PURPOSE: Label adherence for non-vitamin K antagonist oral anticoagulants (NOACs) has not been well evaluated in Asian patients with non-valvular atrial fibrillation (AF). The present study aimed to assess label adherence for NOACs in a Korean AF population and to determine risk factors of off-label prescriptions of NOACs. MATERIALS AND METHODS: In this COmparison study of Drugs for symptom control and complication prEvention of AF (CODE-AF) registry, patients with AF who were prescribed NOACs between June 2016 and May 2017 were included. Four NOAC doses were categorized as on- or off-label use according to Korea Food and Drug Regulations. RESULTS: We evaluated 3080 AF patients treated with NOACs (dabigatran 27.2%, rivaroxaban 23.9%, apixaban 36.9%, and edoxaban 12.0%). The mean age was 70.5±9.2 years; 56.0% were men; and the mean CHA₂DS₂-VASc score was 3.3±1.4. Only one-third of the patients (32.7%) was prescribed a standard dose of NOAC. More than one-third of the study population (n=1122, 36.4%) was prescribed an off-label reduced dose of NOAC. Compared to those with an on-label standard dosing, patients with an off-label reduced dose of NOAC were older (≥75 years), women, and had a lower body weight (≤60 kg), renal dysfunction (creatinine clearance ≤50 mL/min), previous stroke, previous bleeding, hypertension, concomitant dronedarone use, and anti-platelet use. CONCLUSION: In real-world practice, more than one-third of patients with NOAC prescriptions received an off-label reduced dose, which could result in an increased risk of stroke. Considering the high risk of stroke in these patients, on-label use of NOAC is recommended.
Anticoagulants ; Asian Continental Ancestry Group ; Atrial Fibrillation ; Body Weight ; Cohort Studies ; Drug and Narcotic Control ; Drug Labeling ; Female ; Hemorrhage ; Humans ; Hypertension ; Korea ; Male ; Off-Label Use ; Prescriptions ; Prospective Studies ; Risk Factors ; Rivaroxaban ; Stroke

This study compared the efficacy of DA-9601 (Dong-A ST Co., Seoul, Korea) and its new formulation, DA-5204 (Dong-A ST Co.), for treating erosive gastritis. This phase III, randomized, multicenter, double-blind, non-inferiority trial randomly assigned 434 patients with endoscopically proven gastric mucosal erosions into two groups: DA-9601 3 times daily or DA-5,204 twice daily for 2 weeks. The final analysis included 421 patients (DA-5204, 209; DA-9601, 212). The primary endpoint (rate of effective gastric erosion healing) and secondary endpoints (cure rate of endoscopic erosion and gastrointestinal [GI] symptom relief) were assessed using endoscopy after the treatment. Drug-related adverse events (AEs), including GI symptoms, were also compared. At week 2, gastric healing rates with DA-5204 and DA-9601 were 42.1% (88/209) and 42.5% (90/212), respectively. The difference between the groups was −0.4% (95% confidence interval, −9.8% to 9.1%), which was above the non-inferiority margin of −14%. The cure rate of gastric erosion in both groups was 37.3%. The improvement rates of GI symptoms with DA-5204 and DA-9601 were 40.4% and 40.8%, respectively. There were no statistically significant differences between the two groups in both secondary endpoints. AEs were reported in 18 (8.4%) patients in the DA-5204 group and 19 (8.8%) in the DA-9601 group. Rates of AE were not different between the two groups. No serious AE or adverse drug reaction (ADR) occurred. These results demonstrate the non-inferiority of DA-5204 compared to DA-9601. DA-5204 is as effective as DA-9601 in the treatment of erosive gastritis. Registered randomized clinical trial at ClinicalTrials.gov (NCT02282670)
Artemisia ; Double-Blind Method ; Drug-Related Side Effects and Adverse Reactions ; Endoscopy ; Gastritis* ; Humans ; Seoul

PURPOSE: To investigate and document a disaster medical response during the collapse of the Gyeongju Mauna Ocean Resort gymnasium, which occurred on February 17, 2014. METHODS: The official records of each institution were verified to select the study population. All the medical records and emergency medical service records were reviewed by an emergency physician. Personal or telephonic interviews were conducted without a separate questionnaire if the institutions or agencies crucial to disaster response did not have official records or if information from different institutions was inconsistent. RESULTS: One hundred fifty-five accident victims, who were treated at 12 hospitals mostly for minor wounds, were included in this study. The collapse killed 10 people. Although the news of the collapse was disseminated in 4 minutes, it took at lease 69 minutes for a dispatch of 4 disaster medical assistance teams to take action; 4.5% of patients were treated on-site, 56.7% were transferred to 2 nearest hospitals, and 42.6% were transferred to hospitals with poor preparation to handle disaster victims. CONCLUSION: In the collapse of the Gyeongju Mauna Ocean Resort gymnasium, the initial triage and distribution of patients were inefficient, with delayed arrival of medical assistance teams. These problems had also been noted in prior mass casualty incidents. Government agencies are implementing improvements, and this study could aid the implementation process.
Disaster Victims ; Disasters* ; Emergencies ; Emergency Medical Services ; Government Agencies ; Gyeongsangbuk-do ; Health Resorts* ; Humans ; Mass Casualty Incidents ; Medical Assistance ; Medical Records ; Social Networking ; Triage ; Wounds and Injuries

OBJECTIVE: To investigate and document the disaster medical response during the Gyeongju Mauna Ocean Resort gymnasium collapse on February 17, 2014. METHODS: Official records of each institution were verified to select the study population. All the medical records and emergency medical service run sheets were reviewed by an emergency physician. Personal or telephonic interviews were conducted, without a separate questionnaire, if the institutions or agencies crucial to disaster response did not have official records or if information from different institutions was inconsistent. RESULTS: One hundred fifty-five accident victims treated at 12 hospitals, mostly for minor wounds, were included in this study. The collapse killed 10 people. Although the news of collapse was disseminated in 4 minutes, dispatch of 4 disaster medical assistance teams took at least 69 minutes to take the decision of dispatch. Four point five percent were treated at the accident site, 56.7% were transferred to 2 hospitals that were nearest to the collapse site, and 42.6% were transferred to hospitals that were poorly prepared to handle disaster victims. CONCLUSION: In the Gyeongju Mauna Ocean Resort gymnasium collapse, the initial triage and distribution of patients was inefficient and medical assistance arrived late. These problems had also been noted in prior mass casualty incidents.
Disaster Victims ; Disasters* ; Emergencies ; Emergency Medical Services ; Gyeongsangbuk-do ; Health Resorts* ; Humans ; Mass Casualty Incidents ; Medical Assistance ; Medical Records ; Social Networking ; Triage ; Wounds and Injuries

The aim of the present study was to determine whether serotonergic drugs could reverse lipopolysaccharide (LPS) -induced anorexia in rats. LPS (500microgram/kg body weight) and all serotonergic drugs, except for 8-OH-DPAT (subcutaneous), were injected intraperitoneally into Sprague-Dawley rats. Without the LPS injection, 8-OH-DPAT (1A agonist), metergoline (1/2 antagonist), and mianserin (2A/2C antagonist) exerted no effects on food intake at any of the doses tested, but ketanserin (2A antagonist) caused an increase of food intake at 4 mg/kg. RS-102221 (2C antagonist) reduced food intake at 2 and 4 mg/kg. LPS reduced food intake 1 hour after injection, and food intake remained low until the end of measurement period (24 hours) (p< 0.05). Pretreatment of rats with 8-OH-DPAT partially recovered of cumulative food intake at all measured times (2, 4, 6, 8, and 24 hours after LPS injection). Pretreatment with metergoline resulted in a partial recovery of cumulative food intake at 2, 4, 6, and 8 hours, but not at 24 hours. Ketanserin caused partial recovery at 2 and 4 hours only. Mianserin and RS-102221 had no effects on LPS-reduced food intake. A variety of serotonergic drugs ameliorated anorexic symptoms, which suggesting that the serotonin system plays a role in LPS-induced anorexia.
8-Hydroxy-2-(di-n-propylamino)tetralin ; Animals ; Anorexia* ; Diethylpropion ; Eating ; Ketanserin ; Metergoline ; Mianserin ; Rats* ; Rats, Sprague-Dawley ; Serotonin ; Serotonin Agents*

BACKGROUND: The facilitatory effect of spinal prostaglandins (PGs) on nociceptive transmission suggests that early PG synthesis after nerve injury could be important in the development of allodynia. METHODS: The aim of this study is to examine the effects of diclofenac (nonselective COX inhibitor), SC-560 (selective COX-1 inhibitor), and NS-398 (selective COX-2 inhibitor) on mechanical allodynia and thermal hyperalgesia in the neuropathic pain model. The rats underwent right L5 spinal nerve ligation (SNL) and were assigned to three COX inhibitor groups to be injected intraperitoneally with different administration dosages (0.2 mg, 1 mg, 5 mg) 30 minutes before, and at 1, 2, and 3 days after SNL. The withdrawal threshold of both hindpaws in response to mechanical stimulation was measured by dynamic plantar anesthesiometer and the withdrawal ratio of right to left hindpaw was calculated. The thermal stimulation applied to both hindpaws by the plantar test was calculated different administration dosages were compared with the vehicle group. RESULTS: There were no differences in mechanical allodynia among the lower dosage groups (0.2 mg) until 14 days after SNL. However, 1 mg of NS-398 decreased mechanical allodynia compared with the vehicle group at 14 days after SNL, and 5 mg of NS-398 decreased mechanical allodynia at 3 days after SNL. However, there was no difference in thermal hyperalgesia between the groups. CONCLUSIONS: These results suggest that intraperitoneal administration of COX inhibitor (especially selective COX-2 inhibitor) after nerve ligation injury can attenuate the development of mechanical allodynia.
Animals ; Cyclooxygenase Inhibitors* ; Diclofenac ; Hyperalgesia ; Ligation* ; Neuralgia* ; Prostaglandin-Endoperoxide Synthases* ; Prostaglandins ; Rats* ; Spinal Nerves*

P. marneffei is a fungus that causes life-threatening disseminated infection in a geographically distinct areas of the world. Following the first case of human infection in 1959, the incidence of this infection has risen markedly during the past 5 years. However, even in the midst of such rapid increase, the infection has always occurred only in a limited geographic distributions or in persons who have visited this limited geographic areas. These areas include Myanmar, Hong Kong, Indonesia, Laos, Malaysia, Singapore, Taiwan, Thailand, Vietnam, and the Guangxi province of southern China. P. marneffei infection occurs mostly in immunocompromised patients, particularly AIDS patients. P. marneffei infection commonly presents with skin and subcutanous tissue infection, fungemia, diarrhea, bone marrow infection, and generalized lymphadenopathy with hepatosplenomegaly. We report the case of continuous ambulatory peritoneal dialysis-associated peritonitis caused by P. marneffei. The case occurred in Korea, a non-endemic area of P. marneffei, in a non-AIDS patient who has not been exposed to any of the endemic areas. This warrants further consideration in determining the yet unknown transmission route of this fungal organism. P. marneffei was diagnosed without delay by 18sRNA PCR and sequencing, and was later confirmed by culture. PCR and sequencing may contribute to the early diagnosis of the P. marneffei infection, which is important given this infection's ability to progress to a systemic infection with high mortality rate when diagnosis and management are delayed.
Bone Marrow ; China ; Diagnosis ; Diarrhea ; Early Diagnosis ; Fungemia ; Fungi ; Hong Kong ; Humans ; Immunocompromised Host ; Incidence ; Indonesia ; Korea ; Laos ; Lymphatic Diseases ; Malaysia ; Mortality ; Myanmar ; Penicillium* ; Peritoneal Dialysis, Continuous Ambulatory* ; Peritonitis* ; Polymerase Chain Reaction ; Singapore ; Skin ; Taiwan ; Thailand ; Vietnam

BACKGROUND: It is doubtful that aging causes deteriorated glucose metabolism and insulin resistance of skeletal muscle. Some researchers had different results about it. So we have studied the mechanism responsible for the abnormal glucose tolerance associated with aging in rapidly growing and matured rats. MATERIALS AND METHODS: Animals were used S.D. rats. Growing rats were 7 weeks old (BW: 160-190 gm) and matured rats were 28 weeks old (BW: 420-525 gm). RESULTS: Fasting blood glucose and plasma insulin levels were significantly elevated in matured rat compared with growing rats. And during oral glucose tolerance test the glucose level was also significantly elevated in matured rats. These results confirmed an insulin resistant state of aging. Insulin levels at 30 minutes of oral glucose tolerance test was significantly elevated in growing rat. But at 120 minutes it was maintained at higher level in matured rats than in growing rats. It suggested the possibility of increased insulin secretion by initial stimulation of beta-cells in growing rats, and increased secretion and decreased catabolic rate of insulin in matured rats. Glucose uptake rate of soleus muscle in matured rats was lower than that of growing rats, but the difference was not statistically significant. The dose(insulin)- responsive (glucose uptake) curve of soleus muscle was only slightly deviated to the right side. CONCLUSION: Glucose metabolism of rat skeletal muscle was worsened by aging. The data of glucose uptake experiments suggested the possibility of insulin resistance of skeletal muscle in matured rats, but the mechanism of insulin resistance of skeletal muscle need further studies.
Aging ; Animals ; Blood Glucose ; Fasting ; Glucose Tolerance Test ; Glucose* ; Insulin ; Insulin Resistance ; Metabolism* ; Muscle, Skeletal* ; Plasma ; Rats*

The purpose of the present study was to determine whether chronic high-fat diet (HF) induces insulin resistance independently of obesity. We randomly divided 40 rats into two groups and fed them either with a HF or with a high-carbohydrate diet (HC) for 8 weeks. Whole body glucose disappearance rate (Rd) was measured using a euglycemic hyperinsulinemic clamp. Firstly, we defined whether insulin resistance by HF was associated with obesity. Plasma glucose and triglyceride concentrations were significantly increased in HF. Rd was decreased (10.6+/-0.2 vs. 9.1+/-0.2 mg/kg/min in HC and HF, respectively) and the hepatic glucose output rate (HGO) was increased in HF (2.2+/-0.3 vs. 4.5+/-0.2 mg/kg/min in HC and HF, respectively). Rd was significantly correlated with %VF (p<0.01). These results implicate that visceral obesity is associated with insulin resistance induced by HF. In addition, to define whether dietary fat induces insulin resistance regardless of visceral obesity, we compared Rd and HGO between groups 1) after matching %VF in both groups and 2) using an ANCOVA to adjust for %VF. After matching %VF, Rd in HF was significantly decreased by 14% (p<0.001) and HGO was significantly increased by 110% (p<0.001). Furthermore, statistical analyses using an ANCOVA also showed Rd for HF was significantly decreased even after adjusting %VF. In conclusion, we suggest that dietary fat per se could induce insulin resistance in rats fed with chronic HF independently of obesity.
Adipose Tissue/*pathology ; Animal ; Dietary Carbohydrates/administration &age ; Dietary Fats/*administration &age ; Fatty Acids, Nonesterified/metabolism ; Female ; *Insulin Resistance ; Obesity/etiology ; Rats ; Rats, Sprague-Dawley ; Viscera

The purpose of the present study was to determine the preventive effects of combined interventional trial of fish oil treatment and exercise training on insulin resistance of skeletal muscle in high-fat fed rats. Male Wistar rats were randomly divided into chow diet (CD), high-fat diet (HF), high-fat diet with fish oil (FO), high-fat diet with exercise training (EX), and FO+EX groups. The rats in control group were fed chow diet containing, as percents of calories, 58.9% carbohydrate, 12.4% fat, and 28.7% protein. High-fat diet provided 32% energy as lard, 18% as corn oil, 27% as carbohydrate and 23% as casein. The fish oil diet had the same composition as the high fat diet except that 100 g menhaden oil was substituted for corn oil. Insulin sensitivity was assessed by in vitro glucose transport in the soleus muscle after diet treatment and treadmill running for 4 weeks. While the FO or EX only partially prevented insulin resistance on glucose transport and visceral obesity induced by high-fat diet, these interventions completely corrected hyperinsulinemia and hyperglycemia from the high-fat diet. The rats in the FO+EX showed normalized insulin action on glucose transport, plasma chemicals and visceral fat mass. Insulin-mediated glucose transport was negatively associated with total visceral fat mass (r=-0.734; p<0.000), plasma triglyceride (r=-0.403; p<0.05) and lepin (r=-0.583; p<0.001) concentrations with significance. Multiple stepwise regression analysis showed that only total visceral fat mass was independently associated with insulin-mediated glucose transport (r=-0.668; p<0.000). In conclusion, combined interventional trial of FO+EX recovered insulin resistance on glucose transport of skeletal muscle induced by high-fat diet. Visceral fat mass might be more important factor than plasma TG and leptin to induce insulin resistance on glucose transport of skeletal muscle in high-fat fed rats.
Animals ; Caseins ; Corn Oil ; Diet ; Diet, High-Fat* ; Glucose* ; Humans ; Hyperglycemia ; Hyperinsulinism ; Insulin Resistance ; Insulin* ; Intra-Abdominal Fat ; Leptin ; Male ; Muscle, Skeletal* ; Obesity, Abdominal ; Plasma ; Rats* ; Rats, Wistar ; Running ; Triglycerides