Published papers

© 2018, The Author(s). Summary: This cohort study conducted in Japan showed that severe age-related kyphosis was visually detected. The visual assessment of kyphosis was associated with declines in ADL, suggesting that we can easily identify people at high risk to develop future ADL reduction in the community setting. Purpose: Age-related kyphosis is related with declines in activities of daily living (ADL). Its conventional diagnosis has been made by orthopedic surgeons and trained examiners using specialized equipment such as X-rays. We investigated whether visual classification of kyphosis by laypersons accurately predicted future ADL decline. Methods: This study was part of the Kurabuchi Study, a cohort study of community-dwelling elderly Japanese. Between 2009 and 2010, three layperson raters used reference illustrations to classify 532 participants without ADL decline at study baseline into four categories. Other examiners used conventional methods to assess kyphosis in the same participants: curve ruler, Spinal Mouse, and the block method. ADL decline was defined as the development of dependence according to the Katz Index, admission to a nursing home, or certification of long-term care need. Results: Thirty-five of the participants (6.6%) were classified with the most severe degree of kyphosis at baseline by visual assessment. Interrater agreement was high (Kappa = 0.73) for the most severe group. During 4.5 years of follow-up, 106 participants (19.9%) showed ADL decline. On the basis of visual assessment, the adjusted risk ratio for ADL decline among the participants with the most severe kyphosis was 2.6 (95% CI: 1.4–4.6). Assessments of kyphosis made with the Spinal Mouse also accurately predicted ADL decline. Conclusions: Visual assessment of kyphosis predicted future declines in ADL in this study. Since our method requires no special tools or training, it may be useful for identifying those at high risk of ADL decline.

© 2019 The Authors. Journal of Occupational Health published by John Wiley & Sons Australia, Ltd on behalf of The Japan Society for Occupational Health Objectives: To establish an enzymatic deconjugation method to separately quantify urinary o-toluidine (OT), its six metabolites, another six chemicals present in an OT-processing plant, and one metabolite of p-toluidine, and to propose optimal urinary biological monitoring items of OT exposure. Methods: Thirty-six urine samples of an OT-processing plant's workers were obtained and pretreated by an enzymatic deconjugation method employing β-glucuronidase/arylsulfatase for 3 hours at 37°C and measured by liquid chromatograph-mass spectrometry (LC-MS). An alkaline hydrolytic pretreatment and 1-chlorobutane extraction procedure was also examined as a widely used urinary OT measurement method. Results: The 14 chemicals were separated by LC-MS condition set by us and 13 chemicals other than 2-chloroaniline showed satisfiable linearity and limits of determination. Standard substances of six OT metabolites decomposed after the alkaline heating. In the 36 urine samples, OT, N-(4-hydroxy-2-methylphenyl) acetamide (NHM), and 4-amino-m-cresol (ACR) accounted for approx. 90% of the total OT and OT metabolites, but inter-individual variation of the three substance excretion seemed to be wide. Time course of urinary excretion revealed that concentration of the three substances was higher 24 hours after the work shift's end rather than just after the work shift. Conclusions: OT and its six metabolites can each be determined with LC-MS. The alkaline method is not so optimal for exact biological monitoring. Rather, the sum of urinary OT, NHM, and ACR measured by the enzymatic method is a better index, and "end of the workweek" is a good urine-sampling time for the biological monitoring of OT exposure.

© 2018 The Authors. International Journal of Geriatric Psychiatry Published by John Wiley & Sons Ltd. Objectives: The purpose of this study is to clarify the influence of social interaction on the effect of a cognitive intervention program using Go. Methods: A single-blind, randomized controlled trial using a classical board game “Go” was conducted. A total of 72 community-dwelling older adults, without previous experience playing Go, were randomly assigned to three groups: (1) a face-to-face group (FG) in which members attended 12 Go group lessons held once a week; (2) a non-face-to-face group (NFG) in which members individually underwent the same Go lessons as the FG using a tablet computer; or (3) a health education control group (CG). The main outcome variable, working memory, was assessed before and after the interventions using the Visual Memory Span Test (VMST) and the Visual Memory Span Backward (VMSB) task. Go performance and additional cognitive domains were also examined. Results: Analysis of covariance revealed that VMST scores significantly improved after the intervention in both the FG and NFG (both P <.05). Compared with the CG, the effect size of the FG (Cohen's d = 0.89) was greater than that of the NFG (Cohen's d = 0.67). Although VMSB scores significantly improved after the intervention in the FG (P <.05), no significant changes were observed in other groups. Conclusions: This study showed that Go game could improve visual working memory regardless of social interaction. Furthermore, findings suggested that playing board games face-to-face with others is more effective for cognitive function than playing alone.

© Article author(s). Objectives: To clarify the priority given to periodical medical examination items among occupational physicians in Japan. Methods: Sixty-two occupational physicians who participated in this study selected statutory and non-statutory items within two types of budget plans: one lower (8,500 yen) than the total fee of statutory medical examinations (9,250 and 11,290 yen), and the other higher (12,000 yen) than the total fee. Medical fee points were used to set the cost of each medical examination item. A three round Delphi method was used from May to July 2016 to clarify the consensus opinion of occupational physicians. Results: The statutory items (selection rate: between 66 and 100%), except for waist circumference (15%) and sputum examination (0%), and serum creatinine (58%, non-statutory item ) were included in the smaller budget plan (8,500 yen) . In the larger budget plan (12,000 yen), the statutory items (selection rate: between 92 and 100%), except for waist circumference (39%) and sputum examination (0%), and some non-statutory items, namely serum creatinine (95%), leukocytes (92%), uric acid (89%), and fecal occult blood reaction (81%), had a selection rate over 80%. In addition, statutory items with higher accuracy were preferred, which included the following: air conduction pure-tone audiometry (92%), imaging diagnosis of thoracic X-ray examinations by a specialist (97%), glycated hemoglobin levels (98%), and electrocardiogram assessment by a specialist (100%). Conclusion: The statutory items, except for waist circumference and sputum examination, and some of the non-statutory items (e.g., serum creatinine ) were given higher priority among occupational physicians in Japan.

© 2018, The Japanese Society of Hypertension. While the association between 24-h urinary sodium and potassium excretion with blood pressure is well established, the relationships of these ions to spot urine measurements are unclear. Our purpose is to assess the association between blood pressure and the estimated 24-h sodium and potassium excretion from repeated single-spot urine samples. Spot urine and blood pressure were collected annually during a 5-year period from 4360 Japanese workers with ages ranging from 19 to 55 years. Estimates of 24-h sodium and potassium excretion were based on Tanaka’s formula. Overall, a single standard deviation increase in the estimated sodium excretion (36.5 mmol/day) was associated with a 1.3 mmHg higher systolic blood pressure and a 0.8 mmHg higher diastolic blood pressure (P < 0.001). A single standard deviation increase in estimated potassium excretion (8.9 mmol/day) was associated with a 1.1 mmHg lower systolic blood pressure and a 0.7 mmHg lower diastolic blood pressure (P < 0.001). As a combined measure of the excretion of both electrolytes, the estimated 24-h sodium-to-potassium ratio was positively associated with both blood pressures (P < 0.001). Associations of blood pressure with sodium and the sodium-to-potassium ratio increased with age and were stronger in men compared to women. Associations with potassium and the sodium-to-potassium ratio were stronger in individuals who were overweight. The findings provide evidence for an association between blood pressure and the estimated 24-h sodium and potassium excretion from repeated single-spot urine samples. As convenient measures of dietary intake for each electrolyte, repeated spot urine samples may be useful for assessing hypertension risk, especially in men, older individuals, and overweight individuals.

We aimed to evaluate the associations of individual-level social capital (SC) and physical activity (PA) among Japanese elderly men and women. Individuals aged 65 or above were selected via population-based random sampling of 3000 adults, aged 20 years or above and living in Fujisawa city, who were asked to complete self-administered questionnaires. The sample consisted of 260 men [median (25-75% tile) age 73 (68-78) yrs] and 274 women [73 (68-78) yrs]. The daily duration of PA, SC [e.g., norms of reciprocity (mutual support in the community), social networks (relationship with community people, exchange with other generations), social participation (participation in community organization activities)], socio-economic status [educational attainment, work with income, perceived household economic status], and demographic characteristics [sex, age, living arrangements, BMI, physical limitations] were assessed. Multivariate logistic regression analyses were used to calculate odds ratios (OR) for associations of SC with PA, stratified by sex. High level of mutual support in the community, relationship with community people, and exchange with other generations were associated with longer PA time in men after adjusting for potential confounders in the final model (OR = 2.40 (95% CI: 1.24-4.67), 5.28 (1.42-19.66), and 4.24 (1.15-15.67), respectively). In women, relationship with community people and participation in community organization activities were associated with longer PA time (3.10 (1.32-7.26) and 2.50 (1.27-4.91), respectively). The association of individual-level SC and PA differed between men and women. Future studies can investigate whether similar results can be obtained in other areas or attempt to conduct a large-scale survey.

© 2018 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd Background and Aim: Studies on the characteristics of elderly-onset ulcerative colitis (EOUC) and non-elderly-onset ulcerative colitis (NEOUC) have reported conflicting findings. The aim of this study was to compare disease characteristics of EOUC and NEOUC by analyzing the database of the Japanese nationwide inflammatory bowel disease (IBD) registry. Methods: We analyzed the age of disease onset, sex, disease severity, and disease extent in patients with ulcerative colitis that were newly diagnosed and registered within 1 year between 2004 and 2009 (n = 28 179). We also analyzed the medical treatment, rate of IBD-related surgery, and postoperative complications. We compared them between younger than 65 years old (NEOUC group) and 65 years old or older (EOUC group) patients. Results: A total of 25 401 (90.1%) and 2778 (9.9%) patients were included in the NEOUC and EOUC groups, respectively. In the EOUC group, disease activity was significantly higher, and extent of pathological changes in the colon more extended significantly. Laboratory findings showed that inflammatory markers were elevated significantly in the EOUC group. The proportion of those with IBD-related hospitalization was significantly higher in the EOUC group (54.2% vs 35.7%, P < 0.001). The proportion of patients who were treated with corticosteroids was significantly higher in the EOUC group (36.7% vs 30.8%, P < 0.001). Significantly more number of patients underwent IBD-related surgery in the EOUC group (0.68% vs 0.27%, P < 0.001). Conclusion: Elderly patients show higher disease activity, with a higher proportion requiring IBD-related hospitalization and IBD-related surgery, according to the nationwide registry in Japan.

© 2018 Medknow. All rights reserved. Objective: This study aims to ascertain the incidence and association of falls and physical inactivity in patients with gastrointestinal cancer and hand-foot syndrome (HFS) after receiving chemotherapy or targeted therapy. Methods: The present cross-sectional study was conducted on 50 outpatients with HFS of Grade 1 or above, according to the National Cancer Institute Common Terminology Criteria for Adverse Events, following the receipt of chemotherapy or targeted therapy for gastrointestinal cancer in Japan between November 2016 and February 2017. For measurement, Dermatology Life Quality Index (DLQI) and the International Physical Activity Questionnaire were used. Data were analyzed by logistic regression analysis. Results: Of the participants, 18% experienced falls and 60% reported physical inactivity. Multivariate logistic regression revealed that the DLQI treatment domain score was the only factor associated with falls (odds ratio [OR] =8.01, 95% confidence interval [CI] =1.27-50.63, P = 0.027). Physical inactivity was associated with DLQI symptom and feeling domain scores (OR = 5.54, 95% CI = 1.26-24.33, P = 0.023) and the with-oxaliplatin or paclitaxel regimen (OR = 3.71, 95% CI = 1.06-13.03, P = 0.041). Conclusions: The results of the present study suggest patients should be informed that HFS is a risk factor for physical inactivity and falls.

The development of high-throughput metabolite measurement technologies has enabled the use of metabolomics for epidemiologic studies by profiling metabolite concentrations in large cohorts of human blood samples. Standard protocols are necessary to obtain unbiased profiles through multiple runs over long periods of time and to allow reliable statistical analyses. This study assessed the effects of sampling procedures and storage conditions on the stability of metabolomic profiles in plasma and serum. Charged metabolomic profiles were determined by capillary electrophoresis-mass spectrometry (CE-MS) and compared by multivariate analyses. The effects of pre-analytical procedures, including times for clotting and incubation of serum and plasma, respectively; incubation temperatures; and number of freeze-thaw cycles, were assessed. Overall, inter-individual differences in profiles were larger than intra-individual differences, and profiles in plasma showed better stability than those in serum. These quantified datasets of metabolites, along with their stability and variation, may help in interpreting data from long-term cohort studies.

Purpose: Prejudices against palliative care are a potential barrier to quality end-of-life care. There have been few large-scale community-wide interventions to distribute appropriate information about palliative care, and no studies have investigated their impact on cancer patients, their families, and the general public. Thus, we conducted a 3-year community intervention and evaluated the effects of distributing such information at the community level, and explored associations among levels of exposure, perceptions, knowledge, and the sense of security achieved. Methods: Over a period of 3 years, we provided flyers, booklets, posters, and public lectures about palliative care in four regions of Japan, and carried out pre- and post-intervention surveys with repeated cross-sectional samplings of cancer patients (pre 859, post 857), bereaved family members (1110, 1137), and the general public (3984, 1435). The levels of exposure to the provided information were measured by a multiple-choice questionnaire after intervention. Multiple logistic regression analyses were used to estimate multivariable-adjusted odds ratios (ORs) for perceptions of palliative care, knowledge about opioids, and sense of security among the exposure groups. Results: Overall perceptions of palliative care, opioids, and receiving care at home improved significantly among the general public and families, but not among the patients at the community level. However, multiple regression revealed that patients of extensive exposure category had significantly more positive perceptions of palliative care to those of non-exposure category (p = 0.02). The sense of security regarding cancer care of all patients, family members, and the general public improved. Among others, the respondents who reported extensive exposure in the general public and family members scored significantly higher sense of security. Conclusion: Our findings indicate that providing palliative care information via small media and lectures in the community is effective in improving perceptions of palliative care and knowledge about opioids among the community dwellers, especially for caregivers of the patients. The acquisition of adequate knowledge about palliative care from various information sources may improve people’s sense of security regarding cancer.

To determine the most important drivers of successful ageing at extreme old age, we combined community-based prospective cohorts: Tokyo Oldest Old Survey on Total Health (TOOTH), Tokyo Centenarians Study (TCS) and Japanese Semi-Supercentenarians Study (JSS) comprising 1554 individuals including 684 centenarians and (semi-)supercentenarians, 167 pairs of centenarian offspring and spouses, and 536 community-living very old (85 to 99years). We combined z scores from multiple biomarkers to describe haematopoiesis, inflammation, lipid and glucose metabolism, liver function, renal function, and cellular senescence domains. In Cox proportional hazard models, inflammation predicted all-cause mortality with hazard ratios (95% CI) 1.89 (1.21 to 2.95) and 1.36 (1.05 to 1.78) in the very old and (semi-)supercentenarians, respectively. In linear forward stepwise models, inflammation predicted capability (10.8% variance explained) and cognition (8.6% variance explained) in (semi-)supercentenarians better than chronologic age or gender. The inflammation score was also lower in centenarian offspring compared to age-matched controls with δ (95% CI)=-0.795 (-1.436 to -0.154). Centenarians and their offspring were able to maintain long telomeres, but telomere length was not a predictor of successful ageing in centenarians and semi-supercentenarians. We conclude that inflammation is an important malleable driver of ageing up to extreme old age in humans.

Purpose: To examine the relation of work type with health-related quality of life (HRQoL) in healthy workers. Methods: We cross-sectionally examined 4427 (3605 men and 822 women) healthy workers in Japan, aged 19–69 years. We assessed HRQoL based on scores for five scales of the SF-36. Multiple regression was applied to examine the relation of work type (nighttime, shift, day to night, and daytime) with the five HRQoL norm-based scores, lower scores of which indicate poorer health status, adjusted for confounding factors, including sleeping duration. Results: Shiftwork was inversely related to role physical [regression estimate (β) = −2.12, 95 % confidence intervals (CI) −2.94, −1.30, P < 0.001], general health (β = −1.37, 95 % CI −2.01, −0.72, P < 0.001), role emotional (β = −1.24, 95% CI −1.98, −0.50, P < 0.001), and mental health (β = −1.31, 95% CI −2.01, −0.63, P < 0.001) independent of confounding factors, but not to vitality. Day-to-nighttime work was inversely related to all the five HRQoL subscales (Ps 0.012 to <0.001). Conclusion: Shiftwork was significantly inversely related to four out of the five HRQoL, except for vitality, and day-to-nighttime work was significantly inversely related to all five HRQoL, independent of demographic and lifestyle factors.

Poor oral health and hygiene are increasingly recognized as major risk factors for pneumonia among the elderly. To identify modifiable oral health-related risk factors, we prospectively investigated associations between a constellation of oral health behaviors and incident pneumonia in the community-living very elderly (i.e., 85 years of age or older). At baseline, 524 randomly selected seniors (228 men and 296 women; mean age, 87.8 years) were examined for oral health status and oral hygiene behaviors as well as medical assessment, including blood chemistry analysis, and followed up annually until first hospitalization for or death from pneumonia. During a 3-year follow-up period, 48 events associated with pneumonia (20 deaths and 28 acute hospitalizations) were identified. Among 453 denture wearers, 186 (40.8%) who wore their dentures during sleep were at higher risk for pneumonia than those who removed their dentures at night (log rank P = 0.021). In a multivariate Cox model, both perceived swallowing difficulties and overnight denture wearing were independently associated with an approximately 2.3-fold higher risk of the incidence of pneumonia (for perceived swallowing difficulties, hazard ratio [HR], 2.31; and 95% confidence interval [CI], 1.11-4.82; and for denture wearing during sleep, HR, 2.38; and 95% CI, 1.25-4.56), which was comparable with the HR attributable to cognitive impairment (HR, 2.15; 95% CI, 1.06-4.34), history of stroke (HR, 2.46; 95% CI, 1.13-5.35), and respiratory disease (HR, 2.25; 95% CI, 1.20-4.23). In addition, those who wore dentures during sleep were more likely to have tongue and denture plaque, gum inflammation, positive culture for Candida albicans, and higher levels of circulating interleukin-6 as compared with their counterparts. This study provided empirical evidence that denture wearing during sleep is associated not only with oral inflammatory and microbial burden but also with incident pneumonia, suggesting potential implications of oral hygiene programs for pneumonia prevention in the community.

Purpose To explore the associations between place of death and quality of death and dying and caregiver burden in terminally ill patients with cancer and their families. Methods Two bereavement surveys were conducted in October 2008 and October 2011. A total of 2,247 family caregivers of patients with cancer who were deceased responded to the mail surveys (response rate, 67%). Family members reported patient quality of death and dying and caregiver burden by using the Good Death Inventory and Caregiving Consequences Inventory. Results Patient quality of death and dying was significantly higher at home relative to other places of dying after adjustment for patient and/or family characteristics (adjusted means): 5.0 (95% CI, 4.9 to 5.2) for home, 4.6 (95% CI, 4.5 to 4.7) for palliative care units, and 4.3 (95% CI, 4.2 to 4.4) for hospitals. For all combinations, pairwise P < .001; the size of the difference between home and hospital was moderate (Hedges' g, 0.45). Home was superior to palliative care units or hospitals with respect to " dying in a favorite place," " good relationships with medical staff," " good relationships with family, " and " maintaining hope and pleasure " ( P < .001 for all combinations of home v palliative care units and home v hospitals). Home death was significantly associated with a lower overall (P = .03) and financial caregiver burden ( P = .004) relative to hospital death. Conclusion Dying at home may contribute to achieving good death in terminally ill patients with cancer without causing remarkably increased caregiver burden. Place of death should be regarded as an essential goal in end-of-life care.