On Restricted Wythoff’s Nim

We shall study the following restricted Wythoff’s Nim. Let Si (1 ≤ i ≤ 3) be the set of positive integers. Each player can remove the number of tokens s1 ∈ S1 from the first pile and s2 ∈ S2 from the second pile and remove the same number of tokens s3 ∈ S3 from both piles. We shall identify (m, n) to a position of this nim, where m is the number of tokens in the first pile and n is the number of tokens in the second pile. In the case |S2| < ∞, we will show the Sprague-Grundy sequence(or simply G-sequences) gS(m, n) is periodic for fixed m

NDBを用いた新たな患者追跡手法の開発

The National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) is a comprehensive database containing health insurance claim information. The structure of the NDB complicates long-term cohorts for two main reasons. First, the NDB data are stored on a per-claim basis. Second, the NDB is a billing-focused record structure. Therefore, the objective of this study was to use ID0 to modify the data structure to allow for long-term cohorts, provided that the data volume is not increased and the runtime per data year is maintained within one month. The NDB uses two primary keys (ID1 and ID2) made from hash values that mask personally identifiable information. ID0 is our recently developed key from ID1 and ID2, which improves patient-matching efficiency with excellent long-term tracing performance. Our study used claim data with filing dates between April 2013 and March 2016 to trace hospitalizations of one month or longer, including outpatient care, in three steps. In Step 1, claims were transferred to a CD-record format. As some diagnosis procedure combination (DPC) claim records contain a mixture of overlapping comprehensive and piece-rate data, we sorted and reorganized them. In Step 2, pharmacy and medical outpatient claims were integrated using the ID0 key, the medical institution code for issuing a prescription, and the prescription issue date. In Step 3, the transferred data were combined and converted from consecutive hospitalization days into sequences based on ID0, the medical institution code, and hospital ward classification. Consequently, the size of the originally extracted comma-separated variable dataset for three years (approximately 10.5 TB) was reduced to an approximately 6 TB main database file that was usable for processing. The process took approximately three months. With similar conventional methods, the data size was 30 times larger, and it took more than seven months to process a year's worth of data. In addition, to demonstrate the application of this method, we conducted a six-year mortality cohort for all Japanese citizens. Our technique makes it easy to perform follow-up and longitudinal cohort surveys while accurately tracing patient data in large-scale medical claims databases.博士（医学）・甲第854号・令和4年12月22日Copyright: ©2022 The Author(s). This is an open access article distributed under the terms of the Creative Commons BY 4.0 International (Attribution) License (https:// creativecommons.org/licenses/by/4.0/legalcode), which permits the unrestricted distribution, reproduction and use of the article provided the original source and authors are credited

季節と天候による骨折リスクの差 : 日本のレセプト情報データベースを用いた、全ての年齢・部位に関する包括的な分析

Although age- and season-specific effects on fracture risk have been reported, the effects of seasonality across different age groups and for different fracture sites have not yet been clarified. Therefore, our study aimed to comprehensively investigate the effects of seasonality on fracture risk across age and fracture sites using a large-scale population database of fracture incidence. Fracture data were accumulated over a 3-year period in the region of Tokyo and in surrounding areas, which accounts for a total population of 42 million. Information on fracture occurrence, fracture site, and patient demographics were obtained from the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB). Over the study period, 508,051 fractures were identified across the following five age groups: 0-19, 20-39, 40-64, 65-79, and 80+ years. The incidence rate for fractures in 10 site groups was calculated. Fracture risk was the highest in the spring and autumn for children aged 0-19 years and was the highest in the winter for elderly individuals (65-79 and 80+ years). Toe fractures, which occurred more frequently in the summer, were the most notable exception. The risk of fracture of the distal radius and hip was associated with daily temperature and rainfall and was elevated on days with a mean temperature higher than that of the previous day. Fracture risk exhibited seasonal variations that differed between children and elderly individuals and between toe fractures and fractures at other sites. These findings can help us understand the epidemiology of fractures and develop preventive strategies, as well as aid in the allocation of healthcare resources.博士（医学）・甲第718号・令和元年9月27

重症低血糖後の急性冠症候群の絶対リスク : 日本のナショナルデータベースを用いた一般集団対象の2年間のコホート研究

Aims/introduction: Although the epidemiological relationship between hypoglycemia and increased risk of acute coronary syndrome (ACS) has been well established, the time period for increased risk of ACS after a severe hypoglycemic episode remains unknown. The present study aimed to determine the ACS risk after a severe hypoglycemic episode. Materials and methods: We carried out a retrospective population-based cohort study based on national claims data in Japan. We retrieved data of diabetes patients aged ≥35 years collected from April 2014 to March 2016. The absolute risk of ACS was defined as the occurrence of an emergency percutaneous coronary intervention after a severe hypoglycemic episode. Results: In total, data of 7,909,626 patients were included in the analysis. The absolute risk of ACS was 2.9 out of 1,000 person-years in all patients. ACS risk in patients with severe hypoglycemic episodes was 3.0 out of 1,000 person-years. Severe hypoglycemic episodes increased the absolute risk of ACS in patients aged ≥70 years, but not in patients aged <70 years. The absolute risk of ACS was 10.6 out of 1,000 person-years within 10 days of a severe hypoglycemic episode. There was a significant trend between shorter duration after an episode and higher ACS risk. Conclusions: Severe hypoglycemia was associated with an increased risk of ACS in elderly diabetes patients. ACS risk increased with a shorter period after a severe hypoglycemic episode, suggesting that severe hypoglycemia leads to an increased risk of ACS in diabetes patients. These findings show that it is important to avoid severe hypoglycemia while treating diabetes, particularly in elderly patients.博士（医学）・甲第732号・令和2年3月16日© 2019 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License(https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made

Response Rate Is Associated with Prolonged Survival in Patients with Advanced Non-small Cell Lung Cancer Treated with Gefitinib or Erlotinib

Introduction:Gaining a higher response rate (RR) has usually been determined as a primary end point in phase II trials evaluating the efficacy of new molecular targeted drugs. However, a relationship between clinical response and survival benefit has not been well studied in the patients treated with molecular targeted agents.Methods:Prospective trials of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) monotherapy in non-small cell lung cancer were extracted from MEDLINE, EMBASE, and the annual meetings in 2007 of the American Society of Clinical Oncology, European Cancer Conference, and World Conference on Lung Cancer.Correlation between clinical response and survival was examined using linear regression analysis. We also tried to compare the significance of RR as surrogate markers for survival with that of disease control rate (DCR) by calculating the area under their receiver operating characteristic (ROC) curves.Results:We identified 24 phase II trials and 4 phase III trials with a total of 6171 patients and 30 treatment arms, including 22 arms for the gefitinib group and 8 arms for the erlotinib group. Both RR and DCR strongly correlated with median survival time (MST; p < 0.0001 and p = 0.003, respectively). In an ROC analysis, the area under the ROC curve predicting MST prolongation by RR was 0.918, which was higher than the area under the ROC curve by DCR.Conclusions:We found a significant relationship between RR and MST in clinical trials with EGFR-TKIs. RR could be an independent surrogate marker for MST in the current response criteria in the clinical trials of EGFR-TKIs

High Efficacy of Preoperative Low-Dose Radiotherapy with Sanazole (AK-2123) for Extraskeletal Ewing's Sarcoma: A Case Report

Extraskeletal Ewing's sarcoma is a rare soft tissue tumor that is morphologically indistinguishable from Ewing's sarcoma of bone. We report a case of extraskeletal Ewing's sarcoma with several systemic problems. A 69-year-old man presented with a 5-month history of a rapidly enlarging mass in the right thigh. Because preoperative radiotherapy with sanazole (AK-2123) contributed the tumor mass reduction down to 40% in size, the tumor was successfully resected with clear surgical margins and repaired with a musculocutaneous flap. The high efficacy of pre-operative low-dose radiotherapy with sanazole was histologically confirmed that the resected tumor specimen involved no viable tumor cells and showed 100% necrosis. Based on clinical outcomes in this case, the combined modality of pre-operative low-dose radiotherapy with hypoxic cell radiosensitizer and adequate surgical resection might provide for the useful clinical application of extraskeletal Ewing's sarcoma treatment

日本における保険診療全透析患者追跡と死亡数の現状

Background: The survival rate of chronic dialysis patients in Japan remains the highest worldwide, so there is value in presenting Japan's situation internationally. We examined whether aggregate figures on dialysis patients in the National Database of Health Insurance Claims and Special Health Checkups of Japan (NDB), which contains data on insured procedures of approximately 100 million Japanese residents, complement corresponding figures in the Japanese Society for Dialysis Therapy Renal Data Registry (JRDR). Methods: Subjects were patients with medical fee points for dialysis recorded in the NDB during 2014-2018. We analyzed annual numbers of dialysis cases, newly initiated dialysis cases- and deaths. Results: Compared with the JRDR, the NDB had about 6-7% fewer dialysis cases but a similar number of newly initiated dialysis cases. In the NDB, the number of deaths was about 6-10% lower, and the number of hemodialysis cases was lower, while that of peritoneal dialysis cases was higher. The cumulative survival rate at dialysis initiation was approximately 6 percentage points lower in the NDB than in the JRDR, indicating that some patients die at dialysis initiation. Cumulative survival rate by age group was roughly the same between the NDB and JRDR in both sexes. Conclusion: The use of the NDB enabled us to aggregate data of dialysis patients. With the definition of dialysis patients used in this study, analyses of concomitant medications, comorbidities, surgeries, and therapies will become possible, which will be useful in many future studies.博士（医学）・甲第818号・令和4年3月15日© 2021. The Author(s).　Open Access This article is licensed under a Creative Commons Attri bution 4.0 International License, which permits use, sharing, adapta tion, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/