Collateral Effect of the Coronavirus Disease 2019 Pandemic on Emergency Department Visits in Korea.

Background and Objectives: The ongoing coronavirus disease 2019 (COVID-19) pandemic represents a global public health crisis that has had a serious impact on emergency department (ED) utilization trends. The aim of this study was to investigate the collateral effects of the COVID-19 pandemic on ED utilization trends by patients with mild and severe conditions as well as on 7-day fatality rates. Materials and Methods: We analyzed entries in the Korean National Health Insurance claims database between 1 January 2018 and 31 December 2020. Six target patient groups were identified using the main diagnosis codes in the 10th revision of the International Classification of Diseases. Numbers of patients visiting the ED, their age, regional differences, 7-day fatality rate, and rate of emergency procedures were compared between 2018 and 2019 as the control period and 2020, when the COVID-19 pandemic was in full force. Results: During the 2020 COVID-19 pandemic, the number of patients who visited the ED with low-acuity diseases and severe acute respiratory infection diseases sharply decreased to −46.22% and −56.05%, respectively. However, the 7-day fatality rate after ED visits for low-acuity diseases and severe acute respiratory infection diseases increased to 0.04% (p < 0.01), and 1.65% (p < 0.01), respectively, in 2020 compared to that in the control period. Conclusions: During the 2020 COVID-19 pandemic, ED utilization impacted and 7-day fatality rate after ED visit increased. Health authorities and health care providers must strive to ensure prompt delivery of optimal care in EDs for patients with severe or serious symptoms and time-dependent diseases, even during the ongoing COVID-19 or potential future pandemics.

Pharmacokinetics of 2-phenoxyethanol and its major metabolite, phenoxyacetic acid, after dermal and inhaled routes of exposure: application to development PBPK model in rats.

2-Phenoxyethanol (PE), ethylene glycol monophenyl ether, is widely used as a preservative in cosmetic products as well as in non-cosmetics. Since PE has been used in many types of products, it can be absorbed via dermal or inhaled route for systemic exposures. In this study, the pharmacokinetic (PK) studies of PE and its major metabolite, phenoxyacetic acid (PAA), after dermal (30 mg and 100 mg) and inhaled administration (77 mg) of PE in rats were performed. PE was administered daily for 4 days and blood samples were collected at day 1 and day 4 for PK analysis. PE was rapidly absorbed and extensively metabolized to form PAA. After multiple dosing, the exposures of PE and PAA were decreased presumably due to the induction of metabolizing enzymes of PE and PAA. In dermal mass balance study using [14C]-phenoxyethanol ([14C]PE) as a microtracer, most of the PE and its derivatives were excreted in urine (73.03%) and rarely found in feces (0.66%). Based on these PK results, a whole-body physiologically-based pharmacokinetic (PBPK) model of PE and PAA after dermal application and inhalation in rats was successfully developed. Most of parameters were obtained from the literatures and experiments, and intrinsic clearance at steady-state (CLint,ss) were optimized based on the observed multiple PK data. With the developed model, systemic exposures of PE and PAA after dermal application and inhalation were simulated following no-observed-adverse-effect level (NOAEL) of 500 mg/kg/day for dermal application and that of 12.7 mg/kg/day for inhalation provided by the Environmental Protection Agency. The area under the concentration-time curve at steady state (AUCss) in kidney and liver (and lung for inhalations), which are known target organs of exhibiting toxicity of PE, as well as AUCss in plasma of PE and PAA were obtained from the model.

Impact of the COVID-19 Pandemic on Emergency Department Workload and Emergency Care Workers' Psychosocial Stress in the Outbreak Area.

Background and Objectives: Due to the unexpected spread of coronavirus disease 2019 (COVID-19), there was a serious crisis of emergency medical system collapse. Healthcare workers working in the emergency department were faced with psychosocial stress and workload changes. Materials and Methods: This was a cross-sectional survey of healthcare workers in the emergency department in Daegu and Gyeongbuk, Korea, from November 16 to 25, 2020. In the survey, we assessed the general characteristics of the respondents; changes in the working conditions before and after the COVID-19 pandemic; and resulting post-traumatic stress disorder, depression and anxiety statuses using 49 questions. Results: A total of 529 responses were collected, and 520 responses were included for the final analyses. Changes in working conditions and other factors due to COVID-19 varied by emergency department level, region and disease group. Working hours, intensity, role changes, depression and anxiety scores were higher in the higher level emergency department. Isolation ward insufficiency and the risk of infection felt by healthcare workers tended to increase in the lower level emergency department. Treatment and transfer delay were higher in the fever and respiratory disease groups (M = 3.58, SD = 1.18; M = 4.08, SD = 0.95), respectively. In all the disease groups, both treatment and transfer were delayed more in Gyeongbuk than in Daegu. Conclusions: Different goals should be pursued by the levels and region of the emergency department to overcome the effects of the COVID-19 pandemic and promote optimal care.

Volume of hospital is important for the prognosis of high-risk patients with nonvariceal upper gastrointestinal bleeding (NVUGIB).

BACKGROUND AND AIM: Nonvariceal upper gastrointestinal bleeding (NVUGIB) is a potentially life-threatening hospital emergency requiring hemodynamic stabilization and resuscitation. This study is carried out to determine whether hospital volume can influence outcome in patients with NVUGIB. METHOD: This is a retrospective study with a prospective cohort database (KCT 0000514. cris.nih.go.kr). Eight teaching hospitals were divided into two different groups: high-volume centers (HVC, ≥60 NVUGIB patients/year, four clinics) and low-volume centers (LVC, <60 NVUGIB patients/year, four clinics). Baseline characteristics of patients, risk stratification, and outcomes between hospitals of different volumes were compared. From February 2011 to December 2013, a total of 1584 NVUGIB patients enrolled in eight clinics were retrospectively reviewed. The main outcome measurements consisted of continuous bleeding after treatment, re-bleeding, necessity for surgical/other retreatments, and death within 30 days. RESULTS: Similar baseline characters for patients were observed in both groups. There was a significant difference in the incidence of poor outcome between the HVC and LVC groups (9.06 vs. 13.69%, P = 0.014). The incidence rate of poor outcome in high-risk patients (Rockall score ≥8) in HVC was lower than that in high-risk patients in LVC (16.07 vs. 26.92%, P = 0.048); however, there was no significant difference in poor outcome in the lower-risk patients in either group (8.72 vs. 10.42%, P = 0.370). CONCLUSIONS: Significant correlation between hospital volume and outcome in NVUGIB patients was observed. Referral to HVC for the management of high-risk NVUGIB patients should be considered in clinical practice.

The Novel Scoring System for 30-Day Mortality in Patients with Non-variceal Upper Gastrointestinal Bleeding.

BACKGROUND: Although the mortality rates for non-variceal upper gastrointestinal bleeding (NVUGIB) have recently decreased, it remains a significant medical problem. AIM: The main aim of this prospective multicenter database study was to construct a clinically useful predictive scoring system by using our predictors and compare its prognostic accuracy with that of the Rockall scoring system. METHODS: Data were collected from consecutive patients with NVUGIB. Logistic regression analysis was performed to identify the independent predictors of 30-day mortality. Each independent predictor was assigned an integral point proportional to the odds ratio (OR) and we used the area under the curve to compare the discrimination ability between the new predictive model and the Rockall score. RESULTS: The independent predictors of mortality included age >65 years [OR 2.627; 95 % confidence interval (CI) 1.298-5.318], hemodynamic instability (OR 2.217; 95 % CI 1.069-4.597), serum blood urea nitrogen level >40 mg/dL (OR 1.895; 95 % CI 1.029-3.490), active bleeding at endoscopy (OR 2.434; 95 % CI 1.283-4.616), transfusions (OR 3.811; 95 % CI 1.640-8.857), comorbidities (OR 3.481; 95 % CI 1.405-8.624), and rebleeding (OR 10.581; 95 % CI 5.590-20.030). The new predictive model showed a high discrimination capability and was significantly superior to the Rockall score in predicting the risk of death (OR 0.837;95 % CI 0.818-0.855 vs. 0.761; 0.739-0.782; P = 0.0123). CONCLUSIONS: The new predictive score was significantly more accurate than the Rockall score in predicting death in NVUGIB patients. We need to prospectively validate the accuracy of this score for predicting mortality in NVUGIB patients.

Simultaneous determination of ß-sitosterol, campesterol, and stigmasterol in rat plasma by using LC-APCI-MS/MS: Application in a pharmacokinetic study of a titrated extract of the unsaponifiable fraction of Zea mays L.

A liquid chromatography with atmospheric pressure chemical ionization tandem mass spectrometry method was developed and validated to investigate the pharmacokinetic properties of ß-sitosterol, campesterol, and stigmasterol in rat plasma. Cholesterol-d6 was used as an internal standard. To avoid interference of the three phytosterols in rat plasma and minimize matrix effects, a small volume (10 µL) of 4% bovine serum albumin was used as a surrogate matrix for making calibrators and quality control samples. Rat plasma (10 µL) samples were extracted by liquid-liquid extraction with methyl tert-butyl ether and separated on a Kinetex C18 column. The detection was performed on a triple quadrupole tandem mass spectrometer in selected reaction monitoring mode using positive atmospheric pressure chemical ionization. This assay was linear over concentration ranges of 250-5000 ng/mL (ß-sitosterol), 250-5000 ng/mL (campesterol), and 50-2000 ng/mL (stigmasterol). Additionally, a second set of quality controls made in rat plasma was also evaluated against calibration curves made using the surrogate matrix. All the validation data, including the specificity, precision, accuracy, recovery, matrix effect, stability, and incurred sample reanalysis conformed to the acceptance requirements. Our method was successfully applied to study the pharmacokinetics of three phytosterols in rats.

In Vitro Inhibition of Human UDP-Glucuronosyl-Transferase (UGT) Isoforms by Astaxanthin, ß-Cryptoxanthin, Canthaxanthin, Lutein, and Zeaxanthin: Prediction of in Vivo Dietary Supplement-Drug Interactions.

Despite the widespread use of the five major xanthophylls astaxanthin, ß-cryptoxanthin, canthaxanthin, lutein, and zeaxanthin as dietary supplements, there have been no studies regarding their inhibitory effects on hepatic UDP-glucuronosyltransferases (UGTs). Here, we evaluated the inhibitory potential of these xanthophylls on the seven major human hepatic UGTs (UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A9, UGT2B7 and UGT2B15) in vitro by LC-MS/MS using specific marker reactions in human liver microsomes (except UGT2B15) or recombinant supersomes (UGT2B15). We also predicted potential dietary supplement-drug interactions for ß-cryptoxanthin via UGT1A1 inhibition. We demonstrated that astaxanthin and zeaxanthin showed no apparent inhibition, while the remaining xanthophylls showed only weak inhibitory effects on the seven UGTs. ß-Cryptoxanthin mildly inhibited UGT1A1, UGT1A3, and UGT1A4, with IC50 values of 18.8 ± 2.07, 28.3 ± 4.40 and 34.9 ± 5.98 µM, respectively. Canthaxanthin weakly inhibited UGT1A1 and UGT1A3, with IC50 values of 38.5 ± 4.65 and 41.2 ± 3.14 µM, respectively; and lutein inhibited UGT1A1 and UGT1A4, with IC50 values of 45.5 ± 4.01 and 28.7 ± 3.79 µM, respectively. Among the tested xanthophyll-UGT pairs, ß-cryptoxanthin showed the strongest competitive inhibition of UGT1A1 (Ki, 12.2 ± 0.985 µM). In addition, we predicted the risk of UGT1A1 inhibition in vivo using the reported maximum plasma concentration after oral administration of ß-cryptoxanthin in humans. Our data suggests that these xanthophylls are unlikely to cause dietary supplement-drug interactions mediated by inhibition of the hepatic UGTs. These findings provide useful information for the safe clinical use of the tested xanthophylls.

Simultaneous determination of sarpogrelate and its active metabolite in human plasma by liquid chromatography with tandem mass spectrometry and its application to a pharmacokinetic study.

We established a rapid and simple liquid chromatography with tandem mass spectrometry method for the simultaneous determination of sarpogrelate and its active metabolite, M-1, in human plasma. Sarpogrelate, M-1, and the internal standard, ketanserin, were extracted from a 50 µL aliquot of human plasma by protein precipitation using acetonitrile. Chromatographic separation was performed on a Shim-pack GIS ODS C18 column (100 × 3.0 mm; 3 µm) with an isocratic mobile phase consisting of 10 mM ammonium acetate and acetonitrile (70:30, v/v) at a flow rate of 0.6 mL/min; the total run time was <2.5 min. Mass spectrometric detection was conducted in selected reaction-monitoring mode with positive electrospray ionization at m/z 430.35 → 135.10 for sarpogrelate, m/z 330.30 → 58.10 for M-1, and m/z 395.70 → 188.85 for ketanserin. The linear ranges of concentration for sarpogrelate and M-1 were 1-1000 and 0.5-500 ng/mL, respectively. The coefficient of variation for the assay's precision was ≤9.95%, and the accuracy was 90.6-107%. All analytes were stable under various storage and handling conditions, and no relevant crosstalk and matrix effect was observed. This method was successfully applied to a pharmacokinetic study after oral administration of a 100 mg sarpogrelate tablet to healthy male Korean volunteers.

Development and validation of a liquid chromatography with tandem mass spectrometry method for the quantification of vitisin B in rat plasma and urine.

A new, rapid, and sensitive liquid chromatography with tandem mass spectrometry method was developed for the determination of vitisin B and validated in rat plasma and urine using carbamazepine as an internal standard. The plasma (0.05 mL) or urine (0.2 mL) samples were extracted by liquid-liquid extraction with ethyl acetate and separated on an Eclipse Plus C18 column (100 × 4.6 mm, 3.5 µm) with a mobile phase consisting of acetonitrile and 0.1% formic acid water (60:40, v/v) at a flow rate of 0.7 mL/min. Detection and quantification were performed by mass spectrometry in selected reaction-monitoring mode with positive electrospray ionization. The calibration curves were recovered over the concentration ranges of 10-5000 ng/mL (correlation coefficients, r≥0.9833) in plasma and 5-2500 ng/mL (r≥0.9977) in urine, respectively. All validation data, including the specificity, precision, accuracy, recovery, and stability, conformed to the acceptance requirements. No matrix effects were observed. The developed method was successfully applied to pharmacokinetic studies of vitisin B following intravenous administration of 0.5 and 1 mg/kg and intraperitoneal injection of 5, 10, and 25 mg/kg to rats. This is the first report on the pharmacokinetic properties of vitisin B. The results provide a meaningful basis to evaluate preclinical or clinical applications of vitisin B.

Effect of the potent CYP2D6 inhibitor sarpogrelate on the pharmacokinetics and pharmacodynamics of metoprolol in healthy male Korean volunteers.

1. Recently, we demonstrated that sarpogrelate is a potent and selective CYP2D6 inhibitor in vitro. Here, we evaluated the effect of sarpogrelate on the pharmacokinetics and pharmacodynamics of metoprolol in healthy subjects. 2. Nine healthy male subjects genotyped for CYP2D6*1/*1 or *1/*2 were included in an open-label, randomized, three treatment-period and crossover study. A single oral dose of metoprolol (100 mg) was administered with water (treatment A) and sarpogrelate (100 mg bid.; a total dose of 200 mg and treatment B), or after pretreatment of sarpogrelate for three days (100 mg tid.; treatment C). Plasma levels of metoprolol and α-hydroxymetoprolol were determined using a validated LC-MS/MS method. Changes in heart rate and blood pressure were monitored as pharmacodynamic responses to metoprolol. 3. Metoprolol was well tolerated in the three treatment groups. In treatment B and C groups, the AUCt of metoprolol increased by 53% (GMR, 1.53; 90% CI, 1.17-2.31) and by 51% (1.51; 1.17-2.31), respectively. Similar patterns were observed for the increase in Cmax of metoprolol by sarpogrelate. However, the pharmacodynamics of metoprolol did not differ significantly among the three treatment groups. 4. Greater systemic exposure to metoprolol after co-administration or pretreatment with sarpogrelate did not result in clinically relevant effects. Co-administration of both agents is well tolerated and can be employed without the need for dose adjustments.

Pharmacokinetic properties of trifolirhizin, (-)-maackiain, (-)-sophoranone and 2-(2,4-dihydroxyphenyl)-5,6-methylenedioxybenzofuran after intravenous and oral administration of Sophora tonkinensis extract in rats.

1. SKI3301, a standardized dried 50% ethanolic extracts of Sophora tonkinensis, contains four marker compounds (trifolirhizin, TF; (-)-maackiain, Maack; (-)-sophoranone, SPN, and (2-(2,4-dihydroxyphenyl)-5,6-methylenedioxybenzofuran, ABF), is being developed as an herbal medicine for the treatment of asthma in Korea. This study investigates the pharmacokinetic properties of SKI3301 extract in rats. 2. The dose-proportional AUCs suggest linear pharmacokinetics of TF, Maack, SPN and ABF in the SKI3301 extract intravenous dose range of 5-20 mg/kg. After the oral administration of 200-1000 mg/kg of the extract, TF and Maack exhibited non-linearity due to the saturation of gastrointestinal absorption. However, linear pharmacokinetics of SPN and ABF were observed. 3. The absorptions of TF, Maack, SPN and ABF in the extract were increased relative to those of the respective pure forms due to the increased solubility and/or the decreased metabolism by other components in the SKI3301 extract. 4. No accumulation was observed after multiple dosing, and the steady-state pharmacokinetics of TF, Maack, SPN and ABF were not significantly different from those after a single oral administration of the extract. 5. The pharmacokinetics of TF, SPN and ABF were not significantly different between male and female rats after oral administration of the extract, but a significant gender difference in the pharmacokinetics of Maack in rats was observed. 6. Our findings may help to comprehensively elucidate the pharmacokinetic characteristics of TF, Maack, SPN and ABF and provide useful information for the clinical application of SKI3301 extract.

Metabolic drug-drug interaction potential of macrolactin A and 7-O-succinyl macrolactin A assessed by evaluating cytochrome P450 inhibition and induction and UDP-glucuronosyltransferase inhibition in vitro.

Macrolactin A (MA) and 7-O-succinyl macrolactin A (SMA), polyene macrolides containing a 24-membered lactone ring, show antibiotic effects superior to those of teicoplanin against vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus. MA and SMA are currently being evaluated as antitumor agents in preclinical studies in Korea. We evaluated the potential of MA and SMA for the inhibition or induction of human liver cytochrome P450 (CYP) enzymes and UDP-glucuronosyltransferases (UGTs) in vitro to assess their safety as new molecular entities. We demonstrated that MA and SMA are potent competitive inhibitors of CYP2C9, with Ki values of 4.06 µM and 10.6 µM, respectively. MA and SMA also weakly inhibited UGT1A1 activity, with Ki values of 40.1 µM and 65.3 µM, respectively. However, these macrolactins showed no time-dependent inactivation of the nine CYPs studied. In addition, MA and SMA did not induce CYP1A2, CYP2B6, or CYP3A4/5. On the basis of an in vitro-in vivo extrapolation, our data strongly suggested that MA and SMA are unlikely to cause clinically significant drug-drug interactions mediated via inhibition or induction of most of the CYPs involved in drug metabolism in vivo, except for the inhibition of CYP2C9 by MA. Similarly, MA and SMA are unlikely to inhibit the activity of UGT1A1, UGT1A4, UGT1A6, UGT1A9, and UGT2B7 enzymes in vivo. Although further investigations will be required to clarify the in vivo interactions of MA with CYP2C9-targeted drugs, our findings offer a clearer understanding and prediction of drug-drug interactions for the safe use of MA and SMA in clinical practice.

Pharmacokinetics and tissue distribution of ginsenoside Rh2 and Rg3 epimers after oral administration of BST204, a purified ginseng dry extract, in rats.

1. BST204, a purified ginseng dry extract containing a high concentration of racemic Rh2 and Rg3 mixtures, is being developed for supportive care use in cancer patients in Korea. This study investigates the pharmacokinetics and tissue distribution of BST204 in rats. 2. After oral administration of BST204, only the S epimers, S-Rh2 and S-Rg3, could be determined in rat plasma. The poor absorption of the R-epimers, R-Rh2 and R-Rg3, may be attributed to lower membrane permeability and extensive intestinal oxygenation and/or deglycosylation into metabolites. The AUC and Cmax values of both S-Rh2 and S-Rg3 after BST204 oral administration were proportional to the administered BST204 doses ranged from 400 mg/kg to 2000 mg/kg, which suggested linear pharmacokinetic properties. 3. There were no statistically significant differences in the pharmacokinetics of S-Rh2 and S-Rg3 after oral administration of pure S-Rh2 (31.5 mg/kg) and S-Rg3 (68 mg/kg) compared with oral administration of BST204, 1000 mg/kg. These indicated that the presence of other components of BST204 extract did not influence the pharmacokinetic behavior of S-Rh2 and S-Rg3. 4. After oral dosing of BST204, S-Rh2 and S-Rg3 were distributed mainly to the liver and gastrointestinal tract in rats. 5. Our finding may help to understand pharmacokinetic characteristics of S-Rh2, R-Rh2, S-Rg3, and R-Rg3, comprehensively, and provide useful information in clinical application of BST204.

Direct measurement of active thiol metabolite levels of clopidogrel in human plasma using tris(2-carboxyethyl)phosphine as a reducing agent by LC-MS/MS.

A simple, robust, and rapid LC-MS/MS method has been developed and validated for the simultaneous quantitation of clopidogrel and its active metabolite (AM) in human plasma. Tris(2-carboxyethyl)phosphine (TCEP) was used as a reducing agent to detect the AM as a disulfide-bonded complex with plasma proteins. Mixtures of TCEP and human plasma were deproteinized with acetonitrile containing 10 ng/mL of clopidogrel-d4 as an internal standard (IS). The mixtures were separated on a C18 RP column with an isocratic mobile phase consisting of 0.1% formic acid in acetonitrile and water (90:10, v/v) at a flow rate of 0.3 mL/min. Detection and quantification were performed using ESI-MS. The detector was operated in selected reaction-monitoring mode at m/z 322.0→211.9 for clopidogrel, m/z 356.1→155.2 for the AM, and m/z 326.0→216.0 for the IS. The linear dynamic range for clopidogrel and its AM were 0.05-20 and 0.5-200 ng/mL, respectively, with correlation coefficients (r) greater than 0.9976. Precision, both intra- and interday, was less than 8.26% with an accuracy of 87.6-106%. The validated method was successfully applied to simultaneously analyze clinical samples for clopidogrel and its AM.

Benzisothiazolinone: Pharmacokinetics, Tissue Distribution, and Mass Balance Studies in Rats.

Humans are continuously exposed to benzisothiazolinone (BIT), which is used as a preservative, through multiple routes. BIT is known to be a sensitizer; in particular, dermal contact or aerosol inhalation could affect the local toxicity. In this study, we evaluated the pharmacokinetic properties of BIT in rats following various routes of administration. BIT levels were determined in rat plasma and tissues after oral inhalation and dermal application. Although the digestive system rapidly and completely absorbed orally administered BIT, it underwent severe first-pass effects that prevented high exposure. In an oral dose escalation study (5-50 mg/kg), nonlinear pharmacokinetic properties showed that Cmax and the area under the curve (AUC) increased more than dose proportionality. In the inhalation study, the lungs of rats exposed to BIT aerosols had higher BIT concentrations than the plasma. Additionally, the pharmacokinetic profile of BIT after the dermal application was different; continuous skin absorption without the first-pass effect led to a 2.13-fold increase in bioavailability compared with oral exposure to BIT. The [14C]-BIT mass balance study revealed that BIT was extensively metabolized and excreted in the urine. These results can be used in risk assessments to investigate the relationship between BIT exposure and hazardous potential.

Epidemiologic Characteristics of Work-related Eye Injuries and Risk Factors Associated with Severe Eye Injuries: A Registry-based Multicentre Study.

Purpose: Work-related eye injuries have been reported with a variety of epidemiologic and clinical characteristics. We aimed to identify epidemiologic characteristics of work-related eye injuries and risk factors associated with severe injury in a large metropolitan city.Methods: This multicentre, retrospective, observational study used a prospective eye injury registry. We included patients with work-related eye injuries at four tertiary teaching hospitals in Daegu, South Korea, between August 2016 and July 2018. Severe injuries were defined as subjects fulfilled one or more of the following criteria: 1) presented with open globe injury; 2) required emergency eye surgery or observation after hospitalization; 3) developed eye injury-associated complications or 4) impaired final visual acuity.Results: The study included 1,424 patients. One hundred seventy-three patients (12.1%) had severe injuries. The median age and interquartile range (IQR; 25th and 75th percentiles) of the subjects were 48.0 years (IQR, 36.0-57.0), and the majority (91.9%) were male. Among the subjects, 61 patients (4.2%) suffered eye injuries despite the use of protective eyewear at the time of injury. Multivariable logistic regression analysis revealed age ≥70 years (odds ratio: 4.02, 95% confidence interval: 1.77-9.15), hammering/nailing (6.80, 2.80-16.53), and mowing (4.87, 1.77-9.15) as activities that conferred a high risk of ocular trauma with severe injury.Conclusion: Age over 70 years, hammering/nailing, and mowing were risk factors for severe injury from work-related ocular trauma. Severe eye injury could occur in spite of the use of protective eyewear; appropriate, well-fitting protective eyewear should be emphasized in the future.

A 5-year change of knowledge and willingness by sampled respondents to perform bystander cardiopulmonary resuscitation in a metropolitan city.

BACKGROUND: Nationwide and regional interventions can help improve bystander cardiopulmonary resuscitation (CPR) awareness, knowledge, and the willingness. Periodic community investigation will help monitor the effect. This study aimed to compare the experience of CPR education, CPR knowledge, and CPR willingness, during a 5-year interval. METHODS: This is a pre and post study. Two surveys were done in February 2012 and December 2016. National and regional intervention including legislation promoting public involvement, standardizing CPR education programs, training CPR instructors, and installing supporting organizations were done at the period. In both surveys, respondents were selected via quota sampling in Daegu Metropolitan City and answered the survey through face-to-face interview. Respondents' general demographic characteristics, CPR educational experience, CPR knowledge and CPR willingness were questioned. RESULTS: Total of 2141 respondents (1000 in 2012, 1141 in 2016) were selected. The percentage of respondents who received CPR education itself and recent education were higher after intervention compared to before intervention (36.2% vs. 55.1%, 16.9% vs. 30.1%, respectively). Correct knowledge of performing CPR seems to be improved overall (1.6% vs. 11.7%, odd ratio 14.28, 95% confidence interval 5.68-35.94). However, less respondents were willing to perform CPR on strangers (54.5% vs 35.0%). CONCLUSION: Nationwide and regional interventions to promote bystander CPR and CPR education were associated with increased CPR education experience and improved correct CPR knowledge in performing bystander CPR. Willingness to perform bystander CPR on family did not increase significantly and CPR willingness to strangers was decreased. Additional legal and technological measures should be implemented to promote bystander CPR.

Comparison of traffic collision victims between older and younger drivers in South Korea: Epidemiologic characteristics, risk factors and types of collisions.

OBJECTIVE: This study aimed to show the epidemiological characteristics and the difference in the risk factors and types of collision between older and younger drivers in Korea. METHODS: We collected data from the Emergency Department-based Injury In-depth Surveillance retrieved by the Korea Centers for Disease Control and Prevention from 2011 to 2015. We included injured drivers aged ≥ 18 years who were registered in the database, who were limited to drivers of four-wheeled vehicles. The enrolled patients were divided according to age into older (≥ 65 years) and younger (< 65 years) drivers. The total number of enrolled drivers was 37,511; 2,361 (6.3%) of them were older drivers. The epidemiological characteristics (e.g., age, sex, fatality rate) of traffic collision victims for 5 years were determined, and the risk factors (e.g., seat belt use) and types of collision (single- vs. multi-vehicle) between the two groups were compared. RESULTS: The median age and interquartile range (IQR; 25th and 75th percentiles) of all drivers were 41.0 (IQR, 32.0-52.0), and 24,544 (65.4%) of them were men. The median age increased from 40.0 (IQR, 31.0-50.0) to 43.0 (IQR, 33.0-54.0) between 2010 and 2015 (P < 0.001). The proportion of older drivers increased from 5.0% to 8.4% annually during the study period (P < 0.001). Between 2010 and 2015, the fatality rate decreased from 3.1% to 1.2% (P = 0.287) for older drivers and from 0.9% to 0.5% (P = 0.009) for younger drivers. The proportion of single-vehicle collision (25.9% vs. 20.3%) was higher in older than in younger drivers (P < 0.001). Older drivers had a lower rate of seat-belt use than younger drivers (79.0% vs. 83.0%, P < 0.001). CONCLUSIONS: The proportion of older drivers increased annually during the study period, and older drivers experienced more single-vehicle collision and used seat belt less frequently than younger drivers. A national policy support to reduce traffic collision in older drivers and public relation activities to enhance their seat belt use should be strengthened in the future.

Identification and characterization of in vitro inhibitors against UDP-glucuronosyltransferase 1A1 in uva-ursi extracts and evaluation of in vivo uva-ursi-drug interactions.

Uva-ursi leaf is widely used to treat symptoms of lower urinary tract infections. Here, we evaluated the in vitro inhibitory effects of uva-ursi extracts on 10 major human UDP-glucuronosyltransferases (UGT) isoforms. Of the 10 tested UGT isoforms, uva-ursi extracts exerted the strongest inhibitory effect on UGT1A1-mediated ß-estradiol 3-glucuronidation with the lowest IC50 value of 8.45 ±â€¯1.56 µg/mL. To identify the components of uva-ursi extracts showing strong inhibitory effects against UGT1A1, the inhibitory effects of nine major constituents of the extracts were assessed. Among the tested compounds, gallotannin exerted the most potent inhibition on UGT1A1, followed by 1,2,3,6-tetragalloylglucose; both demonstrated competitive inhibition, with Ki values of 1.68 ±â€¯0.150 µM and 3.55 ±â€¯0.418 µM. We found that gallotannin and 1,2,3,6-tetragalloylglucose also inhibited another UGT1A1-specific biotransformation, SN-38-glucuronidation, showing the same order of inhibition. Thus, in vitro UGT1A1 inhibitory potentials of uva-ursi extracts might primarily result from the inhibitory activities of gallotannin and 1,2,3,6-tetragalloylglucose present in the extracts. However, in rats, co-administration with uva-ursi extracts did not alter the in vivo marker for UGT1A1 activity, expressed as the molar ratio of AUCSN-38 glucuronide/AUCSN-38, because plasma concentrations of gallotannin and 1,2,3,6-tetragalloylglucose may be too low to inhibit the UGT1A1-mediated metabolism of SN-38 in vivo. The poor oral absorption of gallotannin and 1,2,3,6-tetragalloylglucose in uva-ursi extracts might cause the poor in vitro-in vivo correlation. These findings will be helpful for the safe and effective use of uva-ursi extracts in clinical practice.

Results of a phase III, 8-week, multicenter, prospective, randomized, double-blind, parallel-group clinical trial to assess the effects of amlodipine camsylate versus amlodipine besylate in Korean adults with mild to moderate hypertension.

BACKGROUND: Amlodipine besylate has been used in Korea for the treatment of hypertension for >17 years, with well-established efficacy and tolerability. Amlodipine camsylate is a newer formulation developed for generic use. It has been assessed in terms of physical stability and pharmacokinetic and pharmacodynamic properties and been found to be effective in lowering blood pressure in preclinical and Phase I and II trials. However, to date, no studies have compared the clinical effectiveness of amlodipine camsylate and amlodipine besylate in treating hypertension. OBJECTIVE: This study was designed to determine the effectiveness and tolerability of amlodipine camsylate compared with amlodipine besylate in Korean patients with mild to moderate hypertension. METHODS: This Phase III, 8-week, prospective, randomized, double-blind, parallel-group study was conducted in 13 cardiology centers across the Republic of Korea. Male and female Korean patients aged 18 to 75 years having uncomplicated, mild to moderate, essential hypertension (sitting diastolic blood pressure [SiDBP] 90-<110 mm Hg) and receiving no antihypertensives in the 2 weeks before randomization were eligible. Patients were randomly assigned to receive oral treatment with amlodipine camsylate or amlodipine besylate. For the first 4 weeks, patients received amlodipine 5 mg QD (morning). After 4 weeks, if either blood pressure was > or =140/ > or =90 mm Hg or SiDBP had not decreased by > or =10 mm Hg from baseline, the dose of amlodipine was increased to 10 mg QD for 4 weeks. Trough blood pressure and heart rate were measured in duplicate with the patient in the sitting position at each clinic visit (baseline [week 0] and weeks 4 and 8 of treatment); mean values were calculated and recorded. At weeks 4 and 8, tolerability was assessed using history taking and laboratory analysis, and compliance was assessed using pill counts. The primary end point was change from baseline in SiDBP at week 8. Secondary end points were change from baseline in sitting systolic blood pressure (SiSBP) at week 8 in the total population and in the subgroup of patients who had previously received antihypertensive treatment versus those who had not. RESULTS: A total of 189 patients were enrolled (mean age, 53 years; 105 women, 84 men; mean body weight, 65.8 kg). One patient in the amlodipine camsylate group dropped out of the study at week 0 of treatment (this patient did not use any study medication) and was excluded from the modified intent-to-treat (ITT) analysis. Thus, 188 patients were treated and included in the ITT analysis (94 patients per treatment group; ITT analysis); 161 patients were included in the perprotocol (PP) analysis (n = 80 for amlodipine camsylate, n = 81 for amlodipine besylate) (14 patients in the amlodipine camsylate group and 13 patients in the amlodipine besylate group were excluded from the PP analysis due to consistent withdrawal or protocol violation). Mean (SD) SiSBP and SiDBP were significantly decreased from baseline in both groups (amlodipine camsylate, from 146.7 [12.3]/96.6 [5.4] to 127.9 [14.8]/83.4 [7.7] mm Hg [both, P < 0.001]; amlodipine besylate, from 146.8 [12.8]/96.7 [5.1] to 128.0 [10.1]/83.8 [7.5] mm Hg [both, P < 0.001]). The differences in SiSBP/SiDBP between the 2 groups at week 8 were not significant. The SiDBP response rates in the subgroups that had and had not been previously treated with antihypertensives were statistically similar (56/69 [81.2%] and 83/92 [90.2%], respectively). The prevalences of clinical adverse events (AEs) were not significantly different between the 2 treatment groups (amlodipine camsylate, 27.3 %; amlodipine besylate, 28.7%). The most common AEs were dizziness and dyspnea (both in 3/94 [3.2%] and 1/94 [1.1%] patients who received amlodipine camsylate and amlodipine besylate, respectively). CONCLUSION: The effectiveness and tolerability of amlodipine camsylate were not significantly different from those of amlodipine besylate in these Korean adults with mild to moderate hypertension.