The purpose of this study was to determine the influence of a 6-month unsupervised, flexible and fairly light intensity walking program on endurance fitness, strength, lipids and lipoproteins and bone health in a group of middle-aged sedentary women. Six pre-menopausal and 8 post-menopausal women, aged 54 yr, served as the walk training group (W) and 9 women (2 post-menopausal), aged 49yr, served as controls (C) . W walked an average of 10, 000 steps per day for 6 months, which included an average of 5, 000 steps of brisk walking for 30 min, 4 to 5 days per week. Workloads, heart rates and double-product break point (during incremental maximal ergometer exercise), body weight and %fat, serum lipids, leg strength and bone density (by ultrasound) and induces of bone metabolism were measured at baseline and after 3 and 6 months. Walk training in W resulted in a significant improvement in maximal workload during the exercise test compared with C. Double product break point in W during exercise significantly shifted towards higher workloads and resting heart rate was reduced. Isokinetic muscular strength of leg extensors and abdominal muscular endurance measured by situps were also significantly increased in W. Estimated calcaneal bone density showed a tendency to increase after 6 months of training in W. Indicators of bone resorption and growth remained unchanged. Changes in serum lipids and lipoproteins were also favorable, but not significant. In conclusion, these results show that a flexible and self-regulated walking program is sufficient to elicit improvements in cardiovascular endurance, aerobic capacity measured by DPBP and strength of leg and abdominal muscles. Bone strength and serum lipids were not clearly improved after 6 months with this walking program. If training time were extended to 12 months, significant improvements in these measures can be expected because tendencies toward improvements were observed.

Purpose: In terminally ill patients with advanced cancer,it is recognized that delirium is reversible in 20-50% of the patients with it. Identification of its cause is vital to ensure the quality of life of the patients with delirium at the end of life. We would like to report a case of the advanced cervical cancer patient with delirium, successfully treated by intravenous administration of vitamin B1. Case: An 83-year-old woman, who was diagnosed the advanced cervical cancer with carcinomatous peritonitis, was admitted to Shizuoka Cancer Center Palliative Care Unit. Four days after the admission, she presented sleep-wake cycle disturbance, poor attention, poor concentration,and short-term memory loss, and these conditions were diagnosed with delirium. Vitamin B1 deficiency was suspected by normal examinations including laboratory results and head computed tomography except for the low level (19ng/ml) of vitamin B1. One week after starting intravenous administration of vitamin B1, the symptoms of delirium were improved. Conclusion: In this case, delirium by vitamin B1 deficiency developed even though having adequate oral intake (about 1,000kcal/day), indicating malabsorption of vitamin B1 due to hypoperistalsis and edema of the bowel. Advanced cancer patients can easily develop vitamin B1 deficiency due to inadequate oral intake, increased consumption of vitamin B1 and malabsorption of vitamin B1. Therefore,the examination of vitamin B1 deficiency is necessary for patients with delirium that cannot be specified. Palliat Care Res 2009; 4(2): 330-333

A Task Force team consisting of members from pharmaceutical companies --a central player to develop and implement RMP (Risk Management Plan)-- as well as health care professionals and members from academia was established in JSPE. The Task Force developed guidance for scientific approach to practical and ICH-E2E-compliant Pharmacovigilance Plan (PVP) stated in Japanese Risk Management Plan issued in April 2012 by the Ministry of Health, Labour and Welfare. The guidance contains the following topics.
1．Introduction: JSPE's activities and this task force's objectives for pharmacovigilance activities
2．How to select Safety Specification (SS) and describe its characteristics
・Selection of SS
・Characterization of SS
・Association with Research Questions (RQ)
3．How to define and describe RQ
・What is RQ ?
・RQ interpretation in other relevant guidelines
・Methodology to develop RQ for PVP with examples
・Best approach to integrating PVP for whole aspects of safety concern
4．How to optimize PVP for specific RQ
・Routine PVP or additional PVP ?
・Additional PVP design (RQ and study design, RQ structured with PICO or GPP's research objectives, specific aims, and rationale)
・Checklist to help develop PVP
5．Epilogue:
・What can/should be “Drug use investigation” in the context of ICH-E2E-compliant PVP.
・Significance of background incidence rate and needs for comparator group
・Infrastructure for the future PVP activities
6．Appendix: Checklist to help develop PVP activities in RMP
The task force team is hoping that this guidance help develop and conduct SS and PVP in accordance with ICH E2E, as stated in Japanese Risk Management Plan Guideline.

The Standardized Structured Medical record Information eXchange (SS-MIX) was started in 2006 as the project supported by the Ministry of Health, Labour and Welfare (MHLW) for promoting the exchange of the standardized medical information. Free soft wares developed in the project allow the storage of medical information to receive HL7 messages for prescription, laboratory test results, diagnoses and patient demographics in the hospital information system (HIS). We encourage the use of the SS-MIX standardized storage for postmarketing surveys and clinical studies. The recommendations consist of the following 7 parts. [1] In surveys and clinical studies, the information of drugs and laboratory test results in the SS-MIX standardized storage can be directly transferred to the electronic questionnaire and the investigators may obtain the information with high accuracy and granularity. [2] The SS-MIX standardized storage works as the backup system for the HIS because it can provide the minimum information essential in patient care even under the disastrous condition like earthquake or unexpected network failure. [3] The SS-MIX standardized storage may be useful to conduct a good pharmacoepidemiology study not only because it provides the information in the storage efficiently but also it can be used to identify “new users” who started the drug after some period of non-use.The “new user” design is often essential to have the unbiased results. [4] When the drug company conducts postmarketing surveys according to the current regulation, the use of the SS-MIX standardized storage will facilitate the fast and efficient collection of data to develop the timely measure to minimize the drug-related risk. With the SS-MIX standardized storage, it is also expected that many types of study design can be employed and the quality of data is improved in the survey. [5] The SS-MIX standardized storage maybe also useful to evaluate the risk minimization action plan by comparing the prescription pattern or incidence of the targeted adverse event between two periods before and after the implementation of the action plan. [6] In planning clinical trials, the SS-MIX standardized storage may be used to estimate the size of eligible patients. The storage may also allow conducting cross-sectional studies to know characteristics of diseases or drug treatment. In addition, cohorts of those who had coronary artery angiography, new users of a drug and those with a rare disease may be readily identified. Using such cohorts, investigators can initiate a case-control study nested within the cohort, pharmacogenomic studies and comparative effectiveness researches. [7] The SS-MIX standardized storage may be used as the formal data source in clinical trials in the future when some conditions are satisfied. For instance, the formal agreement should be reached between industry, government and academia on the use of standards of data structure in Clinical Data Interchange Standards Consortium (CDISC) and on the operation of computerized system validation (CSV) in the clinical trials.

OBJECTIVE: Programmed cell death-ligand 1 (PD-L1) is expressed in tumor cells and has been shown to predict clinical outcomes of several types of malignancies. The aim of this study was to investigate the effects of carbon-ion (C-ion) beam irradiation on PD-L1 expression in human uterine cervical adeno/adenosquamous carcinoma (UCAA) cells and clinical samples and to identify the prognostic factors for outcomes after C-ion radiotherapy (CIRT).METHODS: The effects of C-ion irradiation on PD-L1 expression in human UCAA and cervical squamous cell carcinoma cells were examined by flow cytometry. We examined PD-L1 expression in UCAA biopsy specimens from 33 patients before CIRT started (pre-CIRT) and after 12 Gy (relative biological effectiveness [RBE]) irradiation (post-12Gy-C) in 4 fractions of CIRT to investigate the correlation between PD-L1 status and clinical outcomes.RESULTS: The PD-L1 expression was upregulated by C-ion beam in a dose-dependent manner in HeLa and SiHa cells through phosphorylated Chk1. The overall frequencies of pre-CIRT and post-12Gy-C PD-L1 positivity were 45% (15/33) and 67% (22/33), respectively. The post-12Gy-C PD-L1 expression was significantly elevated compared to the pre-CIRT PD-L1 expression. There was no significant relationship between the pre-CIRT PD-L1 status and clinical outcomes, such as local control (LC), progression-free survival (PFS), and overall survival (OS). However, the post-12Gy-C PD-L1 expression had better correlation with PFS, but not with LC and OS.CONCLUSION: CIRT can induce PD-L1 expression in UCAA and we propose that PD-L1 expression after starting CIRT may become as a predictive prognostic marker in CIRT for UCAA.
Antigens, CD274 ; Biopsy ; Carcinoma, Squamous Cell ; Disease-Free Survival ; Flow Cytometry ; Heavy Ion Radiotherapy ; Humans ; Radiotherapy ; Treatment Outcome ; Uterine Cervical Neoplasms

OBJECTIVE: Programmed cell death-ligand 1 (PD-L1) is expressed in tumor cells and has been shown to predict clinical outcomes of several types of malignancies. The aim of this study was to investigate the effects of carbon-ion (C-ion) beam irradiation on PD-L1 expression in human uterine cervical adeno/adenosquamous carcinoma (UCAA) cells and clinical samples and to identify the prognostic factors for outcomes after C-ion radiotherapy (CIRT). METHODS: The effects of C-ion irradiation on PD-L1 expression in human UCAA and cervical squamous cell carcinoma cells were examined by flow cytometry. We examined PD-L1 expression in UCAA biopsy specimens from 33 patients before CIRT started (pre-CIRT) and after 12 Gy (relative biological effectiveness [RBE]) irradiation (post-12Gy-C) in 4 fractions of CIRT to investigate the correlation between PD-L1 status and clinical outcomes. RESULTS: The PD-L1 expression was upregulated by C-ion beam in a dose-dependent manner in HeLa and SiHa cells through phosphorylated Chk1. The overall frequencies of pre-CIRT and post-12Gy-C PD-L1 positivity were 45% (15/33) and 67% (22/33), respectively. The post-12Gy-C PD-L1 expression was significantly elevated compared to the pre-CIRT PD-L1 expression. There was no significant relationship between the pre-CIRT PD-L1 status and clinical outcomes, such as local control (LC), progression-free survival (PFS), and overall survival (OS). However, the post-12Gy-C PD-L1 expression had better correlation with PFS, but not with LC and OS. CONCLUSION CIRT can induce PD-L1 expression in UCAA and we propose that PD-L1 expression after starting CIRT may become as a predictive prognostic marker in CIRT for UCAA.

Aims: This study aimed at investigating the status of polypharmacy and the experience and perception of bereaved family members of patients with advanced cancer regarding the burden of oral medication. Methods: Self-administered questionnaires were mailed to 303 bereaved family members of patients with advanced cancer, and 102 valid responses were analyzed (response rate, 33.7%). Results: The number of patients in the polypharmacy group (patients taking six or more tablets at a time) was 65 and that in the non-polypharmacy group (patients taking less than six tablets at a time) was 37. The percentage of bereaved family members who felt that the oral administration burden of patients was significantly higher in the polypharmacy group (43.1% vs. 10.8%, p<0.01). The results of the analysis indicated that the bereaved families wanted to reduce the number of tablets taken at a time for alleviating the burden of polypharmacy. The bereaved families of patients in the polypharmacy group were greatly concerned that the number of oral medications was too large. They also expressed the need for medical staff from whom they could seek explanation and counseling regarding the oral medication of patients. Conclusion: It is suggested that medical staff need to be fully aware of the concerns of patients’ families regarding drugs besides checking the compliance status.