Spontaneously Reported Hepatic Adverse Drug Events in Korea: Multicenter Study

Hepatic adverse drug reactions (ADRs) to certain drugs may differ within each country, reflecting different patterns of prescription, socioeconomic status, and culture. The purpose of this study was to assess the suspected cause of hepatic ADRs using the spontaneously reported pharmacovigilance data from Korea. A total of 9,360 spontaneously reported adverse drug events (ADEs) from nine Pharmacovigilance Centers were analyzed. Risk of hepatic ADEs was assessed by calculating the reporting odds ratio (ROR). Of the 9,360 cases, 567 hepatic ADEs were reported. The most frequently prescribed drug classes inducing hepatic ADEs were anti-tuberculotics, cephalosporins, valproic acids, penicillins, quinolones, non-steroidal anti-inflammatory drugs (NSAIDs), anti-viral agents, and statins. ROR values were especially high in anti-tuberculosis drugs, systemic antifungal drugs for systemic use, anti-epileptics, propylthiouracil, and herbal medicines. Underlying diseases such as tuberculosis (6.9% vs 0.9%), pneumonia (4.9% vs 1.7%), intracranial injury including skull fracture (4.5% vs 0.9%), HIV (3.4% vs 0.4%), subarachnoid hemorrhage (2.8% vs 0.5%), and osteoporosis (2.4% vs 1.4%) were significantly more common in hepatic ADE group. In conclusion, anti-infective drugs, anti-epileptics, NSAIDs and statins are the most common suspects of the spontaneously reported hepatic ADEs, in Korea. Careful monitoring for such reactions is needed for the prescription of these drugs.

Development of a List of Potentially Inappropriate Drugs for the Korean Elderly Using the Delphi Method / 대한의료정보학회지

OBJECTIVES: This study aimed to develop a list of potentially inappropriate drugs for the elderly in Korea using the Delphi technique. METHODS: A Delphi evaluation with a two-round survey was used to reach a consensus on the criteria for inappropriate medications for the elderly in an outpatient setting. The expert panel consisted of 7 family medicine specialists, 3 psychiatrists, 1 neurologist and 3 clinical pharmacists. The level of inappropriateness was determined by considering clinical importance of the risk and availability of alternative therapy, and was rated on a scale of 1 (very low) to 4 (very high). The drugs were categorized into three groups. The first group (Group 1) was drugs that should be avoided. The second (Group 2) was for drugs that need to be monitored. And the third (Group 3) was for drugs with a low level of risk. RESULTS: We took a list of 60 ingredients for drugs and created a list of 57 potentially inappropriate ingredients for the elderly, independent of diagnosis. Forty-two drugs were classified as Group 1. 13 drugs were classified as Group 2. And 2 drugs were classified as Group 3. Ninety-three drugs were potentially inappropriate for the elderly with 29 diagnoses. Groups 1, 2, and 3 included 63, 28, and 3 drugs, respectively. CONCLUSIONS: This study is an important development of a list of drugs potentially inappropriate for the elderly in Korea. The application of this list may be useful for identifying potentially inappropriate medication uses and decreasing drug-related problems.

Therapeutic Efficacy of Alendronate for Glucocorticoid Induced Metabolic Bone Disease in Children with Nephrotic Syndrome

PURPOSE: Children with nephrotic syndrome(NS) are under high risk for metabolic bone disease(MBD) as a complication of long-term glucocorticoid therapy. We prospectively evaluated the effect of oral bisphosphonate(alendronate) therapy in children with NS, which has proven efficacy in adult patients with glucocorticoid induced MBD. METHODS: Among 58 children with NS, aged 5 to 8 years and having a disease duration of more than 2 years, 30(51.7%) were enrolled to meet the selection criteria, less than -1.0 Z- scores of lumbar spine bone mineral density(BMD) by dual energy X-ray absorptiometry (DEXA). These 30 children were divided into three groups and each were assigned to receive alendronate, calcitriol, and no-medication, respectively for one year. Lumbar spine BMD was followed up every 6 months and the biochemical indexes were measured before and 1 year after the treatment. There were no significant difference among groups with respect to the average age, the initial BMD, and the cumulative steroid doses. Analysis of the treatment efficacy was done by the % change of BMD and by the changes in Z-scores of lumbar spine BMD. RESULTS: Mean age and disease duration of patients at the initial lumbar spine BMD evaluation was 7.4+/-1.7 years and 2.2+/-1.2 years, respectively. Twenty-three of 30 children(76%) had osteopenia, and seven(23%) had osteoporosis. There was no difference in the biochemical values among the groups, before and 1 year after the treatment(P<0.05). Twenty two children(73.3%) with frequent relapsing or steroid dependant NS had more frequent MBD, compared to the 8 children(26.6%) with infrequent relapsing NS. The one year % changes of BMD were 8.56 in alendronate group, 5.79 in calcitriol group, and 1.9 in no-medication group. The changes in Z-score of lumbar spine BMD increased in the alendronate group and the calcitriol group, but not in the no-medication group. One year % changes of BMD were different among groups(P=0.0002). Significant differences were found between the alendronate and the no-medication group, and between the calcitriol and the no-medication group(P< 0.05). There was no difference between the alendronate and the calcitriol group. No serious adverse effect was observed in the alendronate group. CONCLUSION: Children with NS receiving high dose steroids are under the high risk of BMD and should undergo regular BMD evaluation. Z-score of lumbar spine BMD was a useful parameter in diagnosing low bone mass in children. Alendronate weekly oral therapy was effective and relatively safe in increasing the lumbar spine BMD in children with NS having steroid induced MBD.

Pattern of Asthma Management by Primary Physicians in Seoul / 결핵

BACKGROUND: Asthma is one of the most prevalent diseases in Korea. Although the guidelines of asthma management were reported in Korea, the present pattern of asthma management by primary physicians has not been studied. The purpose of this study is to elucidate the pattern of asthma management by primary physicians. METHODS: In November 2002, 710 primary physicians specializing in internal medicine in Seoul, Korea were provided with two scenarios of asthmatic patients, one mild and the other severe. By mail or interview, the physicians were asked several questions about their present pattern of asthma management for the patients in each scenario. RESULTS: Among 710 primary physicians, we obtained the answers from 325 physicians (response rate 46%). The most preferred prescription was oral theophylline. 71% and 81% of the physicians answered that they would prescribe oral theophylline for the mild and severe asthmatics, respectively. The next prescription preferred were mucolytics and oral beta2-agonist, in that order. However, 36% and 56% of the physicians answered that they would prescribe inhaled steroids for the mild and severe asthmatics, respectively. Among diagnostic tests, physicians preferred pulmonary function test to the rank next tochest radiography. CONCLUSION: The primary physicians in Seoul prefer oral bronchodilators to inhaled steroids in asthma management. More efforts should be made to reduce the difference between the present pattern of asthma management by primary physicians and the asthma guidelines.

A Randomized, Double-Blind, Placebo-Controlled Trial of Early Ursodeoxycholic Acid Administration for Prevention of Total Parenteral Nutrition-Induced Hepatobiliary Complications / 대한소아소화기영양학회지

PURPOSE: Ursodeoxycholic acid (UDCA) is known to decrease hepatic injury by promoting the biliary secretion of retained toxic endogenous bile acids in hepatobiliary diseases complicated by total parenteral nutrition (TPN). However, most studies have focused on treatment for complications after TPN. We investigated the preventive role of early administration of UDCA in TPN-induced hepatobiliary complications by a randomized, double-blind, placebo-controlled trial. METHODS: Between May 2000 and May 2002, thirteen patients, who were given TPN more than 10 days in the hospital, were assigned randomly to two groups. One was the case group (7 patients) who were given UDCA simultaneously with TPN regimen, and the other, the control group (6 patients) who were given placebo. Their age ranged from 1 day to 13 years. They were affected with diseases impossible for enteral nutrition, such as prematurity, cerebral palsy, chronic diarrhea, anorexia nervosa, pancreatitis, and cyclic vomiting. The duration of TPN ranged from 10 to 70 days. Hematologic parameters including liver function test were measured at regular intervals, and the duration, composition, administration rate, total calorie of TPN were recorded. The serum levels of total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase were compared between groups after cessation of the study. RESULTS: The autoregressive coefficient of the control group was 0.4419 (p=0.0651) in bilirubin, -0.0431 (p=0.7923) in AST, 0.2398 (p=0.2416) in ALT, and 0.2459 (p=0.1922) in alkaline phosphatase by mixed procedure model when the parameters were referred to the case group. CONCLUSION: The serum level of total bilirubin did not increase in comparison with that of the control group, but statistically insignificant, when both TPN and UDCA were administered simultaneously from the beginning.

The Comparative Study of Effect on Speech before and after Orthognathic Surgery of Patients

0.05).3. The soft palate was displaced posteriorly superiorly after immediated operative period and remained to its changed position at 6 months postoperatively(p<0.05). ANS-PNS-SPT angle increasing, PPU-PPPo distance narrowing was showed after surgery, and remained its appearance 6 months postoperatively(p<0.05). 4. There were significant changes in formant value and squre diagram of vowel sound after the orthognathic surgery and the follow-up period. There were significant changes in /sound and posterior tongue sound. 5. The posterior movement of tongue and the posteriosuperior movement of soft palate was correlated with mandibular setback amount after orthognathic surgery. On the vowel squre diagram, the author found that the place of articulation after operation moved downward, backward, upward. 6. In assessing speech abnormalities, dental occlusion should be considered as a contributing factor. The vast majority of subjects with preoperative misarticulations eliminated or reduced their errors following orthognathic surgery. There was significant difference in speech impovement between pre- and post-operation.

Medical Therapy in Children with Persistent Hyperinsulinemic Hypoglycemia of Infancy(PHHI)

PURPOSE: Persistent hyperinsulinemic hypoglycemia of infancy(PHHI), which is characterised by inappropriate insulin secretion in spite of hypoglycemia, needs urgent treatment to prevent cerebral hypoglycemic damage. Although pancreatectomy is the treatment of choice for PHHI, there are several complications which follow treatment. We suggest that aggressive medical therapy, when effective, is preferable to partial pancreatectomy. METHODS: We evaluated 8 patients with PHHI admitted to the Department of Pediatrics, Samsung Medical Center from November 1996 to January 1999. Children with hypoglycemia in the range of 3-50mg/dl were included. Octreotide was administered at dosage of 100-150 microgram/day. When the patients did not respond to octreotide, diazoxide and nifedipine were given in addition. RESULTS: In four of eight patients, octreotide was discontinued after 15 to 165 days. One patient was given diazoxide instead. The remaining 3 patients are still being treated with octreotide. CONCLUSION: We believe that maximum effort should be made to attain euglycemia with medication, and pancreatectomy should be reserved for patients in whom these measures fail to restore normoglycemia.