A pragmatic randomised controlled trial of the effectiveness and cost-effectiveness of Well Parent Japan in routine care in Japan: The training and nurturing support for mothers (TRANSFORM) study.

BACKGROUND: Well Parent Japan (WPJ) is a new hybrid group parent training programme combining sessions to improve mothers' psychological well-being with a culturally adapted version of the New Forest Parenting Programme (NFPP). This study investigates the effectiveness and cost-effectiveness of WPJ against treatment as usual (TAU) within Japanese child mental health services. METHODS: TRANSFORM was a pragmatic multi-site randomised controlled trial (RCT) with two parallel arms. Altogether 124 mothers of 6-12-year-old children with DSM-5 ADHD were randomised to WPJ (n = 65) or TAU (n = 59). Participants were assessed at baseline, post-treatment and three-month follow-up. The primary outcome was parent-domain stress following intervention. Secondary outcomes included maternal reports of child-domain stress, parenting practices, parenting efficacy, mood, family strain, child behaviour and impairment. Objective measures of the parent-child relationship were collected at baseline and post-treatment. Data analysis was intention to treat (ITT) with treatment effects quantified through analysis of covariance (ANCOVA) via multilevel modelling. An incremental cost-effectiveness ratio (ICER) assessed WPJ's cost-effectiveness. RESULTS: WPJ was superior to TAU in reducing parent-domain stress post-treatment (adjusted mean difference = 5.05, 95% CI 0.33 to 9.81, p = .036) and at follow-up (adjusted mean difference 4.82, 95% CI 0.09 to 9.55, p = .046). Significant WPJ intervention effects were also observed for parenting practices, parenting efficacy and family strain. WPJ and TAU were not significantly different post-intervention or at follow-up for the other secondary outcomes. The incremental cost of WPJ was 34,202 JPY (315.81 USD). The probability that WPJ is cost-effective is 74% at 10,000 JPY (USD 108.30) per one-point improvement in parenting stress, 92% at 20,000 JPY (216.60 USD). The programme was delivered with high fidelity and excellent retention. CONCLUSIONS: WPJ can be delivered in routine clinical care at modest cost with positive effects on self-reported well-being of the mothers, parenting practices and family coping. WPJ is a promising addition to psychosocial interventions for ADHD in Japan.

Mechanisms of pulmonary disease in F344 rats after workplace-relevant inhalation exposure to cross-linked water-soluble acrylic acid polymers.

BACKGROUND: Recently in Japan, six workers at a chemical plant that manufactures resins developed interstitial lung diseases after being involved in loading and packing cross-linked water-soluble acrylic acid polymers (CWAAPs). The present study focused on assessing lung damage in rats caused by workplace-relevant inhalation exposure to CWAAP and investigated the molecular and cellular mechanisms involved in lung lesion development. METHODS: Using a whole-body inhalation exposure system, male F344 rats were exposed once to 40 or 100 mg/m3 of CWAAP-A for 4 h or to 15 or 40 mg/m3 of CWAAP-A for 4 h per day once per week for 2 months (9 exposures). In a separate set of experiments, male F344 rats were administered 1 mg/kg CWAAP-A or CWAAP-B by intratracheal instillation once every 2 weeks for 2 months (5 doses). Lung tissues, mediastinal lymph nodes, and bronchoalveolar lavage fluid were collected and subjected to biological and histopathological analyses. RESULTS: A single 4-h exposure to CWAAP-A caused alveolar injury, and repeated exposures resulted in regenerative changes in the alveolar epithelium with activation of TGFß signaling. During the recovery period after the last exposure, some alveolar lesions were partially healed, but other lesions developed into alveolitis with fibrous thickening of the alveolar septum. Rats administered CWAAP-A by intratracheal instillation developed qualitatively similar pulmonary pathology as rats exposed to CWAAP-A by inhalation. At 2 weeks after intratracheal instillation, rats administered CWAAP-B appeared to have a slightly higher degree of lung lesions compared to rats administered CWAAP-A, however, there was no difference in pulmonary lesions in the CWAAP-A and CWAAP-B exposed rats examined 18 weeks after administration of these materials. CONCLUSIONS: The present study reports our findings on the cellular and molecular mechanisms of pulmonary disease in rats after workplace-relevant inhalation exposure to CWAAP-A. This study also demonstrates that the lung pathogenesis of rats exposed to CWAAP-A by systemic inhalation was qualitatively similar to that of rats administered CWAAP-A by intratracheal instillation.

Diagnostic Accuracy of Mann Assessment of Swallowing Ability for Predicting Dysphagia in Patients with Psychiatric Disorders.

Dysphagia occurs in various diseases and constitutes a major concern in patients with psychiatric disorders. The Mann Assessment of Swallowing Ability (MASA) comprises 24 clinical parameters designed to identify swallowing disorders. One item in MASA, the "gag reflex", involves an unpleasant stimulus, which means that it is often omitted when the test is administered. The aims of this study were to determine the presence/absence of dysphagia in patients with psychiatric disorders using the MASA and determine its diagnostic accuracy when the gag reflex item was excluded in patients with psychiatric disorders. The study participants comprised patients admitted to a hospital psychiatric ward in whom dysphagia had been suspected based on oral intake status. The following items were determined: age, total MASA score (23 out of 24 items, giving a score out of 195 points), body mass index score, milligram equivalents of chlorpromazine, and the Food Intake Level Scale score. The patients were divided into two groups according to the presence or absence of swallowing problems as assessed by videoendoscopic or videofluoroscopic examination. The scores for each item investigated in the MASA, including the total score, were compared between the two groups. Receiver operating characteristic curve analysis was carried out to determine the optimum cut-off value. The total MASA score, which excluded the "gag reflex" item, was lower in the problematic swallowing group than in the non-problematic swallowing group. The MASA scores for cooperation, respiratory, dysphasia, tongue coordination, oral preparation, pharyngeal phase, and pharyngeal response tended to be lower in the problematic swallowing group. Furthermore, an optimum cut-off value of 169 points (sensitivity, 0.92; specificity, 0.68; likelihood ratio, 2.84) was identified. These results indicate that the cut-off MASA score is effective in screening for dysphagia, even when the "gag reflex" item is excluded.

Pulmonary dust foci as rat pneumoconiosis lesion induced by titanium dioxide nanoparticles in 13-week inhalation study.

BACKGROUND: Most toxicological studies on titanium dioxide (TiO2) particles to date have concentrated on carcinogenicity and acute toxicity, with few studies focusing of pneumoconiosis, which is a variety of airspace and interstitial lung diseases caused by particle-laden macrophages. The present study examined rat pulmonary lesions associated with pneumoconiosis after inhalation exposure to TiO2 nanoparticles (NPs). METHODS: Male and female F344 rats were exposed to 6.3, 12.5, 25, or 50 mg/m3 anatase type TiO2 NPs for 6 h/day, 5 days/week for 13 weeks using a whole-body inhalation exposure system. After the last exposure the rats were euthanized and blood, bronchoalveolar lavage fluid, and all tissues including lungs and mediastinal lymph nodes were collected and subjected to biological and histopathological analyses. RESULTS: Numerous milky white spots were present in the lungs after exposure to 25 and 50 mg/m3 TiO2 NPs. Histopathological analysis revealed that the spots were alveolar lesions, characterized predominantly by the agglomeration of particle-laden macrophages and the presence of reactive alveolar epithelial type 2 cell (AEC2) hyperplasia. We defined this characteristic lesion as pulmonary dust foci (PDF). The PDF is an inflammatory niche, with decreased vascular endothelial cells in the interstitium, and proliferating AEC2 transformed into alveolar epithelial progenitor cells. In the present study, the AEC2 in the PDF had acquired DNA damage. Based on PDF induction, the lowest observed adverse effect concentration for pulmonary disorders in male and female rats was 12.5 mg/m3 and 6.3 mg/m3, respectively. The no observed adverse effect concentration for male rats was 6.3 mg/m3. There was a sex difference in lung lesion development, with females showing more pronounced lesion parameters than males. CONCLUSIONS: Inhalation exposure to TiO2 NPs caused PDF, an air-space lesion which is an alveolar inflammatory niche containing particle-laden macrophages and proliferating AEC2. These PDFs histopathologically resemble some pneumoconiosis lesions (pulmonary siderosis and hard metal pneumoconiosis) in workers and lung disease in smokers, suggesting that PDFs caused by exposure to TiO2 NPs in rats are an early pneumoconiosis lesion and may be a common alveolar reaction in mammals.

Two-year intermittent exposure of a multiwalled carbon nanotube by intratracheal instillation induces lung tumors and pleural mesotheliomas in F344 rats.

BACKGROUND: A mounting number of studies have been documenting the carcinogenic potential of multiwalled carbon nanotubes (MWCNTs); however, only a few studies have evaluated the pulmonary carcinogenicity of MWCNTs in vivo. A 2-year inhalation study demonstrated that MWNT-7, a widely used MWCNT, was a pulmonary carcinogen in rats. In another 2-year study, rats administered MWNT-7 by intratracheal instillation at the beginning of the experimental period developed pleural mesotheliomas but not lung tumors. To obtain data more comparable with rats exposed to MWNT-7 by inhalation, we administered MWNT-7 to F344 rats by intratracheal instillation once every 4-weeks over the course of 2 years at 0, 0.125, and 0.5 mg/kg body weight, allowing lung burdens of MWNT-7 to increase over the entire experimental period, similar to the inhalation study. RESULTS: Absolute and relative lung weights were significantly elevated in both MWNT-7-treated groups. Dose- and time-dependent toxic effects in the lung and pleura, such as inflammatory, fibrotic, and hyperplastic lesions, were found in both treated groups. The incidences of lung carcinomas, lung adenomas, and pleural mesotheliomas were significantly increased in the high-dose group compared with the control group. The pleural mesotheliomas developed mainly at the mediastinum. No MWNT-7-related neoplastic lesions were noted in the other organs. Cytological and biochemical parameters of the bronchoalveolar lavage fluid (BALF) were elevated in both treated groups. The lung burden of MWNT-7 was dose- and time-dependent, and at the terminal necropsy, the average value was 0.9 and 3.6 mg/lung in the low-dose and high-dose groups, respectively. The number of fibers in the pleural cavity was also dose- and time-dependent. CONCLUSIONS: Repeated administration of MWNT-7 by intratracheal instillation over the 2 years indicates that MWNT-7 is carcinogenic to both the lung and pleura of rats, which differs from the results of the 2 carcinogenicity tests by inhalation or intratracheal instillation.

Dose-response relationship of pulmonary disorders by inhalation exposure to cross-linked water-soluble acrylic acid polymers in F344 rats.

BACKGROUND: In Japan, six workers handling cross-linked water-soluble acrylic acid polymer (CWAAP) at a chemical plant suffered from lung diseases, including fibrosis, interstitial pneumonia, emphysema, and pneumothorax. We recently demonstrated that inhalation of CWAAP-A, one type of CWAAP, causes pulmonary disorders in rats. It is important to investigate dose-response relationships and recoverability from exposure to CWAAPs for establishing occupational health guidelines, such as setting threshold limit value for CWAAPs in the workplace. METHODS: Male and female F344 rats were exposed to 0.3, 1, 3, or 10 mg/m3 CWAAP-A for 6 h/day, 5 days/week for 13 weeks using a whole-body inhalation exposure system. At 1 h, 4 weeks, and 13 weeks after the last exposure the rats were euthanized and blood, bronchoalveolar lavage fluid, and all tissues including lungs and mediastinal lymph nodes were collected and subjected to biological and histopathological analyses. In a second experiment, male rats were pre-treated with clodronate liposome or polymorphonuclear leukocyte-neutralizing antibody to deplete macrophages or neutrophils, respectively, and exposed to CWAAP-A for 6 h/day for 2 days. RESULTS: CWAAP-A exposure damaged only the alveoli. The lowest observed adverse effect concentration (LOAEC) was 1 mg/m3 and the no observed adverse effect concentration (NOAEC) was 0.3 mg/m3. Rats of both sexes were able to recover from the tissue damage caused by 13 weeks exposure to 1 mg/m3 CWAAP-A. In contrast, tissue damage caused by exposure to 3 and 10 mg/m3 was irreversible due to the development of interstitial lung lesions. There was a gender difference in the recovery from CWAAP-A induced pulmonary disorders, with females recovering less than males. Finally, acute lung effects caused by CWAAP-A were significantly reduced by depletion of alveolar macrophages. CONCLUSIONS: Pulmonary damage caused by inhalation exposure to CWAAP-A was dose-dependent, specific to the lung and lymph nodes, and acute lung damage was ameliorated by depleting macrophages in the lungs. CWAAP-A had both a LOAEC and a NOAEC, and tissue damage caused by exposure to 1 mg/m3 CWAAP-A was reversible: recovery in female rats was less than for males. These findings indicate that concentration limits for CWAAPs in the workplace can be determined.

Evaluation of an advance care planning training program for practice professionals in Japan incorporating shared decision making skills training: a prospective study of a curricular intervention.

BACKGROUND: We developed a novel training program for health care professionals that incorporated shared decision making (SDM) skills training into an advance care planning (ACP) training course, the first in Japan. This study aimed to assess the training program's impact on health care professionals' knowledge, skill, attitudes, and confidence to initiate ACP. METHODS: Using the novel Japanese educational program, we evaluated the effect of 8-month programs conducted eight community training sites of professionals who can practice ACP in a local area in Aichi Prefecture (the Aichi ACP Project). SDM skills training was provided during the workshops conducted in the ACP training course, and the participants' satisfaction and understanding of the training were assessed. After the completion of two workshops, information on SDM skill results from the training and submitted assignments were collected anonymously from the training sites. RESULT: A total of 404 participants completed all education programs. After the first workshop, at least 95% of trainees stated that they were satisfied with the training and that it was useful for ACP practice. The evaluation of the results between the first and second workshops indicated improvement in SDM skills on some items of the SDM measures. In the second workshop, at least 90% of participants submitted implementation reports, and after the second workshop, a survey of confidence in ACP practice was administered, with responses indicating improvement. There were high levels of interest in education related to the ACP practices of oneself and others. CONCLUSIONS: This educational program can be an effective for developing professionals who can practice ACP with SDM skills.

Adapting the patient and physician versions of the 9-item shared decision making questionnaire for other healthcare providers in Japan.

BACKGROUND: In Japan, the number of older people with various health problems and difficulties in living is increasing. In order to practice patient-centered care for them, not only medical professionals but also multidisciplinary teams including care professionals and patients need to practice shared decision making (SDM) in the context of long-term care. For this reason, a measure of SDM in consultations with healthcare professionals (HCPs) other than physicians is needed. Therefore, this study aimed at adapting the patient and physician versions of the 9-item Shared Decision Making Questionnaire (SDM-Q-9, SDM-Q-Doc) for consultations with HCPs other than physicians in Japan. METHODS: A pair of SDM measures that can be used by HCPs other than physicians, "Care SDM-Questionnaire for care receivers (SDM-C-patient)" and "Care SDM-Questionnaire for care providers (SDM-C-provider)" were prepared based on the Japanese versions of the SDM-Q-9 and SDM-Q-Doc. The internal consistency and conceptual structure of these measures were tested by secondary analysis of data from 496 participants from a workshop on SDM for different HCPs. Measurement invariance were tested by multigroup confirmatory factor analysis (CFA) for the patient (SDM-C-patient and SDM-Q-9) and provider (SDM-C-provider vs. SDM-Q-Doc) versions. RESULTS: Both the Japanese SDM-C-patient and SDM-C-provider demonstrated high internal consistencies (Cronbach's α coefficient was 0.90 and McDonald's ω coefficient was 0.90 for both measures). CFA showed one-factor structures for both measures and original measures for physicians. Moreover, multigroup CFA showed configural and metric invariance between the novel care measures and original physician's measures. CONCLUSIONS: Thus, the novel SDM measures for care providers in Japan as well as the original physician's measures could be used in training setting. As these measures were tested only in a training setting, their reliability and validity as new measures for care should be tested in a clinical setting in future.

Assessment of microvessel perfusion of pituitary adenomas: a feasibility study using turbo spin-echo-based intravoxel incoherent motion imaging.

OBJECTIVES: To evaluate the feasibility of assessment of microvessel perfusion of pituitary adenomas with intravoxel incoherent motion (IVIM) imaging using single-shot turbo spin-echo-based diffusion-weighted imaging (SS-TSE-DWI). METHODS: We examined 51 consecutive patients with pituitary adenomas (35 non-functioning and 16 functioning) and 32 patients with normal pituitary glands using SS-TSE-DWI IVIM. The diffusion coefficient (D), the perfusion fraction (f), and the pseudo-diffusion coefficient (D*) were calculated pixel-by-pixel for each adenoma and normal pituitary gland. We also obtained the pathological microvessel area (MVA) of each adenoma. The IVIM parameters in adenomas were compared with those in normal pituitary glands using the Mann-Whitney U test. The correlation between the MVA and IVIM f of adenomas was analyzed using Spearman's rank correlation coefficient. RESULTS: The mean D (× 10-3 mm2/s) in adenomas was 0.723 ± 0.253, which was significantly lower than that in normal pituitary glands (0.862 ± 0.128; p < 0.0001). The mean f (%) in adenomas was 10.74 ± 4.51, which was significantly lower than that in normal pituitary glands (13.26 ± 4.32, p = 0.0251). No significant difference was found in the mean D*. We found a significant positive correlation between MVA and f in non-functioning adenomas (ρ = 0.634, p < 0.0001) as well as in all adenomas (ρ = 0.451, p = 0.0009). CONCLUSIONS: Assessment of microvessel perfusion of pituitary adenomas based on SS-TSE-DWI IVIM is feasible. Compared to normal pituitary glands, pituitary adenomas were characterized by lower D and f. KEY POINTS: • Assessment of microvessel perfusion of pituitary adenomas based on SS-TSE-IVIM is feasible. • SS-TSE-IVIM helps with evaluation of the vascularity of pituitary lesions. • Pituitary adenomas were characterized by lower D and f than normal pituitary glands.

Number of Teeth and All-Cause and Cancer Mortality in a Japanese Community: The Takayama Study.

BACKGROUND: The association between the number of teeth and mortality among community-dwelling people has been examined in many epidemiological studies. However, few Japanese studies have included cancer mortality as an endpoint. We prospectively investigated the association between number of remaining teeth and all-cause and cancer mortality in a Japanese community. METHODS: This study included participants in the Takayama Study who were aged 35-70 years old at baseline in 1992. Information on the number of remaining teeth was obtained from 11,273 participants via questionnaire at the second survey in 2002. The response rate was 66.9%. Deaths and their causes were ascertained during 11.8 years of follow-up. RESULTS: A total of 1,098 deaths (435 cancer-related and 235 cardiovascular-related) were identified during the follow-up period. After adjusting for covariates, participants with 0 to 9 teeth were at moderate but significantly increased risk of all-cause mortality (hazard ratio [HR] 1.19; 95% confidence interval [CI], 1.03-1.39) and cancer mortality (HR 1.31; 95% CI, 1.03-1.67) compared to those with 20 or more teeth. With regard to cancer site, a significant association was observed for lung cancer (HR for 0-9 teeth vs. 20 or more teeth, 1.75; 95% CI, 1.08-2.83). This association was somewhat strengthened among never-smokers (HR 3.56; 95% CI, 1.02-12.45). CONCLUSIONS: We observed that a lower number of remaining teeth was significantly associated with increased risk from all-cause and lung cancer mortality. Further studies on the number of teeth and lung and other types of cancer are needed.

Dietary Soy Intake Is Inversely Associated with Risk of Type 2 Diabetes in Japanese Women but Not in Men.

BACKGROUND: Whole soy foods, as well as their components, including protein and isoflavones, have garnered attention because they may have beneficial effects against diabetes. OBJECTIVES: We examined associations between the intake of soy foods, soy protein, and soy isoflavones and the risk of diabetes in the Japanese population. METHODS: This prospective cohort study included 13,521 residents (5883 men and 7638 women; 35-69 y old) of Takayama City, Japan. The subjects responded to a self-administered baseline questionnaire in 1992 and to a follow-up questionnaire seeking information about diabetes in 2002. Their mean ± SD body mass index was 22.6 ± 2.6 kg/m2 (men) and 22.1 ± 2.7 (women). The intakes of total soy foods, fried soy foods, nonfried soy foods, soy protein, and soy isoflavones were estimated through the use of a validated food-frequency questionnaire administered in 1992. Associations between soy intake and the risk of diabetes were evaluated through the use of Cox proportional hazards models incorporating age, education level, physical activity, smoking status, alcohol consumption, history of hypertension, use of vitamin supplements, menopausal status, and dietary factors including glycemic load, total energy, total fat, meat, fruit, vegetables, and coffee. RESULTS: During a 10-y follow-up, 438 participants reported physician-diagnosed diabetes. Women in the highest tertile of intakes of total soy foods, fried soy foods, nonfried soy foods, soy protein, and soy isoflavone had significantly lower HRs, after controlling for covariates, than those with the lowest intakes. For example, HRs were 0.45 (95% CI: 0.30, 0.68; P-trend <0.001) for total soy food intake. In men, there were no significant associations between soy intake and the risk of diabetes. CONCLUSIONS: These results suggest that a high soy intake may be associated with a lower risk of diabetes in Japanese women.

Maternal Acrylamide Intake during Pregnancy and Sex Hormone Levels in Maternal and Umbilical Cord Blood and Birth Size of Offspring.

Exposure to acrylamide during pregnancy may disturb pregnancy hormones and the growth of the fetus. The present study aimed to examine the association of maternal acrylamide intake with maternal and cord sex hormone levels during pregnancy and at birth and birth size of offspring. The study subjects were 204 pregnant Japanese women and their newborn girls. Intake of acrylamide was assessed based on 5-day diet records at approximately the 29th week of pregnancy. The concentrations of estradiol, estriol, and testosterone were measured in maternal serum at the 29th weeks of pregnancy and at delivery and umbilical cord blood at delivery. Birth weight, length, and head circumference were measured at the delivery. After controlling for covariates, higher intake of acrylamide was significantly positively associated with higher level of umbilical cord estradiol at the delivery (p for trend = .01), but not with any hormone levels measured in maternal blood. A positive association between acrylamide intake and head circumference was of borderline significance (p for trend = .06). Overall, there were no consistent associations between maternal acrylamide intake and sex hormone levels during pregnancy. However, as this is the first study to examine these associations, additional studies are needed.

Histogram analysis of amide proton transfer-weighted imaging: comparison of glioblastoma and solitary brain metastasis in enhancing tumors and peritumoral regions.

OBJECTIVES: Differentiation of glioblastomas (GBMs) and solitary brain metastases (SBMs) is an important clinical problem. The aim of this study was to determine whether amide proton transfer-weighted (APTW) imaging is useful for distinguishing GBMs from SBMs. METHODS: We examined 31 patients with GBM and 17 with SBM. For each tumor, enhancing areas (EAs) and surrounding non-enhancing areas with T2-prolongation (peritumoral high signal intensity areas, PHAs) were manually segmented using fusion images of the post-contrast T1-weighted and T2-weighted images. The mean amide proton transfer signal intensities (APTSIs) were compared among the EAs, PHAs, and contralateral normal appearing white matter (NAWM) within each tumor type. Furthermore, we analyzed APTSI histograms to compare the EAs and PHAs of GBMs and SBMs. RESULTS: In GBMs, the mean APTSI in EAs (2.92 ± 0.74%) was the highest, followed by that in PHAs (1.64 ± 0.83%, p < 0.001) and NAWM (0.43 ± 0.83%, p < 0.001). In SBMs, the mean APTSI in EAs (1.85 ± 0.99%) and PHAs (1.42 ± 0.45%) were significantly higher than that in NAWM (0.42 ± 0.30%, p < 0.001), whereas no significant difference was found between EAs and PHAs. The mean and 10th, 25th, 50th, 75th, and 90th percentiles for APT in EAs of GBMs were significantly higher than those of SBMs. However, no significant difference was found between GBMs and SBMs in any histogram parameters for PHA. CONCLUSIONS: APTSI in EAs, but not PHAs, is useful for differentiation between GBMs and SBMs. KEY POINTS: • Amide proton transfer-weighted imaging and histogram analysis in the enhancing tumor can provide useful information for differentiation between glioblastomas and solitary brain metastasis. • Amide proton transfer signal intensity histogram parameters from peritumoral areas showed no significant difference between glioblastomas and solitary brain metastasis. • Vasogenic edema alone can substantially increase amide proton transfer signal intensity which may mimic tumor invasion.

Intake of starch and sugars and total and cause-specific mortality in a Japanese community: the Takayama Study.

Studies on the intake of different types of carbohydrates and long-term mortality are sparse. We examined the association of starch, total and each type of sugar and free sugars with the risk of total and cause-specific mortality in a cohort of the general population in Japan. Study subjects were 29 079 residents from the Takayama Study, Japan, who responded to a self-administered questionnaire in 1992. Diet was assessed by a validated FFQ at the baseline. Mortality was ascertained during 16 years of follow-up. We noted 2901 deaths (974 cancer related and 775 cardiovascular related) in men and 2438 death (646 cancer related and 903 cardiovascular related) in women. In men, intake of starch was inversely associated with total mortality after controlling for covariates (hazard ratio (HR) for the highest quartile v. lowest quartile: 0·71; 95 % CI 0·60, 0·84; Ptrend < 0·001). Intakes of total sugars, glucose, fructose, sucrose, maltose and free and naturally occurring sugars were significantly positively associated with total mortality in men (HR for the highest v. lowest quartile of total sugar: 1·27; 95 % CI 1·12, 1·45; Ptrend < 0·0001). Similar relations were observed for cardiovascular mortality and non-cancer, non-cardiovascular mortality in men. In women, there was no significant association between any type of carbohydrates and mortality except that intake of free sugars was significantly positively associated with total and non-cancer, non-cardiovascular mortality. Data suggest that the high intake of starch reduces mortality, whereas the high intake of sugars, including glucose, fructose and sucrose, increases mortality in Japanese men.

Green tea intake and colorectal cancer risk in Japan: the Takayama study.

BACKGROUND: Reportedly, green tea has a preventive effect against colorectal cancer in animal models. Nevertheless, results from epidemiological studies of the association between green tea consumption and colorectal cancer have been inconsistent. We aimed to evaluate colorectal cancer risk in relation to green tea consumption in a population-based prospective cohort study. METHODS: Subjects were 13 957 men and 16 374 women aged ≥35 years in September 1992. The participants' green tea consumption was elicited by administering a food frequency questionnaire. The colorectal cancer incidence was confirmed through regional population-based cancer registries and histological identification from colonoscopy in two main hospitals in the study area. Colorectal cancer was defined as the sum of code C18 (colon cancer) and codes C19 and C20 (rectal cancer) according to ICD-10. RESULTS: Up to March 2008, 429 men and 343 women were diagnosed with colorectal cancer. No significant association was found between green tea consumption and colorectal cancer in men and women, respectively. However, for men, compared with the group of 'none or less than once per day' of green tea consumption, the multiple-adjusted relative risks (95% CIs) for colon cancer were 1.32 (0.90, 1.94), 0.76 (0.57, 1.02), and 0.78 (0.49, 1.22), respectively, in the group of 'once per day,' '2-3 times per day', and 'four times per day or more' (trend P = 0.045). CONCLUSIONS: This study observed no overall significant associations between green tea consumption and colorectal cancer risk, except that there was a weak trend for greater consumption of green tea with decreased risk of male colon cancer.

Cedar Pollinosis and Mortality: A Population-Based Prospective Cohort Study in Japan.

BACKGROUND: Cedar pollinosis is one of the most prevalent forms of seasonal allergic reaction in Japan. Only one prospective study has examined the association between cedar pollinosis and mortality. Using a symptom-based questionnaire on cedar pollinosis, we investigated the association of cedar pollinosis with all-cause and cause-specific mortality. METHODS: Data came from the Takayama Study, which recruited residents aged ≥35 years in 1992 from Takayama city in Gifu Prefecture, Japan. The current study used information on cedar pollinosis that was obtained from the second survey in 2002. A total of 12,471 persons who were 45-80 years old and had no history of cancer, coronary heart disease, or stroke responded to a questionnaire asking about four symptoms related to cedar pollinosis. Mortality and migration data were obtained throughout the follow-up period up to March 2013. Cox proportional hazard models were used to examine the relation between cedar pollinosis and mortality. RESULTS: A total of 1,276 persons died during follow-up period. Among these, there were 504 neoplasm, 278 cardiovascular, and 181 respiratory deaths. After adjusting for potential confounders, cedar pollinosis was associated with significantly lower all-cause mortality (hazard ratio [HR] 0.79; 95% confidence interval [CI], 0.65-0.95) and respiratory mortality (HR 0.38; 95% CI, 0.18-0.82). There was no significant association between cedar pollinosis and mortality due to neoplasm or cardiovascular disease. CONCLUSIONS: We found an inverse association between cedar pollinosis and the risk of all-cause and respiratory mortality. Further research is needed to elucidate the association between cedar pollinosis and mortality.

The Hekinan Children's Study: Design and Profile of Participants at Baseline.

BACKGROUND: The early life environment is now recognized as a key factor contributing to susceptibility to certain diseases in later life. METHODS: We initiated a cohort study among school children in 2011 to primarily investigate the associations between lifestyle and environmental factors and some surrogate markers of chronic diseases, such as cardiometabolic risk factors (ie, obesity, high blood pressure, high blood glucose, insulin, or lipids) and cancer risk factors (ie, height and age at menarche). A baseline questionnaire asked for information, including demographic variables, medical history and use of medication, dietary habits, physical activity, sleep habits, and behavioral and emotional problems of children. Follow-up surveys are planned for the fourth grade of elementary school and the first grade of junior high school. At these follow-up surveys, fasting blood samples will be obtained to measure cardiometabolic markers. We also checked the validity of a food frequency questionnaire, which was originally created for 6-year-olds but was modified for use in older children. RESULTS: A total of 3,141 first-year students at elementary schools in Hekinan City, Aichi Prefecture, participated in the study. The response rate was 87.4%. The means of age and body mass index were 6.99 (standard deviation, 0.28) years and 15.3 (standard deviation, 1.7) kg/m2, respectively, in the 3,067 Japanese children (1,639 boys and 1,428 girls). CONCLUSIONS: This cohort will reveal determinants of cardiometabolic risk factors and cancer risk factors during childhood.

Associations between coffee consumption and all-cause and cause-specific mortality in a Japanese city: the Takayama study.

OBJECTIVE: Epidemiological studies suggest that coffee consumption is inversely associated with all-cause and cause-specific mortality. Evidence from studies targeting non-white, non-Western populations is still sparse, although coffee is popular and widely consumed in Asian countries. DESIGN: Population-based, prospective cohort study. We used Cox proportional hazards models with adjustment for dietary and lifestyle factors to estimate associations between coffee consumption and all-cause and cause-specific mortality. Dietary intake including coffee consumption was assessed only at baseline using a validated FFQ. SETTING: A Japanese city. PARTICIPANTS: Individuals aged 35 years or older without cancer, CHD and stroke at baseline (n 29 079) and followed from 1992 to 2008. RESULTS: From 410 352 person-years, 5339 deaths were identified (mean follow-up = 14·1 years). Coffee consumption was inversely associated with mortality from all causes and CVD among all participants, but not from cancer. Compared with the category of 'none', the multivariate hazard ratio (95 % CI) for all-cause mortality was 0·93 (0·86, 1·00) for <1 cup/d, 0·84 (0·76, 0·93) for 1 cup/d and 0·81 (0·71, 0·92) for 2-3 cups/d. The multivariate hazard ratio (95 % CI) for cardiovascular mortality were 0·87 (0·77, 0·99) for <1 cup/d, 0·76 (0·63, 0·92) for 1 cup/d and 0·67 (0·50, 0·89) for 2-3 cups/d. Inverse associations were also observed for mortality from other causes, specifically infectious and digestive diseases. CONCLUSION: Drinking coffee, even 1 cup/d, was inversely associated with all-cause mortality and mortality from cardiovascular, infectious and digestive diseases.

Association between exposure to household smoking and dental caries in preschool children: a cross-sectional study.

BACKGROUND: We aimed to examine the association of exposure to environmental tobacco smoke with dental caries among preschool children. Exposure to environmental tobacco smoke was assessed in terms of urinary cotinine concentrations and pack-years of exposure to smoking by parents and other family members at home. METHODS: This cross-sectional study included 405 preschool children aged 3-6 years from two preschools in Japan in 2006. Information on the smoking habits of family members living with the child was obtained from parent-administered questionnaires. Dental examination was conducted to assess dental caries, that is, decayed and/or filled teeth. Urinary cotinine levels were measured using first-void morning urine samples. RESULTS: Overall, 31.1% of the children had dental caries, and 29.5% had decayed teeth. Exposure to current maternal and paternal smoking was positively associated with the presence of dental caries after controlling for covariates. More than three pack-years of exposure to maternal smoking and more than five pack-years of exposure to smoking by all family members were significantly associated with the presence of dental caries as compared with no exposure (odds ratio [OR] = 5.55, 95% confidence interval [CI] = 2.17-14.22, P for trend < 0.001 and OR = 2.00, 95% CI = 1.12-3.58, P for trend = 0.004, respectively). These exposure variables were similarly associated with the presence of decayed teeth (OR = 2.92, 95% CI = 1.23-6.96, P for trend = 0.01 and OR = 1.75, 95% CI = 0.96-3.20, P for trend = 0.03, respectively). As compared with lowest tertile of the urinary cotinine level, the highest tertile of the urinary cotinine level was significantly associated with the presence of dental caries as well as decayed teeth; the ORs for the highest vs. lowest tertile of urinary cotinine levels were 3.10 (95% CI = 1.71-5.63, P for trend = 0.012) and 2.02 (95% CI = 1.10-3.70, P for trend = 0.10), respectively. CONCLUSIONS: These data suggest that exposure to tobacco smoke may have a dose-dependent influence on the development of caries.

Associations of Acrylamide Intake With Urinary Sex Hormone Levels Among Preschool-Age Japanese Children.

Acrylamide may affect the sex hormone system in the prepubertal period. This study examined the cross-sectional associations between dietary acrylamide intake and sex hormone levels among preschool-age Japanese children. The study was conducted in 2006 among 230 boys and 198 girls aged 3-6 years in Aichi, Japan. Acrylamide intake was assessed using 3-day diet records. Urinary concentrations of estrone, estradiol, testosterone, and androst-5-ene-3ß, 17ß diol (hereafter referred to as androstenediol) were measured by liquid chromatography-electrospray ionization-tandem mass spectrometry. Sex hormone levels were adjusted for urinary creatinine levels. The estimated acrylamide intake was 1.00 µg/kg of body weight per day. After controlling for age and other covariates, acrylamide intake was significantly positively associated with urinary levels of testosterone and androstenediol in boys. On average, boys in the highest quartile of acrylamide intake had 96.9% higher testosterone (95% confidence interval: -1.8, 295; P for trend = 0.048) and 34.5% higher androstenediol levels (95% confidence interval: -5.9, 92.3; P for trend = 0.04) than boys in the lowest quartile. In girls, there were no significant associations between acrylamide intake and the hormones measured. Acrylamide intake may alter androgen metabolism in preschool-age boys. Because this is a first observation, our findings require confirmation in additional studies.