Comparative Cost-Effectiveness of Tofacitinib With Continuing Conventional Synthetic Disease-Modifying Anti-Rheumatic Drugs for Active Rheumatoid Arthritis in South Korea.

INTRODUCTION: The objective of this study was to evaluate the cost-effectiveness of initiating treatment with tofacitinib and subsequently incorporating it into a conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) treatment sequence and to compare the cost-effectiveness of this sequence with that of continuing csDMARDs alone in patients with active rheumatoid arthritis (RA). METHODS: A cohort-based Markov model was used to evaluate the cost-effectiveness of two tofacitinib treatment sequences compared with that of continuing the csDMARD treatment sequence over a lifetime. Of the two tofacitinib sequences, the first consisted of initial tofacitinib treatment followed by biologic DMARDs (bDMARDs) and the second consisted of csDMARD treatments followed by tofacitinib. A third treatment sequence, continuing the csDMARD treatment sequence before starting bDMARDs, was used as a comparator. Efficacy was assessed using the American College of Rheumatology (ACR) response rates (ACR 20, ACR 50, and ACR 70) after 6 months, which were converted to changes in the health assessment questionnaire-disability index (HAQ-DI) score. Utility was estimated by mapping from the HAQ-DI score, costs were analyzed from a Korean societal perspective, and outcomes were considered in terms of quality-adjusted life-years (QALYs). One-way sensitivity analysis and probabilistic sensitivity analysis were performed to assess the robustness of the model. RESULTS: The incremental cost-effectiveness ratios over a lifetime for starting with tofacitinib and incorporating tofacitinib into the csDMARD treatment sequence versus continuing csDMARDs only were US$14,537 per QALY and US$7,086 per QALY, respectively. One-way sensitivity analysis and probabilistic sensitivity analysis confirmed the robustness of these results. CONCLUSION: Starting with tofacitinib and incorporating it into a csDMARDs treatment sequence is cost-effective compared to continuing csDMARDs alone in patients with RA.

The clinical and economic burden of community-onset complicated skin and skin structure infections in Korea.

BACKGROUND/AIMS: To investigate epidemiologic characteristics, clinical and economic burdens, and factors associated with mortality in complicated skin and skin structure infection (cSSSI) patients in Korea. METHODS: A retrospective, observational, nationwide study was conducted between April to July 2012 at 14 tertiary-hospitals in Korea. Eligible patients were hospitalized adults with community acquired cSSSI, who underwent surgical intervention and completed treatment between November 2009 and October 2011. Data on demography, clinical characteristics, outcomes and medical resource utilization were collected through medical record review. Direct medical costs were calculated by multiplying quantities of resources utilized by each unit price in Korea. RESULTS: Of 473 patients enrolled, 449 patients (except 24 patients with no record on surgical intervention) were eligible for analysis. Microbiological testing was performed on 66.1% of patients and 8.2% had multiple pathogens. Among culture confirmed pathogens (n = 297 patients, 340 episodes), 76.2% were gram-positive (Staphylococcus aureus; 41.2%) and 23.8% were gram-negative. The median duration of hospital stay was 16 days. Among treated patients, 3.3% experienced recurrence and 4.2% died in-hospital. The mean direct medical costs amounted to $4,195/ person, with the greatest expenses for hospitalization and antibiotics. The in-hospital mortality and total medical costs were higher in combined antibiotics therapy than monotherapy (p < 0.05). Charlson's comorbidity index ≥ 3, standardized early warning scoring ≥ 4, sub-fascia infections and combined initial therapy, were all found to be associated with higher mortality. CONCLUSION: Korean patients with community-onset cSSSI suffer from considerable clinical and economic burden. Efforts should be made to reduce this burden through appropriate initial treatment.

Assessment of patient-reported outcomes (PROs): treatment satisfaction, medication adherence, and quality of life (QoL) and the associated factors in postmenopausal osteoporosis (PMO) patients in Korea.

Patient-reported outcomes (PROs) provide practical guides for treatment; however, studies that have evaluated PROs of women in Korea with postmenopausal osteoporosis (PMO) are lacking. This cross-sectional, multi-center (29 nationwide hospitals) study, performed from March 2013 to July 2014, aimed to assess PROs related to treatment satisfaction, medication adherence, and quality of life (QoL) in Korean PMO women using osteoporosis medication for prevention/treatment. Patient demographics, clinical characteristics, treatment patterns, PROs, and experience using medication were collected. The 14-item Treatment Satisfaction Questionnaire for Medication (TSQM) (score-range, 0-100; domains: effectiveness, side effects, convenience, global satisfaction), Osteoporosis-Specific Morisky Medication Adherence Scale (OS-MMAS) (score-range, 0-8), and EuroQol-5 dimensions questionnaire (index score range, - 0.22 to 1.0; EuroQol visual analog scale score range, 0-100) were used. To investigate factors associated with PROs, linear (treatment satisfaction/QoL) or logistic (medication adherence) regression analyses were conducted. A total of 1804 patients (age, 62 years) were investigated; 60.1% used bisphosphonate, with the majority (67.2%) using weekly medication, 27.8% used daily hormone replacement therapy, and 12.1% used daily selective estrogen receptor modulator. Several patients reported gastrointestinal (GI) events (31.6%) and dental visits due to problems (24.1%) while using medication. Factors associated with the highest OS-MMAS domain scores were convenience and global satisfaction. GI events were associated with non-adherence. TSQM scores for effectiveness, side effects, and GI risk factors were significantly associated with QoL. Our study elaborately assessed the factors associated with PROs of Korean PMO women. Based on our findings, appropriate treatment-related adjustments such as frequency/choice of medications and GI risk management may improve PROs.

The Impact of Molecularly Targeted Treatment on Direct Medical Costs in Patients with Advanced Non-small Cell Lung Cancer.

PURPOSE: To investigate the impact of targeted treatment on direct medical costs of patients with advanced non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Medical records of 108 stage IIIB/IV NSCLC patients treated in Seoul National University Hospital between 2003 and 2009, were reviewed to collect medical resources utilization data from the diagnosis of stage IIIB/IV NSCLC to the end of active anti-cancer treatment. The direct medical costs were calculated by multiplying the number of medical resources used by the unit price. All costs were expressed in US dollars for each patient. RESULTS: The mean total direct medical costs were $34,732 (standard deviation, 21,168) in the study cohort. The mean total direct medical costs were higher in epidermal growth factor receptor ( EGFR ) mutation (EGFR MT)-positive patients than EGFR wild-type (EGFR WT) patients ($41,403 vs. $30,146, p=0.005). However, the mean monthly direct medical costs did not differ significantly between EGFR MT-positive patients and EGFR WT patients ($2,120 vs. $2,702, p=0.119) because of the longer duration of active anti-cancer treatment in EGFR MT-positive patients. This discrepancy was mainly attributable to EGFR MT-positive patients' lower non-chemotherapy costs ($948 vs. $1,522, p=0.007). The total and monthly direct medical costs of ALK fusion-positive patients who did not receive ALK inhibitors did not differ from WT/WT patients. CONCLUSION: This study suggests that the availability of targeted agents for EGFR MT-positive patients lowers the mean monthly medical costs by prolonging survival and diminishing the use of other medical resources, despite the considerable drug costs.

Investigating the Time Lag Effect between Economic Recession and Suicide Rates in Agriculture, Fisheries, and Forestry Workers in Korea.

Previous studies on the vast increase in suicide mortality in Southeast Asia have indicated that suicide rates increase in parallel with a rise in unemployment or during periods of economic recession. This paper examines the effects of economic recession on suicidal rates amongst agriculture, fisheries, and forestry workers in Korea. Monthly time-series gross domestic product (GDP) data were linked with suicidal rates gathered from the cause of death records between1993-2008. Data were analyzed using generalized additive models to analyze trends, while a polynomial lag model was used to assess the unconstrained time lag effects of changes in GDP on suicidal rate. We found that there were significant inverse correlations between changes in GDP and suicide for a time lag of one to four months after the occurrence of economic event. Furthermore, it was evident that the overall relative risks of suicide were high enough to bring about social concern.

Association between Cerebral Performance Category, Modified Rankin Scale, and discharge disposition after cardiac arrest.

BACKGROUND: Cerebral Performance Category (CPC), Modified Rankin Scale (mRS) and discharge disposition are commonly used to determine outcomes following cardiac arrest. This study tested the association between these outcome measures. METHODS: Retrospective chart review of subjects who survived to hospital discharge between 1/1/2006 and 12/31/2009 was conducted. Charts were reviewed for outcomes (CPC, mRS, and discharge disposition). Discharge disposition was classified in 6 categories: home with no services, home with home healthcare, acute rehabilitation facility, skilled nursing facility, long term acute care facility, and hospice. Intra-and inter-rater reliabilities were calculated for outcome measures. Rates of "good outcome" (defined as a CPC of 1-2, mRS of 0-3, or discharge disposition to home or acute rehabilitation facility) were also determined. Kendall's tau correlation coefficients explored relationships among measures. RESULTS: A total of 211 charts were reviewed. Mean age was 60 years (SD 16), the majority (75%) were white males, in- and out-of hospital cardiac arrests were equally prevalent, and ventricular dysrhythmia was most common (N=109, 52%). Half of the subjects were comatose following resuscitation and 75 (35%) received therapeutic hypothermia. Inter-rater percentage agreement for CPC and mRS abstraction was 95.24% (kappa 0.89, p<0.001) and 95.24% (kappa 0.90, p<0.001) respectively. "Good outcomes" were found in 44 subjects (20%) using the CPC definition, 47 subjects (22%) using the mRS definition, and 129 subjects (61%) subjects using discharge disposition definition. There was fair relationship between the CPC and mRS (tau 0.43) and poor relationships between CPC and discharge disposition (tau 0.23) and between mRS and discharge disposition (tau 0.25). CONCLUSIONS: Determination of the CPC, mRS and discharge disposition at hospital discharge is reliable from chart review. These instruments provide widely differing estimates of "good outcome". Agreement between these measures ranges from poor to fair. A more nuanced outcome measure designed for the post-cardiac arrest population is needed.

Quantitative assessment of hTERT mRNA expression in dysplastic nodules of HBV-related hepatocarcinogenesis.

BACKGROUND: Telomerase reverse transcriptase (hTERT) is the rate-limiting determinant of telomerase, which is critical for carcinogenesis. Dysplastic nodules (DNs) appear to be preneoplastic lesions of hepatocellular carcinomas (HCCs). In this study, in order to characterize DNs, hTERT mRNA, hTERT gene dosage, and mRNA for c-myc, a transcriptional activator of hTERT were studied in human multi-step hepatocarcinogenesis. METHODS: Fifty four hepatic nodules including 5 large regenerative nodules, 14 low-grade DNs, 7 high-grade DNs, 11 DNs with HCC foci and 17 HCCs, 23 livers with chronic hepatitis/cirrhosis, and 6 normal livers were examined. Transcript levels were measured by real-time quantitative RT-PCR and gene dosages by real-time PCR and Southern blotting. RESULTS: The hTERT mRNA levels increased with the progression of hepatocarcinogenesis, and a significant induction in the transition between low- and high-grade DNs was seen. Most high-grade DNs strongly expressed hTERT mRNA at levels similar to those of HCCs. Twenty-one percent of low-grade DNs had high levels of hTERT mRNA, up to those of high-grade DNs and there was no difference in the pathological features between low-grade DNs with and without increased hTERT mRNA levels. No correlation was found between hTERT mRNA levels, hTERT gene dosage, and c-myc mRNA levels. CONCLUSIONS: These results suggest that the induction of hTERT mRNA is an important early event and that its measurement by real-time quantitative RT-PCR is a useful tool to detect premalignant/malignant tendencies in hepatic nodules. However, hTERT gene dosage and c-myc expression are not the main mechanisms regulating hTERT expression in hepatocarcinogenesis.

Preparation of (188) Re-labeled paper for treating skin cancer.

For homogeneous delivery of beta radiation to skin cancer, we developed a simple method for preparing (188) Re-labeled nitrocellulose paper. The homogeneity and stability of the labeled paper were investigated. Absorbed dose estimates were calculated using the Monte-Carlo method. A 74-MBq (188) Re-labeled paper with 1-cm diameter delivered 147.2 Gy up to 1-mm depth after 2-h irradiation. Animal experiments on tumor-bearing mice showed that 50 Gy is an adequate dose for treating skin cancer. Tumors disappeared 7 days after irradiation in all the groups irradiated by 50 or 100 Gy. The (188) Re-labeled paper provided a convenient, economical, effective, and non-invasive method of treating skin cancer.