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1.  Association between Combined Lifestyle Factors and Non-Restorative Sleep in Japan: A Cross-Sectional Study Based on a Japanese Health Database 
PLoS ONE  2014;9(9):e108718.
Background
Although lifestyle factors such as cigarette smoking, excessive drinking, obesity, low or no exercise, and unhealthy dietary habits have each been associated with inadequate sleep, little is known about their combined effect. The aim of this study was to quantify the overall impact of lifestyle-related factors on non-restorative sleep in the general Japanese population.
Methods and Findings
A cross-sectional study of 243,767 participants (men, 39.8%) was performed using the Specific Health Check and Guidance System in Japan. A healthy lifestyle score was calculated by adding up the number of low-risk lifestyle factors for each participant. Low risk was defined as (1) not smoking, (2) body mass index<25 kg/m2, (3) moderate or less alcohol consumption, (4) regular exercise, and (5) better eating patterns. Logistic regression analysis was used to examine the relationship between the score and the prevalence of non-restorative sleep, which was determined from questionnaire responses. Among 97,062 men (mean age, 63.9 years) and 146,705 women (mean age, 63.7 years), 18,678 (19.2%) and 38,539 (26.3%) reported non-restorative sleep, respectively. The prevalence of non-restorative sleep decreased with age for both sexes. Compared to participants with a healthy lifestyle score of 5 (most healthy), those with a score of 0 (least healthy) had a higher prevalence of non-restorative sleep (odds ratio, 1.59 [95% confidence interval, 1.29–1.97] for men and 2.88 [1.74–4.76] for women), independently of hypertension, hypercholesterolemia, diabetes, and chronic kidney disease. The main limitation of the study was the cross-sectional design, which limited causal inferences for the identified associations.
Conclusions
A combination of several unhealthy lifestyle factors was associated with non-restorative sleep among the general Japanese population. Further studies are needed to establish whether general lifestyle modification improves restorative sleep.
doi:10.1371/journal.pone.0108718
PMCID: PMC4182544  PMID: 25268956
2.  Budget impact analysis of chronic kidney disease mass screening test in Japan 
Background
Our recently published cost-effectiveness study on chronic kidney disease mass screening test in Japan evaluated the use of dipstick test, serum creatinine (Cr) assay or both in specific health checkup (SHC). Mandating the use of serum Cr assay additionally, or the continuation of current policy mandating dipstick test only was found cost-effective. This study aims to examine the affordability of previously suggested reforms.
Methods
Budget impact analysis was conducted assuming the economic model would be good for 15 years and applying a population projection. Costs expended by social insurers without discounting were counted as budgets.
Results
Annual budget impacts of mass screening compared with do-nothing scenario were calculated as ¥79–¥−1,067 million for dipstick test only, ¥2,505–¥9,235 million for serum Cr assay only and ¥2,517–¥9,251 million for the use of both during a 15-year period. Annual budget impacts associated with the reforms were calculated as ¥975–¥4,129 million for mandating serum Cr assay in addition to the currently used mandatory dipstick test, and ¥963–¥4,113 million for mandating serum Cr assay only and abandoning dipstick test.
Conclusions
Estimated values associated with the reform from ¥963–¥4,129 million per year over 15 years are considerable amounts of money under limited resources. The most impressive finding of this study is the decreasing additional expenditures in dipstick test only scenario. This suggests that current policy which mandates dipstick test only would contain medical care expenditure.
doi:10.1007/s10157-014-0943-8
PMCID: PMC4271136  PMID: 24515308
CKD; Budget impact; Dipstick test; Mass screening; Proteinuria; Serum creatinine assay
3.  Methylglyoxal (MG) and Cerebro-Renal Interaction: Does Long-Term Orally Administered MG Cause Cognitive Impairment in Normal Sprague-Dawley Rats? 
Toxins  2014;6(1):254-269.
Methylglyoxal (MG), one of the uremic toxins, is a highly reactive alpha-dicarbonyl compound. Recent clinical studies have demonstrated the close associations of cognitive impairment (CI) with plasma MG levels and presence of kidney dysfunction. Therefore, the present study aims to examine whether MG is a direct causative substance for CI development. Eight-week-old male Sprague-Dawley (SD) rats were divided into two groups: control (n = 9) and MG group (n = 10; 0.5% MG in drinking water), and fed a normal diet for 12 months. Cognitive function was evaluated by two behavioral tests (object exploration test and radial-arm maze test) in early (4–6 months of age) and late phase (7–12 months of age). Serum MG was significantly elevated in the MG group (495.8 ± 38.1 vs. 244.8 ± 28.2 nM; p < 0.001) at the end of study. The groups did not differ in cognitive function during the course of study. No time-course differences were found in oxidative stress markers between the two groups, while, antioxidants such as glutathione peroxidase and superoxide dismutase activities were significantly increased in the MG group compared to the control. Long-term MG administration to rats with normal kidney function did not cause CI. A counter-balanced activation of the systemic anti-oxidant system may offset the toxicity of MG in this model. Pathogenetic significance of MG for CI requires further investigation.
doi:10.3390/toxins6010254
PMCID: PMC3920260  PMID: 24402234
cerebro-renal interaction; methylglyoxal; cognitive impairment; chronic kidney disease
4.  Skin Autofluorescence Is Associated with the Progression of Chronic Kidney Disease: A Prospective Observational Study 
PLoS ONE  2013;8(12):e83799.
Background
Advanced glycation end product (AGE) accumulation is thought to be a measure of cumulative metabolic stress that has been reported to independently predict cardiovascular disease in diabetes and renal failure. The aim of this study was to evaluate the association between AGE accumulation, measured as skin autofluorescence, and the progression of renal disease in pre-dialysis patients with chronic kidney disease (CKD).
Methods
Skin autofluorescence was measured noninvasively with an autofluorescence reader at baseline in 449 pre-dialysis patients with CKD. The primary end point was defined as a doubling of serum creatinine and/or need for dialysis.
Results
Thirty-three patients were lost to follow-up. Forty six patients reached the primary end point during the follow-up period (Median 39 months). Kaplan-Meier analysis showed a significantly higher risk of development of the primary end points in patients with skin autofluorescence levels above the optimal cut-off level of 2.31 arbitrary units, derived by receiver operator curve analysis. Cox regression analysis revealed that skin autofluorescence was an independent predictor of the primary end point, even after adjustment for age, gender, smoking history, diabetes, estimated glomerular filtration rate and proteinuria (adjusted hazard ratio 2.58, P = 0.004).
Conclusions
Tissue accumulation of AGEs, measured as skin autofluorescence, is a strong and independent predictor of progression of CKD. Skin autofluorescence may be useful for risk stratification in this group of patients; further studies should clarify whether AGE accumulation could be one of the therapeutic targets to improve the prognosis of CKD.
doi:10.1371/journal.pone.0083799
PMCID: PMC3861518  PMID: 24349550
5.  Association of High Pulse Pressure With Proteinuria in Subjects With Diabetes, Prediabetes, or Normal Glucose Tolerance in a Large Japanese General Population Sample 
Diabetes Care  2012;35(6):1310-1315.
OBJECTIVE
To examine whether there is a difference in the association between high pulse pressure and proteinuria, independent of other blood pressure (BP) indices, such as systolic or diastolic BP, among subjects with diabetes, prediabetes, or normal glucose tolerance.
RESEARCH DESIGN AND METHODS
Using a nationwide health checkup database of 228,778 Japanese aged ≥20 years (mean 63.2 years; 39.3% men; none had pre-existing cardiovascular disease), we examined the association between high pulse pressure, defined as the highest quintile of pulse pressure (≥63 mmHg, n = 40,511), and proteinuria (≥1+ on dipstick, n = 12,090) separately in subjects with diabetes (n = 27,913), prediabetes (n = 100,214), and normal glucose tolerance (n = 100,651).
RESULTS
The prevalence of proteinuria was different among subjects with diabetes, prediabetes, and normal glucose tolerance (11.3 vs. 5.0 vs. 3.9%, respectively; P < 0.001). In subjects with diabetes, but not those with prediabetes or normal glucose tolerance, high pulse pressure was associated with proteinuria independently of significant covariates, including systolic BP (odds ratio 1.15 [95% CI 1.04–1.28]) or diastolic or mean BP (all P < 0.01). In patients with diabetes, a +1 SD increase of pulse pressure (+13 mmHg) was associated with proteinuria, even after adjustment for systolic BP (1.07 [1.00–1.13]) or diastolic or mean BP (all P < 0.05).
CONCLUSIONS
Among the Japanese general population, there was a significant difference in the association between high pulse pressure and proteinuria among subjects with diabetes, prediabetes, and normal glucose tolerance. Only in diabetes was high pulse pressure associated with proteinuria independent of systolic, diastolic, or mean BP levels.
doi:10.2337/dc11-2245
PMCID: PMC3357237  PMID: 22474041
6.  New diffusion metrics for spondylotic myelopathy at an early clinical stage 
European Radiology  2012;22(8):1797-1802.
Objectives
To investigate the use of root mean square displacement (RMSD) and mean diffusional kurtosis (DK) metrics of q-space imaging data to estimate spinal cord compression in patients with early cervical spondylosis.
Methods
We studied 50 consecutive patients at our institution (22 male, 28 female; mean age 58 years; age range 20–86 years) who had clinical signs and symptoms suggestive of early clinical stage cervical myelopathy. After conventional magnetic resonance (MR) imaging, diffusion tensor and q-space image data were acquired using 3-T MR imaging. Fractional anisotropy (FA), apparent diffusion coefficient (ADC), RMSD and mean DK values were calculated and compared between compressed and uncompressed spinal cords.
Results
FA and mean DK values were significantly lower and RMSD was significantly higher (P = 0.0060, 0.0020 and 0.0062, respectively; Mann–Whitney U test with the Bonferroni correction) in compressed spinal cords than in uncompressed cords. ADC was also higher in compressed cords, but this difference was not statistically significant.
Conclusions
In the evaluation of spinal cord damage in early cervical spondylosis, mean DK and RMSD values in the spinal cord may be highly sensitive indicators of microstructural change and damage.
Key Points
• Absolute surgical indications for cervical spondylosis with myelopathy remain to be established.
• Diffusion tensor MRI shows abnormalities in normal-appearing but compressed spinal cord.
• Non-Gaussian diffusion analysis is highly sensitive in revealing spinal cord damage.
doi:10.1007/s00330-012-2410-9
PMCID: PMC3387361  PMID: 22411307
Cervical spondylosis; Spinal cord; Non-Gaussian; Diffusion kurtosis imaging; Diffusion tensor imaging
7.  Cost-effectiveness of chronic kidney disease mass screening test in Japan 
Background
Chronic kidney disease (CKD) is a significant public health problem. Strategy for its early detection is still controversial. This study aims to assess the cost-effectiveness of population strategy, i.e. mass screening, and Japan’s health checkup reform.
Methods
Cost-effectiveness analysis was carried out to compare test modalities in the context of reforming Japan’s mandatory annual health checkup for adults. A decision tree and Markov model with societal perspective were constructed to compare dipstick test to check proteinuria only, serum creatinine (Cr) assay only, or both.
Results
Incremental cost-effectiveness ratios (ICERs) of mass screening compared with do-nothing were calculated as ¥1,139,399/QALY (US $12,660/QALY) for dipstick test only, ¥8,122,492/QALY (US $90,250/QALY) for serum Cr assay only and ¥8,235,431/QALY (US $91,505/QALY) for both. ICERs associated with the reform were calculated as ¥9,325,663/QALY (US $103,618/QALY) for mandating serum Cr assay in addition to the currently used mandatory dipstick test, and ¥9,001,414/QALY (US $100,016/QALY) for mandating serum Cr assay and applying dipstick test at discretion.
Conclusions
Taking a threshold to judge cost-effectiveness according to World Health Organization’s recommendation, i.e. three times gross domestic product per capita of ¥11.5 million/QALY (US $128 thousand/QALY), a policy that mandates serum Cr assay is cost-effective. The choice of continuing the current policy which mandates dipstick test only is also cost-effective. Our results suggest that a population strategy for CKD detection such as mass screening using dipstick test and/or serum Cr assay can be justified as an efficient use of health care resources in a population with high prevalence of the disease such as in Japan and Asian countries.
doi:10.1007/s10157-011-0567-1
PMCID: PMC3328680  PMID: 22167460
Chronic kidney disease; Cost-effectiveness; Dipstick test; Mass screening; Proteinuria; Serum creatinine

Results 1-7 (7)