Experiences and Opinions Related to End-of-Life Discussion: From Oncologists' and Resident Physicians' Perspectives / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The aims of this study were to explore how oncologists and resident physicians practice end-of-life (EOL) discussions and to solicit their opinions on EOL discussions as a means to improve the quality of EOL care. MATERIALS AND METHODS: A survey questionnaire was developed to explore the experiences and opinions about EOL discussions among oncologists and residents. Descriptive statistics, the t test, and the chisquare test were performed for the analyses. RESULTS: A total of 147 oncologists and 229 residents participated in this study. The study respondents reported diverse definitions of “terminal state,” and mostrespondents tried to disclose the patient's condition to the patient and/or family members. Both groups were involved in EOL care discussions, with a rather low satisfaction level (57.82/100). The best timing to initiate discussionwas consideredwhen metastasis or disease recurrence occurred orwhen withdrawal of chemotherapy was anticipated. Furthermore, the study respondents suggested that patients and their family members should be included in the EOL discussion. Medical, legal, and ethical knowledge and communication difficulties along with practical issues were revealed as barriers and facilitators for EOL discussion. CONCLUSION: This study explored various perspectives of oncologists and resident physicians for EOL discussion. Since the Life-Sustaining-Treatment Decision-Making Act will be implemented shortly in Korea, now is the time for oncologists and residents to prepare themselves by acquiring legal knowledge and communication skills. To achieve this, education, training, and clinical tools for healthcare professionals are required.

The Association between End-of-Life Care and the Time Interval between Provision of a Do-Not-Resuscitate Consent and Death in Cancer Patients in Korea / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: We explored the relationship between the use of each medical intervention and the length of time between do-not-resuscitate (DNR) consent and death in Korea. MATERIALS AND METHODS: A total of 295 terminal cancer patients participated in this retrospective study. Invasive interventions (e.g., cardiopulmonary resuscitation, intubation, and hemodialysis), less invasive interventions (e.g., transfusion, antibiotic use, inotropic use, and laboratory tests), and the time interval between the DNR order and death were evaluated. The subjects were divided into three groups based on the amount of time between DNR consent and death (G1, time interval ≤ 1 day; G2, time interval > 1 day to ≤ 3 days; and G3, time interval > 3 days). RESULTS: In general, there were fewer transfusions and laboratory tests near death. Invasive interventions tended to be implemented only in the G1 group. There was also less inotrope use and fewer laboratory tests in the G3 group than G1 and G2. Moreover, the G3 group received fewer less invasive interventions than those in G1 (odds ratio [OR], 0.16; 95% confidence interval [CI], 0.03 to 0.84; 3 days before death, and OR, 0.16; 95% CI, 0.04 to 0.59; the day before death). The frequency of less invasive interventions both 1 and 3 days before death was significantly lower for the G3 group than the G1 (p ≤ 0.001) and G2 group compared to G1 (p=0.001). CONCLUSION: Earlier attainment of DNR permission was associated with reduced use of medical intervention. Thus, physicians should discuss death with terminal cancer patients at the earliest practical time to prevent unnecessary and uncomfortable procedures and reduce health care costs.

A Phase I Study of Oral Paclitaxel with a Novel P-Glycoprotein Inhibitor, HM30181A, in Patients with Advanced Solid Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study is to determine the maximum tolerated dose (MTD), safety, pharmacokinetics, and recommended phase II dose of an oral drug composed of paclitaxel and HM30181A, which is an inhibitor of P-glycoprotein, in patients with advanced cancers. MATERIALS AND METHODS: Patients with advanced solid tumors received standard therapy were given the study drug at escalating doses, using a 3+3 design. The study drug was orally administered on days 1, 8, and 15, with a 28-day cycle of administration. The dose of paclitaxel was escalated from 60 to 420 mg/m2, and the dose of HM30181A was escalated from 30-210 mg/m2. RESULTS: A total of twenty-four patients were enrolled. Only one patient experienced a dose-limiting toxicity-a grade 3 neutropenia that persisted for more than 2 weeks, at 240 mg/m2 of paclitaxel. MTD was not reached. The maximum plasma concentration was obtained at a dose level of 300 mg/m2 and the area under the curve of plasma concentration-time from 0 to the most recent plasma concentration measurement of paclitaxel was reached at a dose level of 420 mg/m2. The absorption of paclitaxel tends to be limited at doses that exceed 300 mg/m2. The effective plasma concentration of paclitaxel was achieved at a dose of 120 mg/m2. Responses of 23 patients were evaluated; 8 (34.8%) had stable disease and 15 (65.2%) had progressive disease. CONCLUSION: The study drug appears to be well tolerated, and the effective plasma concentration of paclitaxel was achieved. The recommended phase II dose for oral paclitaxel is 300 mg/m2.

A Combination of Melphalan, Prednisone, and 50 mg Thalidomide Treatment in Non-Transplant-Candidate Patients with Newly Diagnosed Multiple Myeloma

BACKGROUND/AIMS: The clinical efficacy and safety of a three-drug combination of melphalan, prednisone, and thalidomide were assessed in patients with multiple myeloma who were not candidates for high-dose therapy as a first-line treatment. Because the side effects of thalidomide at a dose of > or = 100 mg daily can be a barrier to effective treatment for these patients, we evaluated the efficacy and safety of a reduced dose of thalidomide, 50 mg, for non-transplant candidates. METHODS: Twenty-one patients were treated in 4-week cycles, receiving 4 mg/m2 melphalan and 40 mg/m2 prednisone on days 1-7 and 50 mg thalidomide daily. The primary efficacy outcome was the overall response rate. Aspirin (100 mg daily) was also provided as prophylactic treatment for thromboembolism. RESULTS: The overall response rate was 57.1%; a complete response was seen in 23.8% of patients, a partial response in 33.3%, and stable disease in 9.5%. After a median follow-up time of 16.1 months, the median time to progression was 11.4 months (95% confidence interval, 2.1 to 20.6); the median overall survival was not reached. Grades 3 and 4 adverse events included infection (10%), peripheral neuropathy (5%), diarrhea (5%), thrombosis (10%), and loss of consciousness (10%). Two patients discontinued treatment due to loss of consciousness and neuropathy. CONCLUSIONS: Low-dose thalidomide (50 mg) plus melphalan and prednisone is an effective combination drug therapy option for newly diagnosed myeloma patients who are ineligible for high-dose chemotherapy.

A Case of Blastic Plasmacytoid Dendritic Cell Neoplasm Initially Mimicking Cutaneous Lupus Erythematosus / Journal of the Korean Cancer Association, 대한암학회지

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare disease. The prognosis is poor in most cases with rapid progression despite administering chemotherapy. A 67-year-old man complained of skin rashes on his back and this spread to the trunk, face, arms and thighs, and he was initially diagnosed with cutaneous lupus erythematosus according to the skin biopsy. The skin rashes then became aggravated on a trial of low dose methylprednisolone for 3 months. Repeated skin biopsy revealed a diffuse infiltration of lymphoid cells with medium sized nuclei, positive for CD4 and CD56, negative for Epstein-Barr virus (EBV), indicating a diagnosis of BPDCN. Further workups confirmed stage IVA BPDCN involving the skin, multiple lymph nodes, the peripheral blood and the bone marrow. He was treated with six cycles of combination chemotherapy consisting of ifosphamide, methotrexate, etoposide, prednisolone and L-asparaginase, and he achieved a partial response. Herein we report on a rare case of BPDCN that was initially misinterpreted as cutaneous lupus erythematosus.

A Case of Wernicke's Encephalopathy Following Fluorouracil-based Chemotherapy

The pyrimidine antimetabolite 5-fluorouracil (5-FU) is a chemotherapeutic agent used widely for various tumors. Common side effects of 5-FU are related to its effects on the bone marrow and gastrointestinal epithelium. Neurotoxicity caused by 5-FU is uncommon, although acute and delayed forms have been reported. Wernicke's encephalopathy is an acute, neuropsychiatric syndrome resulting from thiamine deficiency, and has significant morbidity and mortality. Central nervous system neurotoxicity such as Wernicke's encephalopathy following chemotherapy with 5-FU has been reported rarely, although it has been suggested that 5-FU can produce adverse neurological effects by causing thiamine deficiency. We report a patient with Wernicke's encephalopathy, reversible with thiamine therapy, associated with 5-FU-based chemotherapy.

The Results of Danazol Therapy in Patients with Chronic Immune Thrombocytopenic Purpura Who Failed with Corticosteroid Therapy

BACKGROUND: Most of adult patients with chronic immune thrombocytopenic purpura (ITP) that was refractory or relapsed to high-dose corticosteroid have been treated with splenectomy as a 2nd line treatment. However, these patients may have increased morbidity and mortality according to the operation and the increased risk of infection for a lifetime after splenectomy. Despite of the above risks, 30~40% of these patients can't maintain remission. Furthermore, the remission rate after splenectomy is relatively lower in patients with corticosteroid-refractory chronic ITP than that in those patients with corticosteroid-responsiveness. We studied whether danazol, an attenuated androgen, is useful or safe as 2nd line treatment for chronic ITP instead of splenectomy and which factors are associated with the response to danazol. METHODS: Among the patients with chronic ITP who failed corticosteroid therapy in our hospital, 28 patients who received danazol as the 2nd line treatment were analyzed retrospectively. A complete response was defined that the platelet count was increased to 150 x 10(3)/microL, and a partial response was defined that the platelet count was increased above 50 x 10(3)/microL or there was an increased platelet count of more than 20 x 10(3)/microL from the pre-treatment platelet count when the platelet count was above 50 x 10(3)/microL at the time of danazol therapy. RESULTS: The median age of patients was 44 years (range: 19~67) and the number of male patients was 9 (32.1%) and the number of females was 19 (67.9%). The starting daily doses of danazol were variable from 200 to 600mg, though most of the patients were treated with 400mg daily (18 cases, 64.3%). The median duration of danazol therapy was 201.5 days (range: 13~973) and the median duration from ITP diagnosis to danazol treatment was 56 days (range: 20~2,430). Among the accrued 28 patients, 22 patients showed a response to danazol (78.5%); there were 6 patients (21.4%) with a complete response and 16 patients (57.1%) with a partial response. The median duration from danazol treatment to response was 30 days (range: 0~180). The median response duration of danazol treatment was 330 days (95% CI: 182~478) by the Kaplan-Meiyer method. For the danazol-responsive patients, 9 patients (40.9%) remained in remission and 13 patients (59.1%) relapsed. Grade 3~4 toxicity was observed in two patients and three patients stopped danazol because of adverse effects. Hepatotoxicity was the most common toxicity. CONCLUSION: Our findings suggest that danazol is a beneficial, safe choice as the 2nd line treatment for patients with chronic ITP that was refractory or relapsed to corticosteroid.

Comparison of the NIH Stroke Scale and the Modified NIH Stroke Scale by Classification and Location of Cerebral Infarction

BACKGROUND: The National Institutes of Health Stroke Scale (NIHSS) is regarded as a valid and reliable tool to measure the severity of neurological deficits in acute stroke, but has been criticized for its complexity and variability. Therefore, the modified NIHSS (mNIHSS) was developed, eliminating redundant and less reliable items from the full version of the NIHSS. The aim of the present study was to evaluate the validity of the mNIHSS according to the subtypes of stroke and the location of affected arterial territories. METHODS: The severity of stroke in 155 patients with acute cerebral infarction was measured. Each patient was evaluated by two neurologists using both the NIHSS and mNIHSS, and the stroke subtype was determined according to the TOAST classification. The vascular territory of lesion was classified into an anterior and posterior circulation. The criterion-related validity was evaluated by the Pearson Correlation Coefficient between the NIHSS and mNIHSS scores. RESULTS: When considering the NIHSS scores as the gold criteria, the Pearson correlation coefficients of the mNIHSS were 0.96 in the subtype of large artery atherosclerosis, 0.91 in small vessel occlusion, 0.98 in cardioembolism, and 0.99 in undetermined etiology. On the other hand, the correlation coefficient was 0.98 in patients with an anterior circulation infarction, and was 0.94 in patients with a posterior circulation infarction. CONCLUSIONS: The criterion-related validity of the mNIHSS scoring system was very high in general. However, the correlations were relatively low in patients with the TOAST subtype of small vessel occlusion and also a posterior circulation infarction.

Exacerbation of Sarcoidosis Following Interferon-alpha Therapy for Chronic Active Hepatitis C / 결핵및호흡기질환

Interferon alpha is an immunomodulator that is used as an antiviral agent to treat chronic active viral hepatitis C. However, interferon can induce or exacerbate sarcoidosis. We report a case of 42-year-old man with an exacerbation of pulmonary sarcoidosis after the cessation of interferon and ribavirin therapy for chronic hepatitis C. The patient's sarcoidosis improved spontaneously and he continues to be monitored regularly without steroid therapy.

Validity and Reliability of Retrospective NIH Stroke Scale Assessment for Initial Stroke Severity

BACKGROUND: The retrospective severity scoring system of NIHSS for acute stroke patients was found to be valid and reliable by using patients' medical records in studies abroad. However, in Korea, medical records are often summarized and contain missing information which makes it difficult to conduct a restropective outcome study. The purpose of this research was to evaluate the validity and reliability of the retrospective NIHSS scoring system according to patients' medical records with written clinical histories and physical admission notes. METHODS: An algorithm for the retrospective NIHSS scoring system was developed and applied to 75 patients with acute ischemic stroke. Missing data on physical examination results were scored as normal. One neurologist who was blinded to this study measured the NIHSS score prospectively on the initial patient examination. After the patient's discharge, two other neurologists, blinded to the patient's clinical condition, evaluated the NIHSS score independently based on the information collected from the patient's physical admission notes. The criterion-related validity was evaluated by the Pearson Correlation Coefficient, and the measure of agreement between two raters was evaluated by the Kappa Statistic. RESULTS: The criterion-related validities of the retrospective NIHSS scoring system were high in the total and each itemized scores, except for the items of LOC command, limb ataxia, dysarthria, and neglect. The interrater reliabilities were also high except for the items of LOC command, limb ataxia, and dysarthria. CONCLUSIONS: The retrospective NIHSS scoring algorithm was found to be a reliable and unbiased tool even when some physical examination elements are missing from the written medical records.

The Usage of Intravenous Heparin in Acute Ischemic Stroke in 10 Teaching Hospitals

BACKGROUND: Treatment with heparin has been an area of great controversy among neurologists. The goal of this study was to compare the actual usage patterns of intravenous heparin according to the stroke subtype, location, severity of the stroke, different hospitals, and various departments. METHODS: The records of 1204 patients with acute ischemic stroke admitted to 10 teaching hospitals between January 2000 and December 2000 were reviewed. The patients were divided into two groups of whether or not they were given intravenous heparin. Cases of acute ischemic stroke were subdivided according to the TOAST classification. Patients with NIH Stroke Scale scores were categorized as having mild, moderate, and severe stroke. Terminal hospital stays were subdivided further by department: internal medicine, neurology, neurosurgery, rehabilitation medicine, and others. RESULTS: 512 patients (42.5%) were treated with heparin. The usage of heparin in the case of large artery atherosclerosis occupied 46%, small vessel occlusion 31 percent, cardioembolism 73%, other determined etiology 33%, and undetermined etiology 46%. Heparin was used to treat 46% of the patients with a lesion of anterior circulation, 49% of posterior circulation, and 38% of both anterior and posterior circulation. Heparin was more frequently used for moderate and severe strokes compared to mild strokes. CONCLUSIONS: The utilization of intravenous heparin was more frequent in treatment of the cardioembolism subtype and moderate-to-severe strokes. Practice variation according to the hospitals and discharge departments were manifested.

Developing a Statistical Software for Predicting Hospital Bankruptcy using Data Mining Tool / 대한의료정보학회지

Since the hospital bankruptcy rate is increasing, it has been an important issue to predict the bankruptcy of hospital using the existing hospital management information. Fortunately, the implementation of data mining methodology and decision support system(DSS) are becoming popular. Therefore, this study developed the statistical software for predicting hospital bankruptcy using data mining tool. Stepwise procedures were taken as follows: 1) adopting the HGLM and Logit Models; 2) implementing the input and output processes; 3) linking to the iBITs interface, the data miming tool; and 4) evaluating the software by fitting the hospital management data in practice. The software is written in Visual C++ 5.0 under windows NT/95, and allows the interconnection with other interfaces and libraries. This program initiates encouragement of implementation of DSS models using data mining methodology, in health care fields. This kind of software will play a pivotal role in improving the efficiency and adequacy of managing health care institutions.

Burden of disease of major cancers assessment using years of lives with disability in Korea / 예방의학회지

This study was carried out for the burden of disease of major cancers assessment using years of lives with disability in Korea. With the years of lives with disability, this indicator was applied in order to estimate burden of major cancer disease. For this work, We also estimated incidence rate, remission rate, case fatality rate, average age of onset, expected duration with disability in each cancer disease. As sources of information, national health insurance data and national mortality registration data were analyzed. The results of the study are as follows; The top five causes of the burden of major cancer disease are evaluated as stomach cancer, liver cancer, colon and rectum cancer , esophageal cancer, lung cancer in male. The top five causes of the burden of major cancer disease are evaluated as stomach cancer, esophageal cancer, liver cancer, uterine cervix cancer ovarian cancer in female. The process of evaluating the burden disease of major cancers in Korea has not finished with this paper. This study should be seen as the first in a series in Korea. It is necessary to analyse with more accuracy the assumptions behind the methodology.