Bilaterally positive head-impulse tests can differentiate AICA infarction from labyrinthitis.

Introduction: Video head-impulse tests (video-HITs) often fail to detect anterior inferior cerebellar artery (AICA) infarction due to peripheral and central vestibular system involvement. Anecdotal studies suggest that video-HITs may reveal bilateral impairment in AICA infarction. However, the diagnostic utility of video-HITs has not been established, particularly when compared to labyrinthitis, which accounts for the majority of acute audiovestibular syndrome (AAVS) cases. Methods: We reviewed the medical records of consecutive patients presenting with new-onset acute hearing loss and spontaneous vertigo (i.e., AAVS) between March 2018 and July 2023 at a tertiary hospital in South Korea. Video-HIT patterns were categorized as follows: (1) ipsilaterally positive, (2) contralaterally positive, (3) bilaterally normal, and (4) bilaterally positive. Results: Twenty-eight patients with AICA infarction (mean age ± standard deviation = 67 ± 15 years; 14 men) and 51 with labyrinthitis (63 ± 17 years, 26 men) were included in the analyses. Among the 28 patients with AICA infarction, 15 presented with AAVS in isolation, without other co-morbid neurologic deficits (15/28, 54%). The vestibulo-ocular reflex (VOR) gains of ipsilesional horizontal canals (HCs) ranged from 0.21 to 1.22 (median = 0.81, interquartile range [IQR] = 0.50-0.89). However, those for contralateral HC gain ranged from 0.57 to 1.19 (median = 0.89 [IQR = 0.73-0.97]). Collectively, HITs were bilaterally positive in 13 patients (including 12 patients with bilaterally positive HITs for the horizontal canal), normal in eight, ipsilesionally positive in six, and contralesionally positive in one patient with AICA infarction. The VOR gains were typically decreased ipsilaterally in 28 (28/51, 55%), normal in 17 (17/51, 33%), and decreased bilaterally in six patients with labyrinthitis (6/51, 12%). Logistic regression analysis revealed that bilaterally positive HITs (p = 0.004) and multiple vascular risk factors (p = 0.043) were more frequently associated with AICA infarction than labyrinthitis. Discussion: Among patients presenting with AAVS, bilaterally positive HITs can be indicative of AICA infarction in patients with multiple vascular risk factors.

Machine Learning Based Abnormal Gait Classification with IMU Considering Joint Impairment.

Gait analysis systems are critical for assessing motor function in rehabilitation and elderly care. This study aimed to develop and optimize an abnormal gait classification algorithm considering joint impairments using inertial measurement units (IMUs) and walkway systems. Ten healthy male participants simulated normal walking, walking with knee impairment, and walking with ankle impairment under three conditions: without joint braces, with a knee brace, and with an ankle brace. Based on these simulated gaits, we developed classification models: distinguishing abnormal gait due to joint impairments, identifying specific joint disorders, and a combined model for both tasks. Recursive Feature Elimination with Cross-Validation (RFECV) was used for feature extraction, and models were fine-tuned using support vector machine (SVM), random forest (RF), and extreme gradient boosting (XGB). The IMU-based system achieved over 91% accuracy in classifying the three types of gait. In contrast, the walkway system achieved less than 77% accuracy in classifying the three types of gait, primarily due to high misclassification rates between knee and ankle joint impairments. The IMU-based system shows promise for accurate gait assessment in patients with joint impairments, suggesting future research for clinical application improvements in rehabilitation and patient management.

Clinical profile and treatment outcomes of idiopathic intracranial hypertension: a multicenter study from Korea.

BACKGROUND: Currently, there is a relative lack of detailed reports regarding clinical presentation and outcome of idiopathic intracranial hypertension in Asians. This study aims to describe the clinical features and treatment outcomes of Korean patients with idiopathic intracranial hypertension. METHODS: We prospectively recruited patients with idiopathic intracranial hypertension from one hospital and retrospectively analyzed the medical records of 11 hospitals in Korea. We collected data regarding preceding medical conditions or suspected medication exposure, headache phenotypes, other associated symptoms, detailed neuroimaging findings, treatments, and outcomes after 1-2 and 3-6 months of treatment. RESULTS: Fifty-nine (83.1% women) patients were included. The mean body mass index was 29.11 (standard deviation, 5.87) kg/m2; only 27 patients (45.8%) had a body mass index of ≥ 30 kg/m2. Fifty-one (86.4%) patients experienced headaches, patterns of which included chronic migraine (15/51 [29.4%]), episodic migraine (8/51 [15.7%]), probable migraine (4/51 [7.8%]), chronic tension-type headache (3/51 [5.9%]), episodic tension-type headache (2/51 [3.9%]), probable tension-type headache (2/51 [3.9%]), and unclassified (17/51 [33.3%]). Medication overuse headache was diagnosed in 4/51 (7.8%) patients. After 3-6 months of treatment, the intracranial pressure normalized in 8/32 (25.0%), improved in 17/32 (53.1%), no changed in 7/32 (21.9%), and worsened in none. Over the same period, headaches remitted or significantly improved by more than 50% in 24/39 patients (61.5%), improved less than 50% in 9/39 (23.1%), and persisted or worsened in 6/39 (15.4%) patients. CONCLUSION: Our findings suggest that the features of Asian patients with idiopathic intracranial hypertension may be atypical (i.e., less likely obese, less female predominance). A wide spectrum of headache phenotypes was observed. Medical treatment resulted in overall favorable short-term outcomes; however, the headaches did not improve in a small proportion of patients.

Trend of incidence rate of age-related diseases: results from the National Health Insurance Service-National Sample Cohort (NHIS-NSC) database in Korea: a cross- sectional study.

BACKGROUND: This study aimed to identify and select age-related diseases (ARDs) in Korea, which is about to have a super-aged society, and to elucidate patterns in their incidence rates. METHODS: The National Health Insurance Service-National Sample Cohort, comprising 1 million health insurance and medical benefit beneficiaries in Korea from 2002 to 2019, was utilized. We selected 14 diseases with high disease burden and prevalence among Koreans from the 92 diseases defined in the Global Burden of Diseases, Injuries, and Risk Factors Study as ARDs. The annual incidence rate represented the number of patients newly diagnosed with an ARD each year from 2006 to 2019, excluding those with a history of ARD diagnosis from 2002 to 2005. The incidence rate by age was categorized into 10-year units based on age as of 2019. The number of patients with ARDs in each age group was used as the numerator, and the incidence rate for each age group was calculated with the age group as the denominator. RESULTS: Regarding the annual incidence rates of ARDs from 2006 to 2019, chronic obstructive pulmonary disease, congestive heart failure, and ischemic heart disease decreased annually, whereas dyslipidemia, chronic kidney disease, cataracts, hearing loss, and Parkinson's disease showed a significant increase. Hypertension, diabetes, cerebrovascular disease, osteoporosis, osteoarthritis, and age-related macular degeneration initially displayed a gradual decrease in incidence but exhibited a tendency to increase after 2015. Concerning age-specific incidence rates of ARDs, two types of curves emerged. The first type, characterized by an exponential increase with age, was exemplified by congestive heart failure. The second type, marked by an exponential increase peaking between ages 60 and 80, followed by stability or decrease, was observed in 13 ARDs, excluding congestive heart failure. However, hypertension, ischemic heart disease, cerebrovascular disease, chronic obstructive pulmonary disease, and hearing loss in men belonged to the first type. CONCLUSIONS: From an epidemiological perspective, there are similar characteristics in age-specific ARDs that increase with age, reaching a peak followed by a plateau or decrease in Koreans.

Comparative Pharmacokinetic Profiles of a Novel Low-Dose Micronized Formulation of Raloxifene 45 mg (AD-101) and the Conventional Raloxifene 60 mg in Healthy Subjects.

Raloxifene hydrochloride shows poor bioavailability (only 2%) when orally administered because of its poor aqueous solubility and its extensive first-pass metabolism. A new micronized formulation of raloxifene was developed to improve bioavailability via enhanced gastrointestinal absorption. The primary objective of this study was to evaluate the pharmacokinetic characteristics of a new micronized raloxifene formulation (AD-101) in comparison with the conventional raloxifene formulation. This study was designed as an open-label, randomized, 2-treatment-period, crossover study with a 2-week washout period. Two treatments consisted of micronized raloxifene 45 mg daily; and conventional raloxifene 60 mg daily administered in fasting conditions. Plasma raloxifene concentrations were determined by a validated method using ultra-fast liquid chromatography-tandem mass spectrometry, and pharmacokinetic parameters were calculated using a noncompartmental model. In total, 49 subjects completed the study. The geometric mean ratio (micronized/conventional) of the maximum concentration and the area under the plasma concentration-time curve from time zero to the last concentration values were 1.08 (90% CI, 0.95-1.24) and 0.97 (90% CI, 0.89-1.05), respectively. The adverse event profile did not differ between the 2 formulations. The results demonstrate that micronized formulation of raloxifene 45 mg is equivalent to conventional formulation of raloxifene 60 mg when administered at the single dose in the fasted state. After single oral dosing of AD-101, there were no serious or unexpected adverse events.

Effect of a Hospital-To-Home Transitional Intervention Based on an Interaction Model of Client Health Behavior for Adult Patients with Stroke.

To develop and identify the effectiveness of a hospital-to-home transitional intervention based on an interaction model of client health behavior in adult patients with stroke. A non-equivalent control group pretest-posttest. Thirty-eight patients participated (18=intervention, 20=control); the intervention group received 12 weeks of the intervention. The intervention influenced anxiety, disease severity, health behavior adherence, patient satisfaction, and quality of life in adult patients with stroke. Transitional programs have potential to improve the health behaviors of subjects, and community health nurses can assist in the implementation of these programs. Health behaviors and quality of life scores were significantly higher in the intervention group than in the control group; these findings support the need for continuity of nursing care during the transitional period for patients with stroke. Given the challenges faced by adult stroke patients after stroke, community nurses should pay attention to patients' transitional experiences.

Analyses of Head-Impulse Tests in Patients With Posterior Circulation Stroke and Vestibular Neuritis.

BACKGROUND AND OBJECTIVES: The interpretation of video head-impulse tests (video-HITs) can often be complicated, limiting their clinical utility in acute vestibular syndrome. We aimed to determine video-HIT findings in patients with posterior circulation strokes (PCSs) and vestibular neuritis (VN). METHODS: We retrospectively analyzed the results of video-HITs in 59 patients with PCS. Irrespective of the actual lesion revealed later on MRIs, ipsilateral and contralateral sides were assigned according to the direction of slow phase of spontaneous nystagmus (SN). Then, the patterns of video-HIT findings were classified according to the vestibulo-ocular reflex (VOR) gain for the horizontal canals; (1) ipsilaterally positive, (2) contralaterally positive, (3) bilaterally normal, and (4) bilaterally positive. The abnormal responses were further defined into (5) wrong-way saccades, (6) perverted, and (7) early acceleration followed by premature deceleration. We also analyzed the asymmetry of the corrective saccadic amplitude between the sides, calculated from the sum of cumulative saccadic amplitudes on both sides. The results were compared with video-HIT results from 71 patients with VN. RESULTS: Video-HITs were normal in 32 (54%), ipsilaterally positive in 11 (19%), bilaterally positive in 10 (17%), and contralaterally positive in 6 (10%) patients with PCS. Wrong-way saccades were more frequently observed in VN than in PCS (31/71 [44%] vs 5/59 [8%], p < 0.001). Saccadic amplitude asymmetry was greater in VN than in PCS (median 100% [interquartile range 82-144, 95% CI 109-160] vs 0% [-29 to 34, -10 to 22, p < 0.001]). When differentiating VN from PCS, the sensitivity was 81.7%, and specificity was 91.5% at the cutoff value of 71% for saccadic amplitude asymmetry with an area under the curve (AUC) of 0.91 (95% CI 0.86-0.97). The AUC for saccadic amplitude asymmetry was larger than that for the ipsilateral VOR gain (p = 0.041) and other parameters. DISCUSSION: Patients with PCS may show various head-impulse responses that deviate from the findings expected in VN, which include normal, contralaterally positive, and negative saccadic amplitude asymmetry (i.e., greater cumulative saccadic amplitude contralaterally). A thorough analysis of corrective saccades in video-HITs can improve the differentiation of PCS from VN even before MRIs.

Patient-Centered Integrated Model of Home Health Care Services in South Korea (PICS-K).

Introduction: As South Korea is fast becoming an aging society, the need for integrated care of the elderly has increased. 'Community Integrated Care Initiatives' have been implemented by the Ministry of Health and Welfare. However, home healthcare is insufficient to meet this need. Description: The National Health Insurance Service (NHIS) launched the initiative, 'Patient-Centered Integrated model of Home Health Care Services in South Korea (PICS-K)'. Its purpose is to coordinate home healthcare providers by establishing a home health care support center (HHSC) in public hospitals starting in 2021. The PICS-K has six main features: integration of primary care-hospital-personal care-social services through a consortium, HHSC in hospitals with primary care collaboration, increased accessibility, interdisciplinary team (IDT), patient-centeredness, and education. Discussion: Integrating healthcare, personal care, and social services at multiple levels is necessary. Accordingly, platforms to share participant information and service records, and institutional payment system reforms are required. Conclusion: In public hospitals, the HHSC supported primary care, which provides home healthcare. The model combined community healthcare and social services to accomplish the aging-in-place of the homebound population by focusing on their needs. This model will be applicable to other regions in Korea.

10-year follow-up study on medical expenses and medical care use according to biological age: National Health Insurance Service Health Screening Cohort (NHIS-HealS 2002~2019).

OBJECTIVES: The world is witnessing a sharp increase in its elderly population, accelerated by longer life expectancy and lower birth rates, which in turn imposes enormous medical burden on society. Although numerous studies have predicted medical expenses based on region, gender, and chronological age (CA), any attempt has rarely been made to utilize biological age (BA)-an indicator of health and aging-to ascertain and predict factors related to medical expenses and medical care use. Thus, this study employs BA to predict factors that affect medical expenses and medical care use. MATERIALS AND METHODS: Referring to the health screening cohort database of the National Health Insurance Service (NHIS), this study targeted 276,723 adults who underwent health check-ups in 2009-2010 and kept track of the data on their medical expenses and medical care use up to 2019. The average follow-up period is 9.12 years. Twelve clinical indicators were used to measure BA, while the total annual medical expenses, total annual number of outpatient days, total annual number of days in hospital, and average annual increases in medical expenses were used as the variables for medical expenses and medical care use. For statistical analysis, this study employed Pearson correlation analysis and multiple regression analysis. RESULTS: Regression analysis of the differences between corrected biological age (cBA) and CA exhibited statistically significant increases (p<0.05) in all the variables of the total annual medical expenses, total annual number of outpatient days, total annual number of days in hospital, and average annual increases in medical expenses. CONCLUSIONS: This study quantified decreases in the variables for medical expenses and medical care use based on improved BA, thereby motivating people to become more health-conscious. In particular, this study is significant in that it is the first of its kind to predict medical expenses and medical care use through BA.

Efficacy and safety of oxiracetam in patients with vascular cognitive impairment: A multicenter, randomized, double-blinded, placebo-controlled, phase IV clinical trial.

BACKGROUND: Oxiracetam may have a modest effect on preventing cognitive decline. Exercise can also enhance cognitive function. This trial aims to investigate the effect of oxiracetam on post-stroke cognitive impairment and explore whether this effect is modified by exercise. Furthermore, the mechanisms that mediate this effect will be investigated through a neural network analysis. METHODS: This is a multicenter, randomized, double-blind, placebo-controlled phase IV trial. Patients who complained of cognitive decline 3 months after stroke and had a high risk of cognitive decline were eligible. Patients were randomly assigned to receive either 800 mg of oxiracetam or placebo twice daily for 36 weeks. After randomization, a predetermined exercise protocol was provided to each participant, and the degree of physical activity was assessed using wrist actigraphy at 4, 12, 24, and 36 weeks. Resting-state functional MRI was obtained in baseline and 36-week follow-up. Co-primary endpoints are changes in the Mini-Mental State Examination and Clinical Dementia Rating-Sum of Boxes. Secondary endpoints include changes in the NINDS-CSN VCIHS-Neuropsychology Protocol, Euro QoL, patient's global assessment, and functional network connectivity. If there is a significant difference in physical activity between the two groups, the interaction effect between physical activity and the treatment group will be examined. A total of 500 patients were enrolled from February 2018, and the last patient's final follow-up was completed in September 2022. CONCLUSION: This trial is meaningful not only to prove the efficacy of oxiracetam, but also evaluate whether exercise can modify the effects of medication and how cognitive function can be restored. Trial registrationhttp://cris.nih.go.kr (KCT0005137).

Effects of Customized Digital Health Care Service on Metabolic Syndrome Status and Lifestyle Using a Health Care App: Clinical Trial.

BACKGROUND: Untact cultures have rapidly spread around the world as a result of the prolongation of the COVID-19 pandemic, leading to various types of research and technological developments in the fields of medicine and health care, where digital health care refers to health care services provided in a digital environment. Previous studies relating to digital health care demonstrated its effectiveness in managing chronic diseases such as hypertension and diabetes. While many studies have applied digital health care to various diseases, daily health care is needed for healthy individuals before they are diagnosed with a disease. Accordingly, research on individuals who have not been diagnosed with a disease is also necessary. OBJECTIVE: This study aimed to identify the effects of using a customized digital health care service (CDHCS) on risk factors for metabolic syndrome (MS) and lifestyle improvement. METHODS: The population consisted of 63 adults who underwent a health checkup at the National Health Insurance Service Ilsan (NHIS) Hospital in 2020. Measured variables include basic clinical indicators, MS-related variables, and lifestyle variables. All items were measured at NHIS Ilsan Hospital before the use of the CDHCS and 3 months thereafter. The CDHCS used in this study is a mobile app that analyzes the health condition of the user by identifying their risk factors and provides appropriate health care content. For comparison between before and after CDHCS use (pre-post comparison), paired t test was used for continuous variables, and a chi-square test was used for nominal variables. RESULTS: The study population included 30 (47.6%) male and 33 (52.4%) female participants, and the mean age was 47.61 (SD 13.93) years. The changes in clinical indicators before and after intervention results showed a decrease in weight, waist circumference, triglyceride, and high-density lipoprotein cholesterol and increases in systolic blood pressure and diastolic blood pressure. The distribution of the risk group increased from 32 (50.8%) to 34 (54%) and that of the MS group decreased from 18 (28.6%) to 16 (25.4%). The mean metabolic syndrome age-chronological age before the CDHCS was 2.20 years, which decreased to 1.72 years after CDHCS, showing a decrease of 0.48 years in the mean metabolic syndrome age-chronological age after the intervention. While all lifestyle variables, except alcohol consumption, showed a tendency toward improvement, the differences were not statistically significant. CONCLUSIONS: Although there was no statistical significance in the variables under study, this pilot study will provide a foundation for more accurate verification of CDHCS in future research.

Predictive Model of Self-management in Patients With Stroke Based on the Information-Motivation-Behavioral Skills Model.

BACKGROUND: Patients who had a stroke are required to manage risk factors, and self-management for risk factor control in stroke is essential. Recent studies using the information-motivation-behavioral skills model reported that the model is effective for predicting and explaining self-management behavior in chronically ill patients. OBJECTIVES: This study aimed to develop and verify the predictive model of self-management based on the information-motivation-behavioral skills model in patients with stroke. METHODS: This was a descriptive, cross-sectional study; path analysis was conducted to develop and verify the hypothesized predictive model. We recruited 242 patients who had a stroke using convenience sampling from the neurological outpatient clinic. RESULTS: The model's fit indices were adequate. Stroke self-management knowledge, social support, and self-efficacy had a direct effect on stroke self-management, and stroke self-management knowledge and attitude and social support had an indirect effect on stroke self-management, mediated by self-efficacy. Stroke self-management knowledge and attitude, social support, and self-efficacy explained 27.5% of the total variance in stroke self-management. CONCLUSIONS: The information-motivation-behavioral skills model is potentially a predictive model for self-management for patients who had a stroke. Considering the level of stroke knowledge and attitude, social support, and self-efficacy together may help to understand the required level of self-management. In addition, using this model for the development of self-management interventions for patients who had a stroke could be a strategy for improving self-management in patients with stroke.

Relationships among Symptoms, Disability, Type D Personality, and Quality of Life in Patients with Migraine: A Cross-Sectional Study in South Korea.

BACKGROUND: Type D personality as a personality vulnerable to stress consists of negative affectivity and social inhibition, and it is related to symptoms and decreased quality of life in patients with chronic illness. AIM: This study aimed to explore the relationships among migraine symptoms, disability, type D personality, and quality of life in patients with migraine. METHODS: A convenience sample of 135 patients with migraine was collected at the neurologic outpatient clinics of two tertiary hospitals in South Korea. Frequency and severity of migraine symptoms, Migraine Disability Assessment, type D personality, and quality of life were investigated using a structured questionnaire. A descriptive cross-sectional design was used. RESULTS: Sixty-one (45.2%) were classified as type D personality. The intensity of the most severe migraine and Migraine Disability Assessment scores in subjects with type D personality were significantly higher than those in subjects without type D personality. In addition, the quality of life score of subjects with type D personality was significantly lower than in subjects without type D personality. The intensity of the migraine, Migraine Disability Assessment score, and type D personality were significant factors influencing quality of life on stepwise multiple regression analysis. CONCLUSIONS: Type D personality was related to migraine symptoms, disability, and quality of life in patients with migraine.

A randomized, open-label, single-dose, two-way crossover study to assess the pharmacokinetics between two tablets of fixed-dose combination formulation with raloxifene and cholecalciferol and concomitant administration of each agents in healthy male volunteers.

A new fixed-dose combination (FDC) formulation of raloxifene 60 mg and cholecalciferol 800 IU was developed to improve the medication compliance and overall efficacy of raloxifene treatment in postmenopausal osteoporosis patients. The aim of this study was to compare the pharmacokinetics between two tablets of FDC formulation of raloxifene/cholecalciferol and the two products administered concomitantly at respective doses. This randomized, open-label, single-dose, two-treatment, two-way crossover study included 46 volunteers. During each treatment period, subjects received the test formulation (FDC formulation containing raloxifene and cholecalciferol) or the reference formulation (co-administration of raloxifene and cholecalciferol), with a 14-d washout period. Serial blood samples were collected periodically over 96 hours after drug intake. In total, 46 subjects completed the study. The geometric mean ratios and its 90% confidence intervals of the FDC to the single agents for the area under the concentration-time curve from zero to the last quantifiable time point and the maximum plasma concentration met the regulatory criteria for bioequivalence: 1.1364 (1.0584-1.2201) and 1.1010 (0.9945-1.2188) for raloxifene and 1.0266 (0.9591-1.0989) and 1.0354 (0.9816-1.0921) for baseline-corrected cholecalciferol, respectively. Both formulations were well tolerated. No significant differences was observed in the incidence of adverse events between the two treatments. It was concluded that two tablets of the newly developed FDC formulation of raloxifene and cholecalciferol and the corresponding two agents administered concomitantly at respective doses were bioequivalent. Trial Registration: ClinicalTrials.gov Identifier: NCT03010267.

De Novo Sphingolipid Biosynthesis in Atherosclerosis.

Atherosclerosis is the formation of fibrofatty lesions in the arterial wall, and this inflammatory state of the artery is the main cause of advanced pathological processes, including myocardial infarction and stroke. Dyslipidemic conditions with excess cholesterol accumulate within the arterial vessel wall and initiate atherogenic processes. Following vascular reaction and lipid accumulation, the vascular wall gradually thickens. Together with the occurrence of local inflammation, early atherosclerotic lesions lead to advanced pathophysiological events, plaque rupture, and thrombosis. Ceramide and sphingomyelin have emerged as major risk factors for atherosclerosis and coronary artery disease. Currently, the clinical association between de novo sphingolipid biosynthesis and coronary artery disease has been established. Furthermore, therapeutic strategies to modulate this pathway, especially those involving serine palmitoyltransferase and sphingomyelin synthase, against atherosclerosis, cancer, type 2 diabetes, and non-alcoholic fatty liver disease are actively under development. In this chapter, we focus on the relationship between de novo sphingolipid biosynthesis and coronary artery disease.

Upregulation of the serine palmitoyltransferase subunit SPTLC2 by endoplasmic reticulum stress inhibits the hepatic insulin response.

Endoplasmic reticulum (ER) stress is induced by various conditions, such as inflammation and the presence of excess nutrients. Abnormal accumulation of unfolded proteins leads to the activation of a collective signaling cascade, termed the unfolded protein response (UPR). ER stress is reported to perturb hepatic insulin response metabolism while promoting insulin resistance. Here, we report that ER stress regulates the de novo biosynthesis of sphingolipids via the activation of serine palmitoyltransferase (SPT), a rate-limiting enzyme involved in the de novo biosynthesis of ceramides. We found that the expression levels of Sptlc1 and Sptlc2, the major SPT subunits, were upregulated and that the cellular concentrations of ceramide and dihydroceramide were elevated by acute ER stress inducers in primary hepatocytes and HepG2 cells. Sptlc2 was upregulated and ceramide levels were elevated by tunicamycin in the livers of C57BL/6J wild-type mice. Analysis of the Sptlc2 promoter demonstrated that the transcriptional activation of Sptlc2 was mediated by the spliced form of X-box binding protein 1 (sXBP1). Liver-specific Sptlc2 transgenic mice exhibited increased ceramide levels in the liver and elevated fasting glucose levels. The insulin response was reduced by the inhibition of the phosphorylation of insulin receptor ß (IRß). Collectively, these results demonstrate that ER stress induces activation of the de novo biosynthesis of ceramide and contributes to the progression of hepatic insulin resistance via the reduced phosphorylation of IRß in hepatocytes.

Pharmacokinetics and Pharmacodynamics of YYD601, a Dual Delayed-Release Formulation of Esomeprazole, Following Single and Multiple Doses in Healthy Adult Volunteers Under Fasting and Fed Conditions.

Background: YYD601 was developed as a novel dual delayed release (DDR) formulation of esomeprazole to prolong the plasma esomeprazole concentration and extend the duration of acid suppression. Purpose: The pharmacokinetic (PK) and pharmacodynamics (PD) characteristics of YYD601 after single and multiple oral administrations were investigated in healthy Korean adults under fasting and fed conditions, and compared with the original esomeprazole capsule. Methods: In the single-center, randomized, open-label, parallel-design, two-period study, thirty two volunteers were enrolled into four dosing groups, including esomeprazole 40-mg (group A), YYD60130-mg (group B), YYD601 40-mg (group C), and YYD601 60-mg (group D) once daily for 5 days. Blood samples were collected for PK analysis, before and up to 24 h after dosing. For PD characteristics of YYD601, the percentages of time with intragastric pH > 4 over a 24-h period and during night-time following multiple oral administrations were evaluated. Results: A total of 27 subjects completed the study. YYD601 showed a dual-peak PK profile under fasting condition, with delayed Tmax, compared with conventional formulation. There were no significant differences in the AUC values adjusted for dose between the three YYD601 dosage groups and the conventional esomeprazole 40 mg. The esomeprazole AUC following single and multiple administration decreased with food intake by approximately 33%. YYD601 showed a linear pharmacokinetic profile in the dose range studied. There was no statistically significant difference in increase in mean percentage of time with intragastric pH > 4 for 24-hour and during night-time between the three different doses of YYD601 and the conventional formulation. The treatments were well-tolerated during the study and no serious adverse events were observed. Conclusion: YYD601 30 mg has a comparable effect on gastric acid inhibition as conventional esomeprazole 40 mg following once daily oral administration. Single and multiple oral dosing of YYD601 up to 60 mg were safe and well-tolerated throughout the study. Clinical Trial Registry: http://clinicaltrials.gov, NCT03558477 (date of registration: June 15, 2018; study period: between October 2017 and February 2018).

Pharmacokinetic Drug Interaction Between Raloxifene and Cholecalciferol in Healthy Volunteers.

Osteoporosis is a common skeletal disorder, often leading to fragility fracture. Combination therapy with raloxifene, a selective estrogen receptor modulator, and cholecalciferol (vitamin D3 ) has been proposed to improve the overall efficacy and increase compliance of raloxifene therapy for postmenopausal osteoporosis. To our knowledge, there has been no report of any study on the pharmacokinetic interaction between raloxifene and cholecalciferol. This study aimed to evaluate the possible pharmacokinetic interactions between raloxifene and cholecalciferol in healthy adult male Korean volunteers. Twenty subjects completed this open-label, randomized, single-dose, 3-period, 6-sequence, crossover phase 1 study with a 14-day washout period. Serial blood samples were collected from 20 hours before dosing to 96 hours after dosing. The plasma concentrations of raloxifene and cholecalciferol were determined using a validated method for high-performance liquid chromatography with tandem mass spectrometry. The geometric mean ratios (90%CIs) for area under the plasma concentration-time curve from time 0 to the last quantifiable time point and maximum plasma concentration of raloxifene with or without cholecalciferol were 1.02 (0.87-1.20) and 0.87 (0.70-1.08), respectively. For baseline-corrected cholecalciferol, geometric mean ratios (90%CIs) of area under the plasma concentration-time curve from time 0 to the last quantifiable time point and maximum plasma concentration with or without raloxifene were 1.01 (0.93-1.09) and 0.99 (0.92-1.06), respectively. Concurrent treatment with raloxifene and cholecalciferol was generally well tolerated. These results suggest that raloxifene and cholecalciferol have no clinically relevant pharmacokinetic drug-drug interactions when administered concurrently. All treatments were well tolerated, with no serious adverse events.

Influence of Estimated Glomerular Filtration Rate on Clinical Outcomes in Patients with Acute Ischemic Stroke Not Receiving Reperfusion Therapies.

BACKGROUND: We aimed to determine whether estimated glomerular filtration rate (eGFR) is an independent predictor of clinical outcomes in patients with acute ischemic stroke not treated with reperfusion therapy. METHODS: A total of 1420 patients with acute ischemic stroke from a hospital-based stroke registry were included in this study. Patients managed with intravenous thrombolysis or endovascular reperfusion therapy were excluded. The included patients were categorized into five groups according to eGFR, as follows: ≥90, 60-89, 45-59, 30-44, and <30 mL/min/1.73 m2. The effects of eGFR on functional outcome at discharge, in-hospital mortality, neurologic deterioration, and hemorrhagic transformation were evaluated using logistic regression analyses. RESULTS: In univariable logistic regression analysis, reduced eGFR was associated with poor functional outcome at discharge (p < 0.001) and in-hospital mortality (p = 0.001), but not with neurologic deterioration and hemorrhagic transformation. However, no significant associations were observed between eGFR and any clinical outcomes in multivariable analysis after adjusting for clinical and laboratory variables. CONCLUSIONS: Reduced eGFR was associated with poor functional outcomes at discharge and in-hospital mortality but was not an independent predictor of short-term clinical outcomes in patients with acute ischemic stroke who did not undergo reperfusion therapy.

Global Trends of Regional Health Information Systems and Suggested Strategic Utilization of their Medical Information.

OBJECTIVE: Along with the exponentially-growing data produced and accumulated every day through mobile platforms, social networking services, the Internet, and other media, information is becoming increasingly important as a strategic resource. This report presents specific and clear directions and suggests empirical project plans regarding innovations in regional health information systems to promote the utilization of medical information. METHODS: We reviewed and examined documents about global trends and examples of regional health information systems. The problems and solutions of health information utilization and regional health information systems in Korea were analyzed. RESULTS: This study presented examples of the establishment of health information systems, problems in the use of local healthcare information, and an empirical project for improvement. CONCLUSIONS: The results of this study imply the need for long-term and systematic approaches for the use of medical information and the establishment of a local healthcare information system, along with implementation plans. As a first step, it is imperative to clarify the goal of building a medical information system, the information that must be provided to build the system, and the data that should be collected to provide such information, while moving away from the mentality of focusing on technology-oriented medical information services. In addition, it is necessary to consider information governance, data-based service development, and the medical innovation framework, which are ways to efficiently manage, utilize, and systemize the data to be collected.