Increased financial burden among patients with chronic myelogenous leukaemia receiving imatinib in Japan: a retrospective survey.

BACKGROUND: The financial burden of medical expenses has been increasing for cancer patients. We investigated the relationship between household income and financial burden among patients with chronic myelogenous leukaemia (CML) who have been treated with imatinib. METHODS: A questionnaire was distributed to 1200 patients between May and August 2009. We retrospectively surveyed their household incomes, out-of-pocket medical expenses, final co-payments after refunds, and the perceived financial burden of their medical expenses in 2000, 2005 and 2008. RESULTS: A total of 577 patients completed the questionnaire. Their median age was 61 years (range, 15-94). A financial burden was felt by 41.2 % (28 of 68) of the patients treated with imatinib in 2000, 70.8 % (201 of 284) in 2005, and 75.8 % (400 of 528) in 2008. Overall, 182 patients (31.7 %) considered its discontinuation because of the financial burden and 15 (2.6 %) temporarily stopped their imatinib prescription. In 2000, 2005 and 2008, the patients' median annual household incomes were 49,615 US Dollars (USD), 38,510 USD and 36,731 USD, respectively, with an average currency exchange rate of 104 Yen/USD in 2008. Their median annual out-of-pocket expenses were 11,548, 12,067 and 11,538 USD and their median final annual co-payments were 4,375, 4,327 and 3,558 USD, respectively. Older patients (OR = 0.96, 95 % CI: 0.95-0.98, p ≪ 0.0001 for 1-year increments), and patients with higher household incomes (OR = 0.92, 95 % CI: 0.85-0.99, p = 0.03 for 10,000 USD-increments) were less likely to have considered discontinuing their imatinib treatment. Conversely, patients with higher annual final co-payments (OR = 2.21, 95 % CI: 1.28-4.28, p = 0.004 for 10,000 USD-increments) were more likely to have considered discontinuing their imatinib treatment. CONCLUSIONS: The proportion of CML patients who sensed a financial burden increased between 2000 and 2008. During this period, their annual incomes fell by 13,000 USD, although their medical expenses did not change. Financial support for patients being treated with expensive drugs remains a major problem in Japan.

Data mining of mental health issues of non-bone marrow donor siblings.

BACKGROUND: Allogenic hematopoietic stem cell transplantation is a curative treatment for patients with advanced hematologic malignancies. However, the long-term mental health issues of siblings who were not selected as donors (non-donor siblings, NDS) in the transplantation have not been well assessed. Data mining is useful in discovering new findings from a large, multidisciplinary data set and the Scenario Map analysis is a novel approach which allows extracting keywords linking different conditions/events from text data of interviews even when the keywords appeared infrequently. The aim of this study is to assess mental health issues on NDSs and to find helpful keywords for the clinical follow-up using a Scenario Map analysis. FINDINGS: A 47-year-old woman whose younger sister had undergone allogenic hematopoietic stem cell transplantation 20 years earlier was interviewed as a NDS. The text data from the interview transcriptions was analyzed using Scenario Mapping. Four clusters of words and six keywords were identified. Upon review of the word clusters and keywords, both the subject and researchers noticed that the subject has had mental health issues since the disease onset to date with being a NDS. The issues have been alleviated by her family. CONCLUSIONS: This single subject study suggested the advantages of data mining in clinical follow-up for mental health issues of patients and/or their families.

Internet-based survey on medical manga in Japan.

The more manga (Japanese graphic novels) communicate medical information, the more people are likely to be influenced by manga. We investigated through an Internet search using Google the characteristics of medical manga published in Japan, defined as those in which the main character is a medical professional and that occur in a medical setting. As of December 2008, 173 medical manga had been published. For a period of time after the first medical manga by Osamu Tezuka in 1970, the number of publications maintained a steady level, but increased rapidly in the mid 1980s. The professions of the protagonist were 134 doctors, 19 nurses, 3 dentists, 3 medical students, and 1 nursing student. Although the main character was mostly a doctor, manga featuring paramedical professionals have increased since 1990s. Medical manga may be a powerful tool for increasing the awareness of the public regarding medicine.

Why do Japan's advanced medical treatments never get ahead?

Islet cell transplantation is a minimally invasive procedure which effectively controls blood glucose level for diabetic patients but is considered as experimental. After islet transplantation, type 1 diabetic patients could become insulin free with stable glycemic control. But for long term effects, only stable glycemic control was maintained and not insulin free status. In 2004 Kyoto University performed the first Japanese islet cell transplant using non-heart beating donor. Of note, due to the lack of cadaveric donors in Japan, the same group performed the world's first successful case of living donor islet transplantation in 2005. Both patients achieved transit insulin-independence; however excellent glycemic control was able to be maintained for a prolonged period. Even though the series of islet transplants at Kyoto University showed promising results, the leading scientist did not continue his research in Japan. This was because it is extremely difficult to implement newly developed treatment as a standard therapy in Japan.

Interests in beta-cell replacement therapies among Japanese patients with type 1 diabetes.

The purpose of this study is to evaluate patients' perspective about beta-cell replacement therapies. 105 Japanese type 1 diabetic patients answered questionnaire on current treatments, transplantation and necessity of psychosomatic therapy. The motivation of receiving transplantation seems to become insulin-free. Providing adequate information is necessary for wide-spread beta-cell replacement therapies.

Estimation of donor usability for islet transplantation in the United States with the kyoto islet isolation method.

The quality of donor pancreata is important for successful islet isolation. However, in some countries like Japan, the number of donor pancreata is very low; therefore, marginal donors have been used with less restrictive donor criteria. In order to use marginal donor pancreata, we established the Kyoto islet isolation method (KIIM). According to United Network for Organ Sharing (UNOS) in 2005, more than 6,000 pancreata were not clinically used in the US. In this study, we applied the KIIM for brain-dead donors and reevaluated donor usability based on the Japanese islet donor criteria. Islets were isolated with the Ricordi method using pancreata stored in University of Wisconsin (UW) solution (UW group) or by the two-layer method (TLM group) or the TLM combined with ductal injection (DI group). We implemented the KIIM (KIIM group) to confirm the effect of the KIIM on brain-dead donors. Donor charts in Texas from 2005 to 2006 were reviewed. If pancreata were not used clinically, the reason was reviewed and donors were reevaluated based on Japanese criteria. There were no significant differences of islet yield, viability, and purity between the UW and TLM groups. The DI group significantly improved islet yields and isolations were further improved in the KIIM group [UW: 251,663 +/- 60,217 islet equivalent (IE); TLM: 243,738 +/- 54,170 IE; DI: 498,639 +/- 28,853 IE; KIIM: 678,286 +/- 55,853]. The KIIM provided high-quality islets in high numbers from islet isolations from brain-dead donors. A total of 236 donor charts were reviewed and 194 pancreata (82%) were not used. Of these, 185 cases identified the reasons that the pancreata were not used. When we applied the Japanese criteria, an additional 82 cases out of 185 (44%) seem to be suitable for islet isolations. With the KIIM, more than 2,500 additional donor pancreata can be used for islet isolation in the US every year when the Japanese criteria are applied.

SUITO index for evaluation of efficacy of single donor islet transplantation.

Evaluation of engrafted islets mass is important for clinical care of patients after islet transplantation. Recently, we developed the secretory unit of islet transplant objects (SUITO) index, which reflected engrafted islet mass. In this study, we evaluated the SUITO index for the prediction of clinical outcome after single islet transplantation. Single islet transplantations were performed into six type 1 diabetic patients. Isolated islets were quantitatively assessed at the time of transplantation. The SUITO index was calculated as follows: fasting C-peptide (ng/dl)/[fasting blood glucose (mg/dl) - 63] x 1500. Islet yield/recipient's body weight and SUITO index were evaluated, along with HbA(1C), relative insulin dose (insulin dose posttransplant/pretransplant), and M-values. HbA(1C) improved in all cases, irrespective of the SUITO index score or islet yield/body weight. The average SUITO index from postoperative days 3 to 30 (R(2) = 0.728, p < 0.04), but not islet yield/body weight (R(2) = 0.259, p = 0.303), correlated with relative insulin dose. The daily SUITO index strongly correlated with the daily relative insulin dose (R(2) = 0.558, p < 0.0001) and weakly correlated with the daily M-values (R(2) = 0.207, p < 0.02). A SUITO index score of less than 10 was associated with increasing insulin dose even after islet transplantation. The SUITO index seems to be a better predictor of success of islet transplantations than islet yield/body weight. SUITO index is recommended to assess clinical outcome of islet transplantation.

Analysis of donor- and isolation-related variables from non-heart-beating donors (NHBDs) using the Kyoto islet isolation method.

Recently, we demonstrated that islet transplantation from non-heart-beating donors (NHBDs) using the Kyoto islet isolation method (KIIM) successfully reversed patients' diabetes state. In this study, we evaluated the effects of donor- and isolation-related variables on islet isolation results from NHBDs by KIIM. Twenty-one islet preparations from the pancreata of NHBDs were isolated by KIIM. Islet preparations that met transplantation criteria and achieved improved patient diabetes control after transplantation were defined as successful isolations. Potential risk factors deemed to affect islet isolation results, such as age, gender, body mass index, hospital stay, donors' blood biochemical tests, a modified pancreata procurement method, and isolation and purification procedure-related variables, were analyzed. Seventeen out of 21 islet isolations (81%) were successful isolations. Postpurification islet yield was 447,639 +/- 39,902 islet equivalents (IE) in the successful isolation group and 108,007 +/- 31,532 IE in the failure group. Donor age was significantly younger in the success group (41.9 +/- 4.0 years old in the success group vs. 57.5 +/- 2.2 years old in the failure group, p = 0.003). Chronic pancreatitis significantly decreased islet yields (p = 0.006). Phase I time was significantly shorter (p = 0.010) and undigested tissue volume was significantly smaller (p = 0.020) in the success group. Purity was in positive correlation to postpurification islet yield, while donor age was in reverse correlation to postpurification islet yield. KIIM enables us to perform islet transplantation from NHBDs; however, the decision to use pancreata from older donors or those with chronic pancreatitis requires careful consideration.

Follow-up study of the first successful living donor islet transplantation.

BACKGROUND: Islet transplantation has become an option for the treatment of insulin-dependent diabetes mellitus and is usually performed using brain-dead heartbeating donors. However, we have very limited number of such donors in Japan; therefore, it is not allowed to perform islet transplantation with brain-dead donors. In order to perform islet transplantation in Japan, we need to seek new donor resources. METHODS: We performed the first successful living-donor islet transplantation. In this case, the recipient had brittle diabetes with hypoglycemic unawareness. The donor was deemed qualified after undergoing both metabolic and preoperative assessments. Distal pancreatectomy was performed using open laparotomy and more than 400,000 islets were isolated and transplanted immediately. RESULTS: The recipient has been insulin independent posttransplant with positive C-peptide for more than one year. She no longer suffers from hypoglycemic unawareness and displayed a substantial improvement in hemoglobulin (Hb) A1C. The donor's clinical course was uneventful, which allowed her to return to her job within one month. She maintained normal fasting C-peptide and HbA1C levels during follow-up period. CONCLUSION: In our first case of living donor islet transplantation, both the donor and the recipient have been maintaining excellent glycemic control with no untreatable complications for more than one year.