Japan National Institute of Public Health

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Shimura T.,Japan National Institute of Public Health
International Journal of Radiation Biology | Year: 2017

Purpose: Radiotherapy (RT) is a powerful tool in the treatment of cancer, having the advantage of preserving normal tissues. Clinical outcomes of RT are significantly improved by technological advances, enabling increased radiation doses directed very specifically to a tumor. However, tumor radioresistance remains a major impediment to effective RT. We have shown that human tumor cells surviving after repeated exposure to fractionated radiation (FR) of X-rays for 1 month have acquired radioresistance through constitutive activation of AKT and downstream cyclin D1 nuclear retention. Tumor radioresistance is also proposed to be an intrinsic characteristic of cancer stem cells (CSC), whose efficient DNA repair is thought to confer this phenotype. We have isolated radioresistant CD133-positive cells following exposure to long-term FR. These cells exhibited the CSC phenotype with activation of the AKT/cyclin D1 pathway. In this review, I summarize our current understanding of the molecular mechanisms underlying tumor radioresistance and propose a strategy for overcoming radioresistance by targeting the AKT/cyclin D1 pathway. Conclusion: Two different mechanisms: acquired radioresistance of surviving tumor cells after RT and intrinsic radioresistance of CSC are associated with tumor radioresistance. Inhibition of the AKT pathway results in radiosensitization of both types of tumor radioresistance. © 2016 National Institute of Public Health.

Shimura T.,Japan National Institute of Public Health | Fukumoto M.,Tohoku University | Kunugita N.,Japan National Institute of Public Health
Cell Cycle | Year: 2013

The health-related hazards resulting from long-term exposure to radiation remain unknown. Thus, an appropriate molecular marker is needed to clarify these effects. Cyclin D1 regulates the cell cycle transition from the G1 phase to the S phase. Cyclin D1 is degraded as a G1/S checkpoint after 10 Gy of single acute radiation exposure, whereas conversely, cyclin D1 is stabilized when human tumor cells are exposed to fractionated radiation (FR) with 0.5 Gy of x-rays for 31 d. In this article, we review new findings regarding cyclin D1 overexpression in response to long-term exposure to FR. Cyclin D1 overexpression is associated with induction of genomic instability in irradiated cells. Therefore, repression of cyclin D1 expression is likely to cancel the harmful effects of long-term exposure to FR. Thus cyclin D1 may be a marker of long-term exposure to radiation and is a putative molecular radioprotection target for radiation safety. © 2013 Landes Bioscience.

Fujiwara T.,Japan National Institute of Public Health | Kawakami N.,University of Tokyo
Journal of Psychiatric Research | Year: 2011

It is well known that childhood adversities (CAs) are a significant risk factor for mental disorders in later life. However, it is uncertain whether a similar association between CAs and mental disorders can be found in Japan. Few studies have employed an appropriate statistical model that takes into account the high comorbidity of CAs. The purpose of this study is to elucidate the association between CAs and the onset of mental disorders in Japan. We used the data from the World Mental Health Japan, 2002-2004 (n= 1722). Respondents completed diagnostic interviews (the World Health Organization Composite International Diagnostic Interview) that assessed lifetime prevalence of 15 Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV) disorders. Associations of 12 retrospectively reported CAs with the lifetime prevalence of mental disorders were estimated using discrete-time survival analysis. Of the study sample, 32% reported as having experienced at least 1 CA during childhood. The studied CAs were highly comorbid. Parental mental illness showed significant sub-additive effects. The presence of 3 CAs showed a significant interactive effect on any mental health disorder. The number of CAs had a strong interactive effect on the onset of anxiety disorders. Predictive effects of CAs were found only among childhood onset mental disorders. It was confirmed that CAs are one of predictors of the onset of DSM-IV mental disorders, especially during childhood, in Japan. © 2010 Elsevier Ltd.

Tango T.,Center for Medical Statistics | Takahashi K.,Japan National Institute of Public Health
Statistics in Medicine | Year: 2012

Spatial scan statistics are widely used tools for detection of disease clusters. Especially, the circular spatial scan statistic proposed by Kulldorff (1997) has been utilized in a wide variety of epidemiological studies and disease surveillance. However, as it cannot detect noncircular, irregularly shaped clusters, many authors have proposed different spatial scan statistics, including the elliptic version of Kulldorff's scan statistic. The flexible spatial scan statistic proposed by Tango and Takahashi (2005) has also been used for detecting irregularly shaped clusters. However, this method sets a feasible limitation of a maximum of 30 nearest neighbors for searching candidate clusters because of heavy computational load. In this paper, we show a flexible spatial scan statistic implemented with a restricted likelihood ratio proposed by Tango (2008) to (1) eliminate the limitation of 30 nearest neighbors and (2) to have surprisingly much less computational time than the original flexible spatial scan statistic. As a side effect, it is shown to be able to detect clusters with any shape reasonably well as the relative risk of the cluster becomes large via Monte Carlo simulation. We illustrate the proposed spatial scan statistic with data on mortality from cerebrovascular disease in the Tokyo Metropolitan area, Japan. © 2012 John Wiley & Sons, Ltd.

Hiratsuka Y.,Japan National Institute of Public Health
Japanese Journal of Ophthalmology | Year: 2011

Purpose To evaluate the cost-effectiveness of cataract surgery through measurement of the cost per qualityadjusted life-year (QALY) in Japan. Methods A total of 549 patients scheduled for cataract surgery at 12 clinical sites from November 2008 through February 2010 were included in the study. Prospective assessment of patient preference-based quality of life (utility) was performed before and after the surgery using the time tradeoff method, EuroQol, and Health Utilities Index Mark 3. Multiple regression analysis was used to determine the correlation between utility and visual acuity. The QALYs gained through cataract surgery were estimated, and cost-utility analysis was performed.Results The utilities significantly correlated with the visual acuity in the better seeing eye. In all the subgroups (first eye surgery, second eye surgery, and bilateral surgery), mean utility improvement was statistically significant. Average QALYs for unilateral cataract surgery and bilateral cataract surgery were 2.40 and 3.40, respectively. The cost per QALY gained from surgery was estimated at y122,472 (US $1,307) for unilateral surgery and y145,562 (US $1,553) for bilateral surgery.Conclusions Routine cataract surgery in Japan is highly cost-effective. Factors that contribute to this are the high clinical effectiveness of the surgery, the substantial improvement in patient-perceived quality of life, and the reasonable cost of the surgery. © Japanese Ophthalmological Society 2011.

Background: Evidence is lacking on whether health guidance for metabolic syndrome reduces health care expenditures. The author used propensity-score matching to evaluate the effects of health guidance on health care expenditure. Methods: Men who did and did not receive health guidance from a health insurance society (approximately 60 000 covered lives) were matched (n = 397 respectively) using propensity scores. Health insurance claims were compared using cumulative health care expenditures for metabolic syndrome-related outpatient medical care and drug costs for the period from the initial consultation to 3 years later. Results: No difference was observed between intervention and control groups in cumulative outpatient charges or drug costs related to metabolic syndrome. However, regression analysis using the Tobit model showed that health guidance resulted in a small, nonsignificant reduction in health care expenditure. Conclusions: Health guidance for metabolic syndrome did not reduce outpatient charges or drug costs related to metabolic syndrome during the 3-year period after the intervention. Findings from Tobit regression suggest that health guidance might eventually result in savings, but this hypothesis remains untested. © 2013 Japan Epidemiological Association.

Okamoto E.,Japan National Institute of Public Health
Journal of Epidemiology | Year: 2014

Background: Japan's National Database (NDB) includes data on health checks and health insurance claims, is linkable using hash functions, and is available for research use. However, the linkage rate between health check and health insurance claims data has not been investigated. Methods: Linkage rate was evaluated by comparing observed medical and pharmaceutical charges among health check recipients in fiscal year (FY) 2009 (N = 21 588 883) with expected charges from the same population when record linkage was complete. Using the NDB, observed charges were estimated from the first published result of linking health check recipients in FY2009 and their health insurance claims in FY2010. Expected charges were estimated by combining 3 publicly available datasets, including data from the Medical Care Benefit Survey and an ad-hoc report by the Japan Health Insurance Association. Results: Only 14.9% of expected charges were linked by the NDB. The linkage rate was higher for women than for men (18.2% vs 12.4%) and for elderly adults as compared with younger adults (>25% vs <10%). Conclusions: The linkage rate in the NDB was so low that any research linking health check and health insurance claims will not be reliable. Causes for the low linkage rate include differences between health check and health insurance claims data in name format (eg, insertion of a space between family and given names) and date of birth (Japanese vs Gregorian calendar). Investigation of the causes for the low linkage rate and measures for improvement are urgently needed. © 2013 Etsuji Okamoto.

Morikawa M.,Japan National Institute of Public Health
International Journal of Integrated Care | Year: 2014

Introduction: In 2000, Japan implemented a mandatory long-term care insurance system.With the rapid growth of the system, problems became apparent. Several critical alterations were made to long-term care insurance system, particularly with respect to integrated care. Methods: This paper elucidates the policy trends that led to the reforms of the long-term care insurance system, which included new concepts of 'integrated care' and 'community-based care', an agenda of cost containment and service streamlining, and coordination with medical care. Results: Community-based integrated care, as envisaged in the long-term care policy, includes not only the integration of medical care into service provision but also the inclusion of the informal mutual aid, oversight of for-profit providers by an administration that ensures users are not exploited and coordination between systems that cover different geographical areas. Conclusions: Japan's experience in community-based care integration suggests that this project requires multi-faceted care integration in local communities. In the future, it will be necessary to conduct empirical assessments of the effectiveness of these measures.

Tsutsui T.,Japan National Institute of Public Health
International Journal of Integrated Care | Year: 2014

Background: Since 10 years ago, Japan has been creating a long-term vision to face its peak in the number of older people that will be reached in 2025 when baby boomers will turn 75 years of age. In 2003, the government set up a study group called "Caring for older people in 2015" which led to a first reform of the Long-Term Care Insurance System in 2006. This study group was the first to suggest the creation of a community-based integrated care system. Reforms: Three measures were taken in 2006: 'Building an active ageing society: implementation of preventive care services', 'Improve sustainability: revision of the remuneration of facilities providing care' and 'Integration: establishment of a new service system'. These reforms are at the core of the community-based integrated care system. Discussion: The socialization of long-term care that came along with the ageing of the population, and the second shift in Japan towards an increased reliance on the community can provide useful information for other ageing societies. As a super ageing society, the attempts from Japan to develop a rather unique system based on the widely spread concept of integrated care should also become an increasing focus of attention.

Hiratsuka Y.,Japan National Institute of Public Health
Japanese Journal of Ophthalmology | Year: 2013

Objective: To evaluate with the best available clinical data in Japan the cost-effectiveness of cataract surgery through the estimation of the incremental costs per quality-adjusted life years (QALYs) gained. Methods: A Markov model with a probabilistic cohort analysis was constructed to calculate the incremental costs per QALY gained by cataract surgery in Japan. A 1-year cycle length and a 20-year horizon were applied. Best available evidence in Japan supplied the model with data on the course of cataract surgery. Uncertainty was explored using univariate and probabilistic sensitivity analysis. Results: In base case analysis, cataract surgery was associated with incremental costs of Japanese yen (¥) 551,513 (US$ 6,920) and incremental effectiveness of 3.38 QALYs per one cataract patient. The incremental cost effectiveness ratio (ICER) was ¥ 163,331 (US$ 2,049) per QALY. In Monte Carlo simulation, the average patient with cataract surgery accrued 4.65 [95 % confidence interval (CI): 2.75-5.69] more QALYs than patients without surgery, giving an ICER of ¥ 118,460 (95 % CI: 73,516-207,926) (US$ 1,486) per QALY. Conclusions: Cataract surgery in Japan is highly cost-effective even when allowing for the uncertainty of the known variability that exists in estimates of the costs, utilities, and postoperative complication rate. © 2013 Japanese Ophthalmological Society.

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