Objective: To validate and recalibrate Charlson and Elixhauser comorbidity indices (CCI and ECI, respectively) in a Japanese hospital-based administrative database.Methods: In this retrospective, cohort study, derivation and validation cohorts were developed to include all hospitalizations for patients aged ≥ 18 years at admission and discharged in 2015 or 2016, respectively, from an administrative database based on 287 hospitals. Seventeen CCI and 30 ECI conditions were identified using the International Classification of Diseases (ICD) -10 codes at admission or during the stay. Predictability for hospital death was evaluated using C statistics from multivariable logistic regression models including age, sex, and individual CCI/ECI conditions or the CCI/ECI score in the derivation cohort. After stepwise selection, weighted risk scores were re-assigned to each condition based on the odds ratios (CCI) or beta-coefficient (ECI), and these modified models were evaluated in the validation cohort.Results: The original CCI/ECI had good predictive abilities for hospital death: C statistics (95% confidence interval) for individual comorbidities and score models were 0.764 (0.762-0.765) and 0.731 (0.729-0.733) for CCI, and 0.783 (0.781-0.784) and 0.750 (0.748-0.752) for ECI, respectively. Modified CCI and ECI had 13 and 27 conditions, respectively, but maintained comparable predictive abilities: C statistics for modified individual comorbidities and score models were 0.761 (0.759-0.763) and 0.759 (0.757-0.760) for CCI, and 0.784 (0.782-0.785) and 0.783 (0.781-0.785) for ECI, respectively.Conclusions: The original and modified CCI/ECI models, with reduced numbers of conditions, had sufficient and comparable predictive abilities for hospital death and can be used in future studies using this administrative database.

Objective: The Charlson and Elixhauser comorbidity indices (CCI and ECI, respectively) are widely used to study comorbid conditions but these indices have not been validated in Japanese datasets. In this study, our objective was to validate and recalibrate CCI and ECI in a Japanese insurance claims database.Methods: All hospitalizations for patients aged≥18 years discharged between January 2011 and December 2016 were randomly allocated to derivation and validation cohorts. Predictability for hospital death and re-admission was evaluated using C statistics from multivariable logistic regression models including age, sex, and individual CCI/ECI conditions at admission month or the derived score in the derivation cohort. After stepwise variable selection, weighted risk scores for each condition were re-assigned using odds ratios (CCI) or beta coefficients (ECI). The modified models were evaluated in the validation cohort.Results: The original CCI/ECI had good discriminatory power for hospital death: C statistics (95％ confidence interval) for individual comorbidities and score models were 0.845 (0.835-0.855) and 0.823 (0.813-0.834) for CCI, and 0.839 (0.828-0.850) and 0.801 (0.790-0.812) for ECI, respectively. Modified CCI and ECI had reduced numbers of comorbidities (17 to 10 and 30 to 21, respectively) but maintained comparable discriminatory abilities: C statistics for modified individual comorbidities and score models were 0.843 (0.833-0.854) and 0.838 (0.827-0.848) for CCI, and 0.840 (0.828-0.852) and 0.839 (0.827-0.851) for ECI, respectively.Conclusions: The original and modified models showed comparable discriminatory abilities and both can be used in future studies using insurance claims databases.

MHLW released a guideline for Risk Management Plan (RMP) in April 2012, in order to manage the risk of pharmaceutical products from the development stage towards post marketing period. The guideline suggests to determine Safety Specification and to develop Pharmacovigilance Plan (PVP) and Risk Minimization Plan aligned to the ICH E2E guideline. However, in some of the RMPs, which had been published online (as of August 2014), conventional (Special) Drug Use Results Surveys are planned as a “universal” PVP regardless of the impact, severity and characteristics of the risks. Our JPMA taskforce (Data Science Expert Committee) summarized report and published in August 2014. In this report, we explained how to evaluate safety events based on evidence level for safety specification and how to develop PVP. Also, we would like to propose KAIZEN activities for RMP improvement as follows:
1. In order to clarify the research question, rationale and evidence for safety specification should be evaluated carefully.
2. It is essential to be considered in advance how to collect and analyze the safety data for detecting safety specification during clinical development.
3. Safety profiles should be discussed thoroughly on DSUR development among stakeholders in order to clarify safety specification at NDA. Research questions for each different risk and missing information should be established according to PECO, which will flow into appropriate PVP planning.
4. Continuous PDCA cycling is critical for RMP. The first survey or research will bring you next research question (s).
We expect all stakeholders, including clinical development specialists in industry, regulatory authorities, and academia, to have better understating of RMP principle and to manage and implement it more appropriately in a scientific manner.

Placenta previa presents a highest risk to pregnancy, and placenta accreta is the most serious. Placenta accreta requires cesarean delivery and often results in massive obstetric hemorrhage and higher maternal morbidity. Challenges associated with cesarean delivery techniques may contribute to increased maternal blood loss and morbidity rates. Several recent obstetric studies reported the usefulness of transverse uterine fundal incision for managing placenta accreta. We present a case of placenta percreta that was treated by a transverse fundal incision. We successfully avoided cutting through the placenta and helped decrease maternal blood loss. After delivery, the patient underwent a cesarean hysterectomy. Postoperative day 48, she experienced watery discharge and was diagnosed with vaginal fistula. We present our case and review the literature.
Hemorrhage ; Humans ; Hysterectomy* ; Placenta ; Placenta Accreta* ; Placenta Previa ; Pregnancy ; Vaginal Fistula*

In this summary, we reviewed Japanese large databases available as pharmacoepidemiology data sources. In addition to the National Claims Database, two commercially available insurance claims databases are widely used: Japan Medical Data Center(JMCD) and JammNet.Three large pharmacy claims databases are also reviewed.The pharmacy claims database has unique characteristics in Japan because a prescription is valid only for four days and therefore the prescription records are believed to be almost identical to the dispensing records. Two large hospital-based databases are also available.In order to properly use these databases for the pharmacoepidemiological research questions, we need to learn first the medical practice and medical systems in Japan to have a better understanding for data source and data items. Automated large databases can be a powerful tool for pharmacoepidemiology studies by learning strengths and limitations of each database. (Jpn J Pharmacoepidemiol 2012; 17(2): 135-144)

Prostate cancer is the most prevalent cancer in males in Western countries. The reported incidence in Asia is much lower than that in African Americans and European Caucasians. Although the lack of systematic prostate cancer screening system in Asian countries explains part of the difference, this alone cannot fully explain the lower incidence in Asian immigrants in the United States and west-European countries compared to the black and non-Hispanic white in those countries, nor the somewhat better prognosis in Asian immigrants with prostate cancer in the United States. Soy food consumption, more popular in Asian populations, is associated with a 25% to 30% reduced risk of prostate cancer. Prostate-specific antigen(PSA) is the only established and routinely implemented clinical biomarker for prostate cancer detection and disease status. Other biomarkers, such as urinary prostate cancer antigen 3 RNA, may increase accuracy of prostate cancer screening compared to PSA alone. Several susceptible loci have been identified in genetic linkage analyses in populations of countries in the West, and approximately 30 genetic polymorphisms have been reported to modestly increase the prostate cancer risk in genome-wide association studies. Most of the identified polymorphisms are reproducible regardless of ethnicity. Somatic mutations in the genomes of prostate tumors have been repeatedly reported to include deletion and gain of the 8p and 8q chromosomal regions, respectively; epigenetic gene silencing of glutathione S-transferase Pi(GSTP1); as well as mutations in androgen receptor gene. However, the molecular mechanisms underlying carcinogenesis, aggressiveness, and prognosis of prostate cancer remain largely unknown. Gene-gene and/or gene-environment interactions still need to be learned. In this review, the differences in PSA screening practice, reported incidence and prognosis of prostate cancer, and genetic factors between the populations in East and West factors are discussed.
Asia ; epidemiology ; Asian Continental Ancestry Group ; ethnology ; genetics ; European Continental Ancestry Group ; ethnology ; genetics ; Gene Silencing ; Gene-Environment Interaction ; Genetic Predisposition to Disease ; Glutathione S-Transferase pi ; genetics ; Humans ; Incidence ; Male ; Polymorphism, Genetic ; Prostate-Specific Antigen ; blood ; Prostatic Neoplasms ; blood ; epidemiology ; ethnology ; genetics ; Survival Rate ; United States ; epidemiology

Objective: The purpose of this study was to clarify burnout and the characteristics of mental health of caregivers of elderly dementia patients, which have been little studied.Methods: The subjects of this study were 107 caregivers who were engaged in the care of dementia patients at 12 facilities in northern Kyushu. We examined age, sex, status of nursing-care related qualifications, kinds of nursing care-related qualifications, years of working experience, physical health (Present state of health and Presence of perceived ill health), status at work (Problems at work and Job stress) and satisfaction with life using the Maslach Burnout Inventory (MBI) and WHO Subjective Well-Being Inventory (SUBI). The period of survey was five months, between June 1 and October 31, 2006.Results: The most severe level of burnout was found in 27.1% of the subjects. When subjects were classified into the burnout and nonburnout groups, the burnout group represented 53.3% of the subjects. In a comparison of the scores of the SUBI subscales between the burnout and nonburnout group, significant differences were observed in almost all subscales without "Deficiency in Social Contacts."Conclusion: This study clarified that self-care of physical and mental health, family support and social support were very important in maintaining mental health and preventing burnout in caregivers of dementia patients. Improvement of working conditions was considered particularly important for social support.

Objective: Standardized clinical data are invaluable for secondary use of medical information. We constructed a standardized database and a data warehouse called D*D, based on the Standardized Structured Medical Information Exchange(SS-MIX)scheme. D*D enables physicians and researchers to perform complex searches with combined conditions, e.g. time to event. It contains data from 1999 for approximately 400,000 individual patients. The objective of this study was to provide an overview of the features of this database system, especially from the perspective of drug safety research.
Methods: Three models of research questions were identified from established drug-risk combinations:1)gatifloxacin and hypoglycemia;2)statins and rhabdomyolysis;and 3)oral 5-fluorouracil S-1 and hepatotoxicity. D*D was searched using predefined keywords and conditions.
Results: 1)A total of 3,635 patients were treated for diabetes. Among 20 diabetic patients prescribed gatifloxacin, hypoglycemia was recorded in one patient(1/38 prescriptions). 2)Among 5,926 patients who had been prescribed any statin within 10 years in our hospital, 6 patients(0.1%)experienced rhabdomyolysis. The incidence was similar to that for fibrate (1/740, 0.1%). The most confounded diagnosis was stiff shoulder. 3)Among 244 patients prescribed S-1, 19 patients(7.8%) experienced hepatotoxicity higher than CTCAE grade3 within 2 months from the prescription.
Conclusion: With limited data items and search keys in standardized data storage, definitions of exposures and outcomes require careful assessment during protocol development. Considering that the system can be implemented at more than half of the hospitals that have already installed ordering systems, D*D can be one of the Japanese models for distributed research network.

This study was conducted to clarify the validity and availability of inclination of exponential curve-fitting model for oxygen uptake (VO₂) and heart rate (HR) during incremental exercise (I-ECOH) as an index of cardio-pulmonary functional reserve in patients with ischemic heart disease (IHD). A treadmill exercise test was used to measure the VO₂(L/kg/min) and HR (beat/min) during incremental exercise of all subjects. I-ECOH was derived from the following equation : HR=A·exp^B·VO2. The constant "B" represents I-ECOH. The following two identifications were made : 1) the relation between peak oxygen uptake (VO₂peak) and I-ECOH in IHD patients with normal left ventricular function and with chronic heart failure (CHF); 2) the relation between I-ECOH and the New York Heart Association (NYHA) functional classification of IHD patients with CHF.There were significant differences among IHD patients with normal left ventricular function, CHF patients, normal controls and long distance runners in I-ECOH and VO2peak, respectively (p<0.001). There were inverse correlations between I-ECOH and VO2peak in IHD patients with normal left ventricular function (r=-0.64, p<0.001) and CHF (r=-0.63, p<0.001). I-ECOH could be used to discriminate effectively between NYHA functional classes (p<0.001).In conclusion, these results suggest that I-ECOH is adequate and useful as an index of cardio-pulmonary functional reserve in patients with ischemic heart disease.