Integrated high-throughput drug screening microfluidic system for comprehensive ocular toxicity assessment.

Traditional experimental methodologies suffer from a few limitations in the toxicological evaluation of the preservatives added to eye drops. In this study, we overcame these limitations by using a microfluidic device. We developed a microfluidic system featuring a gradient concentration generator for preservative dosage control with microvalves and micropumps, automatically regulated by a programmable Arduino board. This system facilitated the simultaneous toxicological evaluation of human corneal epithelial cells against eight different concentrations of preservatives, allowing for quadruplicate experiments in a single run. In our study, the IC50 values for healthy eyes and those affected with dry eyes syndrome showed an approximately twofold difference. This variation is likely attributable to the duration for which the preservative remained in contact with corneal cells before being washed off by the medium, suggesting the significance of exposure time in the cytotoxic effect of preservatives. Our microfluidic system, automated by Arduino, simulated healthy and dry eye environments to study benzalkonium chloride toxicity and revealed significant differences in cell viability, with IC50 values of 0.0033% for healthy eyes and 0.0017% for dry eyes. In summary, we implemented the pinch-to-zoom feature of an electronic tablet in our microfluidic system, offering innovative alternatives for eye research.

Cost-Utility Analysis of Chuna Manual Therapy and Usual Care for Chronic Neck Pain: A Multicenter Pragmatic Randomized Controlled Trial.

This study aimed to compare the cost-effectiveness of manual therapy and usual care for patients with chronic neck pain. A cost-utility analysis alongside a pragmatic randomized controlled trial was conducted in five South Korean hospitals. Data were procured from surveys and nationally representative data. Participants were 108 patients aged between 19 and 60 years, with chronic neck pain persisting for at least 3 months and a pain intensity score of ≥5 on the numerical rating scale in the last 3 days. The study was conducted for 1 year, including 5 weeks of intervention and additional observational periods. Participants were divided into a manual therapy (Chuna) group and a usual care group, and quality-adjusted life-years, costs, and the incremental cost-effectiveness ratio were calculated. The quality-adjusted life-years of the manual therapy group were 0.024 higher than that of the usual care group. From the societal perspective, manual therapy incurred a lower cost-at $2,131-and was, therefore, the more cost-effective intervention. From a healthcare system perspective, the cost of manual therapy was higher, with an incremental cost-effectiveness ratio amount of $11,217. Manual therapy is more cost-effective for non-specific chronic neck pain management from both a healthcare system and societal perspective.

Factors influencing clinical symptoms and treatment of patients with traffic accident injuries: A retrospective chart review with a questionnaire survey.

This study analyzed factors influencing clinical symptoms and treatment of patients with traffic accident injuries. It used a retrospective chart review and questionnaire survey obtained from 560 patients (266 men and 294 women). It also conducted follow-up observations of progress after car insurance settlements and investigated the usefulness of and patient satisfaction with integrative Korean medicine treatment for traffic accident injuries. Retrospective data of patients admitted for traffic accident injury were obtained. A questionnaire survey was conducted to collect data regarding the degree of traffic accident damage, severity of pain at settlement, any treatment after settlement and duration and cost of such treatment, and patient satisfaction with car insurance services and Korean medicine treatment for traffic accident injury. The results showed no significant association between pain and the degree of damage to the car at the time of traffic accident (P = 0.662), although the degree of damage to the car was more significantly associated with time to reach a car insurance settlement than severity of pain in the patient (P = 0.003). There was no significant association between the degree of damage to the car in a traffic accident and pain after a traffic accident. Greater severity of pain at the time of the car insurance settlement was associated with greater cost and longer time spent in treatment after the car insurance settlement.

Effectively training neural networks for stock index prediction: Predicting the S&P 500 index without using its index data.

We propose a novel method for training neural networks to predict the future prices of stock indexes. Unlike previous works, we do not use target stock index data for training neural networks for index prediction. Instead, we use only the data of individual companies to obtain sufficient amount of data for training neural networks for stock index prediction. As a result, our method can avoid various problems due to training complex machine learning models on a small amount of data. We performed numerous types of experiments to test methods designed for predicting the future price of the S&P 500 which is one of the most commonly traded stock indexes. Our experiments show that neural networks trained using our method outperform neural networks trained on stock index data. Compared with other state-of-the-art methods, our method is conceptually simpler and easier to apply, and achieves better results. We obtained approximately a 5-16% annual return before transaction costs during the test period (2006-2018).

Factors affecting utilisation of traditional Korean medical services by privately insured persons: a retrospective study using Korean Health Panel Survey (KHPS).

OBJECTIVE: This study aimed to use the Korean Health Panel Survey (KHPS) data to identify the key factors that influence decisions regarding the use of traditional Korean medicine (TKM) by privately insured persons. DESIGN: A retrospective study on episodic KHPS data from 2009 to 2013. SETTING: Nationwide-based survey using the KHPS data. PARTICIPANTS: The study included outpatients aged ≥20 years who had used private medical insurance at least once during the 5 years of the survey. After excluding cases where TKM was not used and those with missing values, this study ultimately included 1874 patients. PRIMARY AND SECONDARY OUTCOME MEASURES: The main dependent variable was TKM utilisation (number of outpatient visits and outpatient costs of TKM). We used multiple linear regression analysis to identify determinants of TKM while controlling for clustered errors. RESULTS: Approximately 6.1% (1874) of all doctor visits (30 982) were characterised as TKM services. For therapeutic purposes, TKM visits increased despite not being guaranteed in private health insurance (coefficient=3.0, p=0.045) and TKM outpatient costs decreased (coefficient=-0.3, p=0.001). Women used more therapeutic TKM services than men (coefficient=2.8, p<0.001). Older patient groups used more therapeutic TKM services than younger patient groups (coefficient=11.5, p=0.012), but paid less on outpatient costs than younger groups (coefficient=-1.0, p=0.001). For preventive services, sex and age were not statistically significant factors. Regardless of the purpose of the visit, the more chronic diseases, the more people who have previously experienced TKM service use more TKM services (p<0.001). CONCLUSIONS: Despite a policy to reduce services that are not guaranteed by private health insurance, the increase in the number of outpatient visits for uncovered therapeutic TKM services implies a high public need for TKM in Korea.

Effectiveness and cost-effectiveness of acupuncture with Doin therapy for chronic neck pain: a study protocol for a multicentre, randomised controlled clinical trial.

INTRODUCTION: Doin therapy is a manual therapy used in Korean rehabilitation medicine. Recently, the use of acupuncture with Doin has increased in clinics and clinical trials have demonstrated its effects. However, well-designed studies examining the efficacy and cost-effectiveness of acupuncture with Doin therapy are rare. METHODS AND ANALYSIS: This multicentre, assessor-blinded, randomised controlled trial with two parallel groups aims to evaluate the clinical effects and cost-effectiveness of acupuncture with Doin therapy. A total of 124 patients (with a neck pain duration of 6 months or longer and a Numeric Rating Scale ≥5) will be recruited at five Korean medicine hospitals. Patients will be randomly allocated to acupuncture with Doin therapy (n=62) and acupuncture alone (n=62) for 5 weeks of treatment. This study will be carried out with outcome assessor and statistician blinding. The primary outcome measure will consist of improvement in neck pain using the Visual Analogue Scale at 6 weeks. The secondary outcomes including measures of pain, functional disability, health-related quality of life and economic evaluation will be conducted at 6 weeks, and 3, 6, 9 and 12 months after treatment ETHICS AND DISSEMINATION: The project is approved by the Institutional Review Board (IRB) of the Jaseng Hospital of Korean Medicine and the Kyung Hee University Korean Medicine Hospital at Gangdong. Dissemination will occur after the findings from this study are published in other peer reviewed journals. TRIAL REGISTRATION NUMBERS: NCT03558178; KCT0003068; Pre-results.

Comparative effectiveness and economic evaluation of Chuna manual therapy for chronic neck pain: protocol for a multicenter randomized controlled trial.

BACKGROUND: Neck pain is a highly prevalent medical condition that incurs substantial social burden. Although manual therapy is widely used for treatment of neck pain, the body of evidence supporting its effectiveness and safety is not conclusive. The aim of this study is to examine the effect, safety, and cost-effectiveness of Chuna manual therapy, a traditional Korean manual therapy for treatment of various musculoskeletal complaints. METHODS/DESIGN: This study is the protocol for a two-armed parallel, assessor-blinded, multicenter, randomized controlled trial. A total 108 patients with chronic neck pain (time to onset ≥ 3 months, numeric rating scale [NRS] of neck pain ≥ 5) will be recruited at five Korean medicine hospital sites. Participants will be allotted to one of two groups (n = 54, respectively): the Chuna manual therapy group, and the usual care (conventional physical therapy and medication treatment) group. Ten sessions of Chuna manual therapy or usual care will be administered twice a week for five weeks. Since the study design does not permit patient or physician blinding, the outcome assessor and statistician will be blinded. The primary outcome will be the visual analogue scale (VAS) of neck pain at 5 weeks after randomization. Secondary outcomes include the VAS of radiating arm pain, NRS of neck pain and radiating arm pain, Vernon-Mior neck disability index (NDI), Northwick Park neck pain questionnaire (NPQ), EuroQol-5 Dimension (EQ-5D), EQ-VAS, patient global impression of change (PGIC), economic evaluation, adverse effects, and drug consumption. Follow-up outcome assessments will be conducted at 3, 6, 9, and 12 months after randomization. DISCUSSION: This study will evaluate the comparative effectiveness of Chuna manual therapy and usual care on chronic neck pain. Adverse events, and costs and effectiveness (utility) data will be evaluated to assess safety and exploratory cost-effectiveness (economic evaluation). This study aims to provide evidence on the effectiveness, safety, and cost-effectiveness of Chuna manual therapy. TRIAL REGISTRATION: Clinical Research Information Service (CRIS), KCT0002732 . Registered on 13 March 2018. ClinicalTrials.gov, NCT03294785 . Registered on 27 September 2017.

Current practice and usual care of major cervical disorders in Korea: A cross-sectional study of Korean health insurance review and assessment service national patient sample data.

Neck pain is a highly common condition and is the 4th major cause of years lived with disability. Previous literature has focused on the effect of specific treatments, and observations of actual practice are lacking to date. This study examined Korean health insurance review and assessment service (HIRA) claims data to the aim of assessing prevalence and comparing current medical practice and costs of cervical disorders in Korea.Current practice trends were determined through assessment of prevalence, total expenses, per-patient expense, average days in care, average days of visits, sociodemographic characteristics, distribution of medical costs, and frequency of treatment types of high frequency cervical disorders (cervical sprain/strain, cervical intervertebral disc displacement [IDD], and cervicalgia).Although the number of cervical IDD patients was few, total expenses, per-patient expense, average days in care, and average days of visits were highest. The proportion of women was higher than men in all 3 groups with highest prevalence in the ≥50s middle-aged population for IDD compared to sprain/strain. Primary care settings were commonly used for ambulatory care, of which approximately 70% chose orthopedic specialist treatment. In analysis of medical expenditure distribution, costs of visit (consultation) (22%-34%) and physical therapy (14%-16%) were in the top 3 for all 3 disorders. Although heat and electrical therapies were the most frequently used physical therapies, traction use was high in the cervical IDD group. In nonnarcotics, aceclofenac and diclofenac were the most commonly used NSAIDs, and pethidine was their counterpart in narcotics.This study investigated practice trends and cost distribution of treatment regimens for major cervical disorders, providing current usage patterns to healthcare policy decision makers, and the detailed treatment reports are expected to be of use to clinicians and researchers in understanding current usual care.

Analysis of medical service use of knee osteoarthritis and knee meniscal and ligament injuries in Korea: a cross-sectional study of national patient sample data.

BACKGROUND: Osteoarthritis (OA) and meniscal and ligament injuries of the knee are the two most common knee disorders in Korea. The aim of this study was to analyze the demographic characteristics, medical service use and related costs for these disorders, and the results are expected to help inform practitioners, researchers, and policy-makers. METHODS: The present study aimed to evaluate incidence and patient characteristics, and to assess current medical service use, usual care, and medical expenses of knee disorders by analyzing 2014 national patient sample data from the Korean Health Insurance Review and Assessment Service. Data was extracted using 3% stratified sampling from all Korea national health insurance claims submitted in 2014, and analyzed. Usual care for M17 knee osteoarthritis and S83 knee meniscal and ligament injury codes of the International Classification of Diseases, 10th revision (ICD-10) were determined by investigating total number of patients, sociodemographic characteristics, days in care, number of visits, and expenses. RESULTS: Knee OA showed the highest incidence in females aged ≥60 years, whereas meniscal and ligament injuries of the knee were most prevalent among patients aged <20 years and young adults. Total inpatient care expenses exceeded the cost of ambulatory care for both disorders. Ambulatory care was mainly provided at primary care clinics, with 90% of these visits made to orthopedic specialists. Medical expenses for knee OA and meniscal and ligament injuries were largely due to procedures/surgeries and injections, and procedures/surgeries and hospitalizations, respectively. Total replacement arthroplasty was the most commonly performed surgery for knee OA, while meniscectomy and cruciate ligament reconstruction were the most often performed surgeries for meniscal and ligament injuries. Intra-articular injection rates were 55% in knee OA patients and 3% in meniscal and ligament injury patients. Aceclofenac, diclofenac, and tramadol were the most frequently prescribed analgesics. CONCLUSIONS: The current findings may be used as basic data for establishing medical policies and can benefit researchers and clinicians in recognizing trends and patterns of treatment for knee disorders.

Medical service use and usual care of common shoulder disorders in Korea: a cross-sectional study using the Health Insurance Review and Assessment Service National Patient Sample.

OBJECTIVES: This study examined National Health Insurance claims data to investigate the epidemiology of shoulder disorders in Korea. Detailed information on medical services and related costs was assessed by major shoulder disorder category. DESIGN AND SETTING: The 2014 National Patient Sample dataset provided by the Health Insurance Review and Assessment Service was analysed. Among shoulder-related diagnosis codes, adhesive capsulitis of the shoulder (ACS), rotator cuff syndrome (RCS) and shoulder impingement syndrome (SIS) categories were of highest prevalence. Sociodemographic characteristics and medical service use, frequency and medical costs regarding common shoulder disorders were evaluated. RESULTS: The majority of patients with shoulder disorder received ambulatory care (97%). Total and per-patient expenses were highest in patients with RCS. The number of inpatients with RCS was more than twice that of the other two groups, and patients with RCS were more likely to receive surgical management compared with patients with ACS and SIS. Prevalence of shoulder disorders was highest among subjects in their 50s for all three groups. Primary care physicians treated 75.80% of patients with ACS, 56.99% of patients with RCS and 48.06% of patients with SIS, respectively, outlining the difference in medical institution usage patterns. In all three groups, the highest proportion of patients visited orthopaedic surgeons out of medical departments. In the ACS and SIS groups, cost of visits (consultations) took up the largest part of total expenses at 32.30% and 18.88%, respectively, while cost of procedure/surgery constituted the largest portion in patients with RCS (37.77%). The usage proportion of subcutaneous or intramuscular and intra-articular injections ranged between 20% and 30% for outpatients in all three groups. CONCLUSIONS: Medical service use, frequency and cost distributions relating to major shoulder disorders in Korea were assessed using nationwide claims data. These findings are expected to aid policy-makers as well as researchers and practitioners as basic healthcare data.

Minimum Clinically Important Difference and Substantial Clinical Benefit in Pain, Functional, and Quality of Life Scales in Failed Back Surgery Syndrome Patients.

STUDY DESIGN: .: Prospective observational 1-year study. OBJECTIVE: .: To determine minimum clinically important difference (MCID) and substantial clinical benefit (SCB) of outcome measures in failed back surgery syndrome (FBSS) patients, as these metrics enable assessment of whether and when an intervention produces clinically meaningful effects in a patient. SUMMARY OF BACKGROUND DATA: .: Several methods have been devised to quantify clinically important difference, but MCID and SCB for FBSS patients has yet to be determined. METHODS: .: Patients with persisting/recurrent low back pain (LBP) and/or leg pain after lumbar surgery who completed 16 weeks of treatment (n = 105) at two hospitals in Korea from November 2011 to September 2014 were analyzed. Global perceived effect was used to determine receiver operating characteristic curves in visual analogue scale (VAS), Oswestry disability index (ODI), and short form-36 (SF-36) in an anchor-based approach. RESULTS: .: MCIDs for ODI, LBP and leg pain VAS, physical component summary, mental health component summary (MCS), and overall health scores of SF-36 were 9.0, 22.5, 27.5, 10.2, 4.0, and 8.9, and SCBs were 15.0, 32.5, 37.0, 19.7, 19.3, and 21.1, respectively. MCID and SCB area under the curve was ≥0.8, and ≥0.7, respectively. CONCLUSION: .: LBP and leg pain VAS, ODI, and physical component summary of SF-36 may be used to measure responsiveness in FBSS patients. LEVEL OF EVIDENCE: 3.

Evaluation of use and cost of medical care of common lumbar disorders in Korea: cross-sectional study of Korean Health Insurance Review and Assessment Service National Patient Sample data.

OBJECTIVES: To assess medical care and costs of the 3 highest prevalence lumbar disorders-non-specific low back pain (nLBP), intervertebral disc disorder (IDD) and spinal stenosis (SS)-from national billing data to provide basic information for standards of appropriate management. DESIGN: Retrospective analysis of National Health Insurance National Patient Sample data provided by the Korean Health Insurance Review and Assessment Service (HIRA). SETTING: 2011 claims data from all medical institutions which filed billing statements to HIRA. PARTICIPANTS: A total of 135 561 patients with lumbar disorder who received medical services during 2011. OUTCOME MEASURES: Patient characteristics, medical procedures, medication, cost, injection and surgery. RESULTS: In the nLBP and IDD groups, the 50-59 age range had the highest prevalence, whereas prevalence increased with age in SS. All 3 groups showed a higher percentage in women. The average treatment cost was 196 552 KRW in the nLBP and 362 050 KRW in the IDD group, and highest in the SS group at 439 025 KRW. While in the nLBP group women spent more on medical expenses, in the other 2 groups men showed higher expenditure. Expenditure grew with age in the nLBP and SS groups, whereas that of the IDD group peaked in their 40s. Analgesics were used in 73.43% of patients with nLBP, 82.64% of patients with IDD and 86.46% of patients with SS, and opioids in 4.12% of patients with IDD and 5.36% of patients with SS. Surgery rates were highest in the SS group at 4.85%, with 0.9% for nLBP and 4.59% for IDD. The most frequent injection code was lumbar/caudal epidural nerve block. Expenditure and surgery rates were higher in the injection than in the non-injection subgroup in all 3 groups. CONCLUSIONS: Patterns of medical care of most frequent lumbar disorders from HIRA data showed significant difference between groups and provide a basic standard for future usual care guidelines linked with health policy and budget appropriation.

Development of a highly visual, simple, and rapid test for the discovery of novel insulin mimetics in living vertebrates.

Diabetes mellitus is a global epidemic with major impacts on human health and society. Drug discovery for diabetes can be facilitated by the development of a rapid, vertebrate-based screen for identifying new insulin mimetic compounds. Our study describes the first development of a zebrafish-based system based on direct monitoring of glucose flux and validated for identifying novel anti-diabetic drugs. Our system utilizes a fluorescent-tagged glucose probe in an experimentally convenient 96-well plate format. To validate our new system, we identified compounds that can induce glucose uptake via activity-guided fractionation of the inner shell from the Japanese Chestnut (Castanea crenata). The best performing compound, UP3.2, was identified as fraxidin and validated as a novel insulin mimetic using a mammalian adipocyte system. Additional screening using sets of saponin- and triazine-based compounds was undertaken to further validate this assay, which led to the discovery of triazine PP-II-A03 as a novel insulin mimetic. Moreover, we demonstrate that our zebrafish-based system allows concomitant toxicological analysis of anti-diabetic drug candidates. Thus, we have developed a rapid and inexpensive vertebrate model that can enhance diabetes drug discovery by preselecting hits from chemical library screens, before testing in relatively expensive rodent assays.

A population-based case-crossover study of polyethylene glycol use and acute renal failure risk in the elderly.

AIM: To evaluate the possibility of an association between polyethylene glycol (PEG) and acute renal failure (ARF) in elderly patients using a health insurance claims database. METHODS: We conducted a population-based case-crossover study using information obtained from Korean Health Insurance Review and Assessment Service (HIRA) claims from January 1, 2005 to December 31, 2005 (Seoul, Korea). The study population consisted of elderly patients who received PEG prior to experiencing their first ARF-related hospitalization from April 1, 2005 to December 31, 2005. For each patient, one case and two control periods were matched. PEG use in a 2- or 4-wk window period prior to hospitalization for ARF was compared with PEG use in two earlier 2- or 4-wk control window periods. Conditional logistic regression analysis was used to estimate odds ratios (ORs) and 95% CI, adjusting for concomitant uses of diuretics, angiotensin converting enzyme inhibitors, non-steroidal anti-inflammatory drugs, antibiotics, anti-cancer drugs, and contrast media. RESULTS: Within the HIRA database which contained 1,093,262 elderly patients, 1156 hospitalized ARF cases were identified. Among these cases, PEG was prescribed to 17 (1.5%) patients before hospitalization. The adjusted ORs when applying the 2- and 4-wk window periods were 0.4 (95% CI: 0.03-5.24) and 2.1 (95% CI: 0.16-27.78), respectively. CONCLUSION: No increased risk of ARF was found in elderly PEG users. However, based on the limited number of study subjects, further analysis should be performed to confirm these results.