Risk Factors for Recurrent Intussusception After Fluoroscopy-Guided Air Enema.

OBJECTIVES: The aim of this study was to identify risk factors for recurrent intussusception after a successful reduction by fluoroscopy-guided air enema, the time required for recurrence, and the association between delayed reduction and the recurrence. METHODS: Medical records of 479 consecutive children with intussusception who underwent fluoroscopy-guided air enema between January 2004 and September 2014 were reviewed. Recurrent intussusception was defined as a recurrence within 48 hours of a reduction. Symptom-to-door time was defined as the time from symptom onset to emergency department arrival. Door-to-reduction time was defined as the time from emergency department arrival to reduction. Time-to-recurrence was defined as the time required for recurrence from the first ultrasound diagnosis. RESULTS: Of the 360 eligible children, 32 had recurrent intussusceptions (8.9%). Multivariable logistic regression showed that age 2 years or older is an independent predictor of recurrent intussusception (odds ratio, 2.39; 95% confidence interval, 1.13-5.02; P = 0.02). Median time to recurrence was 25 hours (18.0-36.0 hours). Although symptom-to-door and door-to-reduction times tended to be longer in the recurrence group, these differences were not significant (12.5 vs 7.0 hours, P = 0.18; 154.0 vs 143.0 minutes, P = 0.67, respectively). CONCLUSIONS: Our data suggest that provision for early recurrence and extended observation may be beneficial for children 2 years or older. Delayed reduction was not associated with recurrent intussusception, but further studies with larger sample sizes are needed to explain this issue.

Model for end-stage liver disease score as a predictor of short-term outcome in patients with drug-induced liver injury.

OBJECTIVES: The purposes of this study were to investigate the clinical presentation, cause and outcome of drug-induced liver injury (DILI) and to evaluate the predictive value of the model for end-stage liver disease (MELD) score in DILI. METHODS: Patients diagnosed with DILI between January 1, 2010 and December 31, 2012 in the Emergency Department at Asan Medical Center in Seoul, Korea were analyzed retrospectively. The primary end point was poor outcome, defined as liver transplantation or death within 30 days of the initial hospital visit. RESULTS: Of 213 patients, 13.1% had a 30-day poor outcome. Folk remedies were the most common cause of DILI in 147 patients (69%). Univariate logistic regression analysis showed that multiple drugs (odds ratio [OR] 2.30, 95% confidence interval [CI]: 1.03-5.15), concurrent alcohol consumption (OR 3.69, 95% CI: 1.03-13.18), white blood cell (WBC) count (OR 1.17, 95% CI: 1.07-1.28), hemoglobin (Hb) (OR 0.60, 95% CI: 0.49-0.74), platelet count (OR 0.993, 95% CI: 0.987-0.998), total bilirubin (OR 1.09, 95% CI: 1.06-1.13) and MELD (OR 1.23, 95% CI: 1.15-1.32) were significantly associated with 30-day poor outcomes. Multivariate analysis showed that the MELD (OR 1.21, 95% CI: 1.12-1.30) and Hb (OR 0.77, 95% CI: 0.61-0.98) were independent predictors of poor outcome. For 30-day mortality, the c-statistics for MELD alone and for combination of MELD and Hb were 0.93 (95% CI: 0.89-0.97) and 0.94 (95% CI: 0.90-0.97), respectively. CONCLUSION: The outcome of patients with DILI was poor. MELD score and Hb were reliable predictors of short-term outcome in patients with DILI.

Oropharyngeal airway obstruction after the accidental ingestion of Arisaema amurense.

BACKGROUND: Arisaema amurense is widely known in Korean folklore as a poisonous plant, and its lethal toxicity has long been recognized. The toxicity of Arisaema amurense is due to its content of calcium oxalate, which causes painful oropharyngeal edema, hypersalivation, aphonia, oral ulceration, esophageal erosion, and hypocalcemia. OBJECTIVE: We report a case of accidental poisoning after ingestion of the rhizome of Arisaema amurense, resulting in airway obstruction that required endotracheal intubation. CASE REPORT: A 60-year-old man developed oral pain and swelling after accidentally ingesting a rhizome from the Arisaema amurense plant as a medicinal herb. His symptoms worsened upon his arrival in the Emergency Department, and he was unable to speak due to oral swelling and hypersalivation. The patient underwent endotracheal intubation to protect his airway and was treated with antihistamines and corticosteroids. Three days after treatment, he had improved and was extubated. CONCLUSION: We describe an emergent treatment course for a patient with acute airway obstruction resulting from the ingestion of Arisaema amurense.

Pharmacokinetic and pharmacodynamic properties of the calcimimetic agent cinacalcet (KRN1493) in healthy male Korean subjects: a randomized, open-label, single ascending-dose, parallel-group study.

BACKGROUND: Cinacalcet (KRN1493) was developed to manage secondary hyperparathyroidism in patients with chronic kidney disease. The characteristics of cinacalcet have not been studied in the Korean population. OBJECTIVE: The aim of this study was to evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) properties and tolerability of single-dose cinacalcet 50 to 100 mg in healthy male Korean subjects for the purposes of a New Drug Application package for the Korean Food and Drug Administration. METHODS: A randomized, open-label, single ascending-dose, parallel-group study was conducted in healthy male Korean subjects. Subjects were randomly assigned to receive a single oral dose of cinacalcet 50, 75, or 100 mg. Serial blood samples for PK/PD analysis were taken for up to 96 hours after administration. Plasma cinacalcet concentrations were analyzed by HPLC-MS/MS. PK parameters were determined using noncompartmental methods. Plasma intact parathyroid hormone (iPTH) concentrations, albumin-corrected serum calcium concentrations, and serum phosphorus concentrations were measured for PD evaluation. For the evaluation of tolerability, adverse events (AEs) were collected using investigators' questionnaires, subjects' spontaneous reports, clinical laboratory tests, ECG, and physical examinations including vital sign measurements. RESULTS: Sixteen subjects in the 50-mg group, 16 in the 75-mg group, and 6 in the 100-mg group completed the study and were included in the PK/PD analysis. The mean (SD) age, height, and weight of the study population were 4.3 (3.0) years, 174.8 (4.9) cm, and 68.2 (7.5) kg, respectively. The median T(max) value in each of the 3 dose groups was 6.0 hours. Mean C(max) values in the 50-, 75-, and 100-mg dose groups were 12.0 (5.5), 17.2 (14.9), and 43.1 (15.5) µg/L; mean AUC(0-∞) values were 126.6 (56.4), 184.3 (87.9), and 417.4 (169.9) µg · h/L. Characteristics were not linear, based on the data over the dose range of 50 to 100 mg. Mean plasma iPTH concentrations in the 50-, 75-, and 100-mg dose groups were decreased from baseline by 64.0% (11.7%), 63.1% (14.6%), and 70.6% (6.3%). Albumin-corrected serum calcium concentrations displayed patterns similar to those of the plasma iPTH concentrations. Sixteen AEs were reported in 11 subjects. No clinically significant abnormalities were observed in the tolerability assessments. CONCLUSIONS: A single oral dose of cinacalcet was well-tolerated up to 100 mg in this small, selected population of healthy male Korean subjects. In addition, the PK characteristics of cinacalcet and its accompanying PD changes-the decreases in the concentrations of plasma iPTH and albumin corrected serum calcium-were demonstrated in the same population. ClinicalTrials.gov identifier: NCT00942773.

Influence of Ginkgo biloba extract on the pharmacodynamic effects and pharmacokinetic properties of ticlopidine: an open-label, randomized, two-period, two-treatment, two-sequence, single-dose crossover study in healthy Korean male volunteers.

BACKGROUND: Ginkgo biloba extract is an herbal medicine used in the treatment of vascular disorders that may be coadministered with antiplatelet agents such as ticlopidine. Regulatory authorities requested evaluation of the pharmacodynamic and pharmacokinetic interactions between these entities, according to the drug-development guidance for fixed-dose combination formulations in Korea. OBJECTIVE: This study was performed to evaluate the potential pharmacodynamic and pharmacokinetic interactions between ticlopidine and Ginkgo biloba extract. METHODS: An open-label, randomized, 2-period, 2-treatment, 2-sequence, single-dose crossover study was conducted in healthy Korean male volunteers. All volunteers were randomly assigned to a sequence group for the 2 treatments, which consisted of ticlopidine 250 mg alone and ticlopidine 250 mg with Ginkgo biloba extract 80 mg, separated by a 1-week washout period between the treatments. Bleeding time was determined just before dosing and at 5, 12, and 48 hours after dosing. Platelet aggregation was evaluated before dosing and at 4, 8, 26, and 48 hours after dosing. Blood samples (8 mL) from each of the volunteers were collected from an indwelling intravenous cannula inserted into a forearm vein before dosing and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, and 48 hours after dosing. Ticlopidine concentrations were determined by a validated method using HPLC and ultraviolet detection. Adverse events were identified using general health-related questions, vital signs, physical examinations, ECGs, and laboratory tests. RESULTS: A total of 24 healthy men participated in the study (mean [SD] age, 24.1 [4.3] years; weight, 66.6 [7.4] kg; height, 174.7 [5.0] cm). The baseline corrected bleeding times were not significantly different between the ticlopidine-alone and ticlopidine/ Ginkgo biloba groups, and changes in platelet aggregation were not significantly different between the groups. Likewise, the pharmacokinetic parameters of ticlopidine were not significantly different between the groups; the geometric mean ratios of the ticlopidine/ Ginkgo biloba group to the ticlopidine-alone group were 1.03 (90% CI, 0.92-1.16) for C(max), 1.08 (90% CI, 0.98-1.19) for AUC(0-last), and 1.10 (90% CI, 1.00-1.20) for AUC(0-infinity). A total of 28 adverse events were reported: 11 in the ticlopidine-alone group and 17 in the ticlopidine/Ginkgo biloba group. The adverse events judged to be possibly related to ticlopidine in the ticlopidine-alone group were epigastric discomfort (2 cases), diarrhea (1), skin eruption (1), and a feeling of being cold (1) or hot (1). The adverse events judged to be related to ticlopidine or Ginkgo biloba in the ticlopidine/Ginkgo biloba group were epigastric discomfort (2), diarrhea (2), nausea (2), and headache (1). CONCLUSIONS: In this small group of healthy Korean men, the addition of a single dose of Ginkgo biloba extract did not prolong the bleeding time and was not associated with additional antiplatelet effects compared with the administration of ticlopidine alone. The coadministration of Ginkgo biloba extract with ticlopidine was not associated with any significant changes in the pharmacokinetic profile of ticlopidine compared with ticlopidine administered alone.

Effects of Angelicae tenuissima radix, Angelicae dahuricae radix and Scutellariae radix extracts on cytochrome P450 activities in healthy volunteers.

Three kinds of herbal medicines, commonly used in Korea, Angelicae tenuissima radix, Angelicae dahuricae radix and Scutellariae radix were studied to evaluate their effect on cytochrome P450 (CYP) activities in healthy volunteers. A total of 24 healthy male volunteers were assigned to one of three parallel herbal treatment groups, each consisting of eight volunteers. A cocktail of probe drugs for CYP enzymes was orally administered before and after multiple administrations of herbal medicines, three times a day for 13 days. Probe drugs used to measure CYP activities were caffeine (CYP1A2), losartan (CYP2C9), omeprazole (CYP2C19), dextromethorphan (CYP2D6), chlorzoxazone (CYP2E1) and midazolam (CYP3A4). The probe drugs and their metabolites were quantified in plasma or urine using HPLC or LC-MS/MS. Changes in each CYP activity was evaluated by metabolic ratio of the probe drug (concentration ratio of metabolite to parent form at reference time point) following the herbal medication period, compared to the baseline values. A. dahuricae radix significantly decreased CYP1A2 activity to 10% of baseline activity (95% CI: 0.05-0.21). S. radix also showed significant changes in CYP2C9 and CYP2E1 activities. Compared to baseline values, the metabolic activities of losartan were decreased to 71% (0.54-0.94). In addition, S. radix showed a 1.42-fold (1.03-1.97) increase in chlorzoxazone metabolic activity. However, CYP activities were not meaningfully influenced by A. tenuissima radix. Changes in certain CYP activities were observed after the administration of S. radix and A. dahuricae radix in healthy volunteers. Therefore, herbal medicines containing S. radix or A. dahuricae radix are candidates for further evaluation of clinically significant CYP-mediated herb-drug interactions in human beings.