Introduction of a Program to Improve the Information Sharing System of Food Allergy Patients.

Although the symptoms of food allergy are diverse and sometimes dangerous to life, we have not been able to effectively share information on patients' food allergies. In this study, we developed a program to prescribe the allergic formula for each patient and to establish a series of processes for safe allergenic meal delivery based on the standards and guidelines of food allergy management. We then assessed the utility of the "introduction of food allergy program" by comparing the number of allergic prescriptions before and after the program application for inpatients. Through the development and introduction of the program, all hospital staffs, including medical staff and dieticians, can share information on food allergy patients. Systematic management of food allergy patients from doctor's prescriptions has provided the basis for safe meal preparation.

Gemcitabine and Docetaxel Combination for Advanced Soft Tissue Sarcoma: A Nationwide Retrospective Study.

PURPOSE: This nationwide retrospective study was conducted to evaluate the efficacy and safety of combined gemcitabine and docetaxel (GD) as an off-label therapy for advanced soft tissue sarcoma, which has limited treatment options owing to its rare occurrence. MATERIALS AND METHODS: A total of 228 patients received GD therapy for advanced soft tissue sarcoma from 2009 to 2014 in Korea. We retrospectively reviewed the clinical medical records and claims data of these patients. RESULTS: A total of 218 patients in 20 medical centers were included in the final analysis (median age, 50.0 years). The objective response rate was 15.1% (34/218, in the leiomyosarcoma subgroup; 26.3%). The median overall survival and progression-free survival were 10.3 months (95% confidence interval [CI], 8.4 to 12.2) and 3.3 months (95% CI, 2.8 to 4.7), respectively. The treatment was discontinued in 7.8% of patients owing to adverse events; however, there was no adverse event-related death. Neutropenia (35.7%) and anemia (15.1%) were the most frequent grade 3/4 toxicities. Univariate analysis for identifying the predictors of the progression-free survival period revealed that patients aged ≤ 50 years had a hazard ratio of 1.388 (95% CI, 1.027 to 1.875; p < 0.05) relative to those aged > 50 years, and the group with leiomyosarcoma had a hazard ratio of 0.693 (95% CI, 0.493 to 0.975; p < 0.05) relative to the group with other histopathological subtypes. CONCLUSION: GD therapy was tolerable and effective for Korean patients with soft tissue sarcoma. In conclusion, for patients with advanced soft tissue sarcoma, especially leiomyosarcoma, GD therapy could be an important therapeutic option.

Preclinical efficacy and mechanisms of mesenchymal stem cells in animal models of autoimmune diseases.

Mesenchymal stem cells (MSCs) are present in diverse tissues and organs, including bone marrow, umbilical cord, adipose tissue, and placenta. MSCs can expand easily in vitro and have regenerative stem cell properties and potent immunoregulatory activity. They inhibit the functions of dendritic cells, B cells, and T cells, but enhance those of regulatory T cells by producing immunoregulatory molecules such as transforming growth factor-ß, hepatic growth factors, prostaglandin E2, interleukin-10, indolamine 2,3-dioxygenase, nitric oxide, heme oxygenase-1, and human leukocyte antigen-G. These properties make MSCs promising therapeutic candidates for the treatment of autoimmune diseases. Here, we review the preclinical studies of MSCs in animal models for systemic lupus erythematosus, rheumatoid arthritis, Crohn's disease, and experimental autoimmune encephalomyelitis, and summarize the underlying immunoregulatory mechanisms.

Preclinical and clinical studies on cytokine-induced killer cells for the treatment of renal cell carcinoma.

Renal cell carcinoma (RCC) is the most common malignancy of adult human kidney, which accounts for more than 2 % of all cancers. RCC generally does not respond well to conventional chemotherapy and radiotherapy. Cytokine-induced killer (CIK) cells are ex vivo activated lymphocytes with potent activity against various tumors and minimal side effects. Here, we summarize the data on preclinical and clinical efficacy of CIK cells for RCC treatment. Our preclinical data show that CIK cells have potent anti-tumor activity in vitro and in an in vivo nude mouse xenograft model. Clinical studies for the treatment of RCC patients indicate that CIK cell therapy can induce favorable responses with no serious side effects. These studies suggest that CIK cells may become a valuable strategy for the treatment of patients with RCC.

Sourcing quality-of-life weights obtained from previous studies: theory and reality in Korea.

BACKGROUND: The quality-of-life weights obtained in previous studies are frequently used in cost-utility analyses. The purpose of this study is to describe how the values obtained in previous studies are incorporated into the industry submissions requesting listing at the Korean National Health Insurance (NHI), focusing on the issues discussed in theoretical studies and national guidelines. METHODS: The industry submissions requesting listing at the Korean NHI from January 2007 until December 2009 were evaluated by two independent researchers at the Health Insurance Review and Assessment Service (HIRA). Specifically, we observed the methods that were used to pool, predict joint health state utilities, and retain consistency within submissions in terms of the issues discussed in methodological research papers and recommendations from national guidelines. RESULTS: More than half of the submissions used QALY as an outcome measure, and most of these submissions were sourced from prior studies. Heterogeneous methodologies were frequently used within a submission, with the inconsistent use of upper and lower anchors being prevalent. Assumptions behind measuring joint health state utilities or pooling multiple values for single health states were omitted in all submissions. Most national guidelines were rather vague regarding how to predict joint health states, how to select the best available value, how to maintain consistency within a submission, and how to generalize values obtained from prior studies. CONCLUSIONS: Previously-generated values were commonly sourced, but this practice was frequently related to inconsistencies within and among submissions. Attention should be paid to the consistency and transparency of the value, especially if the value is sourced from prior studies.

ID3 contributes to cerebrospinal fluid seeding and poor prognosis in medulloblastoma.

BACKGROUND: The inhibitor of differentiation (ID) genes have been implicated as promoters of tumor progression and metastasis in many human cancers. The current study investigated the expression and functional roles of ID genes in seeding and prognosis of medulloblastoma. METHODS: ID gene expression was screened in human medulloblastoma tissues. Knockdown of ID3 gene was performed in medulloblastoma cells in vitro. The expression of metastasis-related genes after ID3 knockdown was assessed. The effect of ID3 knockdown on tumor seeding was observed in an animal model in vivo. The survival of medulloblastoma patients was plotted according to the ID3 expression levels. RESULTS: Significantly higher ID3 expression was observed in medulloblastoma with cerebrospinal fluid seeding than tumors without seeding. Knockdown of ID3 decreased proliferation, increased apoptosis, and suppressed the migration of D283 medulloblastoma cells in vitro. In a seeding model of medulloblastoma, ID3 knockdown in vivo with shRNA inhibited the growth of primary tumors, prevented the development of leptomeningeal seeding, and prolonged animal survival. High ID3 expression was associated with shorter survival of medulloblastoma patients, especially in Group 4 medulloblastomas. CONCLUSIONS: High ID3 expression is associated with medulloblastoma seeding and is a poor prognostic factor, especially in patients with Group 4 tumors. ID3 may represent the metastatic/ aggressive phenotype of a subgroup of medulloblastoma.

Assessment of pharmacoeconomic evaluations submitted for reimbursement in Korea.

OBJECTIVE: To assess the quality of pharmacoeconomic evaluations (PEs) submitted with new drug applications for reimbursement and to investigate the role of PEs for coverage decisions in Korea. METHODS: Forty-seven PEs that were submitted by pharmaceutical companies for coverage decisions between June 2005 and December 2009 were included in this study. To assess their appropriateness with regard to the PE guidelines, we used the Health Insurance Review and Assessment services (HIRA) checklist consisting of 20 items based on the PE guidelines. We also evaluated the results for coverage decisions, as "recommended," "recommended with restricted use," or "not recommended," based on the incremental cost-effectiveness ratio and the range of uncertainty. RESULTS: On average, 14 of the 20 items on the HIRA checklist were fulfilled (70.9%, range 35.0%-100%). The compliance rate for the following items was above 70%: presentation of perspectives and evaluation methods, a sufficient time horizon, and appropriateness of comparators and health outcomes. The compliance rate for the following items was below 70%: omission of objectives for the study, inappropriate target population, unclear selection process for effectiveness and cost, inappropriate cost estimation, insufficient justification of generalizability, and description of study limitations. The range of incremental cost-effectiveness ratios per quality-adjusted life-years of PEs from a societal perspective varied from dominant to 59K USD (n = 13): it consisted of dominant to 28K USD for "recommended" submissions (n = 6), 8K to 20K USD for "recommended with restricted use" submissions (n = 4), and 13K to 59K for "not recommended" ones (n = 3). CONCLUSIONS: Our study showed that most PEs in this study have reached an adequate level for coverage decisions. Overall barriers associated with a lack of relevant evidence could account for the low compliance rate with specific items in the PE guidelines. PEs with good quality submitted for coverage decisions have played an important role for selecting cost-effective drugs.

Evaluation on the first 2 years of the positive list system in South Korea.

OBJECTIVE: The South Korean positive list system in pharmaceutical reimbursement was introduced by the Health Care System Reform Act implemented in December 2006. This study introduces this positive list system (PLS), and reports on an evaluation of two years of operation. In addition, decision-making factors are evaluated and current issues and solutions discussed. METHODS: We analyzed 91 submissions with reimbursement decisions completed by December 31, 2008. Submission characteristics and relevant factors related to decision criteria were identified by the decision outcomes (recommended/rejected). RESULTS: Under the new system, Health Insurance Review and Assessment service (HIRA) recommended 64 submissions for reimbursement and rejected 27 submissions. For recommended submissions, 59 met all criteria and 5 were recommended based on the rule of rescue. The primary reason for rejection was unacceptable cost-effectiveness. The likelihood of recommendation was found to be significantly elevated if a drug was superior to its comparator, if treatment cost was not greater than that of its comparator, or if the number of recommended decisions made by other committees increased. CONCLUSIONS: The South Korean PLS has stabilized during the 2 years after its introduction. The recommended submissions were qualified in all decision-making criteria used. Among the various decision criteria, clinical benefit and cost-effectiveness were the main drivers of reimbursement decisions. In addition, there is a certain degree of consistency between the reimbursement decisions of HIRA and other countries.

Low-dose Ultraviolet A1 Phototherapy for Treating Pityriasis Rosea.

BACKGROUND: UVA1 phototherapy has recently demonstrated high levels of efficacy and tolerability for treating a variety of inflammatory and neoplastic skin diseases. OBJECTIVE: The purpose of the present study was to assess the clinical efficacy of UVA1 (340~400 nm) phototherapy for treating pityriasis rosea and to assess the course of the disease after treatment. METHODS: Fifteen patients with extensive pityriasis rosea were treated with low-dose UVA1 phototherapy (starting at 10~20 J/cm(2) and then it was increased to 30 J/cm(2)). The treatments were given 2~3 times a week until complete clearance of lesions was achieved or until there was partial improvement without further amelioration, in spite of 5 additional treatments. The rate of clearing was monitored by estimating the pityriasis rosea severity (PRSS) score and the pruritus score. RESULTS: The extent of disease (PRSS) in all 15 patients lessened during the study (30.1+/-3.6 vs. 2.0+/-1.6, respectively, p<0.05). The overall reduction of the PRSS showed a significant improvement after the second or third treatment. The pruritus of 12 of 15 patients lessened during the treatment period, and it was unchanged in the remaining 3 patients. The mean previous duration of disease was 11.2+/-4.9 days and this did not interfere with the successful outcome of UVA1 phototherapy. CONCLUSION: This study shows that UVA1 phototherapy is a useful, well-tolerated treatment option for patients suffering from pityriasis rosea with extensive eruptions and considerable pruritus.

The Investigation on the Distribution of Malassezia Yeasts on the Normal Korean Skin by 26S rDNA PCR-RFLP.

BACKGROUND: Malassezia yeasts are normal flora of the skin that are discovered in 75~98% of health subjects, but since its association with various skin disorders have been known, many studies have been conducted in the distribution of the yeasts. OBJECTIVE: To isolate, identify, and classify Malassezia yeasts from the normal human skin of Koreans by using the rapid and accurate molecular biology method (26S rDNA PCR-RFLP) which overcome the limits of morphological and biochemical methods, and to gather a basic database that will show its relation to various skin diseases. METHODS: Malassezia yeasts were cultured from clinically healthy human skin using scrub-wash technique at five sites (forehead, cheek, chest, upper arm, and thigh) and swabbing technique at scalp in 160 participants comprised of 80 males and 80 females aged from 0 to 80. Identification of obtained strains were placed into the one of the 11 species by 26S rDNA PCR-RFLP. RESULTS: An overall positive culture rate was 62.4% (599/960). As shown in the experiment groups by their age, the positive culture rate was the highest (74.2%) in the age 21~30 and 31~40 (89/120). In the experiment groups by different body areas, the scalp showed the highest positive culture rate of 90% (144/160). On analysis of 26S rDNA PCR-RFLP, M. globosa was the most predominant species in the age 0~10 (32.8%), 11~20 (28.9%), 21~30 (32.3%). M. restricta was identified as predominant species in the age 41~50 (27.9%), 61~70 (31.5%) and 71~80 (24.0%). In the age 31~40 years, M. sympodialis was found to be the most common species (24.6%). According to body site, M. restricta was more frequently recovered in the scalp (56.8%), forehead (39.8%) and cheek (24.0%) and while M. globosa was more frequently recovered in the chest (36.8%). Higher positive culture rates of Malassezia yeasts were shown in male subjects than female counterparts in all body areas except scalp (p<0.05). Especially in this study, M. dermatis, newly isolated Malassezia species from atopic dermatitis patient in Japan, was isolated and identified in 19 cases (1.9%) in healthy subjects. CONCLUSION: The key is to recognize the existence of a difference in the type of Malassezia species in different ages as well as body areas, which reflects differing skin lipid levels in various ages and different body areas. Moreover, 26S rDNA PCR-RFLP analysis which was opted in this study could provide a sensitive and rapid identification system for Malassezia species, which may be applied to epidemiological surveys and clinical practice.

Isolation of 19 strains of Malassezia dermatis from healthy human skin in Korea.

This research was conducted on the cultured samples of 160 healthy men and women aged 0-80 years without any skin disease. Nineteen clinical isolates of Malassezia dermatis showed positive in a catalase test and all grew in 0.5% Tween-60 and 0.1% Tween-80 added to 2% glucose/1% peptone culture medium. Round and ellipsoidal yeast cells and budding of the yeast cells were observed by microscopy, resembling Malassezia sympodialis, Malassezia furfur and Malassezia nana. The 26S rDNA polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) pattern was the same as for M. dermatis (JCM 11348), the standard strain. 26S rDNA and ITS1 sequencing were performed for exact identification, showing 99% accordance with M. dermatis (AB070361), M. dermatis (AB070356), confirming the species to be new and first to be reported in Korea. Taking a molecular biological classification approach by analyzing the 26S rDNA PCR-RFLP patterns, we have successfully isolated 19 cases of M. dermatis- the first in Korea.