BACKGROUND: The use of therapeutic materials based on new health technology has increased in recent years in the field of medicine, raising concerns for medical practitioners regarding increased spending on the new therapeutic materials amid the rapid population ageing and increase of chronic diseases in Korea. While therapeutic materials have significant importance in the health care system, they have not been given appropriate attention in the academic world of Korea. The purpose of this study is to identify factors that affect the growth of expenditure on therapeutic materials and to derive implications for an effective management considering the diversity of therapeutic materials. METHODS: Using the claims data of the National Health Insurance Services, specific utilization patterns of groups of therapeutic materials in the middle classification level of Health Insurance Review and Assessment Service from 2007 to 2014 were analyzed. Four categories (J5083: drug eluting coronary stent, D0302: nonmetallic anchor, K6014: gauze, K6023: gauze) that exhibit unique patterns with respect to price and volume were selected. Then, decomposition analysis was performed to identify the largest contributor to the spending growth by dividing the products into existing, new, and abandoned products for the period between 2010 and 2013. RESULTS: The effect of new products had larger impact on spending growth than the effect of core items in drug eluting coronary stent (J5083) and nonmetallic anchor (D0302). In addition, existing products in general included items priced relatively lower when compared with another item manufactured by the same company. In the gauze category, however, existing products had the largest impact on expenditure and the effect of volume was greater than that in other categories. CONCLUSION: This study provides evidence that appropriate management measures classified by the characteristics of therapeutic materials are required for therapeutic materials pricing and reassessment in Korea.
Biomedical Technology ; Chronic Disease ; Classification ; Delivery of Health Care ; Health Expenditures* ; Health Status ; Insurance ; Korea ; National Health Programs* ; Stents

Over the last decade, physiologically based pharmacokinetics (PBPK) application has been extended significantly not only to predicting preclinical/human PK but also to evaluating the drug-drug interaction (DDI) liability at the drug discovery or development stage. Herein, we describe a case study to illustrate the use of PBPK approach in predicting human PK as well as DDI using in silico, in vivo and in vitro derived parameters. This case was composed of five steps such as: simulation, verification, understanding of parameter sensitivity, optimization of the parameter and final evaluation. Caffeine and ciprofloxacin were used as tool compounds to demonstrate the “fit for purpose” application of PBPK modeling and simulation for this study. Compared to caffeine, the PBPK modeling for ciprofloxacin was challenging due to several factors including solubility, permeability, clearance and tissue distribution etc. Therefore, intensive parameter sensitivity analysis (PSA) was conducted to optimize the PBPK model for ciprofloxacin. Overall, the increase in C(max) of caffeine by ciprofloxacin was not significant. However, the increase in AUC was observed and was proportional to the administered dose of ciprofloxacin. The predicted DDI and PK results were comparable to observed clinical data published in the literatures. This approach would be helpful in identifying potential key factors that could lead to significant impact on PBPK modeling and simulation for challenging compounds.
Area Under Curve ; Caffeine* ; Ciprofloxacin* ; Computer Simulation ; Drug Discovery ; Humans ; In Vitro Techniques ; Permeability ; Pharmacokinetics* ; Solubility ; Tissue Distribution

Background: There have been recent proposals to categorize healthcare-associated infections (HCAIs) separately from community-acquired infections (CAIs). The aim of this study was to compare the antibiotic resistance of pathogens causing CAIs, HCAIs, and hospital-acquired infections (HAIs) in Korea, and to investigate the need for different empirical antibiotics therapy for CAIs and HCAIs. Materials and Methods: This prospective study was conducted in a university hospital between March and December 2019. Inpatients who underwent a bacterial culture within 2 days of hospitalization, with a Enterobacteriaceae strain identified at the infection site and available antibiotic susceptibility results, were included in the analysis. Infections were classified as CAIs, HCAIs or HAIs, depending on the source. Results: Of the 146 patients included in the analysis, the prevalence of fluoroquinoloneresistant Enterobacteriaceae was 18.8%, 38.5%, and 55.0%; the prevalence of pathogens showing third-generation cephalosporins resistance was 8.3%, 50.0%, and 60.0%; and the prevalence of pathogens showing piperacillin-tazobactam resistance was 8.3%, 7.7%, 15.0% in the CAIs, HCAIs, and HAIs groups, respectively. The prevalence of extended-spectrum beta-lactamase-positive pathogens was 6.3%, 47.3%, and 55.0% in the CAIs, HCAIs, and HAIs group, respectively, with no significant difference between the HCAIs and HAIs groups. Resistance patterns of the HCAIs group more closely resembled those of the HAIs group than those of the CAIs group. Conclusion The pathogens isolated from patients with HCAIs showed resistance patterns that were more similar to those of patients with HAIs than those with CAIs. Thus, CAIs and HCAIs should be distinguished from each other when selecting antibiotic agents.

Background: There have been recent proposals to categorize healthcare-associated infections (HCAIs) separately from community-acquired infections (CAIs). The aim of this study was to compare the antibiotic resistance of pathogens causing CAIs, HCAIs, and hospital-acquired infections (HAIs) in Korea, and to investigate the need for different empirical antibiotics therapy for CAIs and HCAIs. Materials and Methods: This prospective study was conducted in a university hospital between March and December 2019. Inpatients who underwent a bacterial culture within 2 days of hospitalization, with a Enterobacteriaceae strain identified at the infection site and available antibiotic susceptibility results, were included in the analysis. Infections were classified as CAIs, HCAIs or HAIs, depending on the source. Results: Of the 146 patients included in the analysis, the prevalence of fluoroquinoloneresistant Enterobacteriaceae was 18.8%, 38.5%, and 55.0%; the prevalence of pathogens showing third-generation cephalosporins resistance was 8.3%, 50.0%, and 60.0%; and the prevalence of pathogens showing piperacillin-tazobactam resistance was 8.3%, 7.7%, 15.0% in the CAIs, HCAIs, and HAIs groups, respectively. The prevalence of extended-spectrum beta-lactamase-positive pathogens was 6.3%, 47.3%, and 55.0% in the CAIs, HCAIs, and HAIs group, respectively, with no significant difference between the HCAIs and HAIs groups. Resistance patterns of the HCAIs group more closely resembled those of the HAIs group than those of the CAIs group. Conclusion The pathogens isolated from patients with HCAIs showed resistance patterns that were more similar to those of patients with HAIs than those with CAIs. Thus, CAIs and HCAIs should be distinguished from each other when selecting antibiotic agents.

Carisbamate is an antiepileptic drug and it also has broad neuroprotective activity and anticonvulsant reaction. In this study, a liquid chromatography-quadrupole time-of-flight mass spectrometric (LC-qTOF-MS) method was developed and applied for the determination of carisbamate in rat plasma to support in vitro and in vivo studies. A quadratic regression (weighted 1/concentration2), with an equation y = ax2 + bx + c, was used to fit calibration curves over the concentration range from 9.05 to 6,600 ng/mL for carisbamate in rat plasma. Preclinical in vitro and in vivo studies of carisbamate have been studied through the developed bioanalytical method. Based on these study results, human pharmacokinetic (PK) profile has been predicted using physiologically based pharmacokinetic (PBPK) modeling. The PBPK model was optimized and validated by using the in vitro and in vivo data. The human PK of carisbamate after oral dosing of 750 mg was simulated by using this validated PBPK model. The human PK parameters and profiles predicted from the validated PBPK model were similar to the clinical data. This PBPK model developed from the preclinical data for carisbamate would be useful for predicting the PK of carisbamate in various clinical settings.

Carisbamate is an antiepileptic drug and it also has broad neuroprotective activity and anticonvulsant reaction. In this study, a liquid chromatography-quadrupole time-of-flight mass spectrometric (LC-qTOF-MS) method was developed and applied for the determination of carisbamate in rat plasma to support in vitro and in vivo studies. A quadratic regression (weighted 1/concentration2), with an equation y = ax2 + bx + c, was used to fit calibration curves over the concentration range from 9.05 to 6,600 ng/mL for carisbamate in rat plasma. Preclinical in vitro and in vivo studies of carisbamate have been studied through the developed bioanalytical method. Based on these study results, human pharmacokinetic (PK) profile has been predicted using physiologically based pharmacokinetic (PBPK) modeling. The PBPK model was optimized and validated by using the in vitro and in vivo data. The human PK of carisbamate after oral dosing of 750 mg was simulated by using this validated PBPK model. The human PK parameters and profiles predicted from the validated PBPK model were similar to the clinical data. This PBPK model developed from the preclinical data for carisbamate would be useful for predicting the PK of carisbamate in various clinical settings.

Strongyloides stercoralis is an intestinal nematode that infects a large portion of the world's population, especially in tropical areas and other hot, humid regions. In immunocompromised patients, the parasite is augmented by autoinfection, resulting in hyperinfection or systemic dissemination. Pulmonary hemorrhage is a rare presentation of Strongyloides hyperinfection. We experienced a case of Strongyloides hyperinfection with alveolar hemorrhage in an immunocompromised patient. A 63-year-old man with small cell lung carcinoma on chemotherapy presented with abdominal pain and dyspnea. He developed a pulmonary hemorrhage and migrating pneumonia 1 week later, and bronchoalveolar lavage cytology revealed helminthic larvae identified as Strongyloides. The patient received albendazole therapy for 6 weeks, and the Strongyloides hyperinfection and pneumonia were resolved.
Abdominal Pain ; Albendazole ; Bronchoalveolar Lavage ; Dyspnea ; Helminths ; Hemoptysis ; Hemorrhage ; Humans ; Immunocompromised Host ; Larva ; Middle Aged ; Parasites ; Pneumonia ; Small Cell Lung Carcinoma ; Strongyloides ; Strongyloides stercoralis ; Strongyloidiasis

Background and Objectives: Zonulin is a human protein that regulates intercellular tight junctions and increases the permeability of the intestinal epithelium. In light of the increasing focus on zonulin’s role in numerous chronic inflammatory diseases, this study aimed to investigate whether differences exist in serum zonulin levels and bronchial epithelium zonulin expression in vivo between asthma and normal groups, using a mouse model. Methods: Sixteen mice were utilized in this study, divided evenly between the normal and asthma groups. Serum zonulin levels, the expression of zonulin antibody in the bronchial epithelium, and serum cytokine levels were evaluated in both groups. Enzyme-linked immunosorbent assay and RNA in situ hybridization were utilized for the analysis. Results: The asthma group exhibited significantly higher levels of serum zonulin. High zonulin antibody expression was also observed in the bronchial epithelium of the asthma group. Given that our mouse model demonstrated a significant difference in interleukin (IL)-4 and IL-6 between the normal and asthma groups, zonulin may be associated not only with type 2 responses but also with various subtypes of asthma. Further studies are required to investigate this relationship in greater detail. Conclusion Zonulin may play a role in the complex pathophysiology of asthma and could serve as a biomarker in various asthma-related situations.