Search

Introduction: Symptom status and treatment changes among patients with chronic obstructive pulmonary disease (COPD) using inhaler treatment in real-world clinical settings are not well understood, particularly according to class of treatment. We investigated the proportion of symptomatic patients among those with COPD using inhaler treatment, based on COPD Assessment Test (CAT) scores in clinical practice, and changes in inhaler treatments and symptoms at 1-year follow-up., Methods: This was a retrospective analysis of data from a multicenter, prospective cohort study conducted at medical institutions with respiratory specialists in Japan. The primary endpoint was the proportion of patients with CAT scores ≥ 10 or < 10 in each inhaler treatment group at registration., Results: Of 414 patients in the full analysis set, 76 (18.4%), 261 (63.0%), and 77 (18.6%) were using long-acting muscarinic antagonist (LAMA), LAMA + long-acting β 2 -agonist (LABA), and inhaled corticosteroids (ICS) + LABA, respectively, at registration. The proportions of patients with CAT scores ≥ 10 or < 10 per inhaler treatment group at registration, respectively, were 32.9% and 67.1% in the LAMA group, 55.0% and 45.0% in the LAMA + LABA group, and 50.0% and 50.0% in the ICS + LABA group. Most patients (> 75%) in each inhaler treatment group showed no change in inhaler treatment at 1 year, regardless of their CAT score at registration. Approximately 70-80% of patients with CAT scores ≥ 10 at registration still had CAT scores ≥ 10 at 1 year; 10-30% of patients with CAT scores < 10 at registration had CAT scores ≥ 10 at 1 year., Conclusion: In real-world Japanese clinical practice, a considerable proportion of patients have persistent symptoms (CAT score ≥ 10) despite using mono or dual inhaler treatment; > 75% of symptomatic patients with COPD using inhaler treatment did not undergo treatment escalation at 1-year follow-up and remained symptomatic., Trial Registration: ClinicalTrials.gov identifier, NCT05903989., (© 2024. The Author(s).)

The Vulnerable Elders Survey-13 (VES-13) is a well-studied simplified frailty screening tool for elderly patients in the oncology setting. We conducted a prospective clinical trial to evaluate the efficacy and safety of dose-adjusted treatment based on the VES-13 in transplant-ineligible patients with newly diagnosed multiple myeloma (MM). In the Fit group (VES-13 <3), patients were treated with 4 cycles of standard-dose VCD (bortezomib, cyclophosphamide, and dexamethasone) followed by 4 cycles of standard-dose VTD (bortezomib, thalidomide, and dexamethasone). In the Frail group (VES-13 ≥3), patients were treated with 4 cycles of reduced-dose VCD followed by 4 cycles of reduced-dose VTD. The median age was 75 years (66-86 years), and 34% of the cases were classified as PS 3. Among the Fit group (n=16), the overall response rate (ORR) was 87.5%. Among the Frail group (n=31), the ORR was 87.1%. There were no significant differences in progression-free survival (PFS) and overall survival (OS) between the Fit and Frail groups (3-year PFS: 68.8% vs 53.3%, P = 0.658; 3-year OS: 70.0% vs 77.6%, P = 0.919). Personalized VCD-VTD sequential therapy based on the VES-13 was associated with high response rates and showed acceptable safety in elderly frail patients with MM. The study is registered as UMIN000011235., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Red blood cell (RBC) transfusion to neonates is thought to rarely provoke an immune response. Neonatal testing guidelines suggest that antibody screening is not necessary when the mother has no antibodies. Alternatively, maternal blood samples can be used for antibody screening and cross-matching. However, the guidelines are based on small-scale studies of white-dominant populations. Furthermore, transfusion-related alloimmunization is less well established among children and adolescents as a whole among Japanese and East Asians. To elucidate the incidence of transfusion-related alloimmunization among neonates, children, and adolescents, and whether current guidelines are applicable to Japanese populations, a nationwide retrospective multicenter cohort survey was conducted in 50 tertiary-care hospitals in Japan. Between 2001 and 2015 inclusive, recipients of at least 1 allogeneic RBC transfusion were categorized into groups A-F according to their age at the time of transfusion: (A) neonates <1 month; (B) infants 1 to <12 months; (C) children 1 to <5 years; (D) prepubescents 5 to <10 years; (E) young pubescents 10 to <15 years; and (F) adolescents/young adults 15 to <20 years. Excluding maternally derived antibodies and naturally occurring, cold-reactive, and/or nonspecific antibodies, 69 (0.61%) of 11350 RBC recipients <20 years old formed at least 1 clinically significant alloantibody. The alloimmunization rate differed significantly (P < .0001) by age: none (0%) of 3407 in group A; 11 (0.46%) of 2410 in group B; 18 (0.76%) of 2361 in group C; 9 (0.80%) of 1119 in group D; 12 (1.15%) of 1043 in group E; and 19 (1.88%) of 1010 in group F. Clearly different incidences of alloimmunization emerged in group A compared to B, C, D, E, or F, as confirmed by logistic regression analysis adjusted by numbers of donor exposure. Alloimmunization did not occur from RBC transfusions within the first month of life and rarely occurred (0.46%-0.80%) after transfusion within the first decade of life. Alloimmunization occurred in 1.15%-1.88% of young pubescents and adolescents/young adults. These findings support the use of guidelines developed in Europe and the United States for East Asian pediatric recipients., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Second-hand smoke exposure has been associated with poor mental health. However, among Japanese adults, little is known about the association between second-hand smoking and depressive symptoms. We examined this association in a cross-sectional study among a Japanese general adult population sample., Methods: Japanese adults were recruited from the Japan Multi-Institutional Collaborative Cohort Study in the Okazaki area between 2012 and 2017. Second-hand smoke exposure and smoking status were assessed using a self-administered questionnaire. Based on their frequency of exposure to second-hand smoke, non-smokers and smokers were categorized as "almost never," "sometimes," and "almost every day". Depressive symptoms were defined by a Kessler 6 score ≥5 points. We performed a multivariable Poisson regression analysis to obtain adjusted prevalence ratios (PRs) and 95% confidence intervals (CIs) for depressive symptoms., Results: Overall, 5,121 participants (4,547 non-smokers and 574 smokers) were included whose mean age was 63.6 (standard deviation [SD], 10.3) years for non-smokers and 59.33 (SD, 10.2) years for smokers. The association between second-hand smoking and depressive symptoms was significant among non-smokers, but not among smokers. Among non-smokers, PRs compared with "almost never" were 1.25 (95% CI, 1.09-1.42) for "sometimes" and 1.41 (95% CI, 1.09-1.84) for "almost every day" (P for trend <0.001); among smokers, PRs compared with "almost never" were 1.30 (95% CI, 0.82-2.06) for "sometimes" and 1.44 (95% CI, 0.90-2.33) for "almost every day" (P for trend = 0.144)., Conclusions: Second-hand smoking and depressive symptoms were associated among non-smokers. Our findings indicate the importance of tobacco smoke control for mental health.

Objectives: Family caregiver burden is associated with higher psychological distress. However, little is known about the impact of neighbourhood relationships on caregivers' psychological distress. We examined whether neighbourhood relationships of caregivers moderate the association between family caregiver burden and psychological distress., Study Design: This was a cross-sectional study., Methods: We recruited 5321 Japanese adults who participated in the Japan Multi-Institutional Collaborative Cohort Study in the Okazaki area between 2013 and 2017. Participants completed self-reported questionnaires to measure psychological distress (Kessler 6: K6), subjective caregiver burden, and neighbourhood relationships. We performed a multivariable linear regression analysis in which caregiver burden was designated as an independent variable and the K6 score as a dependent variable, adjusting for demographics. The interaction term between caregiver burden and neighbourhood relationships was also included in the analysis., Results: Data from a total of 5069 participants were included (mean age [standard deviation]: 63.1 years [10.3 years]; 2226 [43.9%] female). Caregiver burden was significantly and positively associated with psychological distress (compared with no burden, mild burden: β = 0.24, P = 0.197; severe burden: β = 0.60, P < 0.01; P for trend < 0.01). There was a significant negative interaction effect of caregiver burden × neighbourhood relationship on psychological distress (severe burden × good neighbourhood relationship: β = -3.29, P < 0.01)., Conclusions: A higher caregiver burden was associated with higher psychological distress, and neighbourhood relationships moderated this association. Our findings suggest that good neighbourhood relationships can buffer caregiving-associated psychological distress., (Copyright © 2020 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Usual sleep duration has substantial heritability and is associated with various physical and psychiatric conditions as well as mortality. However, for its genetic locus, only PAX8 and VRK2 have been replicated in previous genome-wide association studies (GWAS). We conducted a GWAS meta-analysis of self-reported usual sleep duration using three population-based cohorts totaling 31 230 Japanese individuals. A genome-wide significant locus was identified at 12q24 (p-value < 5.0 × 10-8). Subsequently, a functional variant in the ALDH2 locus, rs671, was replicated in an independent sample of 5140 Japanese individuals (p-value = 0.004). The association signal, however, disappeared after adjusting for alcohol consumption, indicating the possibility that the rs671 genotype modifies sleep duration via alcohol consumption. This hypothesis explained a modest genetic correlation observed between sleep duration and alcohol consumption (rG = 0.23). A Mendelian randomization analysis using rs671 and other variants as instrumental variables confirmed this by showing a causal effect of alcohol consumption, but not of coffee consumption on sleep duration. Another genome-wide significant locus was identified at 5q33 after adjusting for drinking frequency. However, this locus was not replicated, nor was the PAX8 and VRK2. Our study has confirmed that a functional ALDH2 variant, rs671, most strongly influences on usual sleep duration possibly via alcohol consumption in the Japanese population, and presumably in East Asian populations. This highlights the importance of considering the involvement of alcohol consumption in future GWAS of usual sleep duration, even in non-East Asian populations, where rs671 is monomorphic., (© Sleep Research Society 2019. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Objective: We aimed to examine missing data in FFQ and to assess the effects on estimating dietary intake by comparing between multiple imputation and zero imputation., Design: We used data from the Okazaki Japan Multi-Institutional Collaborative Cohort (J-MICC) study. A self-administered questionnaire including an FFQ was implemented at baseline (FFQ1) and 5-year follow-up (FFQ2). Missing values in FFQ2 were replaced by corresponding FFQ1 values, multiple imputation and zero imputation., Setting: A methodological sub-study of the Okazaki J-MICC study.ParticipantsOf a total of 7585 men and women aged 35-79 years at baseline, we analysed data for 5120 participants who answered all items in FFQ1 and at least 50% of items in FFQ2., Results: Among 5120 participants, the proportion of missing data was 3·7%. The increasing number of missing food items in FFQ2 varied with personal characteristics. Missing food items not eaten often in FFQ2 were likely to represent zero intake in FFQ1. Most food items showed that the observed proportion of zero intake was likely to be similar to the probability that the missing value is zero intake. Compared with FFQ1 values, multiple imputation had smaller differences of total energy and nutrient estimates, except for alcohol, than zero imputation., Conclusions: Our results indicate that missing values due to zero intake, namely missing not at random, in FFQ can be predicted reasonably well from observed data. Multiple imputation performed better than zero imputation for most nutrients and may be applied to FFQ data when missing is low.

Vertebral aspergillosis is a rare infectious disease with a high mortality rate. We herein report a 70-year-old woman with acute myelogenous leukemia with myelodysplasia-related changes, nontuberculous mycobacteriosis, and bronchiectasis who presented with a fever and cough. Her clinical symptoms and laboratory test results suggested febrile neutropenia and pneumonia. However, her clinical course was further complicated by lower extremity weakness. Magnetic resonance imaging of the spine showed consolidation contiguously spreading toward the epidural space between the T4 and T5. Cytological testing of the pleural effusion revealed Aspergillus fumigatus. We also review and summarize previously reported cases of vertebral aspergillosis in Japan.

Intramuscular fat accumulation has come to be associated with loss of muscle strength and function, one of the components of sarcopenia. However, the impact of preoperative quality of skeletal muscle on outcomes after living donor liver transplantation (LDLT) is unclear. The present study evaluated the intramuscular adipose tissue content (IMAC) and psoas muscle mass index (PMI) in 200 adult patients undergoing LDLT at our institution between January 2008 and October 2013. Correlations of IMAC with other factors, overall survival rates in patients classified according to IMAC or PMI, and risk factors for poor survival after LDLT were analyzed. IMAC was significantly correlated with age (r = 0.229, P = 0.03) and PMI (r = -0.236, P = 0.02) in males and with age (r = 0.349, P < 0.001) and branched-chain amino acid (BCAA)-to-tyrosine ratio (r = -0.250, P = 0.01) in females. The overall survival rates in patients with high IMAC or low PMI were significantly lower than those for patients with normal IMAC or PMI (P < 0.001, P < 0.001, respectively). Multivariate analysis showed that high IMAC [odds ratio (OR) = 3.898, 95% confidence interval (CI) = 2.025-7.757, P < 0.001] and low PMI (OR = 3.635, 95% CI = 1.896-7.174, P < 0.001) were independent risk factors for death after LDLT. In conclusion, high IMAC and low PMI were closely involved with posttransplant mortality. Preoperative quality and quantity of skeletal muscle could be incorporated into new selection criteria for LDLT. Perioperative nutritional therapy and rehabilitation could be important for good outcomes after LDLT., (© 2014 American Association for the Study of Liver Diseases.)

In Japan, the use of adjuvant radiotherapy after prostatectomy for prostate cancer has not increased compared with the use of salvage radiotherapy. We retrospectively evaluated the outcome of adjuvant radiotherapy together with prognostic factors of outcome in Japan. Between 2005 and 2007, a total of 87 patients were referred for adjuvant radiotherapy in 23 institutions [median age: 64 years (54-77 years), median initial prostate-specific antigen: 11.0 ng/ml (2.9-284 ng/ml), Gleason score (GS): 6, 7, 8, 9, 10 = 13.8, 35.6, 23.0, 27.6, 0%, respectively]. Rates of positive marginal status, seminal vesicle invasion (SVI) and extra-prostatic extension (EPE) were 74%, 26% and 64%, respectively. Median post-operative PSA nadir: 0.167 ng/ml (0-2.51 ng/ml). Median time from surgery to radiotherapy was 3 months (1-6 months). A total dose of ≥ 60 Gy and <65 Gy was administered to 69% of patients. The median follow-up time was 62 months. The 3- and 5-year biochemical relapse-free survival (bRFS) rates for all patients were 66.5% and 57.1%, respectively. The GS and marginal status (P = 0.019), GS and SVI (P = 0.001), marginal status and EPE (P = 0.017), type of hormonal therapy and total dose (P = 0.026) were significantly related. The 5-year bRFS rate was significantly higher in SVI-negative patients than SVI-positive patients (P = 0.001), and significantly higher in patients with post-operative PSA nadir ≤ 0.2 than in patients with post-operative PSA nadir >0.2 (P = 0.02), and tended to be more favorable after radiotherapy ≤ 3 months from surgery than >3 months from surgery (P = 0.069). Multivariate analysis identified SVI and post-operative PSA nadir as independent prognostic factors for bRFS (P = 0.001 and 0.018, respectively).

Objectives: There are few studies about the association between tinnitus and sleep disorders in the general population worldwide. This study assessed this association in a Japanese community., Methods: A total of 14,027 participants 45 to 79 years of age who were in the Takayama Study responded to a self-administered questionnaire about tinnitus and sleep disorders., Results: Of this population, 13.3% of men and 10.6% of women had current tinnitus. The percentages of insomnia, respectively, among individuals with and without tinnitus were 28.1% in men and 36.1% in women and 18.8% in men and 21.5% in women. There were 1.7-fold (95% confidence interval [CI], 1.4 to 2.1) and 1.8-fold (95% CI, 1.5 to 2.2) increases in the odds ratios (ORs) of insomnia for those with tinnitus compared with those without tinnitus in men and women, respectively. Loud or very loud tinnitus was associated with 2.8-fold (95% CI, 1.8 to 4.3) and 3.3-fold (95% CI, 1.9 to 5.6) increases in the OR of insomnia in men and women, respectively. Even low (ie, quiet) or moderate tinnitus was significantly associated with insomnia. Difficulty initiating sleep, difficulty maintaining sleep, and a poor perceived quality of sleep were also significantly associated with tinnitus., Conclusions: Insomnia and other sleep disorders were significantly associated with tinnitus in Japanese adults.

Dietary supplementation with branched-chain amino acids (BCAAs), including leucine, isoleucine, and valine, has shown potential benefits for the metabolic profile. However, higher blood BCAA levels have been associated with insulin resistance. To our knowledge, there has been no study on dietary BCAAs and the risk of diabetes. We examined the association between BCAA intake and risk of diabetes in a population-based cohort study in Japan. A total of 13,525 residents of Takayama City, Japan, who enrolled in a cohort study in 1992 responded to a follow-up questionnaire seeking information about diabetes in 2002. Diet at baseline was assessed by means of a validated food frequency questionnaire. A high intake of BCAAs in terms of percentage of total protein was significantly associated with a decreased risk of diabetes in women after controlling for covariates; the hazard ratio for the highest tertile versus the lowest was 0.57 (95% confidence interval: 0.36, 0.90; P-trend = 0.02). In men, leucine intake was significantly marginally associated with the risk of diabetes; the hazard ratio for the highest tertile versus the lowest was 0.70 (95% confidence interval: 0.48, 1.02; P-trend = 0.06). Data suggest that a high intake of BCAAs may be associated with a decrease in the risk of diabetes.

Diabetes mellitus (DM) has been reported to be associated with an increased risk of site-specific cancers; however, few studies have assessed associations of DM with both total and site-specific cancers in Japan. We examined the association of a history of DM with cancer incidence in a population-based prospective cohort study in Japan. A total of 14 173 men and 16 547 women over 35 years old, who completed a self-administered baseline questionnaire in 1992, were followed up for cancer incidence from September 1992 to March 2008. At baseline, 6.3% men and 2.9% women had a history of diabetes. A total of 1974 men and 1514 women were identified as newly diagnosed with cancer. Hazard ratios (HR) and 95% confidence intervals (CI) were determined using Cox proportional hazards models. After controlling for potential confounders, men with DM had a modest risk increase of total cancer occurrence compared with those without DM (HR, 1.09; 95% CI, 0.93-1.29). Increased risk of cancer of the liver (HR, 2.18; 95% CI, 1.27-3.74), bile duct (HR, 2.17; 95% CI, 1.01-4.66), and larynx (HR, 3.61; 95% CI, 1.16-11.2) in diabetic men were observed. In women, significant increased risk of total cancer (HR, 1.35; 95% CI, 1.06-1.73) and stomach cancer (HR, 2.15; 95% CI, 1.30-3.54) were observed among diabetic subjects. These data suggest that people with DM may be at increased risk of both total and some site-specific cancers., (© 2013 Japanese Cancer Association.)

The effects of soy or isoflavone intake on breast cancer need to be examined further in epidemiologic studies. We assessed the associations of soy and isoflavone intake with breast cancer incidence in a population-based prospective cohort study in Japan. Participants were members from the Takayama study, aged 35 years or older in 1992. The follow-up was conducted from the time of the baseline study (September 1, 1992) to the end of March 2008. Cancer incidence was mainly confirmed through regional population-based cancer registries. Breast cancer was defined as code C50 according to ICD-10. Soy and isoflavone intakes were assessed with a validated food frequency questionnaire. Using the Cox proportional hazard models, the association of soy and isoflavone intake with breast cancer was assessed after adjustments for age, body mass index, physical activity, smoking, alcohol consumption, education, age at menarche, age at first delivery, menopausal status, number of children and history of hormone replacement therapy. Among the 15,607 women analyzed, 172 had developed breast cancer. The relative risks of postmenopausal breast cancer were lower among women with higher intakes of soy (trend p = 0.023) and isoflavone (trend p = 0.046), although the relative risks of premenopausal breast cancer were not associated with intakes of soy and isoflavone. Decreased risks of breast cancer were found even among women with a moderate intake of soy and isoflavone. These results suggested that soy and isoflavone intakes have a protective effect on postmenopausal breast cancer., (Copyright © 2013 UICC.)

Purpose: We aimed to investigate the associations of sleep disturbance and sleep time with behavioral problems and to assess whether endogenous melatonin was associated with sleep-related factors and behavioral problems., Methods: Subjects were 234 boys and 203 girls, aged 3-6 years, in a cross-sectional study in Japan in 2006. Information related to children's sleep disturbance, sleep time, and behavioral problems was obtained from parent-administered questionnaires. Children's behavioral problems were assessed by the Strengths and Difficulties Questionnaire. The 6-sulfatoxymelatonin levels in first-void morning urine were measured by radioimmunoassay., Results: After multiple adjustments for covariates, children who often snore at night (P = .011), awake at night (P = .019), and looked tired in the daytime (P = .041) had a higher total difficulties score. Earlier time of waking (trend P = .021) and earlier time for bed (trend P = .014) were associated with a lower total difficulties score. Children with higher creatinine-corrected 6-sulfatoxymelatonin had lower total difficulties scores (trend P = .011). There were no associations between creatinine-corrected 6-sulfatoxymelatonin and sleep-related factors., Conclusions: Sleep disturbance, later times of sleeping and waking up, and lower melatonin levels might be involved in the development of pediatric behavioral disorders., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Non-occupational exposure to cadmium has been suspected to be a risk factor for breast cancer. The present study examined the association between urinary cadmium level and the risk of breast cancer in a case-control study among Japanese women. Cases were 153 women newly diagnosed and histologically confirmed with breast cancer at a general hospital in Gifu, Japan. A total of 431 controls individually matched to cases by age, menopausal status, and the period of urine sampling were selected from those who attended a breast cancer mass screening at this hospital. Urinary cadmium levels were measured using spot urine samples. Spot urine samples were collected from cases after surgery but before any cancer therapy. For controls, spot urine samples were obtained at the date of the screening visit. Information on known or suggested breast cancer risk factors was obtained by a self-administered questionnaire. The odds ratios (ORs) and 95 % confidence intervals (CIs) of breast cancer according to the tertile of the creatinine-adjusted cadmium level were calculated using conditional logistic regression models. Women in the highest tertile of the creatinine-adjusted cadmium level (>2.620 μg/g) had significantly elevated OR of breast cancer relative to those in the lowest tertile (<1.674 μg/g) after controlling for covariates [OR = 6.05, (95 % CI 2.90, 12.62)]. The trend of increase in risk with increasing cadmium level was also statistically significant [OR = 1.67, (95 % CI 1.39, 2.01) for every 1.0 μg/g increase in urinary cadmium level, P-trend <0.01]. These data suggested that exposure to cadmium was associated with a risk of breast cancer in Japanese women.

Purpose: We aimed to assess the associations of sex, age, body mass, sex steroid hormones, and lifestyle factors with the levels of melatonin in young children., Methods: This study followed a cross-sectional design and was conducted two preschools in Japan. Subjects were 235 boys and 203 girls, aged 3-6 years. Information related to demographics, body mass, and lifestyle factors was obtained from parent-administered questionnaires. The levels of 6-sulfatoxymelatonin and dehydroepiandrosterone in first-void morning urine were measured by radioimmunoassay. Urinary estrone, estradiol, testosterone, and 5-androstene-3β, 17α diol levels were measured by liquid chromatography-electrospray ionization tandem mass spectrometry., Results: The creatinine-corrected 6-sulfatoxymelatonin levels and the estimated value of 6-sulfatoxymelatonin excretion were higher in girls than in boys. After adjustments for age, the creatinine-corrected 6-sulfatoxymelatonin was negatively associated with weight and body mass index among boys and with weight and height among girls. However, the estimated value of 6-sulfatoxymelatonin excretion was not associated with any indices of body mass. No significant relationships of urinary sex steroids, light exposure at night, sleep time, sedentary lifestyles, or passive smoking with urinary 6-sulfatoxymelatonin were observed., Conclusions: Our findings suggest that melatonin levels depend on sex and body size among young healthy children. Our results should be confirmed in future researches., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Dietary guidelines generally recommend avoiding a high-fat diet. However, the relationship between fat subtypes and mortality remains unclear especially in a population with a relatively low intake of fat. We aimed to prospectively examine the relationship between dietary fat intake and all-cause and cause-specific mortality in a Japanese community. In 1992, a total of 28,356 residents of Takayama, Japan, without cancer, stroke, or coronary heart disease, responded to a validated 169-item FFQ. We identified 4616 deaths during a 16-y follow-up. The HR of mortality according to the percentage of energy from the total and subtypes of fat when substituted for an isoenergic quantity of carbohydrate was calculated after controlling for potential confounders. A high intake of total fat and PUFA was associated with a decrease in all-cause mortality in men; the HR for the highest compared with the lowest quintile were 0.83 (95% CI: 0.70, 0.99; P-trend = 0.048) for total fat and 0.77 (95% CI: 0.62, 0.95; P-trend = 0.05) for PUFA. Both fats were associated with a decrease in mortality from cancer and diseases other than cardiovascular disease. In women, a higher SFA intake was associated with higher all-cause mortality [HR = 1.22 (95% CI: 0.99, 1.49; P-trend = 0.03)]. A favorable effect was suggested for total fat and PUFA intakes on mortality in men except for that from cardiovascular disease, whereas increased SFA intake may be associated with adverse health consequences in women.

Purpose: We investigated whether seaweed intake is associated with sex steroid levels in young Japanese children., Methods: The design of the study was cross-sectional and it was conducted in October-November 2006. Subjects were substantially healthy preschoolers, 230 boys and 198 girls, aged 3-6 years. Dietary data, including seaweed intake, were assessed using 3-day dietary records covering 2 consecutive weekdays and 1 weekend day. Urinary estrone, estradiol, testosterone, and 5-androstene-3β,17α diol levels were measured by liquid chromatography-electrospray ionization tandem mass spectrometry. Urinary dehydroepiandrosterone level was measured with a radioimmunoassay. Steroid hormones were adjusted for urinary creatinine levels., Results: Spearman's correlation coefficient between seaweed intake and estrone level was -0.144 (p = 0.030) in boys and -0.147 (p = 0.041) in girls after adjustments for age, BMI, and total energy intake. Seaweed intake was neither associated with estradiol, testosterone, 3β,17α-AED nor with DHEA among boys and girls., Conclusions: The negative association between seaweed intake and estrone level suggests that dietary seaweed intake might affect estrogen metabolism in childhood.

Purpose: We aimed to assess the association of body size at birth or physical activity with sex steroid levels, independent of body mass among young children., Methods: The cross-sectional study was conducted in 2006. Subjects were 230 boys and 198 girls, aged 3-6 years. Birth weight was based on parents' reports. Questions about physical activity focused on outdoor playtime. Urinary estrone, estradiol, testosterone, and 5-androstene-3β,17α diol (3β,17α-AED) levels were measured by liquid chromatography-electrospray ionization tandem mass spectrometry. Urinary dehydroepiandrosterone level was measured with a radioimmunoassay., Results: After adjustments for age and BMI, girls with lower birth weight had higher testosterone (trend p = 0.038) and 3β,17α-AED (trend p = 0.028). Girls with low birth weight and high birth weight had higher estrone (p = 0.014) and estradiol (p = 0.074) than those who had middle birth weight. Boys who were physically active had lower testosterone (p = 0.028) and 3β,17α-AED (p = 0.003) than those who were not active. Girls who were physically active had lower estrone (p = 0.015)., Conclusions: Sex steroid levels in childhood might be affected by body size at birth or by physical activity during childhood. These effects might differ by sex.

Objective: Prospective studies on physical activity and diet and the onset of natural menopause are scarce. The aim of this study was to examine the association of physical activity and dietary factors potentially related to endogenous estrogen levels such as fats, dietary fiber, soy isoflavones, and alcohol with the onset of menopause in a cohort of premenopausal women., Methods: Study participants were 3,115 premenopausal Japanese women aged 35 to 56 years derived from the participants in the Takayama Study. Physical activity was assessed by a validated questionnaire at baseline, and the metabolic equivalent score was calculated. The dietary intakes were estimated by a validated food frequency questionnaire at baseline and adjusted for total energy. Menopause status was defined as the absence of menstruation for 12 months or more. The Cox proportional hazard model was used to estimate the hazard ratio of the occurrence of menopause after controlling for age, parity, body mass index, smoking status, years of education, and lifelong irregular menstrual cycle., Results: During the 10-year follow-up, 1,790 women experienced natural menopause. A high physical activity level and a high intake of polyunsaturated fat were moderately but significantly associated with the earlier onset of menopause; the hazard ratios for the highest versus lowest quartile were 1.17 (95% CI, 1.02-1.34) for physical activity and 1.15 (95% CI, 1.01-1.31) for polyunsaturated fat intake. Total fat, other types of fat, dietary fiber, soy isoflavones, and alcohol were not associated with the onset of menopause., Conclusions: These data suggest that high levels of physical activity and polyunsaturated fat intake are associated with earlier onset of menopause.

Background/objectives: Diets rich in plant-based foods such as vegetables, fruits and soy foods have been suggested to have beneficial effects on health. However, phytochemicals contained in plant-based foods are generally bitter and acrid. We investigated whether intake of vegetables, fruits and soy foods is associated with sensitivity to bitterness and reluctance to eat new foods (food neophobia) in Japanese preschool children., Subjects/methods: Subjects of this cross-sectional study were healthy Japanese, 167 boys and 156 girls, aged 4-6 years. Intake of vegetables, fruits and soy foods was estimated from 3-day dietary records. Subjects were classified as either tasters or non-tasters of 6-n-propylthiouracil (PROP) based on their ability to taste 0.56 mmol/l PROP. Information on each child's age, height, weight, food neophobia status and food variety, as well as maternal diet and parental control over the child's eating, was obtained by a parent-administered questionnaire. Food neophobia was assessed using the Child Food Neophobia Scale (CFNS)., Results: A high intake of vegetables was significantly associated with a low CFNS score in boys after controlling for covariates (P=0.0008). Among the boys, soy food intake was significantly higher in PROP non-tasters than in tasters, except those with low CFNS scores (P=0.0019). High intake of soy foods was significantly associated with a low neophobia score in PROP tasters but not in non-tasters (P=0.0024)., Conclusions: These data suggest that sensitivity to bitter taste and food neophobia may influence the consumption of vegetables and soy foods among Japanese preschool boys.

Background: An elevated plasma homocysteine level is an independent risk factor for high blood pressure and cardiovascular disease, and its level is regulated by three vitamins; vitamin B6, B12, and folic acid. Until now, the association between the intake of these vitamins and blood pressure has been examined only in adult populations. We purposed to examine the association between dietary intake of these three vitamins and blood pressure of young children., Methods: We conducted a cross-sectional study at Japanese preschools in 2006. Blood pressure was measured among 418 children aged 3-6 years. Diets including vitamins were assessed by a 3-day dietary record. We compared the blood pressure levels among the four groups defined according to quartile of energy-adjusted vitamin intake by using analysis of covariance after controlling for age, sex, and body mass index., Results: The mean systolic blood pressure was 6.6 mm Hg lower and the mean diastolic blood pressure was 5.7 mm Hg lower in the highest quartile than in the lowest quartile of vitamin B12 intake (P for trend was <0.001 and 0.006, respectively). The mean systolic blood pressure was 4.1 mm Hg lower in the highest quartile than in the lowest quartile of folic acid intake (P for trend = 0.004). Vitamin B6 intake was not significantly associated with blood pressure., Conclusions: The data suggest that high intakes of folic acid and vitamin B12 are associated with lower levels of blood pressure among preschool children.

Background: Few studies have examined whether dietary factors might affect blood pressure in children. We purposed to investigate whether seaweed intake is associated with blood pressure level among Japanese preschool children., Methods: The design of the study was cross-sectional and it was conducted in autumn 2006. Subjects were healthy preschoolers aged 3-6 years in Aichi, Japan. Blood pressure and pulse were measured once by an automated sphygmomanometer, which uses oscillometric methods. Dietary data, including seaweed intake, were assessed using 3-day dietary records covering 2 consecutive weekdays and 1 weekend day. Of a total of 533 children, 459 (86.1 percent) agreed to be enrolled in our study. Finally, blood pressure measurement, complete dietary records and parent-reported height and weight were obtained for 223 boys and 194 girls., Results: When we examined Spearman's correlation coefficients, seaweed intake was significantly negatively related to systolic blood pressure in girls (P = 0.008). In the one-way analysis of covariance for blood pressure and pulse after adjustments for age and BMI, the boys with the lowest, middle and highest tertiles of seaweed intake had diastolic blood pressure readings of 62.8, 59.3 and 59.6 mmHg, respectively (P = 0.11, trend P = 0.038). Girls with higher seaweed intake had significantly lower systolic blood pressure readings (102.4, 99.2 and 96.9 mmHg for girls with the lowest, middle and highest tertiles of seaweed intake, respectively; P = 0.037, trend P = 0.030)., Conclusion: Our study showed that seaweed intake was negatively related to diastolic blood pressure in boys and to systolic blood pressure in girls. This suggests that seaweed might have beneficial effects on blood pressure among children.

Objective: To examine the association of smoking and lifestyle factors with pancreatic cancer death in the prospective design., Methods: Mortality from pancreatic cancer in regard to smoking, body mass index, physical activity, and alcohol, coffee and green tea intake, was studied in a prospective cohort of 30,826 inhabitants in Takayama, Japan. In 1992, each subject completed a self-administered questionnaire on demographic information, smoking, drinking habits, diet, exercise and medical histories. The response rate was 85.3%., Results: From 1992 to 1999, 33 men and 19 women died due to pancreatic cancer. Hazard ratios and 95% confidence intervals were determined using Cox proportional hazards models. Women who were defined as current smokers at baseline had significant and increased risk of pancreatic cancer death after adjustment for age, body mass index and history of diabetes mellitus (Hazard ratio: 4.77, 95% confidence intervals: 1.58-14.4). There were significant positive associations of pancreatic cancer death with the years of smoking and the number of cigarettes consumed daily in women in a dose-dependent manner. Current smokers indicated a non-significant risk increase in men (Hazard ratio: 3.81, 95% confidence intervals: 0.88-16.6). Body mass index, physical activity, and alcohol, coffee and green tea intake were not significantly associated with pancreatic cancer death., Conclusions: These data suggested that smoking increases the risk of death from pancreatic cancer in Japanese women.

The aim of the present study was to evaluate the validity and reproducibility of a food frequency questionnaire (FFQ) for use among young Japanese children. Forty-seven mothers of children aged 6 y completed two 3-d diet records and two FFQs over a 6-mo period. The FFQ asked the mothers how often, on average, their children consumed each of the 162 food items listed and what the usual serving size of each item was during the 6 mo prior to the study. Intakes of macro- and micronutrients were estimated by multiplying the frequency by the serving size for each food item. The validity of the FFQ was assessed by comparison of the two 3-d diet records. The reproducibility of the FFQ was based on the first and second FFQ administrations. The validity correlation ranged from 0.05 for α-tocopherol to 0.59 for retinol. The median correlation was 0.40. The reproducibility correlation was higher than 0.50 for all nutrients. For most nutrients, FFQ had acceptable reproducibility, whereas validity showed low to moderate correlations. Our FFQ could reasonably rank individuals according to dietary intake for epidemiologic studies, although the validity of the questionnaire is limited to specific nutrients.

Background: In our previous studies, we found both gender differences among care recipients and predictors that influenced outcomes after discharge from a ward for demented elderly. Here, we investigate predictors that influence the length of stay for each sex., Methods: We studied the data of 390 patients with dementia who were hospitalized in a ward for demented elderly between 1 April 2000 and 31 March 2008, and treated until 31 March 2009. The patients were divided into groups classified by gender. We analyzed the gender differences of characteristics and evaluated the predictors that influenced the length of stay in the ward for demented elderly using Cox's proportional hazards model. A model using the initial scores of the Revised Hasegawa Dementia Scale (HDS-R), Assessment Scale for Symptoms of Dementia (ASSD) and Nishimura's activity of daily living scale (N-ADL), which were examined on admission, was named Model 1. In Model 1, we checked the effect of each patient's characteristics, except for complications and destinations, on their length of stay. Model 2 used the final scores of HDS-R, ASSD and N-ADL including complications and destinations., Results: There was a clear gender difference in the length of stay. The length of stay of women was longer than that of men. It was difficult to predict the length of stay in Model 1. Age was the only predictor in women and no predictor was identified in men. In Model 2, complications and the final HDS-R and N-ADL scores were predictors of the length of stay in men. Age, complications and destinations were predictors of the length of stay in women., Conclusions: It was observed that there were gender differences among predictors of the length of stay. However, it was difficult to predict the length of stay on admission. Retrospectively, the length of stay was determined by physical and psychological conditions, not by the social variables in men. In women, it was supposed that the caregiver's wish to give care at home reduced the length of stay. Besides, complication was a common predictor of the extension of stay in each sex. We have to decrease the number of complications as much as possible to reduce the length of stay., (© 2010 The Authors. Psychogeriatrics © 2010 Japanese Psychogeriatric Society.)

Background: In a previous study, we found gender differences among care recipients and suggested that elderly women living alone have difficulty receiving care from their families. We investigated the gender differences among predictors which influenced outcomes after discharge from a ward for treatment of demented elderly with severe psychotic symptoms., Methods: We enrolled the data of 325 patients with dementia who were hospitalized between 1 April 2000 and 31 March 2007, and discharged by 31 March 2008. Two hundred and ninety-four patients were divided into men and women. We checked the gender differences of their characteristics. After that, they were subdivided into three groups to analyze the effect of each patient's characteristics and care situation on their outcomes: (i) given home care (home); (ii) became institutionalized (institution); and (iii) transferred to another hospital (hospital)., Results: In the hospital groups, the incidence of complications was high for each sex. The differences between the institution group and home group were shown by N-ADL score in men. In contrast, the predictors in women were the HDS-R score, the number of cohabitants and the caregiver., Conclusions: It was observed that there were gender differences among outcome predictors. The outcomes of demented patients were predicted by both complications and condition on admission. Most women did not return to their homes because of the situation in which they received care. It is necessary to establish a clear system for providing care for the demented elderly, especially for women.

There is a growing need for home medicine in our graying society. New efforts are thus required to provide better treatment in the home. The Sakai Medical Association has established a new medical information system which uses the internet to increase the effectiveness of home medicine centered on the clinic and hospital cooperation.

We investigated the association between ectomycorrhizal (ECM) and arbuscular mycorrhizal (AM) fungi and pioneer woody plant species in areas devastated by the eruption of Mt. Usu, Japan, in 2000. We observed eight woody plant species at the research site, most of which were associated with ECM and/or AM fungi. In particular, dominant woody plant species Populus maximowiczii, Salix hultenii var. angustifolia and Salix sachalinensis were consistently associated with ECM fungi and erratically associated with AM fungi. We found one to six morphotypes in the roots of each ECM host and, on average, two in the roots of each seedling, indicating low ECM fungal diversity. ECM colonization ranged from 17 to 42% of root tips. Using morphotyping and molecular analyses, 15 ECM fungi were identified. ECM fungi differed greatly between hosts. However, Laccaria amethystea, Hebeloma mesophaeum, Thelephora terrestris and other Thelephoraceae had high relative colonization, constituting the majority of the ECM colonization in the roots of each plant species. These ECM fungi may be important for the establishment of pioneer woody plant species and further revegetation at Mt. Usu volcano.

We analyzed the long-term outcome and late effects of treatment in 187 patients with childhood acute lymphoblastic leukemia (ALL) diagnosed between 1984 and 1990. Overall survival and event-free survival rates were 68.2% +/- 3.7% and 63.2% +/- 3.6% at 15 years, respectively. Of 55 patients who relapsed after achieving the first complete remission (CR), only 17.4% were rescued by salvage therapy. The advantage of stem cell transplantation over chemotherapy was observed only in those patients with bone marrow relapse during therapy. The SD for score height in patients maintaining the first CR significantly decreased at the time of final follow-up compared with that at diagnosis: 0.059 to -0.800 (P < .0001). The decrease was remarkable in patients younger than 5 years at diagnosis. Other late effects included mild liver dysfunction in 18% and hepatitis C virus infection in 9%. Congestive heart failure was observed in only 2.9% of patients despite the high cumulative dose of daunorubicin (450 mg/m2). Although the survival rates of patients on our protocols were comparable to those of other study groups, some modification, including reduction in dose of cranial irradiation and/or anticancer drugs, should be considered to reduce late adverse effects in survivors of childhood ALL.