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Kazuya Nagasaki,1 Yuji Nishizaki,2,3 Masanori Nojima,4 Taro Shimizu,5 Ryota Konishi,6 Tomoya Okubo,7 Yu Yamamoto,8 Ryo Morishima,9 Hiroyuki Kobayashi,1 Yasuharu Tokuda10 1Department of Internal Medicine, Mito Kyodo General Hospital, University of Tsukuba, Ibaraki, Japan; 2Medical Technology Innovation Center, Juntendo University, Tokyo, Japan; 3Division of Medical Education, Juntendo University School of Medicine, Tokyo, Japan; 4Center for Translational Research, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; 5Department of Diagnostic and Generalist Medicine, Dokkyo Medical University Hospital, Tochigi, Japan; 6Education Adviser Japan Organization of Occupational Health and Safety, Kanagawa, Japan; 7Research Division, The National Center for University Entrance Examinations, Tokyo, Japan; 8Division of General Medicine, Center for Community Medicine, Jichi Medical University School of Medicine, Tochigi, Japan; 9Department of Neurology, Tokyo Metropolitan Neurological Hospital, Tokyo, Japan; 10Muribushi Okinawa for Teaching Hospitals, Okinawa, JapanCorrespondence: Yuji NishizakiMedical Technology Innovation Center, Juntendo University, 2-1-1 Hongo Bunkyo-ku, Tokyo, 113-8421, JapanTel +81-3-3813-3111Fax +81-3-5689-0627Email ynishiza@juntendo.ac.jpPurpose: In Japan, the General Medicine In-training Examination (GM-ITE) was developed by a non-profit organization in 2012. The GM-ITE aimed to assess the general clinical knowledge among residents and to improve the training programs; however, it has not been sufficiently validated and is not used for high-stake decision-making. This study examined the association between GM-ITE and another test measure, the Professional and Linguistic Assessments Board (PLAB) 1 examination.Methods: Ninety-seven residents who completed the GM-ITE in fiscal year 2019 were recruited and took the PLAB 1 examination in Japanese. The association between two tests was assessed using the Pearson product-moment statistics. The discrimination indexes were also assessed for each question.Results: A total of 91 residents at 17 teaching hospitals were finally included in the analysis, of whom 69 (75.8%) were women and 59 (64.8%) were postgraduate second year residents. All the participants were affiliated with community hospitals. Positive correlations were demonstrated between the GM-ITE and the PLAB scores (r = 0.58, p < 0.001). The correlations between the PLAB score and the scores in GM-ITE categories were as follows: symptomatology/clinical reasoning (r = 0.54, p < 0.001), physical examination/procedure (r = 0.38, p < 0.001), medical interview/professionalism (r = 0.25, p < 0.001), and disease knowledge (r = 0.36, p < 0.001). The mean discrimination index of each question of the GM-ITE (mean ± SD; 0.23 ± 0.15) was higher than that of the PLAB (0.16 ± 0.16; p = 0.004).Conclusion: This study demonstrates incremental validity evidence of the GM-ITE to assess the clinical knowledge acquisition. The results indicate that GM-ITE can be widely used to improve resident education in Japan.Keywords: in-training examination, validity, extrapolation, General Medicine In-Training Examination, Professional and Linguistic Assessments Board, medical knowledge, postgraduate medical education

Kensuke Kinoshita,1 Yusuke Tsugawa,2 Taro Shimizu,3 Yusuke Tanoue,4 Ryota Konishi,5 Yuji Nishizaki,6 Toshiaki Shiojiri,7 Yasuharu Tokuda8 1Department of Medicine, Mito Kyodo General Hospital, University of Tsukuba, Mito City, Ibaraki, Japan; 2Department of Health Policy and Management, Harvard T.H. Chan School of Public Health, Boston, MA, USA; 3Tokyo Joto Hospital, Koto-ku, Tokyo, 4Good Medicine Japan, Miyagi, 5Department of General Internal Medicine, Kanto Rosai Hospital, Kawasaki, Kanagawa, 6Department of Cardiology, Juntendo University Graduate School of Medicine, Tokyo, 7Department of General Internal Medicine, Asahi General Hospital, Asahi, Chiba, 8Japan Community Healthcare Organization, Minato-ku, Tokyo, Japan Background: Both clinical workload and access to learning resource are important components of educational environment and may have effects on clinical knowledge of residents. Methods: We conducted a survey with a clinical knowledge evaluation involving postgraduate year (PGY)-1 and -2 resident physicians at teaching hospitals offering 2-year postgraduate training programs required for residents in Japan, using the General Medicine In-Training Examination (GM-ITE). An individual-level analysis was conducted to examine the impact of the number of assigned patients and emergency department (ED) duty on the residents' GM-ITE scores by fitting a multivariable generalized estimating equations. In hospital-level analysis, we evaluated the relationship between for the number of UpToDate reviews for each hospital and for the hospitals' mean GM-ITE score. Results: A total of 431 PGY-1 and 618 PGY-2 residents participated. Residents with four or five times per month of the ED duties exhibited the highest mean scores compared to those with greater or fewer ED duties. Those with largest number of inpatients in charge exhibited the highest mean scores compared to the residents with fewer inpatients in charge. Hospitals with the greater UpToDate topic viewing showed significantly greater mean score. Conclusion: Appropriate ED workload and inpatient caseload, as well as use of evidence-based electronic resources, were associated with greater clinical knowledge of residents. Keywords: workload, online resource, knowledge, resident, postgraduate, Japan

Ikuko Tsukamoto,1,* Akram Hossain,2,3,* Fuminori Yamaguchi,2 Yuko Hirata,2 Youyi Dong,2 Kazuyo Kamitori,2 Li Sui,2 Machiko Nonaka,2 Masaki Ueno,4 Kazuyuki Nishimoto,5 Hirofumi Suda,5 Kenji Morimoto,6 Tsuyoshi Shimonishi,7,† Madoka Saito,8 Tao Song,9 Ryoji Konishi,1 Masaaki Tokuda2 1Department of Pharmaco-Bio-Informatics, Faculty of Medicine, Kagawa University, Miki, Kagawa, Japan; 2Department of Cell Physiology, Faculty of Medicine, Kagawa University, Kagawa, Japan; 3Matsutani Chemical Industry Co, Ltd, Itami, Japan; 4Department of Inflammation Pathology, Faculty of Medicine, Kagawa University, Kagawa, Japan; 5Division of Radioisotope Research, Life Science Research Center, Kagawa University, Kagawa, Japan; 6Rare Sugar Research Center, Kagawa University, Kagawa, Japan; 7IZUMORING LLC, Miki, Kita, Kagawa, Japan; 8Department of Pharmacy, Okayama University Hospital, Okayama, Japan; 9The First Affiliated Hospital, China Medical University, Shenyang, People’s Republic of China *These authors contributed equally to this work†Tsuyoshi Shimonishi has passed away Background: The purpose of this study was to evaluate intestinal absorption, organ distribution, and urinary elimination of the rare sugar D-psicose, a 3-carbon stereoisomer of D-fructose that is currently being investigated and which has been found to be strongly effective against hyperglycemia and hyperlipidemia. Methods: This study was performed using radioactive D-psicose, which was synthesized enzymatically from radioactive D-allose. Concentrations in whole blood, urine, and organs were measured at different time points until 2 hours after both oral and intravenous administrations and 7 days after a single oral administration (100 mg/kg body weight) to Wistar rats. Autoradiography was also performed by injecting 100 mg/kg body weight of 14C-labeled D-psicose or glucose intravenously to C3H mice. Results: Following oral administration, D-psicose easily moved to blood. The maximum blood concentration (48.5±15.6 µg/g) was observed at 1 hour. Excretion to urine was 20% within 1 hour and 33% within 2 hours. Accumulation to organs was detected only in the liver. Following intravenous administration, blood concentration was decreased with the half-life=57 minutes, and the excretion to urine was up to almost 50% within 1 hour. Similarly to the results obtained with oral administration, accumulation to organs was detected only in the liver. Seven days after the single-dose oral administration, the remaining amounts in the whole body were less than 1%. Autoradiography of mice showed results similar to those in rats. High signals of 14C-labeled D-psicose were observed in liver, kidney, and bladder. Interestingly, no accumulation of D-psicose was observed in the brain. Conclusion: D-psicose was absorbed well after oral administration and eliminated rapidly after both oral and intravenous administrations, with short duration of action. The study provides valuable pharmacokinetic data for further drug development of D-psicose. Because the findings were mainly based on animal study, it is necessary to implement human trials to study the metabolism pathway, which would give an important guide for human intake and food application of D-psicose. Keywords: 14C-labeled D-psicose, organ accumulation, pharmacokinetics, autoradiography

Taro Shimizu,1 Yusuke Tsugawa,2,3 Yusuke Tanoue,4 Ryota Konishi,5 Yuji Nishizaki,6 Mitsumasa Kishimoto,7 Toshiaki Shiojiri,8 Yasuharu Tokuda9 1Hospitalist Division, Department of Medicine, Nerima Hikarigaoka Hospital, Tokyo, Japan; 2Division of General Medicine and Primary Care, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA; 3Center for Clinical Epidemiology, St Luke's Life Science Institute, 4Department of Vascular and Oncological Surgery, Hospital of Tokyo University, 5Department of General Internal Medicine, Kanto Rousai Hospital, 6Department of Cardiology, Juntendo University School of Medicine, 7Division of Rheumatology, St Luke's International Hospital, Tokyo, Japan; 8Asahi Chuo Hospital, Chiba, Japan; 9Department of Medicine, Tsukuba University Mito Kyodo General Hospital, Mito City, Ibaraki, Japan Background: It is believed that the type of educational environment in teaching hospitals may affect the performance of medical knowledge base among residents, but this has not yet been proven. Objective: We aimed to investigate the association between the hospital educational environment and the performance of the medical knowledge base among resident physicians in Japanese teaching hospitals. Methods: To assess the knowledge base of medicine, we conducted the General Medicine In-Training Examination (GM-ITE) for second-year residents in the last month of their residency. The items of the exam were developed based on the outcomes designated by the Japanese Ministry of Health, Labor, and Welfare. The educational environment was evaluated using the Postgraduate Hospital Educational Environment Measure (PHEEM) score, which was assessed by a mailed survey 2 years prior to the exam. A mixed-effects linear regression model was employed for the analysis of variables associated with a higher score. Results: Twenty-one teaching hospitals participated in the study and a total of 206 residents (67 women) participated and completed the exam. There were no residents who declined to participate in the exam. The mean GM-ITE score was 58 (standard deviation 8.4). The mixed-effects linear regression analysis showed that a higher PHEEM score was associated with a higher GM-ITE score (P = 0.02). Having a department of general medicine, and hospital location in a provincial community (versus an urban setting), were also shown to have a significant relationship with the higher score (P = 0.03, and P = 0.02, respectively). Conclusion: We found that the performance of the medical knowledge base of resident physicians was significantly associated with the educational environment of their hospitals. Improvement of the educational environment in teaching hospitals might be crucial for enhancing the performance of resident physicians in Japan. Keywords: outcome-based education, postgraduate medical education, educational environment, general medicine, provincial hospital