류마티스 관절염 치료 시 비스테로이드성 소염제 단독 , 위장관 부작용 예방 약제 병용 투여 및 COX - 2 특이 억제제 사용의 한국 비용 - 효과 분석

윤형란(Hyung Ran Yun),(Michael Corzillius),김성윤(Seong Yoon Kim),배상철(Sang Cheol Bae) 대한내과학회 2001 대한내과학회지 Vol.60 No.6

N/A Background : Nonsteroidal anti-inflammatory drugs (NSAIDs) are used in nearly every patient with rheumatoid arthritis (RA) but their use can be associated with gastrointestinal (GI) side effects, which may be prevented with prophylactic prescription of misoprostol and omeprazole. Recently marketed COX-2 specific inhibitor (COX-2) affords protection against gastropathy. This study was performed to assess Korean cost-effectiveness of NSAIDs, NSAIDs with co-treatments to prevent GI toxicity, and COX-2 in the treatment of RA, and compare it with American cost-effectiveness analysis. Methods : Markov (state-transition) models were used to simulate a cohort of RA patients with approximately 2.5:1 female to male ratio and 50 years, taking disease modifying antirheumatic drugs, low dose steroid (prednisone ≤10 mg/day) and one of the following strategies: 1) NSAIDs without prophylaxis, 2) NSAIDs with misoprostol, 3) NSAIDs with proton pump inhibitor (PPI), or 4) COX-2. Data on incidence, USA cost and consequences of adverse events from treatments were taken from the literature. Treatment costs of adverse events in Korea were calculated based on each disease code. Health effects were expressed as quality-adjusted life years (QALYs). Sensitivity analyses of probability of GI complication and cost were performed. Costs and health outcomes were discounted at a rate of 3% per year. Results : Among the strategies to prevent GI toxicity, PPI was the most cost-effective strategy in Korea and COX-2 was in USA, respectively. The incremental C/E (cost/effectiveness) ratio between PPI and no prophylaxis was 38,068×103￦/QALY (32,044$/QALY) in Korea. The incremental

류마티스 관절염과 전신성 홍반성 루푸스가 공존하는 Rhupus 증후군의 임상적 고찰

윤형란 ( Hyung Ran Yun ),전재범 ( Jae Bum Jun ),이명호 ( Myong Ho Lee ),이혜순 ( Hye Soon Lee ),이지현 ( Ji Hyun Lee ),김태환 ( Tae Hwan Kim ),정성수 ( Sung Soo Jung ),이인홍 ( In Hong Lee ),배상철 ( Sang Cheol Bae ),유대현 ( Dae 대한류마티스학회 1999 대한류마티스학회지 Vol.6 No.4

Objective: This study was designed to evaluate clinical features of 20 patients with rhupus syndrome and compare its characteristics with systemic lupus erythematosus(SLE) and rheumatoid arthritis(RA). Methods: Patients considered to have rhupus who met the American College of Rheumatology(ACR) 1997 and 1987 revised criteria for SLE and RA, respectively and age, sex, and disease duration matched 64 patients with RA and 56 patients with SLE were selected for comparison. Results: Twenty patients were all female and their mean age was 43.7±9.6 years (range 25~68). They had 5.5 ACR criteria for RA and 5 criteria for SLE. The mean age at onset of RA was 35.2±10.5 years(19~63) and that of SLE was 38.2±10.0 years(20~63), giving a mean interval between the diagnoses of the two diseases of 3.0±5.7 years (14~(-6)). There were 2 patients(10%) with rheumatoid nodule, and 18 patients(90%) with rheumatoid factor, and 16 patients(80%) with bony erosions on hand or wrist joints. The criteria for SLE included malar rash(20%), discoid rash(0%), photosensitivity(30%), oral ulcer(45%), arthritis(100%), serositis(35%), renal disorder(15%), neurologic disorder(0%), hematologic disorder(100%), immunologic disorder(90%), and positive antinuclear antibody(100%). Anti-dsDNA was more than 7.0U/ml in 15 patients(75%). The patients with rhupus syndrome showed lower amount of 24 hour urine protein, more severe radiologic involvement, younger age at onset of arthritis, higher titer of rheumatoid factor, lower frequency of low C3, and less complicated clinical course when compared with the patients with SLE(p<0.05). More frequent anemia, Rayanud`s phenomenon, and more complicated clinical course in rhupus when compared with the patients with RA(p<0.05), but the radiologic stage of hand and wrist was similar between rhupus and RA. Conclusion: Rhupus syndrome showed something different clinical characteristics and clinical course when compared with SLE and RA.

역류성 식도염 치료에 대한 양자펌프억제제와 ranitidine 사용의 비용 - 효과 분석

윤형란(Hyung Ran Yun),정훈용(Hwoon Yong Jung),박효진(Hyo Jin Park),배상철(Sang Cheol Bae) 대한내과학회 2002 대한내과학회지 Vol.62 No.5

목적: 역류성 식도염은 만성적인 경과를 보이는 비교적 흔한 질환 중의 하나로, 치료를 위해 산 분비 억제제인 H2-수용체 길항제가 사용되었으나 염증이 심한 경우에는 그 효과가 만족스럽지 못하고 재발의 빈도가 높아 강한 산 분비 억제작용을 갖는 양자펌프억제제 (proton pump inhibitors, PPI)가 사용되고 있다. 이에 저자들은 우리나라 현 의료 환경에서 역류성 식도염 치료에 PPI와 H2-수용체 길항제를 사용한 경우, 1예를 완치하는데 소요되는 비용과 decision analytic model을 이용하여 사회학적인 관점에서 비용-효과 분석을 시행하였다. 방법: 역류성 식도염 환자 1예를 완치시키는데 소요되는 1년간의 비용을 비교하기 위해 PPI와 라니티딘으로 8주간 초치료 후 절반 용량으로 12주간 유지요법을 시행한 경우의 총 소요되는 비용을 계산하였다. 대상 환자는 Markov (state transition) 모델을 사용하여 역류성 식도염 코호트를 가정하였다. 이 코호트의 모든 환자는 1. 하루 20 mg의 PPI 2. 하루 300 mg의 라니티딘 투여 중 한 가지의 치료를 받고 약제에 대한 반응에 따라 상태가 변화하는 것으로 가정하였고, 치료 시작 후 5년 간 관찰하는 것으로 가정하였다. Markov state의 결과는 1) 치료 후 역류성 식도염의 증상이 없는 상태 2) 유지 요법 후 재발한 상태 3) 고용량 (하루 40 mg의 PPI, 600 mg 라니티딘)의 약제나 위장관운동촉진제 병용 치료에 호전되었다가 유지요법 후 재발한 상태 4) 고용량의 약제나 위장관운동촉진제 병용 치료에 호전되지 않아 더 이상의 치료를 하지 않는 상태 5) 수술 후 호전된 상태 6) 수술 후에도 증상이 지속되는 상태 7) 수술로 인한 사망 등으로 하였다. 모델에서 사용한 자료는 1966년부터 2001년까지의 MEDLINE을 이용한 의학 문헌의 면밀한 검토에 기초하였다. 비용은 직접 의료 비용을 사용하였고, 건강에 미치는 영향은 질보정수명 (Quality-adjusted life years, QALYs)으로 표시하였고 할인율은 3%를 적 용하였다. 각 치료 방법의 부작용 빈도의 범위와 가격, 할인율, 의료비, 효용 등에 대한 민감도 분석을 시행하였다. 결과: 역류성 식도염 1예 완치에 소요되는 연평균 비용은 PPI를 초치료로 사용한 경우 475,836원, 라니티딘을 초치료로 사용한 경우는 1,064,704원이다. 기본 분석에서 QALYs는 PPI 4.81, 라니티딘 4.26이었고, 가격은 PPI 155,238원, 라니티딘 214,781원이었다. 결과적으로 라니티딘은 PPI보다 가격도 비싸고 QALYs도 낮아, 역류성 식도염 치료에서 PPI가 라니티딘 보다 우월한 치료법이다. 결론: 한국의 의료 환경에서 역류성 식도염의 치료에 PPI가 라니티딘에 비해 비용-효과적이므로 역류성 식도염의 치료에 PPI를 사용하는 것이 한정된 의료자원을 효과적으로 사용하는 방법일 것으로 생각된다. Background: The aim of this study was to compare the cost-effectiveness of proton pump inhibitors (PPI) and ranitidine in gastroesophageal reflux disease (GERD) in Korea. Methods: We assessed the cost-effectiveness two ways. First, mean costs for the complete healing of one patient with GERD within one year were calculated. Second, Markov (state-transition) models were used to simulate a cohort of patients with GERD, taking one of following strategies for 5 years:1) PPI (rabeprazole 10 mg, omeprazole20 mg, or lansoprazole 30mg), 2) ranitidine 300mg per day. Data on healing rate, relapse rate, surgical complication rate, success rate of surgery were taken from the literature. Direct medical costs of each strategy and surgical complications were calculated. Health effects were expressed as quality-adjusted life years (QALYs). Sensitivity analyses using various ranges of probability of healing rates and costs were performed. Costs and health outcomes were discounted at a rate of 3% per year. Results: The mean costs for complete healing of one case within one year was ￦475,836 in PPI and ￦1,064,704 in ranitidine, respectively. In the base case analysis using Markov model, the treatment costs of PPI were ￦155,238 and ￦214,781 in ranitidine and the effects were 4.81 QALYs and 4.26 QALYs, respectively; PPI strategy was more effective and less costly than ranitidine strategy. The sensitivity analyses using varying ranges of probability, cost, discount rate and utility were robust. Conclusion: PPI was superior to ranitidine in terms of cost-effectiveness in the treatment of GERD.(Korean J Med 62:504-512, 2002)

약물 중독 시 위 세척에 의한 산 - 염기 평형 및 전해질의 변화

윤형란(Hyung Ran Yun),손동현(Dong Hyun Sohn),이창범(Chang Bum Lee),이재웅(Jae Woong Lee),양석철(Suck Chul Yang),한동수(Dong Soo Han),손주현(Ju Hyun Sohn),김순길(Soon Kil Kim),김호중(Ho Jung Kim) 대한내과학회 1998 대한내과학회지 Vol.54 No.4

N/A Objectives: There is little information on the imbalance of electrolyte and acid-base metabolism associated with gastric lavage in acute drug intoxication patients. This study was aimed to analyze the acid-base and electrolyte abnormalities associated with gastric lavage in acute drug intoxication patients. Methods: We studied 24 acute drug intoxication patients who had performed gastric lavage with 10 liters of 0.9% NaC1. Electrolyte parameters and arterial blood gas analysis were carried out before and after gastric lavage. Results: After gastric lavage, acidosis was reduced in general. But there was no significant change in pH (7.34±0.02 vs. 7.38±0.15, p=NS). In acid-base balance, the mixed form of metabolic acidosis and respiratory acidosis was reduced from 7 to 2 cases, and the simple form of respiratory acidosis was reduced from 3 to 1 case. In contrast, normal form was increased from 5 to 7 cases and the simple form of metabolic acidosis was increased from 2 to 6 cases. In electrolyte parameters, serum sodium was reduced significantly (145±1.0 mEq/L vs. 141±0.8 mEq/L, p<0.01), but there was no case of significant hyponatremia (<135mEq/L). Bicarbonate level (20±1.1 mEq/L vs. 22±0.9 mEq/L, p< 0.05) and anion gap (19±1.6 mB vs. 13±1.3 mEq/L, p< 0.01) showed significant change. But, blood levels of potassium (3.6±0.1 mEq/L vs. 3.8±0.1 mEq/L, p=NS), chloride (106±0.6 mEq/L vs. 106±0.6 mEq/L, p=NS) and F'aCO2 (36±1.mmHg vs. 37±1.5 mmHg, p=NS) were no significant change before and after gastric lavage. Conclusions: Gastric lavage with 10 liters of 0.9% NaC1 in acute drug intoxication patients did not show clinically significant changes in electrolytes and acid-base balance.

류마티스 관절염 치료시 저용량의 코르티코스테로이드, 비스테로이드성 항염제 사용의 비용-효과 분석

오승일 ( Seung Il Oh ),윤형란 ( Hyung Ran Yun ),배상철 ( Sang Cheol Bae ) 대한류마티스학회 2002 대한류마티스학회지 Vol.9 No.4

Objective: Low dose corticosteroids (steroid) (≤10 mg/day prednisolone) in the treatment of RA is controversial. Although it is effective and possibly disease modifying, concerns exist about potential adverse events (AEs). We reported steroid were dominant compared to nonsteroidal anti-inflammatory drugs (NSAIDs) in terms of cost and effectiveness (Arthrtis Rheum 41:S249, 1998). However, those works were done in the US and the US health care system is different from the Korean. Therefore we assessed costs and health effects of steroid compared with NSAIDs in Korea. Methods: Markov (state-transition) models were used to simulate a cohort of RA patients with 50 years, taking disease modifying anti-rheumatic drugs and either steroid or NSAIDs. The regimens were assumed to be equally effective for the control of RA. Data on incidence and consequences of AEs from steroid and from NSAIDs were taken from the literature. Direct medical costs were measured in 2000 Korean Won; health effects expressed as quality-adjusted life years (QALYs). Sensitivity analyses were performed including best-case scenarios (0.5×AE rate) and worst-case scenarios (1.5×AE rate). Results: In the base-case analysis, the incremental C/E ratio between steroid and NSAIDs was 1,423×103 Won/QALY (1,197 US$/QALY). The sensitivity analyses of AE rate, using best-case and worst-case scenarios showed that the result was sensitive to each combination of AE rate. In contrast, the sensitivity analyses of costs, age and utilities were robust. Using misoprostol or omeprazole prophylaxis with NSAIDs would make steroid dominant. Compared to NSAIDs with cyclooxygenase 2 (COX-2) specific inhibitor, the incremental C/E ratio between COX-2 specific inhibitor and NSAIDs was 139,322×10(3) Won/ QALY (117,274 US$/QALY). Conclusion: Steroid are more cost-effective than NSAIDs in the long-term treatment of RA in Korea.

한국인에서 Adult Onset Still`s Disease의 임상상과 예후 인자에 관한 연구

조균석 ( Kyoon Seok Cho ),유대현 ( Dae Hyun Yoo ),윤형란 ( Hyung Ran Yun ),이명호 ( Myong Ho Lee ),이제경 ( Je Kyung Lee ),심승철 ( Seung Cheol Shim ),장대국 ( Dae Kook Chang ),유태석 ( Tae Seok Yoo ),고희관 ( Hee Kwan Koh ),김태 대한류마티스학회 1998 대한류마티스학회지 Vol.5 No.1

Objective: This study was undertaken to review the disease course, clinical and laboratory manifestations, prognosis and treatment of adult onset Still`s disease (AOSD) in Korea. Methods: Thirty-two patients with AOSD were enrolled from 1986 to 1997 in Hanyang University Hospital. Diagnosis of AOSD was based on the criteria proposed by Yamaguchi. We classified the disease course into self-limited, intermittent, or chronic disease course. Results: Twenty-four (75%) patients were female. Skin rash occurred in 28 (88%) patients, lymphadenopathy in 8 (25%), hepatomegaly in 4 (13%), and pericarditis in 2 (6%) out of 32 patients. The most commonly affected joints were knee joints (88%). Elevated LDH was seen in 18 (60%) patients and decreased CK in 17 (61%) patients. Rheumatoid factor was detected in 4 (13%) patients and ANA in 12(38%) patients. Anemia (Hb<10 g/dL) was seen in 13 (41%) patients and hypoalbuminemia (<3.5 g/dL) in 14 (52%) patients. Elevated ferritin (≥300 ng/mL) level was seen in 23 (79%) patients. Twenty-five (78%) patients had elevated serum transaminase. Bone marrow studies were performed in 16 patients. Nine out of 16 patients showed hyperplasia of the myeloid series and 2 patients displayed the features of a hemophagocytic syndrome. The mean duration of follow up of 32 patients was 32 months (range 3-108). Eight (27%) patients had a self-limited, 9 (30%) an intermittent, and 13 (43%) a chronic disease course. The hypoalbuminemia was significantly associated with an intermittent or chronic disease group(p<0.05). Thirty-two patients received systemic corticosteroids and 21 patients received single or combination of disease modifying antirheumatic drugs. Conclusion: We found that hypoalbuminemia at presentation was significantly associated with an unfavorable outcome, intermittent or chronic disease group. The clinical manifestations and disease course of AOSD in Korea were similar to those previously reported in other countries except significantly lower incidence of lymphadenopathy, hepatomegaly, and pericarditis.

고용량의 면역 글로불린 주사 치료로 호전된 Salmonella 그룹 D 균혈증과 골수섬유증을 동반한 전신성 홍반성 루푸스

이혜순 ( Hye Soon Lee ),배상철 ( Sang Cheol Bae ),윤형란 ( Hyung Ran Yun ),이지현 ( Ji Hyun Lee ),정유성 ( Yu Seong Jeong ),배윤상 ( Yun Sang Bae ),김태환 ( Tae Hwan Kim ),전재범 ( Jae Bum Jun ),정성수 ( Sung Soo Jung ),이인홍 ( I 대한류마티스학회 2000 대한류마티스학회지 Vol.7 No.1

A 22-year-old woman presented with fever and pancytopenia. One year ago, she was diagnosed as Salmonella group D bacteremia and myelofibrosis associated with SLE at another hospital. She was placed on high dose steroid, however, there was no improvement. Two months ago, she was diagnosed as recurrent Salmonella group D bacteremia. After admission to our hospital, she was placed on intravenous antibiotics and high dose intravenous immunoglobulin. A significant improvement in laboratory and clinical condition occurred and bone marrow biopsy showed complete resolution of fibrosis. We report a case of SLE with myelofibrosis and recurrent Salmonella group D bacteremia.

급성 췌장염 예후인자로서 APACHE III 점수의 임상적 유용성

박준용,박경남,한동수,이민호,조윤주,최호순,손주현,함준수,문광호,기춘석,윤형란,양석철 대한소화기학회 1998 대한소화기학회지 Vol.32 No.4

Background/Aims: The various prognostic parameters for predicting the severity and prognosis of acute pancreatitis were used, but these were unfit for clinical utilization. We evaluated a clinical utility of the APACHE III score as a prognostic parameter of acute pancreatitis. Methods: We conducted a retrospeetive review of 40 patients with acute pancreatitis. We compared APACHE III score with Ranson's score, Glasgow's score, CT grading, the severity of complication, and hospital day. Results: The sensitivity of these prognostic parameters for predicting the severity of acute pancreatitis was 69.57% in APACHE III score ($gt;23), 47.83% in Glasgow's score ($gt;3), 39.13% in Ranson's score ($gt;3) and 73.91% in CT pading ($gt;3). The specificity was 64.71% in APACHE III score, 76.41% in Glasgow's score, 64.71% in Ranson's score and 41.18% in CT grading. The positive predictive value of APACHE III score in predicting the severity of acute pancreatitis was 72.73%. We found a good correlation between the severity of complication and APACHE III seore (r =0.607). The severity of complication is poorly correlated with other parameters: Glasgow's score (r=0.387), Ranson's score (r=0.402) and CT grading (r =0.273). There was not statistically significant difference in the APACHE III score (32.41 vs. 22.94, p=0.089) between the groups of alcohol (n =22 cases) and biliary (n =16 cases) associated pancreatitis. Conclusions: The APACHE III score showed a higher sensitivity and specificity than the other prognostic parameters and excellent correlation with the severity of complication and clinically initial systemic states in the acute pancreatitis.