Erratum: Validation of the European Quality of Life-5 Dimensions, 3-Level Version (EQ-5D-3L) in Patients With Osteoporotic Vertebral Fracture and Comparing Their Health-Related Quality of Life with That of the General Population in Korea.

[This corrects the article on p. 64 in vol. 18, PMID: 35557648.].

Validation of the European Quality of Life-5 Dimensions, 3-Level Version (EQ-5D-3L) in Patients With Osteoporotic Vertebral Fracture and Comparing Their Health-Related Quality of Life With That of the General Population in Korea.

Objective: This study examined the validity of the European Quality of Life-5 dimensions, 3-Level version (EQ-5D-3L) in patients with osteoporotic vertebral compression fractures (OVCF) and compared the health-related quality of life (HRQOL) of these patients with that of the general population in Korea. Methods: Study participants completed several questionnaires, such as the EQ-5D-3L, 12-item short-form health survey version 2.0 (SF-12v2), Roland-Morris disability questionnaire (RMQ), and Pain Numeric Rating Scale (Pain NRS). Spearman's correlation analyses of the questionnaire results were conducted to examine the discriminant and convergent validity of the EQ-5D-3L. Finally, EQ-5D-3L results from study participants were compared with those from the comparison group of the general population that were match-sampled according to age and sex from the 2013 Korean National Health and Nutritional Examination Survey. Results: Spearman's correlation coefficients between EQ-5D-3L and pain NRS, SF-12v2, and RMQ were statistically significant. The coefficients between the relevant dimensions, such as mobility in the EQ-5D-3L and physical functioning in the SF-12v2, were higher than those between irrelevant ones. Problems reported by study participants in each dimension of EQ-5D-3L showed statistically significant lower scores in pain NRS, PCS, and MCS from the SF-12v2 and RMQ scores. In comparison with the general population, the problems reported in the patient group were statistically higher than those reported by the general population. Conclusion: This study showed that EQ-5D-3L will be useful for patients with OVCF in Korea because it could be valid. The HRQOL of patients with OVCF was very low in all dimensions of the EQ-5D-3L.

Structural hybridization of pyrrolidine-based T-type calcium channel inhibitors and exploration of their analgesic effects in a neuropathic pain model.

Highly effective and safe drugs for the treatment of neuropathic pain are urgently required and it was shown that blocking T-type calcium channels can be a promising strategy for drug development for neuropathic pain. We have developed pyrrolidine-based T-type calcium channel inhibitors by structural hybridization and subsequent assessment of in vitro activities against Cav3.1 and Cav3.2 channels. Profiling of in vitro ADME properties of compounds was also carried out. The representative compound 17h showed comparable in vivo efficacy to gabapentin in the SNL model, which indicates T-type calcium channel inhibitors can be developed as effective therapeutics for neuropathic pain.

Synthesis and biological evaluation of pyrrolidine-based T-type calcium channel inhibitors for the treatment of neuropathic pain.

The treatment of neuropathic pain is one of the urgent unmet medical needs and T-type calcium channels are promising therapeutic targets for neuropathic pain. Several potent T-type channel inhibitors showed promising in vivo efficacy in neuropathic pain animal models and are being investigated in clinical trials. Herein we report development of novel pyrrolidine-based T-type calcium channel inhibitors by pharmacophore mapping and structural hybridisation followed by evaluation of their Cav3.1 and Cav3.2 channel inhibitory activities. Among potent inhibitors against both Cav3.1 and Cav3.2 channels, a promising compound 20n based on in vitro ADME properties displayed satisfactory plasma and brain exposure in rats according to in vivo pharmacokinetic studies. We further demonstrated that 20n effectively improved the symptoms of neuropathic pain in both SNL and STZ neuropathic pain animal models, suggesting modulation of T-type calcium channels can be a promising therapeutic strategy for the treatment of neuropathic pain.

Uneven recovery patterns of compromised health-related quality of life (EQ-5D-3 L) domains for breast Cancer survivors: a comparative study.

BACKGROUND: Although several studies have evaluated health-related quality of life (HRQoL) in breast cancer survivors, few have compared HRQoL between breast cancer survivors and an age-matched general population in terms of improvement patterns according to time after surgery. Thus, we compared the postoperative changes in HRQoL in breast cancer survivors with those of age-matched general population groups using the EuroQoL five-dimension three-level questionnaire (EQ-5D-3 L). METHODS: EQ-5D-3 L questionnaires were obtained from 686 breast cancer survivors during follow-up visits. They were divided into five groups according to time after surgery: 0-5 months, 6-11 months, 12-35 months, 36-59 months, and ≥ 60 months. Their EQ-5D-3 L data, covering five dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), were compared with those of age-matched general population groups. RESULTS: The mean EQ-5D-3 L index of breast cancer survivors was high in group with longer time after surgery and the mean EQ-5D-3 L index of breast cancer group over 5 years after surgery was similar to that of an age-matched general population (0.919 vs 0.928, p = 0.305). Although there were deficits in all dimensions of breast cancer survivors, motility eventually exceeded that of general population groups and self-care and usual activities of groups over 3 years after surgery matched those of general population however, pain/discomfort and anxiety/depression of survivors over 5 years after surgery remained worse than those of the general population (p = 0.028, p < 0.001). CONCLUSIONS: Motility, self-care, and usual activities decreased in the early postoperative period for breast cancer survivors but showed recovery after 3 years. However, pain/discomfort and anxiety/depression remained poorer in these patients than in the general population for many years.

Discovery of thienopyrrolotriazine derivatives to protect mitochondrial function against Aß-induced neurotoxicity.

Recovery of mitochondrial dysfunction has gained increasing attention as an alternative therapeutic strategy for Alzheimer's disease (AD). Recent studies suggested that the 18 kDa mitochondrial translocator protein (TSPO) has the potential to serve as a drug target for the treatment of AD. In this study, we generated a structure-based pharmacophore model and virtually screened a commercial library, identifying SVH07 as a virtual hit, which contained a tricyclic core structure, thieno[2',3':4,5]pyrrolo[1,2-d][1,2,4]triazine group. A series of SVH07 analogues were synthesized and their effects on the mitochondrial membrane potential and ATP production were determined by using neuronal cells under Aß-induced toxicity. Among these analogues, compound 26 significantly recovered mitochondrial membrane depolarization and ATP production. In vitro binding assays indicated that SVH07 and 26 showed high affinities to TSPO with the IC50 values in a nanomolar range. We believe that compound 26 is a promising lead compound for the development of TSPO-targeted mitochondrial functional modulators with therapeutic potential in AD.

Estimating utility weights and quality-adjusted life year loss for colorectal cancer-related health states in Korea.

We aimed to assess utility weight of health states associated with colorectal cancer (CRC) that reflect the societal preference of the Korean population and to estimate the quality-adjusted life year (QALY) loss with CRC. We recruited 607 individuals from the Korean population; they were surveyed via face-to-face computer-assisted interviews. The participants evaluated each CRC-associated health state using standard gamble. Utility weight for each health state was calculated as the possibility of full health restoration. Moreover, we estimated total QALY loss due to CRC in Korean individuals aged ≥30 years in 2013. To calculate QALY due to morbidity, we yielded utility weights and used epidemiologic data of CRC on severity from the National Cancer Control Institute. QALY loss due to mortality was calculated using mortality of CRC and life expectancy data from the Korean Statistical Information Service. The highest and lowest utility weights were assigned to "adenomatous polyps" and "metastatic colon cancer", respectively. Total QALY loss due to CRC in Korea was 173,662; these patients were more likely to be men or be included in the 70-74-year age group. These utility weights may be useful for conducting cost-utility studies of cancer screening for CRC and for measuring disease burden with QALY.

Estimation of utility weights for human papilloma virus-related health states according to disease severity.

BACKGROUND: A cost-utility study of a human papilloma virus (HPV) vaccine requires that the utility weights for HPV-related health states (i.e., cervical intraepithelial neoplasia (CIN), cervical cancer, and condyloma) be evaluated. The aim of the present study was to determine the utility weights for HPV-related health states. METHODS: Hypothetical standardised health states related to HPV were developed based on patient education material and previous publications. To fully reflect disease progression from diagnosis to prognosis, each health state comprised four parts (diagnosis, symptoms, treatment, and progression and prognosis). Nine-hundred members from the Korean general population evaluated the HPV-related health states using a visual analogue scale (VAS) and a standard gamble (SG) approach, which were administered face-to-face via computer-assisted interview. The mean utility values were calculated for each HPV-related health state. RESULTS: According to the VAS, the highest utility (0.73) was HPV-positive status, followed by condyloma (0.66), and CIN grade I (0.61). The lowest utility (0.18) was cervical cancer requiring chemotherapy without surgery, followed by cervical cancer requiring chemoradiation therapy (0.42). SG revealed that the highest utility (0.83) was HPV-positive status, followed by condyloma (0.78), and CIN grade I (0.77). The lowest utility (0.43) was cervical cancer requiring chemotherapy without surgery, followed by cervical cancer requiring chemoradiation therapy (0.60). CONCLUSIONS: This study was based on a large sample derived from the general Korean population; therefore, the calculated utility weights might be useful for evaluating the economic benefit of cancer screening and HPV vaccination programs.

General internists' perspectives regarding primary care and currently related issues in Korea.

Although primary care has been recognized as an essential element of the healthcare system, the primary healthcare of Korea has not been highly valued. Listening to the voices of physicians who are engaged in primary care should be the first step for improving the level of primary care in Korea. In this study, we conducted a questionnaire survey of general internists to investigate their perspectives regarding primary care, and which included the evaluation of current primary care, perception of the five, key attributes of primary care, and their opinions regarding the management system of chronic diseases. A total of 466 general internists' responses were used in this analysis. The results showed that primary care is considered to have an important role, according to general internists, although their evaluation of the overall status of primary care in Korea indicated that it is poor. The respondents also indicated that the functions of coordination and comprehensiveness in primary care, which can be integral for treating patients with chronic diseases, are most vulnerable. Given the high level of agreement regarding the need for a new medical management system for chronic diseases, based on physicians' autonomy and provided by clinics, establishing a policy encouraging the participation of general internists should be emphasized.

Synthesis and biological evaluation of aryl isoxazole derivatives as metabotropic glutamate receptor 1 antagonists: a potential treatment for neuropathic pain.

Glutamate is the major excitatory neurotransmitter and known to activate the metabotropic and ionotropic glutamate receptors in the brain. Among these glutamate receptors, metabotropic glutamate receptor 1 (mGluR1) has been implicated in various brain disorders including anxiety, schizophrenia and chronic pain. Several studies demonstrated that the blockade of mGluR1 signaling reduced pain responses in animal models, suggesting that mGluR1 is a promising target for the treatment of neuropathic pain. In this study, we have developed mGluR1 antagonists with an aryl isoxazole scaffold, and identify several compounds that are orally active in vivo. We believe that these compounds can serve as a useful tool for the investigation of the role of mGluR1 and a promising lead for the potential treatment of neuropathic pain.

Healthcare organizations' attitudes toward pay-for-performance in Korea.

This study was conducted to assess views of healthcare organizations on pay-for-performance (P4P) in terms of its design, possible effects, and unintended consequences. This is a cross-sectional, self-administered, internet-based survey. Eligible healthcare organizations were 3605 organizations in Korea. Healthcare organizations of 522, including 31 tertiary teaching hospitals, 182 general hospitals, 158 hospitals, and 152 clinics, were participated in this survey. Rates of awareness and support of P4P, preferred P4P program design, and possible effects and unintended consequences resulting from the P4P program were identified. There were variations in the awareness and support from the type of healthcare organization. The preferred design was quite different from the current design of the P4P program. They believed that the P4P program would not have a significant economic impact on their organizations, but that the P4P program could stimulate positive changes in their practice behaviors. They also showed considerable concerns about unintended consequences. P4P implementing agency such as HIRA in Korea should make an effort to improve healthcare organizations' understanding of the program. Also, HIRA could take into consideration of reflecting their reasonable opinions regarding its design components and unintended consequences.