Evaluation of rosuvastatin-induced QT prolongation risk using real-world data, in vitro cardiomyocyte studies, and mortality assessment.

Drug-induced QT prolongation is attributed to several mechanisms, including hERG channel blockage. However, the risks, mechanisms, and the effects of rosuvastatin-induced QT prolongation remain unclear. Therefore, this study assessed the risk of rosuvastatin-induced QT prolongation using (1) real-world data with two different settings, namely case-control and retrospective cohort study designs; (2) laboratory experiments using human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM); (3) nationwide claim data for mortality risk evaluation. Real-world data showed an association between QT prolongation and the use of rosuvastatin (OR [95% CI], 1.30 [1.21-1.39]) but not for atorvastatin (OR [95% CI], 0.98 [0.89-1.07]). Rosuvastatin also affected the sodium and calcium channel activities of cardiomyocytes in vitro. However, rosuvastatin exposure was not associated with a high risk of all-cause mortality (HR [95% CI], 0.95 [0.89-1.01]). Overall, these results suggest that rosuvastatin use increased the risk of QT prolongation in real-world settings, significantly affecting the action potential of hiPSC-CMs in laboratory settings. Long-term rosuvastatin treatment was not associated with mortality. In conclusion, while our study links rosuvastatin use to potential QT prolongation and possible influence on the action potential of hiPSC-CMs, long-term use does not show increased mortality, necessitating further research for conclusive real-world applications.

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.

Effect of improved medication adherence on health care costs in osteoporosis patients.

Osteoporosis is a chronic disease that requires continuous health care spending for pharmacotherapy and examinations. Osteoporotic fractures are a major economic burden. However, little is known about the economic effects of osteoporosis and osteoporotic fractures in Korea.The purpose of this study was to determine the predictors of osteoporosis-related health care costs and to evaluate the economic effects of fracture prevention through medication adherence among osteoporosis patients.Using the Korea National Health Insurance Claims Database (KNHICD), we identified osteoporosis patients aged 50 years and older from 2011 to 2012. Annual health care costs of osteoporosis were analyzed from the insurer's perspective and compared between patients with fractures and those without fractures. Adherents were defined as patients with a medication possession ratio of ≥80%. A generalized linear model (GLM) was used to estimate the predictors of osteoporosis-related health care costs.The major predictors of osteoporosis-related health care costs were age, medication adherence, and the occurrence of fractures (P < .001). The proportion of fractures among non-adherents was approximately 1.1 times the proportion among adherents. Health care costs per patient with fractures were 3.8 times the costs per patient without fractures. Patients with fractures had higher health care costs due to hospitalization and outpatient costs but lower pharmacy costs than non-adherents. We estimated that about $5 million of health insurance expenses could be saved annually if all non-adherents became adherents.Improved osteoporosis medication adherence can reduce osteoporosis-related health care costs by preventing fractures. Persistent pharmacotherapy for osteoporosis is necessary to prevent osteoporotic fractures and to reduce osteoporosis-related health care costs.

Economic Burden of Osteoporosis in South Korea: Claim Data of the National Health Insurance Service from 2008 to 2011.

The purpose of this study was to estimate the current economic burden of osteoporosis in South Korea using national claim data of the Korean National Health Insurance Service (KNHIS) from 2008 to 2011. Patients aged 50 years or older were identified from KNHIS nationwide database for all records of outpatient visits or hospital admissions. Healthcare costs for osteoporotic patients included direct medical costs for hospitalization, outpatient care, and prescription drugs for the year after discharge. Healthcare costs were estimated based on the perspective of KNHIS, and calculated using a bottom-up approach. Between 2008 and 2011, total healthcare costs for osteoporotic patients increased from 3976 million USD to 5126 million USD, with an annual increase of 9.2% which accounted for one-sixth (16.7%) of national healthcare expenditure. Healthcare cost for hospitalization was the highest ($1903 million, 40.0% of total healthcare cost), followed by cost for outpatient care ($1474 million, 31.0%) and cost for prescription drugs ($1379 million, 29.0%). Although total healthcare cost for osteoporotic men was 6 times lower than that for osteoporotic women, the cost per person was 1.5 times higher than that for women. Total healthcare cost for osteoporotic patients without fractures was higher than that for osteoporotic patients with fractures. However, cost per person was the opposite. Osteoporosis entails substantial epidemiologic and economic burden in South Korea. This study provides information about the total healthcare burden, which could be important when determining what attention and awareness osteoporosis should be given in the public health system.

Healthcare Costs of Osteoporotic Fracture in Korea: Information from the National Health Insurance Claims Database, 2008-2011.

BACKGROUND: The present study estimated healthcare costs of osteoporotic fractures including spine, hip, distal radius and humerus in Koreans over 50 years of age using national claims data. METHODS: Korea National Health Insurance data between 2008 and 2011 was searched for all claims records of outpatient visits or hospital admissions of patients ≥50-year-of-age. Osteoporosis-related fractures were identified using certain the International Classification of Diseases, Tenth Revision codes and site-specific physician claims for procedures in a patient age cut-off value of 50 years. The healthcare costs included acute phase costs accounting for emergency medical care given immediately after fracture, costs due to further hospitalization and surgical procedures, physiotherapy sessions according to the site of the fracture, and outpatient visits in the year after discharge. RESULTS: The total estimated healthcare costs of osteoporotic fractures in 2011 was $722 million. From 2008 to 2011, the total number and healthcare costs of osteoporotic fractures increased 28.9% (from 127,070 to 163,823) and 31.6% (from $549 million to $722 million), respectively. The portion of national health care expenditure was ranged from 2.3% in 2008 to 2.2% in 2011. The mean healthcare cost of osteoporotic fractures per person increased 2.1% from $4,321 in 2008 to $4,410 in 2011.The mean healthcare costs were highest for hip fractures followed by spine, humerus, and distal radius fractures. CONCLUSIONS: Total Healthcare costs of osteoporotic fractures in South Koreans ≥50-year-of-age increased between 2008 and 2011. This trend will likely continue, which is an important health problem in the elderly population and economically.

Development of a Korean Fracture Risk Score (KFRS) for Predicting Osteoporotic Fracture Risk: Analysis of Data from the Korean National Health Insurance Service.

BACKGROUND: Asian-specific prediction models for estimating individual risk of osteoporotic fractures are rare. We developed a Korean fracture risk prediction model using clinical risk factors and assessed validity of the final model. METHODS: A total of 718,306 Korean men and women aged 50-90 years were followed for 7 years in a national system-based cohort study. In total, 50% of the subjects were assigned randomly to the development dataset and 50% were assigned to the validation dataset. Clinical risk factors for osteoporotic fracture were assessed at the biennial health check. Data on osteoporotic fractures during the follow-up period were identified by ICD-10 codes and the nationwide database of the National Health Insurance Service (NHIS). RESULTS: During the follow-up period, 19,840 osteoporotic fractures were reported (4,889 in men and 14,951 in women) in the development dataset. The assessment tool called the Korean Fracture Risk Score (KFRS) is comprised of a set of nine variables, including age, body mass index, recent fragility fracture, current smoking, high alcohol intake, lack of regular exercise, recent use of oral glucocorticoid, rheumatoid arthritis, and other causes of secondary osteoporosis. The KFRS predicted osteoporotic fractures over the 7 years. This score was validated using an independent dataset. A close relationship with overall fracture rate was observed when we compared the mean predicted scores after applying the KFRS with the observed risks after 7 years within each 10th of predicted risk. CONCLUSION: We developed a Korean specific prediction model for osteoporotic fractures. The KFRS was able to predict risk of fracture in the primary population without bone mineral density testing and is therefore suitable for use in both clinical setting and self-assessment. The website is available at http://www.nhis.or.kr.

Trends of Incidence, Mortality, and Future Projection of Spinal Fractures in Korea Using Nationwide Claims Data.

Spinal fractures have been recognized as a major health concern. Our purposes were to evaluate the trends in the incidence and mortality of spinal fractures between 2008 and 2012 and predict the number of spinal fractures that will occur in Korea up to 2025, using nationwide data from the National Health Insurance Service (NHIS). A nationwide data set was evaluated to identify all new visits to medical institutes for spinal fractures in men and women aged 50 years or older between 2008 and 2012. The incidence, mortality rates and estimates of the number of spinal fractures were calculated using Poisson regression. The number of spinal fractures increased over the time span studied. Men and women experienced 14,808 and 55,164 vertebral fractures in 2008 and 22,739 and 79,903 in 2012, respectively. This reflects an increase in the incidence of spinal fractures for both genders (men, 245.3/100,000 in 2008 and 312.5/100,000 in 2012; women, 780.6/100,000 in 2008 and 953.4/100,000 in 2012). The cumulative mortality rate in the first year after spinal fractures decreased from 8.51% (5,955/69,972) in 2008 to 7.0% (7,187/102,642) in 2012. The overall standardized mortality ratio (SMR) of spinal fractures at 1 year post-fracture was higher in men (7.76, 95% CI: 7.63-7.89) than in women (4.70, 95% CI: 4.63-4.76). The total number of spinal fractures is expected to reach 157,706 in 2025. The incidence of spinal fractures increased in Korea in the last 5 years, and the socioeconomic burden of spinal fractures will continue to increase in the near future.

Risk assessment of volatile organic compounds benzene, toluene, ethylbenzene, and xylene (BTEX) in consumer products.

Exposure and risk assessment was performed by evaluating levels of volatile organic compounds (VOC) benzene, toluene, ethylbenzene, and xylene (BTEX) in 207 consumer products. The products were categorized into 30 different items, consisting of products of different brands. Samples were analyzed for BTEX by headspace-gas chromatography/mass spectrometry (headspace-GC/MS) with limit of detection (LOD) of 1 ppm. BTEX were detected in 59 consumer products from 18 item types. Benzene was detected in whiteout (ranging from not detected [ND] to 3170 ppm), glue (1486 ppm), oil-based ballpoint pens (47 ppm), and permanent (marking) pens (2 ppm). Toluene was detected in a leather cleaning product (6071 ppm), glue (5078 ppm), whiteout (1130 ppm), self-adhesive wallpaper (15-1012 ppm), shoe polish (806 ppm), permanent pen (609 ppm), wig adhesive (372 ppm), tapes (2-360 ppm), oil-based ballpoint pen (201 ppm), duplex wallpaper (12-52 ppm), shoes (27 ppm), and air freshener (13 ppm). High levels of ethylbenzene were detected in permanent pen (ND-345,065 ppm), shoe polish (ND-277,928 ppm), leather cleaner (42,223 ppm), whiteout (ND-2,770 ppm), and glue (ND-792 ppm). Xylene was detected in permanent pen (ND-285,132 ppm), shoe polish (ND-87,298 ppm), leather cleaner (12,266 ppm), glue (ND-3,124 ppm), and whiteout (ND-1,400 ppm). Exposure assessment showed that the exposure to ethylbenzene from permanent pens ranged from 0 to 3.11 mg/kg/d (men) and 0 to 3.75 mg/kg/d (women), while for xylene, the exposure ranges were 0-2.57 mg/kg/d and 0-3.1 mg/kg/d in men and women, respectively. The exposure of women to benzene from whiteout ranged from 0 to 0.00059 mg/kg/d. Hazard index (HI), defined as a ratio of exposure to reference dose (RfD), for ethylbenzene was 31.1 (3.11 mg/kg/d/0.1 mg/kg/d) and for xylene (2.57 mg/kg/d/0.2 mg/kg/d) was 12.85, exceeding 1 for both compounds. Cancer risk for benzene was calculated to be 3.2 × 10(-5) based on (0.00059 mg/kg/d × 0.055 mg/kg-d(-1), cancer potency factor), assuming that 100% of detected levels in some products such as permanent pens and whiteouts were exposed in a worst-case scenario. These data suggest that exposure to VOC via some consumer products exceeded the safe limits and needs to be reduced.

[Anti-doping policy development process in the sports world (1968~1999): focusing on IOC activities and passive response from Korea].

This study investigated the anti-doping policy promoted by the IOC historical sociologically focusing on the period from 1968 to 1999. Public opinion surrounding doping control has emerged as a large amount of drug possession by athletes who had participated in the 1952 Olympics was caught, as well as following the accident where an athlete had died during the competition as a result of doping. From 1960, as many doping cases in sports games were exposed, several international organizations proclaimed fight against doping in order to seek a preventive measure. In 1961, the IOC newly established a medical commission within the organization. It was decided to implement doping control and female sex testing at the same time for all athletes who participated in the 1967 Olympics, and they were implemented from 1968 winter and summer Olympic Games. In 1971, the provisions for the tests were prescribed as mandatory on the IOC charter. From 1989, the OCT system was introduced as a measure to overcome limitations of the detection during competition period. As political problems and limitations emerged, WADA (World Anti-Doping Agency) was established in 1999 to professionally manage and push for doping control. Female sex testing policy contributed to preventing males from participating in female competition by deceiving their gender to some extent. However, it was abolished due to strong public condemnation such as women's rights issues, social stigma and pain, and gender discrimination debate. In 1984, a doping control center was established in Korea, which enabled drug use or doping in the sports world to emerge to the surface in our society. Korea Sports Council and KOC articles of association that supervise doping related matters of Korean athletes were revised in 1990. The action of inserting doping related issue in the articles of association was taken 20 years after the start of IOC doping policy. Beginning with two international competitions in the 1980s, Korean athletes experienced doping test directly, yet education about doping was limited. However, some national team level athletes tested positive on the doping test and underwent disciplinary action. In addition, athletic federation or leaders acquiesced athletes doping made secretly; this indicated that South Korea was also not free from doping. It was found that Korea world of sports showed very passive countermeasures and development process.