Background: Physician shortage affects mortality at the city level in Japan. The medical administrative district (MAD) covering the area (town, city, etc.) in which the patients live and is the unit responsible for recruiting doctors. The number of physicians or changes in this number in each MAD varies. The relationship between the number, or the change in number, of physicians and the mortality in each MAD has been unclear.
Methods: We designed a descriptive study using publicly-available national statistics. In all 358 MADs in Japan, we analyzed the relationship between the changes in the number of physicians (total, clinic, and hospital) from 2000 to 2005 and the standardized mortality ratio (all causes of death, cancer, heart disease, and stroke).
Results: In MADs, the number of physicians and mortality are not related, nor are changes in number of physicians and mortality. Further investigation including factors associated with mortality is needed.
Conclusion: In MAD, there is no relationship between the number of physician and the mortality, between the change in number of physician and the mortality. Further investigation is needed including factors associated with mortality.

Purpose : The purpose of this study was to determine how frequently cancer patients would be missed if primary care clinics do not participate in the Japanese National Cancer Survey, and to describe the characteristics of those cancer patients who would be missed.
Methods : This research is a case series study. We collected cancer patients who were identified in Ryuocho-Kokuminkenkouhoken Clinic and Yuge medical clinic for 26 years and were registered in the Shiga Cancer survey. We then extracted the records of those cancer patients who would be potentially missed from the national cancer registry and investigated the background.
Results : The total number of cancer patients registered was 441. Of these, 28 (6.3%) patients who did not admit to the hospitals may be missed from the national cancer registry ; ten patients had their cancer diagnosed at an advanced stage and died at home without hospital admission. Two further cases had treatment for cancer (endoscopic resection) completed in the primary care clinic without hospital admission. Twelve patients only attend the hospital outpatient clinic for investigation and died at home without admission. And four patients received only CT scan examination and didn't attend the hospital outpatient clinic and died at home without admission.
Conclusion : Primary care clinics that deal with the cancer patients treated completely in the clinics or home terminal care should participate in the Japanese National Cancer survey.

Objective: Optimizing the time of ingestion and avoiding overdose are important aspects of medication therapy.  However, seeking explanations for selecting the time of ingestion and maximum dose for a certain drug is time consuming.  The aim of this study is to develop a database (DB) that enables a rapid search of the basis for the time of ingestion and maximum dose setting.
Methods: The basis for the time of ingestion and maximum dose setting were surveyed for 38 and 184 drugs, respectively.  Package inserts, interview forms, and other documents preserved in our department were surveyed, and this was followed by an inquiry of the staff of pharmaceutical companies.  Standard responses to a prescription with incorrect timing or dosage were determined and included into a DB together with information whose quality was dissected.  The efficiency of DB was evaluated: the time taken to obtain information and consistency of inquiries to clarify doubts concerning prescription with the use of DB and without the use DB were compared.
Results: The information of newer drugs, but not of the older drugs, were easily obtained without the need to inquire the staff of the pharmaceutical companies.  Operation of the DB was convenient and was acceptable for most pharmacists working in our department.  The DB markedly reduced the time taken to obtain information.  Further, with the aid of DB, the consistency in the responses to inquiries to clarify doubts concerning a pharmacist’s recommendation was remarkably increased.
Conclusion: The DB developed in the present study may contribute to the improvement of not only the efficiency but also the quality of dispensation.

Tissue engineering and bone regeneration techniques using mesenchymal stem cells (MSCs) have started to be applied to the field of oral and maxillofacial surgery. Clinically, a shortened treatment time and improved efficiency are necessary because of the patients' needs and the running cost of cell culture. In the present study, the cultivation process for human MSCs (hMSCs) was examined by regulating the Wnt signaling pathway. We activated Wnt signaling with LiCl and inhibited Wnt signaling with sFRP-3 (secreted Frizzled-Related Protein-3). The proliferation of LiCl-treated hMSCs was examined by studying the cell growth rate and performing BrdU assays. Osteogenic differentiation of sFRP-3-treated hMSCs was examined by alizarin red staining, and osteogenic gene expression on days 7 and 14 after induction was examined by reverse-transcription polymerase chain reaction (RT-PCR) analysis and quantitative real-time RT-PCR analysis. LiCl-treated hMSCs showed increased cell numbers and BrdU-positive cells as compared to the untreated cells. Alizarin red staining showed early mineralization of hMSCs on day 7 of the sFRP-3 treatment. A high expression level of the alkaline phosphatase gene on days 7 and 14 of sFRP-3 treatment was also demonstrated. These results suggest that the regulation of the Wnt signaling pathway contributes to the increased cell numbers and the early osteogenic differentiation of hMSCs. This study supports the possibility that the regulation of the Wnt signaling pathway contributes to the development of effective and efficient bone regeneration techniques.

There have been concerns that neuraminidase inhibitors (oseltamivir, zanamivir, laninamivir, and peramivir) cause neuropsychiatric adverse events (NPAEs).  We evaluated the number of relevant reports, reporting ratio, and reporting odds ratio (ROR) by using spontaneous reporting database, such as the Japanese Adverse Drug Event Report (JADER) (April 2004 to July 2014).  The RORs of oseltamivir, zanamivir, laninamivir, and peramivir were 11.8 (95% confidence interval (CI), 10.8-13.0), 47.0 (95% CI, 40.0-55.3), 9.5 (95% CI, 6.8-13.2), and 3.3 (95% CI, 2.1-5.1), respectively.  The lower limit of the ROR 95% CI of NPAEs of all neuraminidase inhibitors was ≥1.  We analyzed the association of age and gender with NPAEs in patients treated with oseltamivir using a logistic regression model.  The adjusted ROR of NPAEs was 66.9 (95% CI, 50.3-88.9) in male patients treated with osletamivir aged 10-19 years.  The adjusted RORs of NPAEs were increased in male and female patients under the age of 20 years.  Neuraminidase inhibitors including oseltamivir treatment could be associated with NPAEs.  Therefore, these drugs should be used carefully in clinical practice.

Introduction: Dermatological disorders are one of the adverse events caused by cancer chemotherapy and are a dose-limiting factor for some anti-neoplastic agents.  The severe symptoms associated with these disorders affect the patients’ quality of life (QOL).  Early countermeasures for the onset of dermatological disorders associated with anti-neoplastic agent administration might be important.
Materials and Methods: We analyzed the occurrences of dermatological disorders after administration of an anti-neoplastic agent in the Food and Drug Administration Adverse Event Reporting System (FAERS), and compared the adverse event (AE) reporting ratio of the total reports.  In addition, we studied the association between anti-neoplastic agents and dermatological disorders using cluster analysis.  Reports for 15 anti-neoplastic agents (4 anti-neoplastic agents and 11 molecular target drugs) were analyzed.
Results: After excluding duplicate data in FAERS, 6,157,897 reports were analyzed.  The number of reports that showed a dermatological disorder was 534,934.  The reporting ratio of hand-foot syndrome with sorafenib and capecitabine was 11.20% and 7.05%, respectively.
Conclusions: We set the cluster number at six; cluster features obtained were as follows: (1) the reporting ratio of hand-foot syndrome was especially high, followed by the reporting ratio of rash, (2) the reporting ratio of rash and erythema was high.  Similar anti-neoplastic agents may demonstrate similar occurrence tendencies of AEs and cluster features.  Further studies are required to draw conclusions over these findings.  Information services based on the feature of each cluster might be useful to improve patient QOL at the clinical site.

This study aimed to explore the association between various levels of training-energy expenditure (TrEE) and nutritional response during the phases of periodization among male collegiate rugby players. Seventeen Japanese male collegiate rugby players were enrolled in the study. Their TrEE and dietary intake were assessed each day during three separate microcycle training phases in the preparatory phase of periodization (P1 and P2: general training phase consisting of two sessions per day over the term during which the school held classes and during a summer vacation, respectively; and P3: intensive training phase consisting of four sessions per day during a summer vacation) using the factorial method and dietary records, respectively. The TrEE for P3 (1644±273 kcal) was significantly higher than that for P1 (891±230 kcal). However, the total energy intake (EI) for P3 (3274±889 kcal) was significantly lower than that for P1 (3978±938 kcal). The daytime (after waking in the morning and before the evening training session) EI (242±159 kcal) and protein intake (19±12 g) from the ‘high-protein foods group’ during P3 was significantly reduced compared with that during P1 (465±252 kcal, 37±15 g), whereas, EI and carbohydrate intake from the ‘supplements group’ of P3 was significantly increased compared with P1. The increased TrEE during P3 was not compensated by EI; instead, there was a decreased nutrient intake from the high-protein foods group and increased intake from the supplements group. The time of day of multiple or intensive training sessions, i.e. different TrEE, might affect the food choices made by male rugby players.

In Japan, the National Health Insurance (NHI) prices of new drugs are set according to the NHI Drug Price Standard (NHI Price Standard).　The NHI Price Standard was notified by the Ministry of Health, Labour, and Welfare based on the ”Drug Price Calculation Criteria” proposed by the Central Social Insurance Medical Council (Chuikyo) in Japan.　The NHI Price Standard affects the research and development strategy of pharmaceutical companies.　In order to discover undetected relationships, the factors influencing the ”drug price” were evaluated through the association rule mining technique.　We surveyed the Chuikyo‐documents about NHI price listing over the period October 27, 2006 to February 8, 2007.　The number of approved new drugs was 874, while that of drugs completed (”drug price per day”) was 314.　The numbers of new compounds corresponding to a drug price per day of ”below 200 yen,” ”between 200 yen and 1,000 yen,” ”between 1,000 and 10,000 yen,” and ”above or equal to 10,000 yen” were 87 (27.7%), 91 (29.0%), 79 (25.2%), and 57 (18.2%), respectively.　In the association rule mining method, we observed high lift values of the combined items ”above or equal to 30,000 patients expected to be administrated” and ”drugs affecting sensory organs” in the group of drug price per day below 200 yen.　The lift values of the combinations of ”biological preparations” and ”similar efficacy comparison‐based price setting (Ⅱ)” or ”below 30,000 patients expected to be administrated” and ”antineoplastic drug” in the group of ”above or equal to 10,000 yen of drug price per day” were high.　These results provide a basis for the development and application of new drugs in Japan.