Background: Adverse drug reactions (ADRs) are escalating, and their socioeconomic burden is increasing. However, large-scale prospective studies investigating ADRs during hospitalization are rare in Korea. We prospectively investigated the incidence, characteristics, and economic burden of ADRs in hospitalized patients based on electronic medical records (EMRs). Methods: Among patients admitted to three hospitals from October 2016 to October 2017, 5,000 patients were randomly selected and prospectively observed during hospitalization.Research nurses monitored and detected patients who had symptoms, signs, or laboratory findings suspicious for ADRs using an EMR-based detection protocol. Next, allergy and ADR specialists reviewed the medical records to determine the relationship between adverse reactions and drugs. Cases in which a causal relationship was certain, probable/likely, or possible were included in the ADR cases. Clinically meaningful ADR cases or those leading to prolonged hospitalization were defined as significant ADRs. Results: ADRs occurred in 510 (10.2%) patients. The mean length of hospital stay was approximately 5 days longer in patients with ADRs. Opioids accounted for the highest percentage of total ADRs. Significant ADRs were observed in 148 (3.0%) patients. Antibiotics accounted for the highest percentage of significant ADRs. Drug hypersensitivity reactions (DHRs) occurred in 88 (1.8%) patients. Antibiotics accounted for the highest percentage of DHRs. The average medical expenses for one day of hospitalization per patient were highest in significant ADRs, followed by non-significant ADRs, and non-ADRs. Conclusion ADRs in hospitalized patients are an important clinical issue, resulting in a substantial socioeconomic burden. EMR-based strategy could be a useful tool for ADR monitoring and early detection.

Hereditary angioedema (HAE) is a rare disease, but it severely interrupts daily life activities and can sometimes be life-threatening. Therefore, early diagnosis and prompt treatment of HAE attacks are critical. Physicians should be aware of how to diagnose and manage HAE to prepare not to miss a diagnosis when treating HAE patients. Physicians must also carry out tests to confirm the diagnosis of HAEs caused by C1 inhibitor deficiency (type 1) or C1 inhibitor dysfunction (type 2) in patients with recurrent angioedema. In addition, recent studies revealed another type of HAE which is not related to C1 inhibitor (normal C1 inhibitor HAE). Once HAE is confirmed, patients and their caregivers should be given with short-term and long-term treatment plans to relieve or prevent HAE attacks. HAE requires life-long measures, including psychological support for patients and self-management education.

Background: Angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine subtype 2 (TMPRSS2) are key proteins mediating viral entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although gene expressions of ACE2 and TMPRSS2 have been analyzed in various organs and diseases, their soluble forms have been less studied, particularly in asthma. Therefore, we aimed to measure circulating ACE2 and TMPRSS2 in the serum of asthmatics and examine their relationship with clinical characteristics. Methods: Clinical data and serum samples of 400 participants were obtained from an asthma cohort. The soluble ACE2 (sACE2) and soluble TMPRSS2 (sTMPRSS2) level was measured by enzyme-linked immunosorbent assay, and the values underwent a natural log transformation. Associations between sACE2 and TMPRSS2 levels and various clinical variables were analyzed. Results: The patients younger than 70 years old, those with eosinophilic asthma (eosinophils ≥ 200 cells/µL), and inhaled corticosteroids (ICS) non-users were associated with higher levels of sACE2. Blood eosinophils and fractionated exhaled nitric oxide levels were positively correlated with serum ACE2. In contrast, lower levels of sTMPRSS2 were noted in patients below 70 years and those with eosinophilic asthma, while no association was noted between ICS use and sTMPRSS2. The level of sTMPRSS2 also differed according to sex, smoking history, coexisting hypertension, and forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) ratio. The proportion of sputum neutrophils was positively correlated with sTMPRSS2, while the FEV1/FVC ratio reported a negative correlation with sTMPRSS2. Conclusion The levels of ACE2 and TMPRSS2 were differently expressed according to age, ICS use, and several inflammatory markers. These findings suggest variable susceptibility and prognosis of SARS-CoV-2 infection among asthmatic patients.

Hereditary angioedema (HAE) is a rare inherited condition marked by recurrent skin and submucosal edema. HAE is caused by a C1 inhibitor deficiency or decreased C1 inhibitor function. The initial attack may occur during childhood or pregnancy, with symptoms ranging from classic angioedema to nonspecific stomach cramps. In this review, we discuss strategies for children and pregnant women to manage HAE attacks effectively and safely in light of the recent increase in HAE diagnosis. To begin, aggressive work-up is necessary to confirm HAE–1/2 and to determine the most effective countermeasures. Secondly, in the event of an acute attack, plasma-derived C1-inhibitor is the first line of defense for children and pregnant women. Icatibant is also appropriate for use, except in pregnant women. Fresh frozen plasma (FFP) may be suggested as an alternative. Thirdly, proactive measures to prevent HAE attacks should be considered whenever a procedure is performed that may result in an exacerbation. Finally, FFP, attenuated androgen and antifibrinolytic agents are recommended for long-term prophylaxis in South Korea where the C1-inhibitor is scarce. However, when making a decision, it is necessary to consider both the efficacy and the risk of adverse effects. For proper management, written action plans and first-aid kits are required. The action plans should be customized to the patients‘ unique circumstances.

Background: We performed a prospective survey on the adverse reactions following the first dose of two types of vaccines against coronavirus disease 2019 (COVID-19) in healthcare workers (HCWs) in South Korea. Methods: HCWs at a tertiary referral hospital in Seoul, South Korea, received a chimpanzee adenovirus-vectored vaccine (ChAdOx1 nCoV-19) or an mRNA-based vaccine (BNT162b2) between March 5 and March 26, 2021. The HCWs were asked to report adverse reactions through a mobile self-report questionnaire for three days after vaccination. Results: A total of 7,625 HCWs received the first dose of ChAdOx1 or BNT162b2 vaccine during the study period. Of them, 5,866 (76.9%) HCWs (ChAdOx1, n = 5,589 [95.3%];BNT162b2, n = 277 [4.7%]) participated at least once in the survey, of whom 77% were female and 86% were younger than 50 years. The overall adverse reaction rate was 93% in the ChAdOx1 group and 80% in the BNT162b2 group (P < 0.001). Both local and systemic reactions were more commonly reported in the ChAdOx1 group, and the difference was larger in systemic reactions such as fever and fatigue. In the ChAdOx1 group, the incidence of adverse reactions was significantly higher in females and those in the younger age groups, while the BNT162b2 group showed such difference according to age. Conclusion In our prospective survey, vaccine-associated adverse reactions were more commonly reported in the ChAdOx1 group than in the BNT162b2 group. Females and younger age groups experienced vaccine-associated adverse reactions more frequently.

We conducted a prospective, mobile-based survey on the self-reported adverse reactions in healthcare workers (HCWs) who received both doses of the BNT162b2 mRNA vaccine. Of the 342 HCWs who completed the two-dose vaccination, 265 (77.5%) responded to the survey at least once. Overall, the rates of adverse reactions were higher after the second dose compared with the first dose (89.1% vs. 80.1%, P = 0.006). The most common systemic reactions were muscle ache (69.1%), fatigue (65.7%), headache (48.7%), chills (44.2%), and fever (32.1%), and were notably more common after the second dose vaccine as well. We also noted a sex difference in which the frequency of adverse reactions after the second dose of the vaccine was significantly higher in females, which was not observed after the first dose. The rates of adverse reactions were lower in older age groups, and the rates and severities of the adverse reactions decreased during the 3-day period following vaccination.

Background: We performed a prospective survey on the adverse reactions following the first dose of two types of vaccines against coronavirus disease 2019 (COVID-19) in healthcare workers (HCWs) in South Korea. Methods: HCWs at a tertiary referral hospital in Seoul, South Korea, received a chimpanzee adenovirus-vectored vaccine (ChAdOx1 nCoV-19) or an mRNA-based vaccine (BNT162b2) between March 5 and March 26, 2021. The HCWs were asked to report adverse reactions through a mobile self-report questionnaire for three days after vaccination. Results: A total of 7,625 HCWs received the first dose of ChAdOx1 or BNT162b2 vaccine during the study period. Of them, 5,866 (76.9%) HCWs (ChAdOx1, n = 5,589 [95.3%];BNT162b2, n = 277 [4.7%]) participated at least once in the survey, of whom 77% were female and 86% were younger than 50 years. The overall adverse reaction rate was 93% in the ChAdOx1 group and 80% in the BNT162b2 group (P < 0.001). Both local and systemic reactions were more commonly reported in the ChAdOx1 group, and the difference was larger in systemic reactions such as fever and fatigue. In the ChAdOx1 group, the incidence of adverse reactions was significantly higher in females and those in the younger age groups, while the BNT162b2 group showed such difference according to age. Conclusion In our prospective survey, vaccine-associated adverse reactions were more commonly reported in the ChAdOx1 group than in the BNT162b2 group. Females and younger age groups experienced vaccine-associated adverse reactions more frequently.

We conducted a prospective, mobile-based survey on the self-reported adverse reactions in healthcare workers (HCWs) who received both doses of the BNT162b2 mRNA vaccine. Of the 342 HCWs who completed the two-dose vaccination, 265 (77.5%) responded to the survey at least once. Overall, the rates of adverse reactions were higher after the second dose compared with the first dose (89.1% vs. 80.1%, P = 0.006). The most common systemic reactions were muscle ache (69.1%), fatigue (65.7%), headache (48.7%), chills (44.2%), and fever (32.1%), and were notably more common after the second dose vaccine as well. We also noted a sex difference in which the frequency of adverse reactions after the second dose of the vaccine was significantly higher in females, which was not observed after the first dose. The rates of adverse reactions were lower in older age groups, and the rates and severities of the adverse reactions decreased during the 3-day period following vaccination.

PURPOSE: Reduction-oxidation reaction homeostasis is vital for regulating inflammatory conditions and its dysregulation may affect the pathogenesis of chronic airway inflammatory diseases such as asthma. Peroxiredoxin-6, an important intracellular anti-oxidant molecule, is reported to be highly expressed in the airways and lungs. The aim of this study was to analyze the expression pattern of peroxiredoxin-6 in the peripheral blood mononuclear cells (PBMCs) of asthmatic patients and in bronchial epithelial cells (BECs).METHODS: The expression levels and modifications of peroxiredoxin-6 were evaluated in PBMCs from 22 asthmatic patients. Phosphorylated and acetylated peroxiredoxin-6 in hydrogen peroxide-treated human BECs was detected using immunoprecipitation analysis. The expression level of peroxiredoxin-6 was also investigated in BECs treated with hydrogen peroxide. Cycloheximide and proteasome inhibitors were used to determine whether peroxiredoxin-6 is degraded by proteasomes.RESULTS: Peroxiredoxin-6 expression was significantly reduced in the PBMCs of asthmatic patients compared to control subjects. Distinct modification patterns for peroxiredoxin-6 were observed in the PBMCs of asthmatic patients using 2-dimensional-electrophoresis. The levels of phosphorylated serine and acetylated lysine in peroxiredoxin-6 were significantly increased in the BECs following hydrogen peroxide treatment. The level of peroxiredoxin-6 expression was reduced in hydrogen peroxide-stimulated BECs, presumably due to proteasomes.CONCLUSIONS: The expression of peroxiredoxin-6, which is down-regulated in the immune cells of asthmatic patients and BECs, can be modified by oxidative stress. This phenomenon may have an effect on asthmatic airway inflammation.
Asthma ; Cycloheximide ; Epithelial Cells ; Homeostasis ; Humans ; Hydrogen ; Hydrogen Peroxide ; Immunoprecipitation ; Inflammation ; Lung ; Lysine ; Oxidative Stress ; Proteasome Inhibitors ; Protein Processing, Post-Translational ; Serine

PURPOSE: The incidence of drug-induced liver injury (DILI) has been increasing; however, few algorithms are available to identify DILI in electronic health records (EHRs). We aimed to identify and evaluate DILI with an appropriate screening algorithm.METHODS: We collected data from 3 university hospitals between June 2015 and May 2016 using our newly developed algorithm for identifying DILI. Among patients with alanine transferase (ALT) ≤ 120 IU/L and total bilirubin (TB) ≤ 2.4 mg/dL in blood test results within 48 hours of admission, those who either had 1) ALT > 120 IU/L and TB > 2.4 mg/dL or 2) ALT > 200 IU/L at least once during hospitalization were identified. After excluding patients with liver disease-related diagnosis at discharge, medical records were retrospectively reviewed to evaluate epidemiological characteristics of DILI.RESULTS: The total number of inpatients was 256,598, of whom 1,100 (0.43%) were selected by the algorithm as suspected DILI. Subsequently, 365 cases (0.14% of total inpatients, 95% confidence interval, 0.13–0.16) were identified as DILI, yielding a positive predictive value of 33.1%. Antibiotics (n = 214, 47.2%) were the major class of causative drug followed by chemotherapeutic agents (n = 87, 19.2%). The most common causative drug was piperacillin-tazobactam (n = 38, 8.4%); the incidence of DILI by individual agent was highest for methotrexate (19.4 cases/1,000 patients administered the drug). Common reasons for excluding suspected DILI cases were ischemic hepatitis and postoperative liver dysfunction.CONCLUSIONS: Using our EHR-based algorithm, we identified that approximately 0.14% of patients developed DILI during hospitalization. Further studies are needed to modify criteria for more accurate identification of DILI.
Alanine ; Anti-Bacterial Agents ; Bilirubin ; Diagnosis ; Drug-Induced Liver Injury ; Drug-Related Side Effects and Adverse Reactions ; Electronic Health Records ; Hematologic Tests ; Hepatitis ; Hospitalization ; Hospitals, University ; Humans ; Incidence ; Inpatients ; Liver ; Liver Diseases ; Mass Screening ; Medical Records ; Methotrexate ; Pharmacoepidemiology ; Retrospective Studies ; Transferases