차이기반회귀모형을 이용한 이상치 판별

박천건(Chun Gun Park) 한국데이터정보과학회 2018 한국데이터정보과학회지 Vol.29 No.2

다중선형회귀모형에서 이상치는 통계적 추론에 상당한 악영향을 준다. 지금까지 이상치가 회귀분석에 미치는 영향을 회피하고자 다양한 이상치 탐색 기법들이 연구되어 왔다. 이러한 노력에도 불구하고 모형선택과 이상치가 복합적 문제로 발생되면 회귀분석에 상당한 어려움을 주게 된다. 본 연구는 차이기반회귀모형을 소개하고 모형선택에 어느 정도 자유로운 이상치 탐색 알고리즘을 소개한다(Park과 Kim, 2017). 또한 Park과 Kim (2017)이 제시한 이상치 탐색 알고리즘은 “회귀모형에 이상치가 항상 존재해야 한다는 가정”이 있다. 이러한 가정의 약점을 극복하고자 본 연구는 단일 변수에서 강건하게 이상치를 탐색할 수 있는 방법을 기존 알고리즘에 추가하고 모의실험 결과를 제시한다. In a multiple linear regression model, outliers have a significant adverse effect on statistical inference. So far, various outlier detection techniques have been studied in order to avoid the effects of abnormal values on regression analysis. In spite of these efforts, if the model selection and the anomaly occur as a complex problem, the regression analysis becomes difficult. This study introduces the difference based regression model and the somewhat free outlier search algorithm for model selection (Park and Kim, 2017). In addition, Park and Kim (2017) proposed the algorithm for outlier detection in regression that is under “assumption that outliers always exist in the model”. To overcome the weakness of the assumption, this study adds the robust method of outlier detection for single variable to the algorithm and propose simulation studies.

골수이식 후 발생한 출혈성 방광염 환자에서 Polyomavirus의 검출 양상

박민정,강희정,신동훈,이규만,이동건,최정현,김춘추 대한임상병리학회 2000 대한임상병리학회지 Vol.20 No.6

전기분해에 의한 계면활성제 함유 폐수처리에 관한 연구

이춘식,정병윤,하태명,박현건 진주산업대학교 농업기술연구소 2001 農業技術硏究所報 Vol.14 No.-

This study was carried out to investigate the purification effect of wastewater included LAS by electrolysis treatment system. Wastewater included LAS treated electrolysis treatment process, temperature of inner treated system were high than those of this raw wastewater, temperature change was electrolysis oxidation of LAS wastewater both cathode and anode. Electrolysis oxidation was oxidized LAS by oxidants of chlorine and ozone, on the time, according to the result development of treated efficiency on electrolysis contact time.

호중구 감소성 발열환자에게 경험적으로 투여한 Teicoplanin의 효과

이동건,임동석,최수미,박선희,유진홍,최정현,민우성,신완식,김춘추 대한감염학회 2004 감염과 화학요법 Vol.36 No.2

목적 : 호중구감소성 발열 환자에게 경험적으로 teicoplanin을 투여할 때의 효과를 알아보고자 전향적 연구를 시행하였다. 방법 : 2003년 7월부터 12월까지 가톨릭조혈모세포이식센터에 입원하여 항암치료 혹은 조혈모세포이식을 시행하고 호중구감소성 발열이 있는 환자 중 초기 항균요법에 반응이 없어 경험적 teicoplanin 투여가 필요한 49명을 대상으로 A, B 제조회사에서 제공한 teicoplanin을 무작위로 어느 한 쪽 치료군에 배정하여 투여하였다. 용량은 첫날 400㎎ 부하용량을 정맥내 bolus로 투여하고 매 24시간마다 200㎎ 유지용량을 투여하였다. 결과 : A군 27명, B군 22명이 연구에 참여하였고 대부분의 환자가 신독성이 있는 약제를 병용하고 있었다. A군 8명, B군 7명에서 그람양성균이 동정되었고, teicoplanin에 대한 내성률은 A군 22.2%, B군 28.6%로 유의한 차이는 없었다(P=1.00; 0.61<95%CI<1.95). 미생물학적 확인 감염이 있었던 환자 중 평균 53.3%에서 완치 혹은 개선의 반응이 있었고 양 군간 유의한 차이는 없었다(A군 4명 [50.0%], B군 4명 [57.1%], P=1.00; 0.29<95%CI<2.60). 미생물학적 제거율은 평균 62.5% (A군 55.6%, B군 71.4%)이었고 그 외 미생물학적 효과는 A군에서 제거 후 재발 2명(22.2%), 내성 2명(22.2%)이었고 B군에서 각각 0명(0.0%), 2명(28.6%)이었으며 양 군간 유의한 차이는 없었다(P=0.28). 발열기간(P=0.89), teicoplanin 사용기간(P=0.47) 및 전체적인 사망률(P=1.00; 0.78<95%CI<1.24)도 양 군간 유의한 차이는 없었다. 이상반응 중 신독성은 16.3% (A군 18.5%, B군 13.6%)에서 나타났고 양 군에 차이는 없었으며(P=0.72; 0.39<95%CI<3.51), 신기능 이상과 관련있는 약제를 적어도 2개 이상 병용하고 있었다. 피부발진은 A군에서 1명, B군에서 3명 발생하였다(P=0.31; 0.93<95%CI<1.34). 결론 : 호중구감소성 발열환자에게 teicoplanin을 투여하였을 때 임상적 반응률은 평균 53.3%(A군 50.5%, B군 57.1%), 미생물학적 제거율은 평균 62.5%(A군 55.6%, B군 71.4%)이었고 두 제조회사간 차이가 없었고 이상반응도 양 군간 차이가 없었다. 앞으로 국내 호중구감소증 환자에서의 teicoplanin의 적정 용량, 용법 등을 알기 위한 집단 약동학 등의 연구를 시행할 예정이다. Background : This study was done to elucidate the efficacy of teicoplanin as the empirical treatment for febrile neutropenia. Methods : Patients were randomized to two groups according to pharmaceutical company (company A or B). Total of 49 patients (A, 27; B, 22) with neutropenic fever were studied prospectively for 6 months (Jul. 2003-Dec. 2003). Patients received 400 mg i.v. once, then 200 mg i.v. once daily. Results : Groups were matched for all demographic variables. Most of the patients were concurrently receiving nephrotoxic drugs. Gram positive microorganisms were isolated in 8 patients for A and 7 patients for B. Resistance rate against teicoplanin was 22.2% in A and 28.6% in B (P=1.0; 0.61 < 95% confidence interval [Cl] < 1.95). Among the patients with microbiologically documented infection, clinical cure or improvement was seen in 4 (50%) of 8 patients for A and 4 (57.1%) of 7 patients for B (P=1.00; 0.29 <95%CI <2.60). Bacteriologic efficacy was assessed as follows; elimination in 5 (55.6%), elimination with relapse in 2 (22.2%), resistance in 2 (22.2%) out of 9 gram-positive bacteria for A and 5 (51.4%), 0 (0.0%), 2 (28.6%) out of 7 bacteria for B, respectively (P=Q.28). There were no significant differences in duration of fever, duration of use of teicoplanin, and overall mortality. The incidence of nephrotoxicity and ototoxicity was not significant. Conclusion : For using teicoplanin as the empirical therapy for febrile neutropenia, the rate of clinical, microbiological response, and nephrotoxicity was 53.3%, 62.5%, and 16.3% respectively with no significant differences between the 2 preparations of teicoplanin. Supplementary evaluation on the adequate dose and duration of teicoplanin may be required.

국내 혈액질환 환자에서 침습성 진균 감염의 구제치료로서 Caspofungin의 효과와 안전성

최수미,박선희,이동건,최정현,유진홍,민우성,신완식,김춘추 대한감염학회 2005 감염과 화학요법 Vol.37 No.5

목적 : 본 연구에서는 국내 혈액질환 환자들에서 일차 항진균제를 부작용으로 인해 투여할 수 없거나, 일차 항진균제에 반응이 없는 침습성 진균 감염증의 구제치료로서 caspofungin의 효과와 이상반응에 대한 임상 경험을 소개하고, 예후인자를 분석해 보았다. 재료 및 방법 : Caspofungin은 첫날 70 mg, 이틀째 부터 50 mg을 하루 일회 투여하였고, caspofungin 종료시 그리고 종료 4주 후 반응을 평가하였다. 결과 : 총 55명의 환자가 분석에 포함되었고, 남자 32명, 여자 23명, 평균 나이는 38.2세(16-65세)였다. 기저 질환은 급성 백혈병 33명, 골수이형성 증후군 12명, 만성 백혈병 3명, 기타 7명이었다. 진균 감염은 확진 1명, 가능 5명, 추정 47명, 불확실 2명이었고, 감염 장소는 폐를 침범한 경우가 49명, 파종감염 6명이었다. 전체적으로 41.8% 환자에서 양호한 반응을 보였으며, 치료군, 치료후 기저질환의 상태, 침습성 진균 감염 진단시 호중구 감소증 여부, 스테로이드 등 면역억제제 사용 여부가 유의한 예후인자였다. 약제관련 이상반응은 14.5%에서 관찰되었고, 발열, 피부 발진, 간기능 저하 등으로 나타났다. 이중 4명에서 이상반응과 관련하여 투약을 중지하였고, 약제 중단 후 증상은 모두 호전되었다. Caspofungin 관련 신독성은 관찰되지 않았다. 결론 : Caspofungin은 국내 혈액질환 환자에서 침습성 진균 감염증의 구제치료에 효과적으로 안전하게 사용될 수 있겠다. 최근 여러 항진균제들이 개발되어 임상에 도입되고 있는 바, 항진균 작용 범위, 독성, 약역동학적 특성, 비용-효과면 등을 고려하여 환자별로 직절한 항진균제를 선택하도록 해야 할 것이다. Background : Invasive fungal infection (IFI) is an important cause of morbidity and mortality in patients with hematologic malignancy. Patients with IFI who fail to standard therapy have poor prognoses. We investigated the efficacy and safety of caspofungin (CAS) in Korean adults with hematologic diseases and IFI who did not respond to the conventional antifungal therapy. Materials and Methods : Patients with IFI refractory or intolerant to standard antifungal therapy received CAS 50 mg IV daily after 70 mg loading dose on day 1. Efficacy and safety of CAS were assessed in patients who received more than one dose. Favorable response [complete (CR) or partial (PR)] was defined as significant improvement of all clinical symptoms, signs, and radiologic abnormalities. Results : From Feb. 2004 to Feb. 2005, 55 patients who met the inclusion criteria were enrolled. There were 32 male and 23 female patients with mean age of 38.2 years (range, 16-65). Underlying diseases were acute leukemia (33 cases), myelodysplastic syndrome (12 cases), chronic myelogenous leukemia (3 cases), and other hematologic diseases (7 cases). Thirty-six patients were receiving chemotherapy and 13 patients were under hematopoietic stem cell transplantation (HSCT). The number of proven, probable, possible, and indeterminate IFI cases was 1, 5, 47, and 2, respectively. Conventional amphotericin B, intravenous itraconazole, and liposomal amphotericin B were administered for average of 14.9 days prior to administering CAS. Mean duration of CAS therapy was 12.8 days (range, 1-45). Twenty-three patients (41.8%) showed favorable responses (CR : PR=8 : 15) at the end of CAS therapy. Chemotherapy group, neutropenic state, remitted state of underlying disease, and no steroid therapy were significant prognostic factors for favorable response. Eight (14.5%) patients developed drug-related adverse events such as fever, skin eruption, and hepatic dysfunction which were reversible after discontinuation of CAS. Drug-related nephrotoxicity was not observed. Conclusion : On the basis of our investigation, CAS was effective and safe as a salvage therapy of refractory IFI or as an alternative for patients intolerant to standard antifungal agents.

동종 조혈모세포이식 후 발생한 치명적 홍역 폐렴 1예

백창렬,이동건,최정현,정현화,조유경,박훈준,이승훈,박윤희,이교영,민우성,김춘추,신완식 대한감염학회 2001 감염 Vol.33 No.4

As a result of the enlarging pool of unvaccinated children and young adults, there has been an increase in measles in our countries. In these situation, it has been reported that measles associated pneumoinia is easily complicated with fatal respiratory failure, espycially in immunocompromised patients. Herein we report the case of lethal measles pneumonia after allogenic hematopoietic stem cell transplantation in adults proven by autopsy. Recently, one case of measles was encountered in 39-year-old female patients after allogenic bone marrow transplanted case (chronic myelogenous leukemia), who progressed into interstitial pneumonia pattern, despite treatment including antibiotics, immunoglobulin. The patient died of giant cell pneumonia compatible with that of measles which was comfirmed in the section of necropsy lung specimen. (Korean J Infect Dis 33:301∼309, 2001)

조혈모세포이식 환자에서 침습성 진균 감염에 대한 이트라코나졸 액과 플루코나졸 시럽의 예방 효과 : 전향적, 무작위, 비교 임상시험

최수미,이동건,최정현,박선희,엄기성,김유진,김희제,민창기,유진홍,김동욱,이종욱,민우성,신완식,김춘추 대한감염학회 2005 감염과 화학요법 Vol.37 No.2

목적 : 조혈모세포이식 환자에서 호중구 감소 기간 동안 이트라코나졸 액(ITZS)과 플루코나졸 시럽(FCZS)의 진균 감염에 대한 예방 효과를 전향적으로 비교해 보고자 하였다. 재료 및 방법 : 2001년 8월부터 2002년 6월까지 가톨릭 조혈모세포이식센터에 입원하여 동종 조혈모세포이식을 받은 만 18세 이상의 환자들을 각각 ITZS와 FCZS군으로 무작위 배정하여 침습성 진균 감염 발생과 약제 관련 부작용을 전향적으로 조사하였다. 결과 : ITZS군에 40명, FCZS군에 38명이 배정되었고, FCZS군 환자의 평균 나이가 더 많았다. 시험 약제 평균투여기간은 ITZS군 16.4일, FCZS군 21.9일로 ITZS군이 더 짧았다. 이는 ITZS군에서 소화기 부작용으로 인한 약제 중단이 더 많았기 때문으로 보인다. 시험 약제 투여 후 총 빌리루빈 수치의 유의한 증가가 관찰되었으나, 약제 관련 부작용은 모든 환자에서 가역적이었다. 호중구감소 기간동안 표재성 진균 감염은 두 군에서 모두 발생하지 않았고, 침습성 진균 감염은 ITZS군 5명(12.5%), FCZS군 8명(21.1%)으로 FCZS군에서 많았으나, 통계학적으로 유의하지 않았고, 사망률에도 유의한 차이는 없었다. 결론 : 침습성 진균 감염에 대한 이트라코나졸 액과플루코라졸 시럽의 예방 효과에 유의한 차이는 없었으나, 앞으로 더 많은 환자를 대상으로 잘 짝지어진 대조군 연구가 필요할 것으로 보인다. 부작용 중 간독성과 관련하여 이식시 투여되는 여러 약제들과의 상호작용에 대한 연구도 필요할 것이다. Background : Though fluconazole is widely used for antifungal prophylaxis, it is ineffective against mould infections including Aspergillus species. Itraconazole has a broader spectrum than fluconazole but the capsule form shows erratic bioavailability in neutropenic patients. In this study, we compared itraconazole oral solution (ITZS) with fluconazole syrup (FCZS) for the prevention of invasive fungal infection (IFI) in allogeneic hematopoietic stem cell transplant recipients. Materials and Methods : Adults receiving allogeneic hematopoietic stem cell transplantation (HSCT) from september 2001 to June 2002, were randomly allocated to either the ITZS group or the FCZS group. We prospectively evaluated the safety and efficacy of each drug. Results : Out of 78 patients (40 patients in the ITZS group and 38 patients in the FCZS group) who were eligible for this study, 37 patients completed the course of prophylaxis without any evidence of IFI. The mean duration of prophylaxis was 16.4 days for the ITZS group and 21.9 days for the FCZS group (P<0.006). Drug-related adverse events occurred in 28 patients (70.0%) and 19 patients (50.0%) in the ITZS group and the FCZS group, respectively. Common adverse events of ITZS were nausea, vomiting, and diarrhea. Drug-related reversible hepatotoxicity occurred in 4 patients in the ITZS group. There was a significant elevation of total bilirubin level in the ITZS group. The incidence of suspected IFI occurred in 5 patients (12.5%) who received ITZS, compared with 8 (21.1%) who received FCZS (P=0.372). There were no proven IFIs or superficial (oral/vaginal) fungal infections in both groups. Overall mortality was not different between the two groups (2.5% in the ITZS group versus 5.3% in the FCZS group, P=0.610). Conclusion : ITZS and FCZS showed similar protection against IFI during pre-engraftment period. Poor tolerability due to gastrointestinal troubles of ITZS might limit its success as prophylactic therapy. Well matched controlled study with large number of patients will be required in the future.

조혈모세포이식 환자에서 발생한 Cytomegalovirus 질환의 특징 : 일개 대학변원에서 최근 10년간의 경험

최수미,이동건,박선희,김시현,김유진,민창기,김희제,이석,최정현,유진홍,김동욱,이종욱,민우성,신완식,김춘추 대한감염학회 2009 감염과 화학요법 Vol.41 No.1

Background : Studies on cytomegalovirus (CMV) diseases in Korean hematopoietic stem cell transplant (HSCT) recipients are lacking and do not reflect the recent trends of advances and changes. Therefore, we tried to analyze the clinical features of CMV diseases in HSCT recipients over the past 10 years at a tertiary university hospital in Korea. Methods : Retrospective review of medical records was done for all adult HSCT patients who received transplant at the Catholic HSCT Center from January 1998 to January 2008. Results : Forty-four cases (2.2%) of CMV diseases were identified. CMV pneumonia was diagnosed in 17 patients, retinitis in 16 patients, enterocolitis in 7 patients, esophagitis 1 patient, gastritis in 1 patient, duodenitis in 1 patient, and hepatitis in 1 patient. The median onset of symptom was 90 days after transplantation. Late CMV diseases accounted for 47.7%. CMV related death varied from 0 to 58.8% according to the involved organ. CMV retinitis was diagnosed relatively later in the course of transplantation mostly in patients who had chronic graft versus host disease (GVHD). On the contrary, CMV enterocolitis mainly occurred in patients who suffered from acute GVHD. The overall concurrent CMV reactivation was documented to be 63.6%: the concurrent CMV reactivation was observed only in 37.5% of patients with retinitis. Conclusions : We observed some differences in the pattern of CMV disease manifestation according to the involved organ and reconfirmed the fact that CMV pneumonia is the most common and fatal disease in HSCT recipients. Additionally, CMV retinitis was not uncommon in HSCT recipients. Since specific marker does not exist in predicting retinitis, regular ocular examination should be done thoroughly, especially in patients with chronic GVHD.

Purge & Trap-GC를 이용한 의약품 필름코팅 정제 중 잔류용제에 관한 연구

장준식,이명자,소유섭,문춘선,이주헌,박희라,김진숙,강경모,이선옥,방성연,유미자,유문균,금오성,이병욱 식품의약품안전청 2000 식품의약품안전청 연보 Vol.4 No.-

의약품은 약물을 생체에 적풋하기 위하여 유효성분의 효과가 언제나 일정하게 확보되고 사응에 편리하도록 만들어지는 것이므로 유효썽분 이외에 약효에 영향을 주지 않는 성분이 첨가되는 경운가 많다. 이 때 사용되는 용매들은 제피의 광택 및 건쪼시간의 단축 등을 위하여 휘발점이 낮을 용매들이 주로 사용되어진다. 본 연구는 의약품 필름코팅정제 중 잔류용매 4종(chlorofonr benzen, trichloro ethylen, 1,4-dioxane)에 대한 변형된 pirge & trap-GC 장치를 이용한 동시분석방법을 개발하였으며, 각 표준품의 RSD 값은 chloroform 3.03%, benzen 3.17%, trichloroethylen 3.69% and 1,4-dioxane 3.41%였다. 또한 시중 유통중인 의약품 50종에 대하여 잔류웅매 양을 측정하였으며, 검출되는 잔류용매는 한 건도 없었다. This study nras carried out to develope the analytical method for the mixture of chlorefonn, benzen, trichloroethylen and 1,4-dioxane simultaneously and determine the remainingorgauic solvents in coating tablets by Purge & Trap-GC. The results were as follouFs ; 1. Chloroform, benzen, trio:tloroethylen and 1,4-dioxane separated by tenax #5 trap by HP-624GC column by terrlperature programming. The peaks were separated completely at retentiontime of 6.88min for chloroform, 8.21min for benzen, 10.38miu for trichloroethylen and 11.95minfor 1,4-dioxane. 2. Standard RSD were individually chloroform 3.03%, benzen 3.17%, trichloroethylen 3.69%and 1,4-diorane 3.41%. 3. 60 samples were not detrcted chloroform, benzen, trichloroethylen and 1,4-dioxane.

조혈모세포이식 후 발생한 주폐포자층 폐렴에 대한 고찰

주지현,최정현,이동건,백지연,고윤호,이혜정,김세희,신호진,박윤희,박지영,김유진,신완식,김춘추 대한감염학회 2001 감염 Vol.33 No.4

Background : Pneumocytitis cainii pneumonia (PCP) can occur in immunocompromised hosts especially such as AIDS or cancer patients. Although recent research had focused on PCP in AIDS patients, few studies have described the clinical presentations of PCP in recipients of stem cell transplantation (SCT). We evaluated the clinical manifestations of PCP in SCT patients admitted at St. Mary's hospital, Seoul, Korea. Methods : The medical records of 17 PCP patients undergoing SCT between Feb. 1998 and Feb. 2000 were reviewed. The diagnosis of PCP was confirmed through the demonstration of Pneumocytitis cainii via either cytology of brochoalveolar lavage (BAL) or histological technique of lung biopsy. CMV disease and CMV infection were confirmed by BAL culture and antigenemia respectively . Results : Seventeen patients were all recipients of allogeneic SCT and 7 of 17 patients were performed non-sibling SCT. Patients presented with symptoms including brief period (4 ∼23 days) of fever (76%), dyspnea (70%), cough (64%), and signs such as rare(58.8%), Sixteen patients (94%) had been receiving immunosuppressive agent such as cyclosporine A (64%) or Fk506 (35%) without PCP prophylaxis. Eleven patients (64%) were treated with corticosteroid with mean dose of 16 mg/day prednisolone and mean duration of 4.6 months after post-SCT period. Twelve patients were co-infected with CMV. Another co-infected miCroorganisms were Pseudomonas aeruginosa, Mycobacterium tuberculosis, herpes simplex virus, parainfluenza virus, Average duration of treatment with trimethoprim-sulfamethoxazole (TMP/SMX) was 21 ±9 days. Four patients died, and three of them were related with PCP. Conclusion : PCP developed frequently in patients who were taking immunosuppressive drug due to graft versus host disease or were not taking TMP/SMX prophylaxis. High risk patients showing fever, cough, or dyspnea should be considered to take early bronchoscopic intervention for detection of PCP. When treat for PCP, it also be considered to the possibility of coinfection such as CMV. (Korean J Infect Dis 33:273∼279, 2001)