic conditions at the Seoul National University Children’s Hospital were recruited from June to December 2022. A mobile survey questionnaire was sent to their guardians. The presence of adverse events on the day (day 0), 3 weeks (day 21), and 6 months (day 180) after the 1st dose of COVID-19 vaccine was recorded by the guardians. @*Results@#A total of 73 children participated. The median age was 14 years, and 64.4% of the patients were male. On the day of immunization, 65.8% of the patients reported at least one adverse event. Pain at the injection site, fatigue, headache, arthralgia, and myalgia were the most common symptoms. The prevalence of adverse events decreased over time (65.8% on day 0, 27.4% between days 0 and 21, and 24.6% between days 21 and 180). Severe acute respiratory syndrome coronavirus 2 infection after the 1st dose occurred in 17 patients (23.3%) and one of the patients (5.88%) was hospitalized due to infection. @*Conclusions@#Adverse events after COVID-19 vaccination were generally mild in children and adolescents with underlying medical conditions. Our findings provide evidence for the safety of COVID-19 vaccination in the vulnerable 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 twoweeks 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.

Trends in Prescribing of Antiseizure Medications in South Korea: Real-World Evidence for Treated Patients With Epilepsy

Background@#and Purpose We investigated the trends in the prescribing of antiseizure medication (ASM) over a 9-year period, and provide real-world data regarding ASM prescriptions of patients with epilepsy in South Korea. @*Methods@#This study used data in the Korean National Health Information Database for the period from 2009 to 2017. We included 18 oral ASMs, which were classified into older and newer ASMs based on them first becoming available on the market before or after 1991, respectively. The annual trends in ASM prescriptions were plotted over the 9-year study period, and changes in these trends were evaluated as average annual percentage changes (AAPCs) using Poisson regression. Age- and sex-stratified analyses were also conducted. @*Results@#Overall, the proportion of prescriptions involving polytherapy with three or more ASMs increased from 10.08% in 2009 to 10.99% in 2017 (AAPC=0.9%, p<0.001) over the 9-year study period. Among monotherapies, although valproate (VPA) was the most frequently prescribed ASM, the prescription rate of levetiracetam (LEV) steadily increased regardless of age and sex over the study period. The monotherapy prescription trends differed depending on age and sex. In the five most frequently used ASM combination regimens, the prescription rates of VPA/LEV, LEV/oxcarbazepine, and LEV/lamotrigine regimens showed increasing tendencies. In contrast, prescription rates for all combined regimens of older ASMs declined over time in all age groups. @*Conclusions@#This is the first epidemiological study of the changes in prescription trends for ASM in South Korea based on nationwide data from 2009 to 2017. We found progressive increases in the use of newer ASMs for both monotherapy and duotherapy, and for polytherapy with three or more ASMs over the 9-year study period.

Arthralgia and Myalgia Associated with the Use of Bisphosphonate:An Active Monitoring Study

Objective@#We investigated arthralgia and myalgia associated with the use of oral bisphosphonate (BP) by conducting a survey of patient. @*Methods@#The pharmacists conducted a survey between 1 Oct 2019 and 30 Sep 2020 among patients who were dispensed BP in community pharmacies to assess their demographic and medical characteristics, and their experiences with, and process for pain. Logistic regression analyses were performed to find the risk factors associated with the pain, and the odds ratios (OR) and 95% confidence intervals (CI) were determined. @*Results@#A total of 160 patients who used BP participated in the survey (74 [46.3%] used risedronate; 61 [38.1%] used alendronate; 23 [14.4%] used ibandronate), and 20 (12.5%) of them experienced pain. Significant statistical differences of the characteristics between patients who experienced pain or not were observed regarding menopause, and parity. Compared with women who had one or two parity, women who had more than three parity were associated with the decreased risk of pain (OR, 0.24; 95% CI, 0.04-0.98). Moreover, steady exercise was associated with the decreased risk of pain compared to less exercise (OR, 0.37; 95% CI, 0.14-0.98). @*Conclusion@#Our findings suggest that the risk of pain in BP-treated patients might be different regarding the different ingredients of BP, and dosing frequency. This survey highlights a need for a further safety research to understand the factors influencing the pain associated with the BP treatment.

Treatment Patterns of Osteoporosis and Factors Affecting the Prescribing of Bone-forming Agents: From a National Health Insurance Claims Database

Objective@#To analyze osteoporosis treatment patterns and teriparatide prescription-associated factors in Korea by using a national health insurance claims database. @*Methods@#We utilized the Health Insurance Review & Assessment Service National Patients Sample claims database to identify patients (aged ≥50 years) with at least one osteoporosis claim (International Classification of Disease 10th revision code: M80, M81, M82) and at least one prescription for osteoporosis medication (antiresorptive agents:bisphosphonates, selective estrogen receptor modulators, denosumab, and calcitonin; bone-forming agent: teriparatide) in 2018. Demographic characteristics and healthcare utilization patterns were analyzed. Factors associated with teriparatide prescriptions were assessed using a multivariate logistic regression model. @*Results@#Records showed that 44,815 patients were prescribed osteoporosis medications in 2018; the percentage of patients prescribed each treatment was as follows: 86.6% bisphosphonates, 13.9% selective estrogen receptor modulators, 3.1% calcitonin, 2.1% denosumab, and 0.7% teriparatide. A greater proportion of patients prescribed teriparatide were ≥75 years (53.4% vs. 33.8%) and had fractures (63.9% vs. 12.8%) compared to the same for antiresorptives (p<0.001). Patients prescribed teriparatide had higher Charlson comorbidity index values (1.2±1.3 vs. 0.9±1.2) and were more frequently hospitalized (0.8±1.3 vs. 0.1±0.5) than those prescribed antiresorptives (p<0.001). Elderly patients (≥75 years old; adjusted OR=1.66; 95% CI 1.16-2.38) and those with fractures (adjusted OR=6.23; 95% CI 4.76-8.14) were more likely to be prescribed teriparatide than antiresorptives. @*Conclusion@#Patients prescribed teriparatide were older and more likely to have severe osteoporosis than those prescribed antiresorptives.

A survey for Management of Drug Safety Evaluation System for Investigational Product

Objective@#To gather the opinions of hands-on workers for successful introduction of the Development Safety Update Report (DSUR) according to a five-year comprehensive plan for clinical trial development [Ministry of Food and Drug Safety, 2019]. @*Methods@#We conducted a survey on considerations that industry stakeholders may have related to the enforcement of the DSUR. A questionnaire was distributed among pharmacovigilance specialists from 13 pharmaceutical companies in South Korea on June 4, 2020. The questionnaire comprised two sections: 1) current status of the Drug Safety Data Management System and 2) considerations on the implementation and management of the DSUR. @*Results@#All respondents have agreed the introduction of DSUR is inevitable for regulatory harmonization and safety of trial subject. However, most respondents (85%) felt concern about additional workload with DSUR implementation. They answered that format and operation system of DSUR should be harmonized with those of international standards and authorities need to minimize double burden due to related report. @*Conclusion@#All respondents asserted that domestic DSUR should be harmonized with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) E2F guidelines. Respondents from global companies also suggested regulatory authorities allow DSUR written in English to replace Korean version considering their deadline for submission.Moreover, every respondent agreed regulatory authorities need delicate effort when implementing mandatory submission of DSUR to ensure that even small pharmaceutical companies with no experience in DSUR can comply with the system.

Exploring the Perception on Drug Utilization Review System and DUR Modernization Pilot Project: A Qualitative Study Using Focus Group Interviews

Objective@#To explore the perception of drug utilization review (DUR) system and DUR modernization pilot project among healthcare professionals and patients. @*Methods@#We conducted 8 times of focus group interviews (FGI) between August 1, 2019 to December 31, 2019. The healthcare professionals and patients who participated in the DUR modernization pilot project were included in the present study. Based on the type of project participation or medical institution, the participants were divided into the following four groups: group 1, hospital; group 2, clinic; group 3, pharmacy; and group 4, patient. Within each group, interviews were conducted under a pre-defined agenda to identify the implicit perceptions of the participants; the contents of the interviews were, then, categorized. @*Results@#Healthcare professionals established a consensus on the positive aspects of the DUR system and DUR modernization pilot project. However, substantial concerns remain, such as additional workload associated with monitoring adverse events or acquiring consents from patients. Furthermore, a difference of opinion over the DUR convenience system was observed. Among 3 DUR convenience system, the personal medication history review service was highly utilized, but pop-up hold function and communication system was rarely used. @*Conclusion@#We observed that systematic intervention using the DUR system is effective for both healthcare providers and consumers. Adverse events caused by inappropriate drug use can be prevented by continuous patient monitoring. Therefore, the role of DUR system needs to be expanded to establish a safe drug management system.

Survival, Prognosis, and Clinical Feature of Refractory Myasthenia Gravis: a 15-year Nationwide Cohort Study

Background@#Myasthenia gravis (MG) is a rare classic autoimmune disease where immunosuppressant therapies have been successful to reduce MG attributable mortality fairly well. However, patients with refractory MG (rMG) among the actively treated MG (aMG) are nonresponsive to conventional therapy and display high disease severity, which calls for further research. We aimed to determine survival, prognosis, and clinical feature of patients with rMG compared to non-rMG. @*Methods@#Retrospective nationwide cohort study using Korea's healthcare database between 2002 and 2017 was conducted. Patients with rMG (n = 47) and non-rMG (n = 4,251) who were aged > 18 years, followed-up for ≥ 1 year, and prescribed immunosuppressants within 2 years after incident MG diagnosis were included. Patients with rMG were defined as administered plasma exchange or intravenous immunoglobulin at least 3 times per year after receiving ≥ 2 immunosuppressants. All-cause mortality, myasthenic crisis, hospitalization, pneumonia/ sepsis, and emergency department (ED) visits were measured using Cox proportional hazard models and pharmacotherapy patterns for rMG were assessed. @*Results@#The rMG cohort included a preponderance of younger patients and women. The adjusted hazard ratio was 2.49 (95% confidence interval, 1.26–4.94) for mortality, 3.14 (2.25–4.38) for myasthenic crisis, 1.54 (1.15–2.06) for hospitalization, 2.69 (1.74–4.15) for pneumonia/sepsis, and 1.81 (1.28–2.56) for ED visits for rMG versus non-rMG. The immunosuppressant prescriptions were more prevalent in patients with rMG, while the difference was more remarkable before rMG onset rather than after rMG onset. @*Conclusion@#Despite the severe prognosis of rMG, the strategies for pharmacotherapeutic regimens were similar in those two groups, suggesting that intensive monitoring and introduction of timely treatment options in the early phase of MG are required.

Increasing Trends in the Incidence and Prevalence of Epilepsy in Korea

Background@#and Purpose There have been few reports on recent trends in the occurrence of epilepsy. The aim of this study was to estimate the incidence and prevalence of epilepsy and analyze their annual trends in Korea over the period 2009–2017. @*Methods@#This nationwide population-based study was carried out using the National Health Insurance Service of Korea database. A prevalent case was defined as one of a patient receiving a prescription of anticonvulsants under the diagnostic codes for epilepsy or seizure. An incident case was ascertained by confirming the absence of any epilepsy-related diagnostic codes and anticonvulsant prescription for 2 years or more before the operational definition for a prevalent case was met. Alternative operational definitions for epilepsy were tested. The temporal trends of the incidence and prevalence of epilepsy were analyzed using a Poisson regression model, and are expressed as average annual percentage changes (AAPCs). @*Results@#The incidence of epilepsy increased from 28.7/100,000 persons in 2009 to 35.4/100,000 persons in 2017. The prevalence increased gradually from 3.4/1,000 persons in 2009 to 4.8/1,000 persons in 2017. These increasing trends were more evident among elderly subjects aged ≥75 years and in those who had codes for epilepsy or seizure as an additional diagnosis. Age standardization revealed a less prominent but still increasing trend in both incidence (AAPC=0.48%) and prevalence (AAPC=3.11%). @*Conclusions@#There have been increasing trends in both the prevalence and incidence of epilepsy in Korea between 2009 and 2017. This finding appears to be related to societal aging and the high incidence of symptomatic epilepsy in the elderly population.

Clinical outcomes of COVID-19 following the use of angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers among patients with hypertension in Korea: a nationwide study / 한국역학회지

OBJECTIVES@#Recent evidence has shown no harm associated with the use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin-receptor blockers (ARBs) in patients with coronavirus disease 2019 (COVID-19). We sought to further clarify the possible association between ACEI/ARB use and the risk of poor clinical outcomes of COVID-19. @*METHODS@#From the completely enumerated COVID-19 cohort in Korea, we identified 1,290 patients with hypertension, of whom 682 had and 603 did not have records of ACEI/ARB use during the 30-day period before their COVID-19 diagnosis. Our primary endpoint comprised clinical outcomes, including all-cause mortality, use of mechanical ventilation, intensive care unit admission, and sepsis. We used inverse probability of treatment weighting (IPTW) to mitigate selection bias, and a Poisson regression model to estimate the relative risks (RRs) and 95% confidence intervals (CIs) for comparing outcomes between ACEI/ARB users and non-users. @*RESULTS@#Compared to non-use, ACEI/ARB use was associated with lower clinical outcomes (IPTW-adjusted RR, 0.60; 95% CI, 0.42 to 0.85; p=0.005). For individual outcomes, ACEI/ARB use was not associated with all-cause mortality (IPTW-adjusted RR, 0.62; 95% CI, 0.35 to 1.09; p=0.097) or respiratory events (IPTW-adjusted RR, 0.99; 95% CI, 0.84 to 1.17; p=0.904). Subgroup analysis showed a trend toward a protective role of ACEIs and ARBs against overall outcomes in men (IPTW-adjusted RR, 0.84; 95% CI, 0.69 to 1.03; pinteraction=0.008) and patients with pre-existing respiratory disease (IPTW-adjusted RR, 0.74; 95% CI, 0.60 to 0.92; pinteraction=0.002). @*CONCLUSIONS@#We present clinical evidence to support continuing ACE/ARB use in COVID-19 patients with hypertension based on the completely enumerated Korean cohort.

Socioeconomic disparities in Korea by health insurance type during the COVID-19 pandemic: a nationwide study / 한국역학회지

OBJECTIVES@#This study explored socioeconomic disparities in Korea using health insurance type as a proxy during the ongoing coronavirus disease 2019 (COVID-19) pandemic. @*METHODS@#We conducted a retrospective cohort study using Korea’s nationwide healthcare database, which contained all individuals who received a diagnostic test for COVID-19 (n=232,390) as of May 15, 2020. We classified our cohort by health insurance type into beneficiaries of the National Health Insurance (NHI) or Medicaid programs. Our study outcomes were infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and COVID-19-related outcomes, a composite of all-cause death, intensive care unit admission, and mechanical ventilation use. We estimated age-, sex-, and Charlson comorbidity index score–adjusted odds ratios (aORs) with 95% confidence intervals (CIs) using a multivariable logistic regression analysis. @*RESULTS@#Of the 218,070 NHI and 14,320 Medicaid beneficiaries who received COVID-19 tests, 7,777 and 738 tested positive, respectively. The Medicaid beneficiaries were older (mean age, 57.5 vs. 47.8 years), more likely to be males (47.2 vs. 40.2%), and had a higher comorbidity burden (mean CCI, 2.0 vs. 1.7) than NHI beneficiaries. Compared to NHI beneficiaries, Medicaid beneficiaries had a 22% increased risk of SARS-CoV-2 infection (aOR, 1.22; 95% CI, 1.09 to 1.38), but had no significantly elevated risk of COVID-19-related outcomes (aOR 1.10, 95% CI 0.77 to 1.57); the individual events of the composite outcome yielded similar findings. @*CONCLUSIONS@#As socioeconomic factors, with health insurance as a proxy, could serve as determinants during the current pandemic, pre-emptive support is needed for high-risk groups to slow its spread.

Arthralgia and Myalgia Associated with the Use of Bisphosphonate:An Active Monitoring Study

Objective@#We investigated arthralgia and myalgia associated with the use of oral bisphosphonate (BP) by conducting a survey of patient. @*Methods@#The pharmacists conducted a survey between 1 Oct 2019 and 30 Sep 2020 among patients who were dispensed BP in community pharmacies to assess their demographic and medical characteristics, and their experiences with, and process for pain. Logistic regression analyses were performed to find the risk factors associated with the pain, and the odds ratios (OR) and 95% confidence intervals (CI) were determined. @*Results@#A total of 160 patients who used BP participated in the survey (74 [46.3%] used risedronate; 61 [38.1%] used alendronate; 23 [14.4%] used ibandronate), and 20 (12.5%) of them experienced pain. Significant statistical differences of the characteristics between patients who experienced pain or not were observed regarding menopause, and parity. Compared with women who had one or two parity, women who had more than three parity were associated with the decreased risk of pain (OR, 0.24; 95% CI, 0.04-0.98). Moreover, steady exercise was associated with the decreased risk of pain compared to less exercise (OR, 0.37; 95% CI, 0.14-0.98). @*Conclusion@#Our findings suggest that the risk of pain in BP-treated patients might be different regarding the different ingredients of BP, and dosing frequency. This survey highlights a need for a further safety research to understand the factors influencing the pain associated with the BP treatment.

Treatment Patterns of Osteoporosis and Factors Affecting the Prescribing of Bone-forming Agents: From a National Health Insurance Claims Database

Objective@#To analyze osteoporosis treatment patterns and teriparatide prescription-associated factors in Korea by using a national health insurance claims database. @*Methods@#We utilized the Health Insurance Review & Assessment Service National Patients Sample claims database to identify patients (aged ≥50 years) with at least one osteoporosis claim (International Classification of Disease 10th revision code: M80, M81, M82) and at least one prescription for osteoporosis medication (antiresorptive agents:bisphosphonates, selective estrogen receptor modulators, denosumab, and calcitonin; bone-forming agent: teriparatide) in 2018. Demographic characteristics and healthcare utilization patterns were analyzed. Factors associated with teriparatide prescriptions were assessed using a multivariate logistic regression model. @*Results@#Records showed that 44,815 patients were prescribed osteoporosis medications in 2018; the percentage of patients prescribed each treatment was as follows: 86.6% bisphosphonates, 13.9% selective estrogen receptor modulators, 3.1% calcitonin, 2.1% denosumab, and 0.7% teriparatide. A greater proportion of patients prescribed teriparatide were ≥75 years (53.4% vs. 33.8%) and had fractures (63.9% vs. 12.8%) compared to the same for antiresorptives (p<0.001). Patients prescribed teriparatide had higher Charlson comorbidity index values (1.2±1.3 vs. 0.9±1.2) and were more frequently hospitalized (0.8±1.3 vs. 0.1±0.5) than those prescribed antiresorptives (p<0.001). Elderly patients (≥75 years old; adjusted OR=1.66; 95% CI 1.16-2.38) and those with fractures (adjusted OR=6.23; 95% CI 4.76-8.14) were more likely to be prescribed teriparatide than antiresorptives. @*Conclusion@#Patients prescribed teriparatide were older and more likely to have severe osteoporosis than those prescribed antiresorptives.

A survey for Management of Drug Safety Evaluation System for Investigational Product

Objective@#To gather the opinions of hands-on workers for successful introduction of the Development Safety Update Report (DSUR) according to a five-year comprehensive plan for clinical trial development [Ministry of Food and Drug Safety, 2019]. @*Methods@#We conducted a survey on considerations that industry stakeholders may have related to the enforcement of the DSUR. A questionnaire was distributed among pharmacovigilance specialists from 13 pharmaceutical companies in South Korea on June 4, 2020. The questionnaire comprised two sections: 1) current status of the Drug Safety Data Management System and 2) considerations on the implementation and management of the DSUR. @*Results@#All respondents have agreed the introduction of DSUR is inevitable for regulatory harmonization and safety of trial subject. However, most respondents (85%) felt concern about additional workload with DSUR implementation. They answered that format and operation system of DSUR should be harmonized with those of international standards and authorities need to minimize double burden due to related report. @*Conclusion@#All respondents asserted that domestic DSUR should be harmonized with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) E2F guidelines. Respondents from global companies also suggested regulatory authorities allow DSUR written in English to replace Korean version considering their deadline for submission.Moreover, every respondent agreed regulatory authorities need delicate effort when implementing mandatory submission of DSUR to ensure that even small pharmaceutical companies with no experience in DSUR can comply with the system.

Exploring the Perception on Drug Utilization Review System and DUR Modernization Pilot Project: A Qualitative Study Using Focus Group Interviews

Objective@#To explore the perception of drug utilization review (DUR) system and DUR modernization pilot project among healthcare professionals and patients. @*Methods@#We conducted 8 times of focus group interviews (FGI) between August 1, 2019 to December 31, 2019. The healthcare professionals and patients who participated in the DUR modernization pilot project were included in the present study. Based on the type of project participation or medical institution, the participants were divided into the following four groups: group 1, hospital; group 2, clinic; group 3, pharmacy; and group 4, patient. Within each group, interviews were conducted under a pre-defined agenda to identify the implicit perceptions of the participants; the contents of the interviews were, then, categorized. @*Results@#Healthcare professionals established a consensus on the positive aspects of the DUR system and DUR modernization pilot project. However, substantial concerns remain, such as additional workload associated with monitoring adverse events or acquiring consents from patients. Furthermore, a difference of opinion over the DUR convenience system was observed. Among 3 DUR convenience system, the personal medication history review service was highly utilized, but pop-up hold function and communication system was rarely used. @*Conclusion@#We observed that systematic intervention using the DUR system is effective for both healthcare providers and consumers. Adverse events caused by inappropriate drug use can be prevented by continuous patient monitoring. Therefore, the role of DUR system needs to be expanded to establish a safe drug management system.

Survival, Prognosis, and Clinical Feature of Refractory Myasthenia Gravis: a 15-year Nationwide Cohort Study

Background@#Myasthenia gravis (MG) is a rare classic autoimmune disease where immunosuppressant therapies have been successful to reduce MG attributable mortality fairly well. However, patients with refractory MG (rMG) among the actively treated MG (aMG) are nonresponsive to conventional therapy and display high disease severity, which calls for further research. We aimed to determine survival, prognosis, and clinical feature of patients with rMG compared to non-rMG. @*Methods@#Retrospective nationwide cohort study using Korea's healthcare database between 2002 and 2017 was conducted. Patients with rMG (n = 47) and non-rMG (n = 4,251) who were aged > 18 years, followed-up for ≥ 1 year, and prescribed immunosuppressants within 2 years after incident MG diagnosis were included. Patients with rMG were defined as administered plasma exchange or intravenous immunoglobulin at least 3 times per year after receiving ≥ 2 immunosuppressants. All-cause mortality, myasthenic crisis, hospitalization, pneumonia/ sepsis, and emergency department (ED) visits were measured using Cox proportional hazard models and pharmacotherapy patterns for rMG were assessed. @*Results@#The rMG cohort included a preponderance of younger patients and women. The adjusted hazard ratio was 2.49 (95% confidence interval, 1.26–4.94) for mortality, 3.14 (2.25–4.38) for myasthenic crisis, 1.54 (1.15–2.06) for hospitalization, 2.69 (1.74–4.15) for pneumonia/sepsis, and 1.81 (1.28–2.56) for ED visits for rMG versus non-rMG. The immunosuppressant prescriptions were more prevalent in patients with rMG, while the difference was more remarkable before rMG onset rather than after rMG onset. @*Conclusion@#Despite the severe prognosis of rMG, the strategies for pharmacotherapeutic regimens were similar in those two groups, suggesting that intensive monitoring and introduction of timely treatment options in the early phase of MG are required.

Increasing Trends in the Incidence and Prevalence of Epilepsy in Korea

Background@#and Purpose There have been few reports on recent trends in the occurrence of epilepsy. The aim of this study was to estimate the incidence and prevalence of epilepsy and analyze their annual trends in Korea over the period 2009–2017. @*Methods@#This nationwide population-based study was carried out using the National Health Insurance Service of Korea database. A prevalent case was defined as one of a patient receiving a prescription of anticonvulsants under the diagnostic codes for epilepsy or seizure. An incident case was ascertained by confirming the absence of any epilepsy-related diagnostic codes and anticonvulsant prescription for 2 years or more before the operational definition for a prevalent case was met. Alternative operational definitions for epilepsy were tested. The temporal trends of the incidence and prevalence of epilepsy were analyzed using a Poisson regression model, and are expressed as average annual percentage changes (AAPCs). @*Results@#The incidence of epilepsy increased from 28.7/100,000 persons in 2009 to 35.4/100,000 persons in 2017. The prevalence increased gradually from 3.4/1,000 persons in 2009 to 4.8/1,000 persons in 2017. These increasing trends were more evident among elderly subjects aged ≥75 years and in those who had codes for epilepsy or seizure as an additional diagnosis. Age standardization revealed a less prominent but still increasing trend in both incidence (AAPC=0.48%) and prevalence (AAPC=3.11%). @*Conclusions@#There have been increasing trends in both the prevalence and incidence of epilepsy in Korea between 2009 and 2017. This finding appears to be related to societal aging and the high incidence of symptomatic epilepsy in the elderly population.

Clinical outcomes of COVID-19 following the use of angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers among patients with hypertension in Korea: a nationwide study / 한국역학회지

OBJECTIVES@#Recent evidence has shown no harm associated with the use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin-receptor blockers (ARBs) in patients with coronavirus disease 2019 (COVID-19). We sought to further clarify the possible association between ACEI/ARB use and the risk of poor clinical outcomes of COVID-19. @*METHODS@#From the completely enumerated COVID-19 cohort in Korea, we identified 1,290 patients with hypertension, of whom 682 had and 603 did not have records of ACEI/ARB use during the 30-day period before their COVID-19 diagnosis. Our primary endpoint comprised clinical outcomes, including all-cause mortality, use of mechanical ventilation, intensive care unit admission, and sepsis. We used inverse probability of treatment weighting (IPTW) to mitigate selection bias, and a Poisson regression model to estimate the relative risks (RRs) and 95% confidence intervals (CIs) for comparing outcomes between ACEI/ARB users and non-users. @*RESULTS@#Compared to non-use, ACEI/ARB use was associated with lower clinical outcomes (IPTW-adjusted RR, 0.60; 95% CI, 0.42 to 0.85; p=0.005). For individual outcomes, ACEI/ARB use was not associated with all-cause mortality (IPTW-adjusted RR, 0.62; 95% CI, 0.35 to 1.09; p=0.097) or respiratory events (IPTW-adjusted RR, 0.99; 95% CI, 0.84 to 1.17; p=0.904). Subgroup analysis showed a trend toward a protective role of ACEIs and ARBs against overall outcomes in men (IPTW-adjusted RR, 0.84; 95% CI, 0.69 to 1.03; pinteraction=0.008) and patients with pre-existing respiratory disease (IPTW-adjusted RR, 0.74; 95% CI, 0.60 to 0.92; pinteraction=0.002). @*CONCLUSIONS@#We present clinical evidence to support continuing ACE/ARB use in COVID-19 patients with hypertension based on the completely enumerated Korean cohort.