Published papers

Background. Accumulated evidence shows how important spinal posture is for aged populations in maintaining independence in everyday life. However, the cross-sectional designs of most previous studies prevent elucidation of the relationship between spinal posture and future dependence in activities of daily living (ADL). We tried to clarify the association by measuring spinal posture noninvasively in a community-based prospective cohort study of older adults, paying particular attention to thoracic curvature, lumbar curvature, sacral hip angle, and inclination to determine which parameter is most strongly associated with dependence in ADL.Methods. Spinal posture was evaluated in 804 participants (338 men, 466 women, age range: 65-94 years) who were independent in ADL at baseline. We defined dependence in ADL as admission to a nursing home or need of home assistance. During the 4.5-year follow-up period, 126 (15.7%) participants became dependent in ADL. The relationship between the spinal posture parameters and outcome was assessed by dividing the participants into sex-specific quartiles of the parameters.Results. Only inclination (angle subtended between the vertical and a line joining C7 to the sacrum) was associated with outcome, although lumbar curvature also showed a marginal association. The age- and sex-adjusted odds ratio for a 1 unit increase in the quartiles of inclination was 1.79 (confidence interval: 1.44, 2.23). After mutual adjustment for the 4 parameters, statistical significance for inclination still remained, with no substantial changes in the association estimates.Conclusions. This study indicates that spinal inclination is associated with future dependence in ADL among older adults. © 2013 © The Author 2013. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Objectives: The Trp64Arg polymorphism of the beta-3-adrenergic receptor gene has been studied as a potential genetic factor contributing to the development of obesity. Several studies have investigated whether or not this polymorphism affects weight reduction due to exercise, but the results of these studies have not been consistent. Moreover, information on a population characterized by a wide ranges of physical activities is scarce. Thus, to further understand the impact of this polymorphism, we examined whether the polymorphism modulates the relationship between physical activity due to exercise (PAE) and percentage of body fat (%BF). Methods: The study population was 70 Japanese male young adults with a high prevalence of habitual exercise. PAE was estimated by a questionnaire, and %BF was measured by bioelectrical impedance analysis. Genotyping was done by PCR-restriction fragment length polymorphism analysis. Results: The median PAE value of the subjects was 6.9 MET-h/day with an interquartile range of 1.5-10.3 MET-h/day. PAE correlated significantly with %BF in the entire population and within the two subpopulations, namely, carriers or non-carriers of the Arg allele. Multiple regression analysis of PAE, Trp64Arg polymorphism, and the interaction term revealed that while the PAE-derived independent variable was statistically significant, the interaction term was insignificant. When the two regression lines of subjects with and without the Arg allele were considered, the difference between the two slopes did not deviate from zero, nor did the vertical distance of the two regression lines. These findings suggest that the impact of this polymorphism is limited. Conclusions: In our study population of young adult Japanese males, the impact of the Trp64Arg polymorphism on the association between exercise and body composition was weak, if it existed at all. © 2013 The Japanese Society for Hygiene.

Background & Aims: There is controversy over the optimal management strategy for patients with branch-duct type intraductal papillary mucinous neoplasms of the pancreas (BD-IPMNs), precursors to pancreatic cancer. We aimed to identify factors associated with the presence of BD-IPMNs and changes in their diameter. Methods: Two separate analyses were conducted in a cohort of patients who underwent magnetic resonance cholangiopancreatography (MRCP) in a single year (2006). MRCP findings and clinical outcomes of these patients were followed for a maximum of 6 years. We evaluated initial MRCP findings and demographics associated with the presence of BD-IPMNs at baseline and increase in BD-IPMN diameter over time. Results: During the follow-up period, 154 patients developed BD-IPMN and 322 patients did not. Older age, diabetes mellitus, gallbladder adenomyomatosis, and absence of gallstones were associated with the presence of BD-IPMNs at baseline. Increases in diameter of BD-IPMNs were associated with 3 baseline factors: BD-IPMN diameter greater than 17 mm, gallbladder adenomyomatosis, and a common bile duct diameter less than 5.5 mm. Patients with BD-IPMNs could be stratified into 4 groups with varying risk for the enlargement of BD-IPMNs over time: those with 3 risk factors (hazard ratio [HR], 11.4; 95% confidence interval [CI], 3.4-37.8), 2 risk factors (HR, 4.7; 95% CI, 1.7-12.8), or 1 risk factor (HR, 3.1; 95% CI, 1.2-8.2) compared with those without risk factors. Conclusions: For patients with BD-IPMNs, careful follow-up evaluation is particularly important for those with BD-IPMN >17 mm in size, common bile duct diameter <5.5 mm, or gallbladder adenomyomatosis. © 2013 AGA Institute.

Background: In 2009, influenza A (H1N1) infections spread worldwide. Because the use of immunomodulators is associated with an increased risk of infection, inflammatory bowel disease (IBD) patients who are on immunomodulators might be concerned about H1N1 influenza infections. The aim of this study was to investigate the age distribution and risk factors associated with H1N1 influenza of IBD patients in 2009-2010. Methods: A multicenter, prospective study was conducted, and 570 IBD patients were enrolled. Patients were followed up for 10. months to identify any new infections. The incidence and age distribution of the H1N1 influenza infections were analyzed. IBD patients with H1N1 influenza infections and 2 matched, noninfected IBD patients were selected to assess the effect of specifying the medication on the incidence of infections. Results: A total of 38 patients (6.7%) developed H1N1 influenza infections. The incidence of H1N1 influenza infections in patients aged less than 20. years was significantly higher than that among patients in other age groups (p < 0.01). The age distribution for H1N1 influenza infections in IBD patients was comparable to those in the general population. No patients needed hospitalization due to influenza infection. A total of 29 patients (76%) recovered from the H1N1 influenza symptoms within 7. days and 20 patients (53%) received antiviral treatment. The percentage of patients who used steroids or thiopurine was comparable between the cases of H1N1 influenza infection and the control group. Conclusion: Our prospective study showed that younger IBD patients were frequently infected with the influenza A (H1N1) virus as well as general population. Admission and fatal cases due to H1N1 influenza infections were not observed. © 2012 European Crohn's and Colitis Organisation.

Aim: Associations between long-term exposure to particulate matter (PM) and increased cardiovascular mortality have been reported, but few studies have investigated the associated incidence of cardiovascular disease, and none involved men. Methods: We used data on 78,057 participants (37,121 men, 40,936 women) to examine the associations of long-term exposure to PM with mortality and the incidence of cardiovascular diseases. Average PM levels in the relevant area during the study period were used as an index of individual exposure to each subject. Cox models adjusted for age, sex, smoking, environmental smoking, body mass index, and alcohol consumption were used, with further adjustments for nitrogen dioxide and sulfur dioxide exposure, systolic blood pressure, total cholesterol, and diabetes mellitus. Results: Increased PM levels were associated with an increased risk of incident coronary heart disease (CHD) and myocardial infarction (MI), particularly among smokers (adjusted hazard ratio (HR) per 10 μg/m3 increase in PM for CHD: 1.39, 95% confidence interval (CI) 1.01-1.93; for MI: 1.52, 1.08-2.13) and among women (for CHD: 1.63, 0.91-2.92; for MI: 1.99, 1.07-3.70); however, the observed positive association of PM exposure with the incidence of CHD and MI was not robust, and the association disappeared when one of the areas (Akita) was excluded. The association with CHD mortality was not statistically significant (adjusted HR per 10 μg/m3 increase in PM: 1.11, 0.92-1.33). There was an inverse association of long-term PM exposure with stroke mortality and incidence. There was no clear association between PM levels and lung cancer mortality and incidence. Conclusions: Long-term exposure to PM might increase the risk of incident CHD in middle-aged Japanese men and women. Our findings also suggest that women and smokers are especially vulnerable to PM exposure.

Background.Oxidative stress is an important factor in the pathology of age-related hearing loss. Recent animal studies have reported that ultraviolet radiation in sunlight is related to systemic induction of oxidative stress. Chronic sun exposure leads to photodamaged skin, which is manifested as facial skin wrinkling and hyperpigmentation. We hypothesized that sunlight exposure, as assessed by the severity of facial skin photodamage, might be associated with hearing impairment through an oxidative stress mechanism. To examine this, we performed a cross-sectional analysis by using the baseline data from a community-based cohort study of older Japanese.Methods.A total of 805 residents (342 men and 463 women) aged 65 years or older living in Kurabuchi Town, Gunma prefecture, Japan, were examined between 2005 and 2006. Facial skin condition was quantified by image analysis of standardized facial images. Hearing impairment was defined as a failure to hear a 30-dB signal at 1 kHz and a 40-dB signal at 4 kHz in the better ear in pure-tone audiometric tests.Results.In men, facial wrinkle was positively associated with hearing impairment (for highest vs lowest: multivariate-adjusted odds ratio, 2.16; 95% confidence interval, 1.00-4.66; p for trend =. 01). Stratified analysis by age, educational level, smoking status, sunscreen or foundation use, and diabetes showed results similar to those for men as a whole. This association was particularly pronounced in men with the low levels of antioxidants and without occupational noise exposure. We observed no apparent association in women.Conclusions.The results support the hypothesis that chronic sun exposure is a risk factor of hearing impairment. © 2012 The Author.

A population-based influenza surveillance study (using PCR virus subtyping) on Izu-Oshima Island, Japan, found that the cumulative incidence of influenza A(H1N1) pdm09 virus infections 2 seasons after the pandemic was high est for those 10-14 years of age (43.1%). No postpandemic A(H1N1)pdm09 case-patients had been infected with A(H1N1)pdm09 virus during the pandemic season.

OBJECTIVE: Dehydroepiandrosterone sulfate (DHEAS) appears to have a protective effect against depression, but evidence from prospective cohort studies is sparse. Therefore, we examined the association between serum DHEAS levels and depressive symptoms in older community-dwelling Japanese. DESIGN: A community-based cohort study. SETTING: Kurabuchi Town, Gunma Prefecture, Japan. PARTICIPANTS: A total of 554 residents (248 men and 306 women) age 65 years or older without depressive symptoms at baseline. MEASUREMENTS: We performed a baseline examination of the subjects between 2005 and 2006 to determine serum DHEAS levels. The subjects were categorized into three groups based on age strata- and sex-specific tertiles of DHEAS. Depressive symptoms were assessed with the Geriatric Depression Scale 15-item version (GDS-15) in face-to-face home visit interviews carried out once in 2007 and once in 2008. The association of DHEAS with depressive symptoms (GDS-15 ≥ 6) was analyzed with the use of logistic regression models. RESULTS: The incidence of depressive symptoms was 12.1% in men and 19.6% in women. In men, the multiadjusted odds ratio of depressive symptoms was 0.24 (95% confidence interval: 0.06-0.94, Wald χ = 4.20, degrees of freedom = 1, p = 0.04) for the highest tertile compared with the lowest. The association observed for the highest versus the lowest remained significant even after adjustment for physical performance and cognitive function. In women, DHEAS was not associated with depressive symptoms. CONCLUSIONS: In this study, higher serum DHEAS levels were found to be protectively and independently associated with the risk of developing depressive symptoms in men, but not in women.

Background Although the prevalence of inflammatory bowel disease (IBD) is reported to have reached a plateau in Western countries, it is increasing in Asia. The etiology of IBD is still under investigation. We performed an epidemiological study to clarify the characteristics of IBD in Japan, focusing on patients' family history. Methods We obtained clinical data on ulcerative colitis (UC) (46,114 cases) and Crohn's disease (CD) (11,305 cases) in 2007 from an electronic database maintained under the Japanese Ministry of Health, Labour and Welfarés nationwide registry system, and analyzed the differences in disease characteristics between patients with IBD who had a family history of the disease and those who did not. Results A total of 2.7% of the patients with UC and 2.6% of those with CD had a family history. The present age and age at disease onset were lower among the patients with UC who had a family history than among those without (present age: p0.001; age at disease onset: p0.001; Mann-Whitney U-test), but no similar trend was observed in the patients with CD. Disease severity was worse among both the UC and CD patients with a family history. The clinical course of patients with UC was not affected by family history. Levels of independence in daily life were associated with family history among CD patients, whereas age was associated with levels of independence in daily life among UC patients. Conclusion Disease characteristics of IBD vary in some aspects according to the presence or absence of a family history. © 2012 Springer.

Objectives To investigate whether self-reported hearing loss in older adults is associated with a decline in their ability to perform instrumental activities of daily living (IADL) or a decline in social participation. Design Prospective follow-up. Setting Community. Participants One thousand two hundred fifty-four adults aged 65 to 98. Measurements Self-reported hearing loss, IADL, and social participation were evaluated through home-visit surveys. Self-reported hearing loss was measured according to responses to the question, "Do you have difficulty hearing and understanding what a person says to you in a quiet room if they speak normally to you, even when wearing your hearing aid?" Levels of IADL and social participation were measured using the subscales of the Tokyo Metropolitan Institute of Gerontology Index of Competence (TMIG-IC). Results Of the 921 participants with a perfect baseline IADL score and valid follow-up scores, 105 also self-reported hearing loss at baseline. Of this group, 44.8% (total n = 105) reported a decline in their IADL score over the 3-year follow-up period. After adjusting for major confounders, a statistically significant difference in experiencing an IADL decline over the 3-year period was found between those with hearing loss at baseline and those without (odds ratio (OR) = 1.79, 95% confidence interval (CI) = 1.12-2.87). Self-reported hearing loss at baseline did not have a statistically significant effect on decline in social participation (OR = 1.05, 95% CI = 0.63-1.76) over the 3-year follow-up period. Conclusion Self-reported hearing loss was associated with a decline in IADL, but not with social participation. © 2012, The American Geriatrics Society.

Purpose Patients' knowledge, beliefs, or concerns about opioids, palliative care, and homecare can be potential barriers to providing quality palliative care. The primary aim of this study was to clarify knowledge about opioids, beliefs about palliative care, and concerns about homecare in advanced cancer patients. Methods An anonymous questionnaire was sent to 1,619 outpatients with advanced cancer at 25 hospitals in four different regions of Japan. The respondents were asked to report their knowledge about opioids, beliefs about palliative care, and concerns about homecare, in addition to the levels of their sense of security regarding receiving cancer care in the region. Results A total of 925 responses were received. In total, 28% believed that opioids are addictive and/or shorten life; 52% believed that palliative care is only for terminally ill patients; 75% agreed that being taken care of at home puts a heavy burden on the family; and 61% agreed that homevisit services cannot respond to sudden changes in a patient's condition. Levels of patients' sense of security were significantly higher in those who agreed that "opioids can relieve most pain caused by cancer" "palliative care relieves pain and distress", "palliative care is provided along with chemotherapy and/or radiation therapy", and "pain can be alleviated as effectively through home-visit services as it can at the hospital", and those who disagreed with the statements that "home-visit services cannot respond to sudden changes in a patient's condition" and "being taken care of at home puts a burden on the family". Conclusions Advanced cancer patients frequently had incorrect knowledge about opioids, a belief that palliative care is only for terminally ill patients, and concerns about homecare, especially the family burden and responses to sudden changes. Providing appropriate information about the safety of opioids, the availability of palliative care during the entire course of the disease, and realistic information about homecare is of marked importance to promote patients' sense of security. © Springer-Verlag 2011.

Background Functional dyspepsia (FD) is a heterogeneous disease, and categorized into postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS). However, many FD patients have overlap of both PDS and EPS. The present study was designed to examine whether FD could be categorized based on the presence of concomitant gastrointestinal symptoms. Methods A web survey comprised of the Gastrointestinal Symptom Rating Scale (GSRS), Rome III criteria of FD, and demographic information was sent to public participants who have no history of severe illness. Factor and cluster analyses were conducted to identify sub-categories of FD based on GSRS. Key Results A total of 8038 participants completed the survey. A total of 563 participants met the criteria for FD, whereas 6635 participants did not have dyspepsia symptoms. The remainder had either organic disease (377) or uninvestigated dyspepsia (463). The cluster analysis categorized participants as constipation predominant (cluster C), diarrhea predominant (cluster D), or having neither diarrhea nor constipation (cluster nCnD). Cluster C and D were significantly associated with the presence of FD [odds ratio (OR) 2.57, 95% confidence interval (CI) 2.06-3.21; OR 2.80; 95% CI 2.27-3.45, respectively]. In FD, especially in PDS cases, the scores of upper gastrointestinal symptoms were higher in cluster C or D than in cluster nCnD. Conclusions & Inferences The severity of dyspepsia symptoms is associated with the presence of bowel symptoms especially in PDS. This novel categorization of FD based on concomitant constipation or diarrhea may improve classification of patients. © 2012 Blackwell Publishing Ltd.

The Evaluation System of Investigational Medical Care (ESIMeC) is a new clinical trial system that Ministry of Health, Labour and Welfare authorizes the coverage of medical expenses by Japanese health insurance system for the patients participating in the approved clinical trials with high quality control mechanism. This system became effective in 2008. The Kitasato University Clinical Trials Coordinating Center has supported two randomized, phase III trials being conducted under ESIMeC since 2009. One trial is to evaluate the efficacy and safety of intraperitoneal (IP) chemotherapy of Carboplatin for ovarian cancer patients ; another trial is to evaluate the efficacy and safety of new anticancer agent Bevacizumab for recurrent ovarian cancer patients. Carboplatin is approved for ovarian cancer by intravenous administration, but not for IP administration. Bevacizumab is not approved for ovarian cancer. However, the indication-directed trial has been completed for the first line chemotherapy for ovarian cancer, but not for the recurrent setting. In this article, we discuss the issues that need to be improved in the future, as well as the importance of the clinical trial coordinating center, so that ESIMeC will work better to accelerate investigator-initiated clinical trials evaluating new agents/medical techniques with no indication approval in Japan. Critical issues in cancer clinical trial coordination under ESIMeC include being familiar with the system itself, development of the clinical trial team, support of the application process for ESIMeC, establishment of serious adverse event reporting procedures, management of the study agents, and cost-effective study monitoring.

Objectives To elucidate the independent relationship between masticatory and physical performance in community-living oldest old people (mean age ± standard deviation 87.8 ± 2.2, range 85-102). Design Cross-sectional analysis. Setting University research center or home-based examination. Participants Four hundred eighty-nine community-living individuals (219 men, 270 women) aged 85 and older. Measurements Maximum occlusal force (MOF) was measured using an occlusal force measuring device. Sociodemographic and functional factors, oral health, comorbidities, blood chemistry, lower extremity performance, and handgrip strength were assessed. Blood chemistry analyses included serum albumin, C-reactive protein, interleukin (IL)-6, and total and free testosterone. Results MOF was significantly associated with age, body mass index, and cognitive impairment in men but not in women. Comorbidities and blood chemistry were not associated with MOF except for a significant association with IL-6 concentration in women. In a multivariate model adjusted for various confounders, lower MOF was associated with greater risk for poor performance on the timed up and go (TUG) test in men and women (men: odds ratio (OR)=2.34, 95% confidence interval (CI)=1.02-5.38; women: OR=2.44, 95% CI=1.12-5.33). MOF was similarly associated with performance in chair standing, one-leg standing, and handgrip strength only in men. These associations remained after adjustment for number of natural teeth. Conclusion MOF was strongly and independently associated with all measures of physical performance in men and with the TUG test in women after adjustment for various confounders, suggesting that age-related declines in masticatory and skeletal muscle functions share common mechanistic pathways in older age, particularly in men. © 2011, The American Geriatrics Society.

Context Improving palliative care is one of the major issues throughout the world. Objectives The primary aim of this study was to explore how and why a regional palliative care program led to changes in a region. Methods As part of a nationwide mixed-methods study of a regional palliative care program, a qualitative study was performed with 101 health care professionals involved in the implementation of the program. In-depth interviews were done, focusing on perceived changes and the perceived reasons for the changes. We used thematic analyses. Results Seven themes were identified as follows: 1) improved communication and cooperation among regional health care professionals; 2) increased confidence in the system to care for cancer patients at home; 3) improved knowledge/skills, practice, and perception of palliative care; 4) contribution to self-growth; 5) wide variability in perceived changes in the knowledge and perception of patients, family members, and the general public; 6) wide variability in the perceived regionwide effects of the project; and 7) unresolved issues. Participants emphasized improved communication and cooperation among regional health care professionals and stated a variety of ways of how communication and cooperation influenced daily practice. The main reasons for changes included regionwide interdisciplinary conferences and informal interactions at a variety of meetings. Conclusion This study advances understanding of how the regional palliative care program created a change in the region. The findings are useful for developing a conceptual framework and identifying key interventions to improve regional palliative care for clinicians, researchers, and policy makers. © 2014 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

Objectives To examine the association between glycemic levels (glycosylated hemoglobin (HbA1c)) and hearing impairment in a general older population. Design Community-based prospective longitudinal cohort study. Setting Kurabuchi Town, Gunma Prefecture, Japan. Participants Residents (N = 831; 350 men, 481 women) aged 65 and older were examined in 2005 and 2006 and analyzed in a cross-sectional study. Residents without hearing impairment at baseline who participated in audiometric re-examinations 4 years later were analyzed (n = 338). Measurements Hearing impairment was defined as failure to hear a 30-dB signal at 1 kHz and a 40-dB signal at 4 kHz in the better ear in pure-tone audiometric tests. Results Mean HbA1c level (National Glycohemoglobin Standardization Program) was 5.8 ± 0.8% (40 mmol/mol). Odds ratios (ORs) and 95% confidence intervals (CIs) of hearing impairment associated with HbA1c were estimated using a logistic regression model. In the cross-sectional analysis, HbA1c levels were positively associated with hearing impairment (OR per 1.0% increase in HbA1c = 1.30, 95% CI = 1.00-1.68). This association persisted even after excluding 58 participants with a self-reported history of diagnosed diabetes mellitus. Longitudinal analysis revealed the temporality of the discussed association (OR = 1.52, 95% CI = 1.03-2.23). Conclusion The present study provides supportive evidence for a causal link between hyperglycemia and age-related hearing loss. © 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.

Background.Prevention of disability is a major challenge in aging populations; however, the extent to which physical independence can be maintained toward the limit of human life span remains to be determined.Methods.We examined the health and functional status of 642 centenarians: 207 younger centenarians (age: 100-104 years), 351 semi-supercentenarians (age: 105-109 years), and 84 supercentenarians (age: >110 years). All-cause mortality was followed by means of an annual telephone or mailed survey.Results.Age-specific disability patterns revealed that the older the age group, the higher the proportion of those manifesting independence in activities of daily living at any given age of entry. Multiple logistic regression analysis identified male gender and better cognitive function as consistent determinants of physical independence across all age categories. In a longitudinal analysis, better physical function was significantly associated with survival advantage until the age of 110. However, mortality beyond that age was predicted neither by functional status nor biomedical measurements, indicating alternative trajectories of mortality at the highest ages.Conclusions.These findings suggest that maintaining physical independence is a key feature of survival into extreme old age. Future studies illuminating genetic and environmental underpinnings of supercentenarians' phenotypes will provide invaluable opportunities not only to improve preventive strategies but also to test the central hypotheses of human aging. © The Author 2013.