Purpose: Vaccine hesitancy is among the top ten threats to global health, and access to precise data on adverse events following immunization (AEFIs) is imperative to alleviate public concerns surrounding vaccines. This study aimed to present the overall trends of AEFIs reported in South Korea. Materials and Methods: We evaluated the trends of AEFIs using the Korea Institute of Drug Safety & Risk Management-Korea Adverse Event Reporting System database between January 2005 and December 2017. AEFIs were classified into five categories to evaluate associations between vaccines and AEFIs through a case-non-case study: neurologic reactions, general systemic reactions, local reactions, allergic reactions, and others. Results: Among 54378 reported adverse events (AEs) associated with all vaccines approved in South Korea, more than half (56.7%) occurred following influenza vaccination, followed by the pneumococcal (11.6%) and Bacillus Calmette-Guérin (BCG) vaccines (5.0%). After immunization with most vaccines, general systemic reactions were most common, followed by local and neurologic reactions. Adjusted reporting odds ratios were calculated for all neurologic, general, local, and allergic reactions: of all vaccines, rotavirus [neurologic 2.43, 95% confidence interval (CI), 2.25–2.62], BCG (general; 2.20, 95% CI, 1.91–2.53), BCG (local; 3.15, 95% CI, 2.69–3.68), and Japanese encephalitis (allergic 2.38, 95% CI, 1.98–2.87) vaccines showed the highest values. Conclusion The majority of reported AEFIs were non-serious and mostly general systemic reactions. Sufficient knowledge on the AEFIs would secure public confidence on the safety of vaccines, thereby reducing public health burden from vaccine-preventable diseases.

PURPOSE: Statins, metformin, angiotensin-converting enzyme (ACE) inhibitors, and angiotensin receptor blockers (ARBs) have been suggested for treating age-related macular degeneration (AMD) due to their pleiotropic effects. Therefore, we investigated whether these drugs prevent AMD. MATERIALS AND METHODS: We conducted a nested case-control study using the Korean National Health Insurance Service database. Using risk-set sampling of age, sex, cohort entry date, and follow-up duration, we identified incident patients with AMD and 10 matching controls in cohorts with diabetes mellitus or cardiovascular diseases. Exposure was assessed within one year before the index date using patient prescription records. We conducted conditional logistic regression to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) to evaluate the association between cardiovascular medications and AMD. RESULTS: Our study included 2330 cases and 23278 controls from a cohort of 231274 patients. The ORs (95% CI) for AMD occurrence in users prescribed with statins, metformin, ACE inhibitors, and ARBs were 1.12 (0.94–1.32), 1.15 (0.91–1.45), 0.90 (0.61–1.34), and 1.21 (1.05–1.39), respectively. A duration-response was not observed. CONCLUSION: Statins, metformin, ACE inhibitors, and ARBs did not inhibit AMD in elderly patients. The absence of a duration-response supports the lack of a causal relationship.
Aged ; Angiotensin II ; Angiotensin Receptor Antagonists ; Angiotensin-Converting Enzyme Inhibitors ; Angiotensins ; Cardiovascular Diseases ; Case-Control Studies ; Cohort Studies ; Diabetes Mellitus ; Follow-Up Studies ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Logistic Models ; Macular Degeneration ; Metformin ; National Health Programs ; Odds Ratio ; Prescriptions ; Receptors, Angiotensin

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.

Background: Oral retinoids are used to treat various dermatological conditions, and their use is increasing in women of childbearing age. However, there is limited knowledge on the incidence of adverse outcomes after retinoid exposure during pregnancy. We aimed to evaluate the risk of adverse outcomes associated with oral retinoid exposure during pregnancy. Methods: We conducted a retrospective cohort study using the NHIS mother-child linked healthcare database in South Korea. We included all women who gave live birth from April 1, 2009 to December 31, 2020 and their children. The exposure was defined as having ≥ 1 prescription of isotretinoin, alitretinoin, and acitretin from one month before pregnancy to the delivery. The outcomes of interest were adverse child outcomes including major congenital malformations, low birth weight, and neurodevelopmental disorders (autism spectrum disorder and intellectual disorder), and adverse pregnancy outcomes including gestational diabetes mellitus, preeclampsia, and postpartum hemorrhage. Propensity score-based matching weights were used to control for various potential confounders. For congenital malformation, low birth weight, and adverse pregnancy outcomes, we calculated relative risk (RR) with 95% confidence interval (CI) using a generalized linear model and for neurodevelopmental disorders, we estimated hazard ratio (HR) with 95% CI using the Cox proportional hazard model. Results: Of 3,894,184 pregnancies, we identified 720 pregnancies (0.02%) as the oral retinoid-exposed group. The incidence of major congenital malformation was 400.6 per 10,000 births for oral retinoid-exposed group and 357.9 per 10,000 births for unexposed group and the weighted RR was 1.10 (95% CI, 0.65–1.85) in oral retinoid-exposed group compared with unexposed group. The neurodevelopmental disorder showed a potential increased risk, with the weighted HR of 1.63 (95% CI, 0.60–4.41) for autism spectrum disorder and 1.71 (95% CI, 0.60–4.93) for the intellectual disorder, although it did not reach statistical significance. For low birth weight and adverse pregnancy outcomes, no association was observed with oral retinoid exposure during pregnancy. Conclusion This study found no significantly increased risk of congenital malformations, autism spectrum disorders, and intellectual disability associated with oral retinoid exposure during pregnancy; however, given the limitations such as including only the live births and increased point estimate, potential risk cannot be fully excluded.

Poly-gamma-glutamic acid (gamma-PGA) is a mucilaginous and biodegradable compound produced by Bacillus subtilis from fermented soybeans, and is found in the traditional Korean soy product, cheongkukjang. This study was carried out to evaluate the effects of gamma-PGA from a food source on the concentration of the neurotransmitter GABA and its metabolic precursor glutamate in diet-induced obese rats. Eight-week old male Sprague-Dawley rats (n=60) were used. The rats were divided into two groups and obesity was induced by providing either a 10% control fat or 45% high fat diet for 5 weeks. The rats were then blocked into 6 groups and supplemented with a 0.1% gamma-PGA diet for 4 weeks. After sacrifice, brain and serum GABA and glutamate concentrations were analyzed by high performance liquid chromatography with fluorometric detection. The rats fed the high fat diet had significantly increased body weights. gamma-PGA supplementation significantly increased serum concentrations of glutamate and GABA in the control fat diet groups while this effect was not found in the high fat groups. In the brain, glutamate concentrations were significantly higher in the gamma-PGA supplemented groups both in rats fed the normal and high fat diets than in the no gamma-PGA controls. GABA concentrations showed the same tendency. The results indicated that gamma-PGA intake increased GABA concentrations in the serum and brain. However, the effects were not shown in obese rats.
Animals ; Bacillus subtilis ; Body Weight ; Brain ; Chromatography, Liquid ; Diet ; Diet, High-Fat ; gamma-Aminobutyric Acid ; Glutamic Acid ; Humans ; Male ; Neurotransmitter Agents ; Obesity ; Polyglutamic Acid ; Rats ; Rats, Sprague-Dawley ; Soybeans

Antithrombotics are increasingly used for the management and prevention of cardiovascular diseases, and endoscopists often have to decide whether to continue or stop these medications before endoscopy. The development of novel antithrombotics, such as direct oral anticoagulants, has complicated their management before endoscopy. Although the discontinuation of anticoagulants may decrease the incidence of bleeding after endoscopic procedures, discontinuation may also lead to more serious cardiovascular complications. Although the majority of current practice guidelines recommend continuation of antithrombotics before elective endoscopy and biopsy, surveys have shown that many endoscopists do not adhere to these guidelines, probably due to legal aspirations from post endoscopic bleeding. Thus, we examined the current guidelines for the management of antithrombotics before endoscopy.
Anticoagulants ; Aspirations (Psychology) ; Biopsy ; Cardiovascular Diseases ; Endoscopy ; Hemorrhage ; Incidence

Objective: The association between benzodiazepine use and the risk of cognitive impairment or dementia has been controversial. Our study aims to detect this association through a caseon-case method using the Korea Institute of Drug Safety & Risk Management-Korea adverse event reporting system database (KIDS-KD) between 2007 and 2016. Methods: Cases were adverse event (AE)-pairs with suspected cognitive impairment or dementia. 10 non-cases were matched to each case on age and sex. Exposure was defined as use of benzodiazepines, including long-, intermediate-, and short-acting benzodiazepine. We conducted multivariable logistic regression analyses to estimate reporting odds ratios (ROR) and 95% confidence intervals (CI). Results: Of the 1,086,584 AE-pairs, 887 cases were suspected AE-pairs of cognitive impairment or dementia, and 775,444 non-cases were selected. Benzodiazepine use was associated with increased AE-pairs of cognitive impairment or dementia when assessed using those with certain, probable, and/or possible in causality assessments (ROR=2.69, 95% CI=1.66–4.38). Higher ROR estimates were shown in female (2.33, 1.48–3.67) and in those with polypharmacy (2.20, 1.35–3.57). Dementia safety profiles were inconsistent across individual benzodiazepine components. Conclusion These results suggest the potentially increased association between benzodiazepine use and cognitive impairment or dementia in female and those with polypharmacy. Inconsistent safety profiles of benzodiazepine components should be further investigated.

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.

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.

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.