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EGFR is a transmembrane protein that functions as a receptor tyrosine kinase (RTK). Upon ligand binding or by activating mutations (Exon19 deletion, L858R mutation, and others), EGFR turns on the downstream signals that include oncogenic RAS/MEK/ERK, PI3K/AKT/mTOR, and JAK/STAT pathways. EGFR gene mutations and amplifications are frequently found in various human cancers and, in non-small cell lung cancer (NSCLC), the EGFR gene is mutated with 10-15% frequency (about 50% in Asian patients). While the 1st and 2nd generation EGFR inhibitors are effective in targeting EGFR mutants with Exon19 deletion and L858R mutation, additional T790M mutation in the EGFR gene causes resistance. The 3rd generation EGFR inhibitor (Osimertinib) works against EGFR mutants with T790M mutation; however, another EGFR mutation occurs at the amino acid 797 position (C797S), which makes Osimertinib ineffective. This is one of the major resistance mechanisms in Osimertinib-treated patients, and the 4th generation EGFR inhibitor that can target the C797S mutant is needed. We developed a compound that effectively disables various EGFR mutations, including Del19/T790M/C797S, L858R/T790/C797S, Del19/C797S, and L858R/C797S. In vitro kinase assay and cellular assays showed high potency and selectivity. In vivo PK/PD and efficacy tests confirmed the great therapeutic potential of this inhibitor for patients with EGFR mutations. Citation Format: Dongsu Kim, Woo Seung Son, Anna Jang, Yeri Lee, Donggeon Kim, Changyu Choi, Kyung Hoon Min, Sung Pil Choi, Sang Kyun Lim. Discovery of a small-molecule inhibitor that can target EGFR with C797S mutation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3323.

Background. This study aims to examine the validity of European quality of life-5 dimensions, 3-level version (EQ-5D-3L) on patients with osteoporotic vertebral fractures and compare health related quality of life (QOL) of these patients with them of general population in Korea. Methods. Totally, 163 patients with osteoporotic fractures in any vertebrae from outpatient clinics of multiple hospitals. After informed consents, study participants administered general and clinical information including sex, age, fracture site, and fracture age. Then they filled up several questionnaires such as 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). To examine the discriminant and convergent validity of EQ-5D-3L, Spearman's correlation analyses among the questionnaires were conducted. Also, PAIN NRS, physical component summary (PCS) and mental component summary (MCS) from SF-12v2 and RMQ scores were compared on problems reporting of each dimension of EQ-5D-3L. Finally, results in EQ-5D-3L from study participants were compared with those things from the comparison group of general populations which were match-sampled according to age and sex from the 2013 Korean National Health and Nutritional Examination Survey. Results. Spearman's correlation coefficients among EQ-5D-3L and PAIN NRS, SF-12v2, and RMQ were mostly statistically significant. The coefficients between the relevant dimensions such as mobility of EQ-5D-3L and physical functioning of SF-12v2were higher than coefficients between the irrelevant ones. Study participants reporting problems in each dimension of EQ-5D-3L showed lower scores on PAIN NRS, PCS and MCS from SF-12v2 and RMQ scores and those were statistically significant. For comparisons with the general populations, problems reporting in the patient group were statistically higher than those things from the general people. Conclusions. This study showed that EQ-5D-3L could be valid to measure a health related QOL of patients with osteoporotic vertebral fractures in Korea.

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.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.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.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.

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.

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

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.

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 Aβ-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.

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. Electronic supplementary material The online version of this article (doi:10.1186/s12955-016-0566-8) contains supplementary material, which is available to authorized users.

The theoretical cogging torque by the electromagnetic analysis is constant due to the ideal shape rotor and stator. In addition, this phenomenon is a very big clue in the cogging torque reduction. In this paper, the cogging torque according to a mass-production tolerance was considered by experimental review. Therefore, we propose an improvement of the tolerances in the housing for a stabilization of the cogging torque variation.

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.

Scenarios for the different HPV-related health states. (DOCX 38 kb)

Screenshot of computer-assisted questionnaire. (PPTX 8604 kb)

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.

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. Graphical Abstract Keywords: Internal Medicine, Primary Care, Health Policy, Chronic Diseases INTRODUCTION The United States Institute of Medicine defined primary care as "the provision of integrated, accessible health care services by clinicians who are accountable for addressing a large majority of personal health needs, developing a sustained partnership with patients, and practicing in the context of family and community" in 1996 report (1). In Korea, primary care is defined as "the delivery of health care services first encountered by people". It refers to "a discipline in which physicians being well-aware of patients in the context of their family and community, resolve common health care needs of people by maintaining a patient-doctor relationship over time and coordinating health care resources appropriately" (2). Primary care is important in the sense that it is the first and most frequently sought official health care by people in order to deal with their health issues. By establishing the foundation of the health care delivery system, primary care is an efficient health care channel meeting 75%-85% of all medical needs. It also affects the public views regarding doctors and medical service as well as the performance of the overall health care systems (3, 4). In particular, effective primary care can minimize unnecessary expenditure of resources and thus lead to positive health outcomes at lower cost. As patients can access quality health care service through the primary care system regardless of their income level, primary care contributes to the overall health care system by ensuring efficiency, effectiveness, and fairness in care (5, 6). Despite the aforementioned advantages of primary care, Korea has a weak primary care system which has continued to deteriorate over the years, mainly due to the following reasons: 1) undifferentiated health care delivery system which creates competitive rather than cooperative or complementing relationships between hospitals and clinics; and 2) virtual freedom of choice regarding the medical institution through the availability of multiple channels for patients to directly access hospitals without having to obtain referrals from clinics (7, 8, 9, 10). Moreover, as health care providers in Korea are reimbursed according to the fee-for-service system (8), there is a structural barrier to ensuring key attributes of primary care, i.e. comprehensiveness, coordination, and continuity, and it is, therefore, difficult to maintain ideal patient-doctor relationships (11). Nevertheless, in order to deal with the current health care issues in Korea, including an aging society, increase of chronic diseases, growing demands for health care and the rising cost associated with the advancement of medical technologies, dissatisfaction regarding health care among the general public, including patients, and the difficulties encountered by physicians in operating clinics, it is imperative to take an entirely new approach that veers away from that of previous actions. In fact, other countries have undertaken various initiatives to strengthen their primary care in order to deal with the same issues faced in Korea (3, 11). To this end, the OECD has indicated the problems related to Korea's primary care system, including not being able to effectively deal with the challenges of an aging population and chronic diseases, and has stressed the need for a completely new strategy to improve Korea's primary care system by shifting the focus away from acute care services (12, 13). From a global perspective, the Korean primary care system falls at the bottom among comparable OECD countries, and the public trust of its quality is also low (3, 14, 15). Therefore, to actively respond to these issues, an effective action plan must be established to improve the existing primary care system of Korea. Previous studies have examined various aspects of primary care including its concept and relevant perception and have reviewed the best practices abroad to benchmark (2, 3, 17). However, most of these studies have simply introduced the best practices from countries abroad to Korea or have made some suggestions for areas of improvement in the Korean health care system, and very few have addressed the feasibility or specific strategies for benchmarking cases from other countries. Furthermore, little or no attempt has been made to receive the opinions of those directly engaged in primary care and to then provide solutions. Given these issues, our study was intended to understanding the current state, issues, perceptions, and solutions regarding primary care in Korea. The survey was conducted with private practice internists who are specialists and who have been leading Korea's primary care system by representing the largest number of all clinics in Korea.