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Background/objectives: In addition to the potential effects of nutrients on mood, eating behaviors have been suggested to be associated with depressive symptoms. We investigated the prospective association between the accumulation of unhealthy eating behaviors and depressive symptoms in a Japanese working population., Methods: Participants were 914 workers (aged 19-68 years) who did not have depressive symptoms at baseline (April 2012 and May 2013) and attended a 3-year follow-up survey (April 2015 and May 2016). Unhealthy eating behaviors (skipping breakfast, eating dinner just before bedtime, and snacking after dinner) were assessed at baseline. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) scale at follow-up. Multiple logistic regression was used to estimate the odds ratio of depressive symptoms (CES-D score ≥16) at follow-up according to the number of unhealthy eating behaviors., Results: In a model with adjustment of background factors, participants having 2-3 unhealthy eating behaviors at baseline had significantly higher risk of developing depressive symptoms (OR, 2.02; 95% CI, 1.21-3.38) compared with those having no such behaviors. After adjustment for occupational and lifestyle factors, the association was slightly attenuated but remained significant (OR, 1.87; 95% CI, 1.10-3.21). This association was further attenuated and became statistically non-significant after additional adjustment for nutritional factors (OR, 1.67; 95% CI, 0.96-2.90)., Conclusions: Our results suggest that the accumulation of unhealthy eating behaviors is associated with an increased risk of depressive symptoms and that this association may be partly ascribed to a lower intake of nutrients with mood-improving effects., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Diabetes and prediabetes have been linked with morbidity or mortality from cardiovascular disease, cancer, or other physical disorders among working-age populations, but less is known about outcomes directly related to labor loss (eg, Tlong-term sickness absence [LTSA] or pre-retirement death due to physical disorders).This prospective study aimed to examine the association of diabetes and prediabetes with the risk of a composite outcome of LTSA and pre-retirement death due to physical disorders. The present study also examined the associations of severe outcomes (LTSA or death) due to specific physical disorders or injuries/external causes in relation to diabetes and prediabetes., Methods: Data were derived from the Japan Epidemiology Collaboration on Occupational Health study. A total of 60,519 workers from 12 companies were followed for 8 years. Diabetes and prediabetes were defined based on the American Diabetes Association criteria. A Cox proportional hazards regression model was used to examine the association between diabetes/prediabetes and severe outcomes due to physical disorders or injuries/external causes., Results: The adjusted hazard ratios of severe outcomes due to all physical disorders were 1.22 (95% confidence interval [CI], 1.02-1.45) and 2.32 (95% CI, 2.04-2.64) for prediabetes and diabetes, respectively. In cause-specific analyses, an increased risk was observed for severe outcomes due to cancers, cardiovascular diseases, diseases of the musculoskeletal system, and injuries/external causes in relation to either or both diabetes and prediabetes., Conclusion: Diabetes and prediabetes were associated with an increased risk of severe outcomes due to physical disorders or injuries/external causes among Japanese workers.

Background: Metabolic syndrome (MetS) has been associated with various chronic diseases that may lead to long-term sickness absence (LTSA), but there is lacking information on the direct association between MetS and LTSA. The present study aimed to investigate the all-cause and cause-specific associations between MetS and the risk of medically certified LTSA among Japanese workers., Methods: We recruited 67,403 workers (57,276 men and 10,127 women), aged 20-59 years from 13 companies in Japan during their health check-ups in 2011 (11 companies) and 2014 (2 companies), and we followed them for LTSA events (≥30 consecutive days) until March 31, 2020. MetS was defined according to the Joint Interim Statement. A Cox proportional hazards regression model was used to estimate hazard ratios (HRs) and its 95% confidence intervals (CIs) for LTSA associated with MetS and its components., Results: During 408,324 person-years of follow-up, 2,915 workers experienced LTSA. The adjusted HR for all-cause LTSA was 1.54 (95% CI, 1.41-1.68) among those with MetS compared to those without MetS. In cause-specific analysis, HRs associated with MetS significantly increased for LTSA due to overall physical disorders (1.76); cardiovascular diseases (3.16); diseases of the musculoskeletal system and connective tissue (2.01); cancers (1.24); obesity-related cancers (1.35); mental, behavioral, and neurodevelopmental disorders (1.28); reaction to severe stress and adjustment disorders (1.46); and external causes (1.46). The number of MetS components were also significantly associated with increased LTSA risk., Conclusion: MetS was associated with an increase in the risk of LTSA due to various diseases among Japanese workers.

Next-generation sequencing of AML has identified specific genetic mutations in AML patients. Hematologic Malignancies (HM)-SCREEN-Japan 01 is a multicenter study to detect actionable mutations using paraffin-embedded bone marrow (BM) clot specimens rather than BM fluid in AML patients for whom standard treatment has not been established. The purpose of this study is to evaluate the presence of potentially therapeutic target gene mutations in patients with newly diagnosed unfit AML and relapsed/refractory AML (R/R-AML) using BM clot specimens. In this study, 188 patients were enrolled and targeted sequencing was undertaken on DNA from 437 genes and RNA from 265 genes. High-quality DNA and RNA were obtained using BM clot specimens, with genetic alterations successfully detected in 177 patients (97.3%), and fusion transcripts in 41 patients (23.2%). The median turnaround time was 13 days. In the detection of fusion genes, not only common fusion products such as RUNX1-RUX1T1 and KMT2A rearrangements, but also NUP98 rearrangements and rare fusion genes were observed. Among 177 patients (72 with unfit AML, 105 with R/R-AML), mutations in KIT and WT1 were independent factors for overall survival (hazard ratio = 12.6 and 8.88, respectively), and patients with high variant allele frequency (≥40%) of TP53 mutations had a poor prognosis. As for the detection of actionable mutations, 38% (n = 69) of patients had useful genetic mutation (FLT3-ITD/TKD, IDH1/2, and DNMT3A R822 ) for treatment selection. Comprehensive genomic profiling using paraffin-embedded BM clot specimens successfully identified leukemic-associated genes that can be used as therapeutic targets., (© 2023 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background: While it is essential to understand how long is sufficient for return-to-work when designing paid sick-leave systems, little attempt has been done to collect cause-specific information on when and how many of sickness absentees returned to work, became unemployed, or passed away., Methods: We studied the first sick-leave episode of ≥30 consecutive days in those ≤55 years of age during 2012-2013 among employees of 11 Japanese private companies (n = 1,209), which were followed until 2017. Overall and disease-specific cumulative incidences of return-to-work, resignations, and deaths were estimated using competing risk analysis., Results: During the 3.5-year period (follow-up rate: 99.9%), 1,014 returned to work, 167 became unemployed, and 27 died. Overall, return-to-work occurred within 1 year in 74.9% of all absentees and in 89.3% of those who successfully returned to work. Resignation occurred within 1 year in 8.7% of all absentees and in 62.9% of all subjects who resigned. According to ICD-10 chapters, the cumulative incidence of return-to-work ranged from 82.1% for mental disorders (F00-F99) to 95.3% for circulatory diseases (I00-I99). The cumulative incidence of return-to-work due to mental disorders ranged from 66.7% in schizophrenia (F20) to 95.8% in bipolar affective disorders (F31). Death was rarely observed except for cases of neoplasms (C00-D48), of which the cumulative incidence of death reached 14.2% by 1.5 years., Conclusion: Return-to-work and resignations occurred commonly within 1 year of sick leave among long-term sickness absentees in the Japanese private companies. Our findings may assist occupational physicians and employers in developing effective social protection schemes.

While late chronotype and greater social jetlag have been associated with poor dietary behavior among the general population, these associations have not been investigated among workers, who struggle to align their sleep timings with work schedules. We aimed to explore the cross-sectional association of social jetlag and a late chronotype with adherence to a healthy diet among Japanese workers. Participants were 1,435 non-shift workers (18-78 years) who attended a nutritional survey. Social jetlag was defined as the difference in the midpoint of sleep times between weekdays and weekends, while chronotype was estimated using the mid-sleep time on weekends that was corrected with sleep debt on weekdays. We calculated the adherence score of the Japanese Food Guide Spinning Top (JFGST) - healthy diet guidelines for Japanese. Multivariable linear regression analyses were used to calculate the adjusted means and 95% confidence intervals (CI) for adherence scores of social jetlag and chronotype. We found that greater social jetlag was associated with a lower JFGST score. The multivariable-adjusted mean (95% CI) of JFGST scores were 39.7 (39.1-40.2), 38.7 (37.9-39.6), and 38.1 (36.6-39.7) for <1 hour, 1 to <2 hours, and ≥2 hours of social jetlag, respectively ( P-trend  = 0.02). Workers with late chronotypes had significantly lower adherence scores on JFGST [36.3 (34.7-37.8); P-trend  = 0.002]. Results suggest that a late chronotype and social jetlag are inversely associated with adherence to a healthy diet among Japanese workers.

Background & Aims: Limited evidence exists regarding the prospective associations between amino acids and insulin resistance. In addition, amino acids have been suggested to promote insulin resistance with the requirement of obesity in animal studies, but the interaction between amino acids and obesity on the development of insulin resistance has not been examined in epidemiological studies. We aimed to investigate the differences in the prospective associations of serum amino acids with insulin resistance among adults with and without overweight or obesity., Methods: Fasting serum concentrations of 25 amino acids were quantified in 1131 non-diabetic Japanese workers aged 22-71 years at baseline. The homeostasis model assessment of insulin resistance (HOMA-IR) was estimated at baseline and the 3-year follow-up. Generalized linear models were used to assess the associations between amino acids at baseline and HOMA-IR at follow-up with adjustment for potential confounding factors. A Bonferroni-corrected threshold of p = 0.001 was considered significant for multiple tests., Results: The associations for the following amino acids with HOMA-IR at the 3-year follow-up significantly varied by obesity status: isoleucine, valine, tyrosine, alanine, and methionine (all p for interaction <0.05). Higher concentrations of serum isoleucine, valine, tyrosine, and alanine (per 1SD) were significantly associated with higher HOMA-IR levels in overweight/obese participants (multivariable-adjusted β coefficients ranging from 0.09 to 0.12; all p < 0.001), but no association was observed in the underweight/normal-weight participants. The associations for serum methionine were direct among overweight/obese participants, but inverse among underweight/normal-weight participants (all p < 0.001)., Conclusions: This study demonstrated the prospective associations of different individual serum amino acids with insulin resistance, with most pronounced associations being for overweight/obese adults. Our findings support the possibility of heterogeneous effects of individual amino acids, as well as their interplay with obesity in the progression of insulin resistance., Competing Interests: Conflict of interest We have no competing interests to declare., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

High intake of sweet foods such as cakes, cookies, chocolate and ice cream has been reported to be associated with depressive symptoms. However, prospective studies are scarce and no study has been conducted in Asian populations. We prospectively investigated the association between confectionery intake and depressive symptoms in a Japanese working population. Participants were 911 workers (812 men and 99 women; aged 19-68 years) without depressive symptoms at baseline who completed a 3-year follow-up survey. Dietary intake was assessed using a validated self-administered diet history questionnaire. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) scale. Multiple logistic regression was used to estimate the OR of depressive symptoms according to tertile of confectionery intake with adjustment for covariates. At the time of the 3-year follow-up survey, 153 (16·8 %) workers were newly identified as having depressive symptoms (CES-D score ≥ 16). Confectionery intake was significantly associated with increased odds of developing depressive symptoms. The multivariable-adjusted OR of depressive symptoms for the highest v . lowest tertile of confectionery intake was 1·72 (95 % CI 1·03, 2·86) after adjustment for covariates including dietary factors such as folate, vitamin B 6 , vitamin B 12 , n -3 PUFA, Mg, Zn and soft drink ( P for trend = 0·012). Our results suggest that confectionery intake is associated with a higher risk of depressive symptoms in a Japanese working population predominantly comprised of men.

Objectives: To investigate the association of diabetes and prediabetes with long-term sickness absence (LTSA) due to mental disorders or specific mental disorders., Methods: A prospective cohort study was conducted using data from the Japan Epidemiology Collaboration on Occupational Health Study. A total of 62,065 workers who received health check-ups in 2011 (nine companies) or 2014 (two companies) and were followed up to March 31, 2020 were included in this study. Diabetes status was defined based on the American Diabetes Association criteria, and diabetes was differentiated into diabetes with/without anti-diabetic treatment for additional analysis. A Cox proportional hazards regression model was used to investigate these associations., Results: During maximum 8-year follow-up period, 1024 participants underwent LTSA due to mental disorders. The adjusted hazard ratio (aHR) and corresponding 95% confidence interval (CI) of LTSA due to all mental disorders were 1.10 (0.88-1.38) and 1.45 (1.07-1.98) for prediabetes and diabetes, respectively. Diabetic individuals with/without treatment were both at a high risk of LTSA due to mental disorders. For specific mental disorders, diabetes was associated with a higher risk of LTSA due to reaction to severe stress and adjustment disorders (aHR = 3.02, 95% CI = 2.01-4.52) while it was marginally associated with LTSA due to depressive episode (aHR = 1.25, 95% CI = 0.98-1.60). Prediabetes was also associated with LTSA due to reaction to severe stress and adjustment disorders (aHR = 1.41, 95% CI = 1.08-1.84)., Conclusions: The present study suggests the importance of screening diabetes status and providing psychological support for decreasing the risk of LTSA due to mental disorders within working populations., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Although several cross-sectional studies have described an inverse association between green tea consumption and depressive symptoms, only one study has prospectively investigated this association. We investigated the cross-sectional and prospective associations between green tea consumption and depressive symptoms in a working population in Japan. Participants were 1987 workers who participated in the baseline survey for a cross-sectional association, and 916 participants who did not have depressive symptoms at baseline who responded to both the baseline and follow-up surveys for a prospective association. Green tea consumption was evaluated with a validated self-administered diet history questionnaire. Depression symptoms were evaluated with the Center for Epidemiologic Studies Depression (CES-D) scale. Multiple logistic regression was conducted to estimate the odds ratio of depressive symptoms based on green tea consumption. In the cross-sectional analysis, green tea consumption was not associated with the prevalence of depression symptoms. Moreover, consumption at baseline was not associated with depression symptoms after 3 years; the multivariable-adjusted odds ratio of depressive symptoms for ≥2 cups/day of green tea was 1.12 (95% confidence interval 0.65-1.91) compared with <4 cups/week after adjustment for covariates including dietary factors (trend p = 0.67). Our results suggest that there is no association of consumption of green tea with symptoms of depression in Japanese.

The aim of this study was to determine the cross-sectional associations between frequency of eating with others and depressive symptoms in Japanese employees while accounting for lifestyle and dietary factors. We also examined the relationship with stratification by living arrangement. Participants were 1876 workers aged 18-74 years who participated in a health survey at a periodic checkup. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression scale. Frequency of eating with others was categorized into ranges between daily and <1 day/week. Associations between frequency of eating with others and depressive symptoms were assessed using logistic regression analysis, with adjustment for lifestyle and dietary factors. The prevalence of depressive symptoms was 32.9%. The prevalence of depressive symptoms tended to increase with decreasing frequency of eating with others, with multivariate-adjusted odds ratios (95% confidence intervals) for the highest through lowest frequency groups of eating meals with others being 1.00 (reference), 1.27 (0.92-1.74), 1.56 (1.11-2.21), 1.86 (1.29-2.67), and 2.22 (1.53-3.22), respectively (P for trend<0.001). In analysis stratified by living arrangement, a significant association was found with those living with others but not those living alone (P for interaction <0.001). Lower frequency of eating with others may be associated with higher odds of depressive symptoms among Japanese workers living with others, even after controlling for lifestyle and dietary factors., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

IgA nephropathy (IgAN) is the most common form of glomerulonephritis worldwide. Pediatric patients in Japan are diagnosed with IgAN at an early stage of the disease through annual urinary examinations. Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and fibroblast growth factor-inducible 14 (Fn14) have various roles, including proinflammatory effects, and modulation of several kidney diseases; however, no reports have described their roles in pediatric IgAN. In this study, we performed pathological and immunohistochemical analyses of samples from 14 pediatric IgAN patients. Additionally, gene expression arrays of glomeruli by laser-captured microdissection were performed in hemi-nephrectomized high serum IgA (HIGA) mice, a model of IgA nephropathy, to determine the role of Fn14. Glomeruli with intense Fn14 deposition were observed in 80% of mild IgAN cases; however, most severe cases showed glomeruli with little or no Fn14 deposition. Fn14 deposition was not observed in obvious mesangial proliferation or the crescent region of glomeruli, but was detected strongly in the glomerular tuft, with an intact appearance. In HIGA mice, Fn14 deposition was observed mildly beginning at 11 weeks of age, and stronger Fn14 deposition was detected at 14 weeks of age. Expression array analysis indicated that Fn14 expression was higher in HIGA mice at 6 weeks of age, increased slightly at 11 weeks, and then decreased at 26 weeks when compared with controls at equivalent ages. These findings suggest that Fn14 signaling affects early lesions but not advanced lesions in patients with IgAN. Further study of the TWEAK/Fn14 pathway will contribute to our understanding of the progression of IgAN., Competing Interests: The authors have declared that no competing interests exist.

Objective: Accumulating evidence suggests that amino acids, particularly tryptophan and glutamate, play an important role in the pathology of depression, but prospective epidemiologic data on this issue is scarce. We examined the association between circulating amino acids and the risk of depressive symptoms in a Japanese working population., Methods: Participants were 841 workers who were free from depressive symptoms and provided blood at baseline and completed 3-yr follow-up survey. 30 varieties of amino acid concentrations in serum were measured using liquid chromatography/mass spectrometry. Depressive symptoms were defined using the Center for Epidemiologic Studies Depression Scale. Logistic regression was used to calculate the odds ratios of depressive symptoms according to serum amino acids with adjustment for lifestyle factors., Results: A total of 151 (18.0%) workers were newly identified as having depressive symptoms at the follow-up. Baseline tryptophan and glutamate concentrations in serum were not appreciably associated with the risk of depressive symptoms. Risk of depressive symptoms tended to increase with increasing arginine concentrations; the multivariable-adjusted odds ratio for the highest versus lowest tertile of serum arginine was 1.65 (95% confidence interval: 0.96-2.83; P for trend = 0.07). No clear association was found for other amino acids., Conclusions: Results of the present study do not support a significant role of circulating amino acids in the development of depressive symptoms among Japanese., Competing Interests: T.K. and M.E. are health professionals at the Furukawa Electric Corporation. Author I. Kabe is a health professional at the Kubota Corporation. All authors declare no conflict of interest, patents, products in development or marketed products etc. This does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials.

Increased visit-to-visit variability (VVV) of blood pressure, which is calculated based on several readings, has been suggested to be a significant predictor of cardiovascular events and mortality, independent of mean blood pressure. This study examined associations between the VVV of systolic blood pressure (SBP) measured annually and cardiovascular disease (CVD) events among 72,617 Japanese subjects. Data were obtained from the Japan Epidemiology Collaboration on Occupational Health Study, which is an ongoing epidemiological survey of workers in Japan. VVV was calculated as the coefficient of variation of SBP readings from 2008 to 2011; information on fatal and nonfatal CVD events was collected from registries of specific outcomes between April 2012 and March 2019. A Cox proportional hazards model was applied to investigate associations after adjusting for mean SBP between 2008 and 2011 and covariates. During the 7-year follow-up period, there were 63 CVD fatalities and 314 CVD events (combining fatal and nonfatal events). The results showed that a one-standard deviation increase in VVV was associated with a significant increase in the risk of CVD mortality (hazard ratio [HR] = 1.42; 95% confidence interval [CI] = 1.32-1.54); those in the highest tertile had a 3.20 times (95% CI = 1.26-8.17) higher risk of CVD mortality than those in the lowest tertile. We found less pronounced associations regarding CVD events (HR = 1.08, 95% CI = 1.02-1.15). In conclusion, VVV was significantly associated with CVD mortality in our Japanese working population., (© 2021. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Background: While much effort has focused on quantifying disease burden in occupational health, no study has simultaneously assessed disease burden in terms of mortality and morbidity. We aimed to propose a new comprehensive method of quantifying the disease burden in the workplace., Methods: The data were obtained from the Japan Epidemiology Collaboration on Occupational Health (J-ECOH) Study, a large-scale prospective study of approximately 80,000 workers. We defined disease burden in the workplace as the number of working years lost among the working population during a 6-year period (April 2012 to March 2018). We calculated the disease burden according to consequences of health problems (ie, mortality, sickness absence [SA], and ill-health retirement) and disease category. We also calculated the age-group- (20-39 and 40-59 years old) and sex-specific disease burden., Results: The largest contributors to disease burden in the workplace were mental and behavioural disorders (47.0 person-years lost per 10,000 person-years of working years; ie, per myriad [proportion]), followed by neoplasms (10.8 per myriad) and diseases of the circulatory system (7.1 per myriad). While mental and behavioural disorders made a greater contribution to SA and ill-health retirement compared to mortality, the latter two disorders were the largest contributors to the disease burden in the workplace due to mortality. The number of working years lost was greater among younger versus older female participants, whereas the opposite trend was observed in males., Conclusions: Our approach is in contrast to those in previous studies that focused exclusively on mortality or morbidity.

Objective: Prediabetes has been suggested to increase risk for death; however, the definitions of prediabetes that can predict death remain elusive. We prospectively investigated the association of multiple definitions of prediabetes with the risk of death from all causes, cardiovascular disease (CVD), and cancer in Japanese workers., Research Design and Methods: The study included 62,785 workers who underwent a health checkup in 2010 or 2011 and were followed up for death from 2012 to March 2019. Prediabetes was defined according to fasting plasma glucose (FPG) or glycated hemoglobin (HbA 1c ) values or a combination of both using the American Diabetes Association (ADA) or World Health Organization (WHO)/International Expert Committee (IEC) criteria. The Cox proportional hazards regression model was used to investigate the associations., Results: Over a 7-year follow-up, 229 deaths were documented. Compared with normoglycemia, prediabetes defined according to ADA criteria was associated with a higher risk of all-cause mortality (hazard ratio [HR] 1.53; 95% CI 1.12-2.09) and death due to cancer (HR 2.37; 95% CI 1.45-3.89) but not with death due to CVD. The results were materially unchanged when prediabetes was defined according to ADA FPG, ADA HbA 1c , WHO FPG, or combined WHO/IEC criteria. Diabetes was associated with the risk of all-cause, CVD, and cancer deaths., Conclusions: In a cohort of Japanese workers, FPG- and HbA 1c -defined prediabetes, according to ADA or WHO/IEC, were associated with a significantly increased risk of death from all causes and cancer but not CVD., (© 2021 by the American Diabetes Association.)

Background: Few studies have investigated the association between tobacco smoking and sick leave (SL) in Japan., Methods: We followed 70 896 workers aged 20-59 years (60 133 males, 10 763 females) between April 2012 and March 2017. A Cox proportional hazards model was used to investigate the associations between smoking (smoking status and intensity) and long-term SL (ie, SL lasting ≥30 consecutive days). Cause-specific analyses were also conducted., Results: A total of 1777 people took long-term SL during a follow-up of 307 749 person years. Compared with never-smokers, current smokers were at a higher risk of long-term SL (hazard ratio [HR] = 1.32; 95% confidence interval [CI] = 1.19 to 1.48). Cause-specific analyses revealed that current smoking was associated with a higher risk of SL due to all physical disorders (HR = 1.44, 95% CI = 1.22 to 1.69), cancer (HR = 1.49, 95% CI = 1.10 to 2.01), cardiovascular disease (CVD; HR = 2.16, 95% CI = 1.31 to 3.55), and injuries/external causes (HR = 1.83, 95% CI = 1.31 to 2.58). Former smokers were at a higher risk of SL due to cancer at a borderline significance level (HR = 1.38, 95% CI = 0.99 to 1.92). Low-intensity smoking (ie, 1-10 cigarettes smoked per day) was associated with all-cause SL, SL due to CVD, and SL due to injuries/external causes compared with never-smokers., Conclusion: In a large cohort of working-age Japanese, smoking was associated with a greater risk of long-term SL. Greater effort is needed to mitigate disease burden associated with smoking at workplace in Japan., Implications: Our study contributes to the literature on the association between smoking and SL in several ways. First, the study was conducted among a Japanese working population. While the association has been extensively studied in Western setting, few attempts have been made elsewhere. Second, cause-specific analyses were undertaken in our study. Third, we paid attention to the effect of low-intensity smoking on SL given that there is growing evidence of an elevated health risk associated with low-intensity smoking., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved.For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: The effect of weight gain following smoking cessation on cardiovascular risks is unclear. We aimed to prospectively investigate the association of weight gain following smoking cessation with the trajectory of estimated risks of coronary heart disease (CHD)., Methods: In a cohort of 18 562 Japanese male employees aged 30-64 years and initially free of cardiovascular diseases, participants were exclusively grouped into sustained smokers, quitters with weight gain (body weight increase ≥5%), quitters without weight gain (body weight increase <5% or weight loss), and never smokers. Global 10-year CHD risk was annually estimated by using a well-validated prediction model for the Japanese population. Linear mixed models and piecewise linear mixed models were used to compare changes in the estimated 10-year CHD risk by smoking status and weight change following smoking cessation., Results: During a maximum of 8-year follow-up, both quitters with and without weight gain had a substantially decreased level of estimated 10-year CHD risk after quitting smoking, compared with sustained smokers (all ps for mean differences < .001). The estimated 10-year CHD risk within the first year after cessation decreased more rapidly in quitters without weight gain than in quitters with weight gain (change rate [95% confidence interval, CI] -0.90 [-1.04 to -0.75] vs. -0.40 [-0.60 to -0.19] % per year, p < .0001). Thereafter, the estimated 10-year CHD risk in both groups increased at similar rates (change rate [95% CI] -0.07 [-0.21 to 0.07] vs. 0.11 [-0.09 to 0.30] % per year, p = .16, from year 1 to year 2; and 0.10 [0.05 to 0.15] vs. 0.11 [0.04 to 0.18] % per year, p = .80, from year 2 to year 8)., Conclusions: In this population of middle-aged, Japanese male workers, smoking cessation greatly reduces the estimated 10-year risk of CHD. However, weight gain weakens the beneficial effect of quitting smoking in a temporary and limited fashion., Implications: To the best of our knowledge, this study is the first to examine the effect of weight gain following smoking cessation on the trajectory of the absolute risk of CHD. Our data imply that the benefits of cessation for reducing the absolute risk of CHD outweigh the potential risk increase due to weight gain, and suggest that in order to maximize the beneficial effects of quitting smoking, interventions to control post-cessation weight gain might be warranted., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco.)

Objective: Consumption of soft drinks has become a serious public health issue worldwide. However, prospective evidence is limited regarding the relationship between soft drink consumption and depression, especially in Asia. The aim of this study was to investigate the prospective association between soft drink consumption and the development of depressive symptoms., Methods: We evaluated an occupational cohort of 935 adults in Japan (2012-2016), who were free from depressive symptoms at baseline and attended a 3-y follow-up assessment. Soft drink consumption was assessed using a self-administered diet history questionnaire. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression scale. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated from multivariate logistic regression analysis controlling for sociodemographic, lifestyle, dietary, and occupational covariates., Results: Over the 3-y study period, 16.9% (158 cases) of the study participants reported depressive symptoms. Higher soft drink consumption was associated with higher odds of depressive symptoms. The multivariable-adjusted OR was 1.91 (95% CI, 1.11-3.29; P trend  = 0.015) when comparing soft drink consumption of ≥4 cups/wk with consumption of <1 cup/wk., Conclusion: The present results suggested that greater consumption of soft drinks would increase the likelihood of exhibiting depressive symptoms., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To examine the association of diabetes and prediabetes with suicide deaths in a Japanese working population., Methods: A nested case-control study was conducted using data from the Japan Epidemiology Collaboration on Occupational Health Study. During 8 years of follow-up, we identified 56 registered cases of suicide death that had information on fasting plasma glucose or glycated hemoglobin A1c at any health check-up during the past 3 years prior to suicide. For each case, we randomly selected five controls matched for age, sex, and worksite. We used the latest health check-up data for analysis. We defined diabetes status based on the American Diabetes Association criteria and used a conditional logistic regression model to investigate the association., Results: Adjusted odds ratios and 95% confidence intervals for suicide death were 0.67 (0.32-1.41) and 3.53 (1.05-11.91) for prediabetes and diabetes, respectively, compared to normoglycemia. Similar results were obtained when diabetes status was exclusively defined by the fasting plasma glucose or glycated hemoglobin A1c level., Conclusion: Diabetes, but not prediabetes, was associated with a higher risk of suicide death, compared with normoglycemia, among a Japanese working population., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: Evidence from prospective studies on the association between eating speed and metabolic syndrome is limited. We prospectively investigated the association between eating speed and metabolic syndrome in a Japanese working population., Methods: Participants were 1018 workers (ages 19-68 y) without metabolic syndrome at baseline who completed both baseline and 3-y follow-up surveys. Eating speed was self-reported and categorized as slow, medium, or fast. Metabolic syndrome was defined using criteria recommended in a joint interim statement from several international societies. A multiple logistic regression was used to estimate the odds ratio of metabolic syndrome according to eating speed with adjustment for covariates, including total energy intake., Results: At the 3-y follow-up, 67 workers (6.6%) were newly identified as having metabolic syndrome. Fast eating speed was significantly associated with increased odds of developing metabolic syndrome, with multivariable-adjusted odds ratios for eating fast of 2.13 (95% confidence intervals, 1.23-3.68) compared with medium eating speed with an adjustment for covariates, including total energy intake. The association remained statistically significant after an additional adjustment for body mass index (BMI) and BMI change between baseline and follow-up surveys (odds ratio: 1.95; 95% confidence interval, 1.06-3.56)., Conclusions: Fast eating speed was associated with an increased likelihood of developing metabolic syndrome independently of total energy intake, BMI at baseline, and BMI change during the follow-up period., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Spinal muscular atrophy (SMA) is an inherited neuromuscular disorder associated with spinal motor neuron loss and characterized by generalized muscle weakness. Only a few reports exist on SMA epidemiology in Japan. Additionally, nusinersen recently became available as a treatment for this condition. We estimated the prevalence of each type of SMA on Shikoku, Japan's fourth-largest major island., Methods: We sent a questionnaire to all 131 hospitals in Shikoku that have pediatrics or neurology departments from March to September 2019, asking whether each hospital had SMA patients at that time. If so, we sent a second questionnaire to obtain more detailed information on the clinical data and treatment of each patient., Results: A total of 117 hospitals (89.3%) responded to our first questionnaire, and 21 SMA patients were reported, 16 of whom had homozygous deletion of SMN1. Of the 21, nine had SMA type 1, five were type 2, five were type 3, one was type 4, and one was unidentified. The estimated prevalence for all instances of SMA and 5q-SMA was 0.56 and 0.43 per 100,000 people, respectively. Thirteen patients had received nusinersen therapy. Its outcomes varied from no obvious effects and being unable to sit to being able to sit independently., Conclusion: Our data showed the prevalence of SMA types 2 and 3 was relatively low on Shikoku compared with previous reports from other countries, suggesting delayed diagnosis may affect the results. Remaining motor function may be one predicting factor. Greater awareness of SMA among clinicians and patients seems necessary for more accurate epidemiological studies., (Copyright © 2020 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Calcium and phosphate may play an important role in cardio-metabolic abnormalities, including type 2 diabetes; however, epidemiological evidence of the association of calcium and phosphate status with glucose metabolism among Asians is limited. In the current study, we performed a cross-sectional analysis of the association of serum calcium, phosphate, and calcium-phosphate product concentrations with glucose metabolism markers among Japanese individuals. Overall, 1701 workers (aged 18-78 years) who participated in a health survey were enrolled in this study. Multivariable linear regression models were used to estimate means of homeostatic model assessment of insulin resistance (HOMA-IR), homeostatic model assessment of β-cell function (HOMA-β), and glycated hemoglobin (HbA1c). Serum calcium concentration was positively associated with HOMA-IR and HbA1c ( p for trend < 0.01). Multivariable-adjusted means (95% confidence interval (CI)) of HOMA-IR for the lowest and highest quartiles of serum calcium were 0.78 (0.75-0.82) and 1.01 (0.96-1.07), respectively. The corresponding values for HbA1c were 5.24 (5.22-5.27) and 5.29 (5.26-5.32), respectively. Serum phosphate and calcium-phosphate product concentrations were inversely associated with HOMA-IR ( p for trend < 0.01). Multivariable-adjusted means (95% CI) of HOMA-IR for the lowest and highest quartiles of serum phosphate were 1.04 (0.99-1.09) and 0.72 (0.69-0.76), respectively. The corresponding values for calcium-phosphate product were 1.04 (0.99-1.09) and 0.73 (0.69-0.77), respectively. The current findings suggest that higher serum calcium and lower serum phosphate concentrations are associated with IR among apparently healthy adults.

We examined the association of dietary non-enzymatic antioxidant capacity (NEAC) in overall diet, and separately from foods and beverages, with serum liver enzymes in a Japanese working population. This cross-sectional study was conducted among 1791 employees aged 18-69 years, who underwent a comprehensive health checkup in 2012-2013. A brief validated self-administered diet-history questionnaire was used for dietary assessment, and dietary NEAC intake was determined from databases of NEAC values, obtained using ferric reducing-antioxidant power (FRAP) and oxygen radical absorbance capacity (ORAC) assays. The dietary NEAC intake was calculated by multiplying the estimated NEAC values by the amounts consumed and summing the resulting values. A multiple-regression analysis was performed to explore the association between dietary NEAC intake and the serum levels of liver enzymes (aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyltransferase (GGT)), after adjustment for confounding factors. No significant associations were found between overall dietary NEAC intake and AST (FRAP, p for trend = 0.97; ORAC, p = 0.72), ALT (FRAP, p = 0.73; ORAC, p = 0.92), and GGT (FRAP, p = 0.96; ORAC, p = 0.19) levels. Food-derived, but not beverage-derived, NEAC intake was inversely associated with serum GGT levels (FRAP, p for trend = 0.001; ORAC, p = 0.02), particularly among older participants and those with high serum ferritin concentrations. The results imply that overall dietary NEAC intake is not associated with liver dysfunction, and that the NEAC values from foods may be inversely associated with serum GGT levels.

Background: While a growing body of research suggests a protective role of healthy lifestyle against depression, evidence from prospective studies is scarce. We constructed a healthy lifestyle index (HLI) and examined its prospective association with depressive symptoms in a Japanese working population., Methods: Participants were 917 employees (19-68 years old) who were free from depressive symptoms at baseline in 2012-2013 and attended the 3-year follow-up survey. The HLI (range: 0-7 points) was constructed by assigning 1 point to each healthy lifestyle factor, namely, (1) normal body mass index (18.5-24.9 kg/m 2 ), (2) non-smoking, (3) no or moderate alcohol intake (≤23 g ethanol/day), (4) adequate physical activity (≥7.5 metabolic equivalent-hours/week), (5) high vegetable intake (≥350 g/day), (6) high fruit intake (≥200 g/day), and (7) adequate sleep duration (6-8.9 hours/day), which was categorized into three groups (low: 0-2 points; middle: 3-4 points; and high: 5-7 points). Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale., Results: A total of 155 incident cases (17.0%) of depressive symptoms were identified at the follow-up survey. Compared with the low HLI group, multivariable-adjusted odds ratios of depressive symptoms were 0.74 (95% confidence interval, 0.48-1.15) and 0.55 (95% confidence interval, 0.31-0.99) for the middle and high HLI groups, respectively (P-trend = 0.041)., Conclusion: The present study suggests the importance of adherence to multiple healthy lifestyle factors in prevention of depressive symptoms.

The aim of this study was to examine the cross-sectional association between fish and shellfish intake and impaired glucose metabolism with consideration for cooking methods in a Japanese working population. Participants were 1774 workers aged 18-69 years. Dietary intake was assessed using a validated self-administered diet history questionnaire. Participants were asked about their most frequently used cooking method for fish, and the method was classified as either "raw and stewing" or "broiling, deep-frying, and stir-frying". Impaired glucose metabolism was defined by a history of diabetes, current use of anti-diabetic drugs, fasting blood glucose ≥110 mg/dl, or HbA1c ≥6.0%. Logistic regression analysis was used to estimate the odds ratios of impaired glucose metabolism for fish intake by cooking method. Fish intake was not associated with impaired glucose metabolism in either group. When the outcome was defined as diabetes, the odds of diabetes increased with fish intake among participants who most frequently used broiling, deep-frying, or stir-frying methods, albeit they were not statistically significant; the multivariable-adjusted odds ratio for the highest versus the lowest tertiles of fish intake was 1.95 (95%CI, 0.71-5.41). Cooking methods for fish may not modify the association between fish intake and impaired glucose metabolism among Japanese populations.

In occupational settings, smokers may take quitting smoking seriously if they experienced long-term sick leave due to cancer or cardiovascular disease (CVD). However, no study has elucidated the smoking cessation rate after long-term sick leave. We examined the smoking cessation rate after long-term sick leave due to cancer and CVD in Japan. We followed 23 survivors who experienced long-term sick leave due to cancer and 39 survivors who experienced long-term sick leave due to CVD who reported smoking at the last health exam before the leave. Their smoking habits before and after the leave were self-reported. Logistic regression was used to calculate adjusted smoking cessation rates. Smoking cessation rate after long-term sick leave due to cancer was approximately 70% and that due to CVD exceeded 80%. The adjusted smoking cessation rate was 67.6% (95% confidence interval [CI]: 47.0, 88.2) for cancer and 80.7% (95% CI: 67.7, 93.8) for CVD. Smoking cessation rate after a longer duration of sick leave (≥60 d) tended to increase for both CVD and cancer. Although any definite conclusion cannot be drawn, the data suggest that smoking cessation rate after long-term sick leave due to CVD is slightly higher than that for cancer.

Background & Aim: It is not clear whether diet quality influences mental health. We prospectively investigated the association of adherence to the Japanese dietary guidelines with depressive symptoms in a Japanese working population., Methods: Participants were 909 workers (aged 19-68 years) without depressive symptoms at baseline who completed both baseline and 3-year follow-up surveys. Dietary intake was assessed with a validated self-administered diet history questionnaire. Adherence to the Japanese Food Guide Spinning Top was measured based on consumption of the recommended number of servings of grains, vegetables, fish and meat, milk, and fruits, as well as total energy intake and energy from snacks and alcoholic beverages. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) scale. Multiple logistic regression was used to estimate the odds ratio of depressive symptoms according to tertile of adherence score, with adjustment for covariates., Results: At the time of the 3-year follow-up survey, 153 (16.8%) workers were newly identified as having depressive symptoms (CES-D score of ≥16). The adherence score was not associated with depressive symptoms after 3 years. The multivariable-adjusted odds ratios (95% confidence interval) for the lowest through highest tertiles of dietary score were 1.00 (reference), 0.91 (0.57-1.45), and 1.23 (0.76-1.99) (P for trend = 0.41). The odds ratios for severe depressive symptoms (CES-D score of ≥23) tended to decrease with increasing adherence score., Conclusions: Our results suggest that diet based on the Japanese Food Guide Spinning Top was not prospectively associated with risk of depressive symptoms among Japanese., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aims/introduction: We examined the association between hemoglobin A1c (HbA1c) and anemia, which was categorized into three groups according to mean corpuscular volume (MCV), as well as the association between hemoglobin in the non-anemic range and HbA1c., Materials and Methods: We used the 2016 health checkup data from 36,422 workers without diabetes. Anemic people were divided into three groups based on MCV: <80, 80-90 and >90 fL. Non-anemic people were divided into four groups based on their hemoglobin levels. We carried out multiple linear regression models to estimate the means and 95% confidence intervals (CIs) of HbA1c., Results: For men, 0.2% had anemia with MCV <80 fL, 0.5% had anemia with MCV 80-90 fL, 0.9% had anemia with MCV >90 fL and 98.4% had no anemia. For women, the corresponding values were 6.1, 6.4, 2.8 and 84.7%, respectively. The adjusted mean HbA1c (%) values for men with anemia with MCV <80, 80-90 and >90 fL were 5.67 (95% CI 5.60-5.74), 5.58 (95% CI 5.54-5.62) and 5.41 (95% CI 5.37-5.44), respectively. Among men without anemia, HbA1c (%) increased from 5.36 (95% CI 5.34-5.39) in those with hemoglobin ≥17.5 mg/dL to 5.45 (95% CI 5.45-5.46) in those with hemoglobin 13.0 to <14.5 mg/dL (P for trend <0.001). The HbA1c values were higher in men with anemia with MCV <80 fL or MCV 80-90 fL, but lower in men with MCV >90 fL, compared with non-anemic men with hemoglobin 13.0 to <14.5 mg/dL (All P < 0.001). Similar findings were observed in women., Conclusions: We observed elevated HbA1c among anemic people with MCV <80 fL or MCV 80-90 fL, and decreased HbA1c among anemic people with MCV >90 fL, suggesting that different types of anemia might influence HbA1c differently. In addition, non-anemic people with lower hemoglobin levels had higher HbA1c levels, suggesting that hemoglobin levels are in need of consideration when interpreting HbA1c values among non-anemic people., (© 2019 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Background & Aims: Oxidative stress has been suggested to play an important role in the pathophysiology of depression, and a diet high in antioxidants may improve mood. However, studies addressing this issue are scarce. The aim of this cohort study was to investigate the prospective association between dietary non-enzymatic antioxidant capacity (NEAC) in overall diet and depressive symptoms in Japanese employees. Additionally, we examined the association separated by dietary NEAC sources., Method: Participants were 911 workers without depressive symptoms at baseline and participated in 3-y follow-up survey. Dietary NEAC was determined from a database of NEAC measurements obtained by ferric reducing antioxidant power (FRAP) and oxygen radical absorbance capacity (ORAC). Dietary NEAC was calculated by multiplying the estimated NEAC values with the consumed amount and summing up those values. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale. Logistic regression was used to estimate odds ratios of depressive symptoms according to overall NEAC and separately from foods and beverages., Results: At 3-y follow-up, 153 (16.8%) workers were newly identified as having depressive symptom. No significant associations were found between higher level of overall dietary NEAC and decreased risk of depressive symptoms after adjustment for potential confounders (overall: FRAP, P for trend = 0.19 and ORAC, P for trend = 0.20). Likewise, neither higher dietary NEAC from foods nor beverages were related with lower depressive symptoms., Conclusion: Our findings did not support an inverse association between dietary NEAC and the risk of depressive symptoms in Japanese workers., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest. T.K. and M.E. are health professionals at the Furukawa Electric Corporation. I. Kabe is a health professional at Kubota Corporation., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Hypertension has become a major public health issue worldwide. Whole grains contain higher levels and a broader range of nutrients with potential health benefits and may decrease the risk of hypertension. However, no prospective studies have investigated this association in the high-income Asia Pacific region, which has the lowest whole grain intake worldwide. Thus, we examined the prospective association between whole grain consumption and the development of hypertension in Japan. Participants included 944 working Japanese adults aged 19-68 years who had no hypertension at baseline and completed a 3-year follow-up survey. Whole grain consumption was assessed via a self-administered dietary questionnaire. Multivariate logistic regression analysis was carried out to examine the association between whole grain consumption and hypertension, adjusting for potential confounding factors, such as sociodemographic, lifestyle, dietary, and occupational characteristics. After 3 years, 9.4% (86 cases) of the study participants had developed hypertension. More frequent whole grain consumption, classified as an intake frequency of "sometimes or always", was associated with lower odds of hypertension (multivariate-adjusted odds ratio: 0.36; 95% confidence interval: 0.16-0.83; p for trend = 0.04) compared with no consumption. Consuming more whole grains may decrease the risk of developing hypertension., Competing Interests: The authors declare no conflicts of interest. M.E., T.K., and I.K. (Isamu Kabe) are healthcare professionals and employees of the Furukawa Electric Corporation.

Background & Aims: The existing yet limited prospective studies reported conflicting results about obesity and hearing loss. We investigated the prospective association between obesity and hearing loss in a large-scale Japanese working population, as well as the association between metabolic phenotype and hearing loss., Methods: The study included 48,549 employees aged 20-64 years and free of hearing loss at baseline. Pure-tone audiometric testing was performed annually to identify hearing loss at 1 and 4 kHz. Cox proportional hazards regression was used to investigate the risk of hearing loss associated with body mass index (BMI) and metabolic phenotype (based on a BMI of ≥25.0/<25.0 kg/m 2 and presence/absence of ≥2 components of metabolic syndrome, except waist circumference). Baseline and updated information were obtained from annual health checkups., Results: With a median follow-up of 7 years, 1595 and 3625 individuals developed unilateral hearing loss at 1 and 4 kHz, respectively. The adjusted hazard ratios (HR) for hearing loss at 1 kHz were 1.21 (1.08, 1.36) and 1.66 (1.33, 2.08) for those with BMI 25.0-29.9 kg/m 2 and BMI ≥30.0 kg/m 2 , respectively, compared to individuals with BMI <25.0 kg/m 2 . For hearing loss at 4 kHz, the corresponding HRs were 1.14 (1.05, 1.23) and 1.29 (1.09, 1.52). Compared with metabolically healthy non-obese individuals, the adjusted HRs for hearing loss at 1 kHz were 1.19 (1.03, 1.39), 1.27 (1.01, 1.61), and 1.48 (1.25, 1.76) for unhealthy non-obese, healthy obese, and unhealthy obese individuals, respectively. For hearing loss at 4 kHz, the corresponding HRs were 1.13 (1.04, 1.25), 1.21 (1.04, 1.41), and 1.26 (1.12, 1.41)., Conclusions: Overweight and obesity are associated with an increased risk of hearing loss, and metabolically unhealthy obesity may confer additional risk., (Copyright © 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Objective: In contrast to the association between excess weight and sickness absence (SA), the association in relation to underweight has been under-researched. This study aimed to examine the effects of BMI at both extremes of its distribution on SA., Methods: Data came from the Japan Epidemiology Collaboration on Occupational Health study of 77,760 workers aged 20 to 59 years (66,166 males, 11,594 females). Information was collected on medically certified long-term SA (LTSA) (i.e., SA lasting ≥ 30 consecutive days) from April 2012 to March 2017. A sex-specific Cox proportional hazards model was used to investigate the associations., Results: Among males, both obesity (hazard ratio [HR] = 1.81, 95% CI: 1.50-2.17) and underweight (HR = 1.56, 95% CI: 1.23-1.96) were significantly associated with LTSA compared with normal weight. This U-shaped association between BMI categories and LTSA was observed both for mental and physical disorders. Among females, an elevated risk was observed among those with overweight (HR = 1.54, 95% CI: 1.16-2.05)., Conclusions: In a cohort of the Japanese working-age population, both obesity and underweight were associated with a greater risk of LTSA in males. Future research should not overlook the excess risk of LTSA associated with underweight., (© 2020 The Authors. Obesity published by Wiley Periodicals, Inc. on behalf of The Obesity Society (TOS).)

Study Objectives: Social jetlag, a mismatch between biological and social timing, has been reported to be associated with depressive symptoms among general population. However, evidence on this association is lacking among non-shift workers, who are under pressure to adapt themselves to a work schedule. We investigated the cross-sectional association of social jetlag with depressive symptoms among Japanese non-shift workers., Methods: This study included 1,404 employees, aged 18-78 years, who completed a study questionnaire at a periodic health checkup. Social jetlag was calculated as the absolute value of the difference in the midpoint of sleep times between weekdays and weekends. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale. Multivariable logistic regression was used to estimate the odds ratio (OR) with adjustments for potential confounders including diet and chronotype., Results: Of the study participants, 63.5%, 28.4%, and 8.1% had less than 1 hour, 1 to less than 2 hours, and at least 2 hours of social jetlag, respectively. Greater social jetlag was significantly associated with an increased likelihood of having depressive symptoms. The multivariable-adjusted OR (95% confidence interval) were 1.30 (0.95 to 1.78) and 2.14 (1.26-3.62) for 1 to less than 2 hour and at least 2 hours compared to less than 1 hour of social jetlag. The association between social jetlag and depressive symptoms appeared to be linear, according to restricted cubic spline regression., Conclusion: Results suggest that greater social jetlag is associated with an increased likelihood of having depressive symptoms among non-shift workers., (© Sleep Research Society 2019. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Objective: The present study aimed to estimate cumulative incidence of overweight and obesity and describe 5-year longitudinal changes in body mass index (BMI) in a large occupational cohort in Japan., Methods: Participants were 55 229 Japanese employees, who were aged 20-59 years and attended at all subsequent annual health check-ups between 2009 and 2014. Mixed model analysis was performed to examine the effects of age and cohort by gender on BMI change, with age as a random variable. Cumulative incidence of overweight (23.0≤ BMI <27.5 kg/m 2 ) and obesity (BMI ≥27.5 kg/m 2 ) was calculated. Logistic regression analysis was used to estimate odds ratios for the incidence of overweight and obesity according to age group., Results: The incidence of overweight and obesity was approximately double in men (28.3% and 6.7%, respectively) compared to women (14.3% and 3.9%, respectively).The incidence of obesity decreased with age in men, but did not differ according to age in women (P for trend: .02 and .89, respectively). Among overweight participants, the incidence of obesity was higher in women (18.9%) than men (14.5%) and decreased with advancing age (P for trend: <.001 in men and .003 in women). Mean BMI was higher in men than women in all age groups throughout the period. Younger cohorts tended to have a higher BMI change compared with older cohorts., Conclusions: In this Japanese occupational cohort, transition from overweight to obesity is higher in women than men, and the more recent cohorts had a higher change in mean BMI than the older cohorts., (© 2019 The Authors. Journal of Occupational Health published by John Wiley & Sons Australia, Ltd on behalf of The Japan Society for Occupational Health.)

Objective : Successful rheumatoid arthritis (RA) outcome depends on treatment efficacy in the early stages of the disease and its sustainability. It is thus critical to identify factors predicting treatment persistence with biological agents, such as abatacept. We compared clinical profiles, including early changes in autoantibody titres at 3 months, between patients with RA demonstrating sustained persistence and those discontinuing abatacept treatment. Method : We prospectively enrolled 71 and 78 active RA patients treated with abatacept and tumour necrosis factor inhibitors (TNF-Is), respectively, who had previous disease-modifying anti-rheumatic drug) failure. Clinical characteristics were compared between non-continuation and continuation groups stratified according to abatacept or TNF-I persistence for at least 12 months from treatment initiation. Results : Significantly larger decreases in rheumatoid factor titre and anti-citrullinated protein autoantibody (ACPA) titre were observed in the continuation group of abatacept therapy at 3 months, and early reduction in ACPA titre remained a significant and independent predictor of sustained persistence with abatacept in multivariate analysis. In addition, we obtained the area under the receiver operator characteristics curve of 0.904 from a model including baseline ACPA titre and reduction of ACPA titre at 3 months. Sustained reduction of RA disease activity score at 12 months was significantly and independently associated with reduced ACPA titre at 3 months. Conclusions : Persistence with abatacept and sustained therapeutic response are associated with an early reduction in ACPA titre. Prediction of abatacept continuation and efficacy will facilitate the optimal design of therapy in the early stages of RA.

Objectives: We aimed to compare the association of body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR) with risk of cardiovascular disease (CVD) among middle-aged working Japanese men., Methods: A nested case-control study was performed among middle-aged male employees who underwent periodic health checkup. A total of 241 CVD cases were identified and matched individually on age, gender, and worksite with 1205 controls. Data on BMI, WC, WHtR, smoking, hypertension, diabetes, and dyslipidemia collected at 4 years before the event/index date were retrieved. Associations between BMI, WC, WHtR, and CVD risk were assessed by using conditional logistic regression models., Results: The strength of the association of BMI, WC, and WHtR with CVD risk was similar. The smoking-adjusted odds ratio (95% confidence interval) for CVD was 1.60 (1.38-1.85), 1.53 (1.33-1.78), and 1.56 (1.35-1.81) for a 1 SD unit increase in BMI, WC, and WHtR respectively. After further adjustment for hypertension, diabetes, and dyslipidemia, these associations were attenuated but remained statistically significant., Conclusions: Measures of general (BMI) and abdominal (WC and WHtR) obesity were similarly associated with CVD in middle-aged Japanese men., (© 2019 The Authors. Journal of Occupational Health published by John Wiley & Sons Australia, Ltd on behalf of The Japan Society for Occupational Health.)

Objective: To examine whether the cross-sectional association of leisure-time physical activity and walking during commuting to work with depressive symptoms depends on the level of work-related physical activity among Japanese workers., Methods: Participants were 2024 workers aged 19-69 years in two manufacturing companies in Japan. Leisure-time physical activity and walking during commuting to work were ascertained via a self-administered questionnaire. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) scale. The odds ratio (OR) of depressive symptoms (CES-D score ≥16) was estimated by using multiple logistic regression with adjustment for covariates., Results: Leisure-time physical activity was inversely associated with depressive symptoms; multivariable-adjusted ORs (95% confidence intervals) of having depressive symptoms for leisure-time physical activity were 1.00 (reference), 0.85 (0.64, 1.12), 0.69 (0.51, 0.94), and 0.59 (0.44, 0.80) for 0, >0 to <3.0, 3.0 to <10.0, and ≥10.0 MET-h/wk, respectively (P for trend <.001). This inverse trend for leisure-time physical activity was clearer among individuals who had low physical activity at workplace (less than 7.0 MET-h/d). For walking to work, such an inverse association was not observed., Conclusion: Leisure-time physical activity was associated with fewer depressive symptoms, especially in workers with low work-related physical activity., (© 2020 The Authors. Journal of Occupational Health published by John Wiley & Sons Australia, Ltd on behalf of The Japan Society for Occupational Health.)

The potential role of wild boars as a source of erysipelas infection was investigated. An ELISA test of wild boar serum samples from 41 prefectures in Japan revealed that proportions of the Erysipelothrix rhusiopathiae-positive samples were very high in all the prefectures, and the mean positive rate was 95.6% (1312/1372). Serovars of E. rhusiopathiae isolates from wild boars were similar to those of previously reported swine isolates, and all serovar isolates tested were found to be pathogenic to mice. These results suggest that wild boars in Japan constitute a reservoir of E. rhusiopathiae and may pose risks to other animals., (© 2019 The Societies and John Wiley & Sons Australia, Ltd.)

Objective: To investigate the association between suicide death and serum cholesterol levels as measured at times close to suicide death., Methods: We conducted a nested case-control study of 41 cases of suicide deaths and 205 matched controls with serum total cholesterol (TC) levels till 3 years before suicide death in a large cohort of Japanese workers., Results: Individuals in the lowest versus highest tertile/predefined category of TC in a Japanese working population had a three- to four-fold greater risk of suicide death. Each 10 mg/dl decrement of average TC was associated with an 18% increased chance of suicide death (95% confidence interval, 2-35%). Similar results were found for TC levels at each year., Conclusion: These results suggest that a low serum TC level in recent past is associated with an increased risk of suicide death.

The incidence of allergic reactions in patients with chronic renal failure during plasma exchange using fresh frozen plasma is not well known. We retrospectively reviewed 62 patients who underwent plasma exchange between January 2013 and May 2018. The most common indication for plasma exchange was desensitization/preconditioning for kidney transplant (61.3%, 38/62). The incidence of allergic reactions was significantly higher in patients with chronic renal failure than patients without (57.1% vs. 25.0%, P = 0.029). Also, the incidence of allergic reactions tended to be higher in peritoneal dialysis patients (75%, 3/4) than in hemodialysis (58.8%, 10/17) and preemptive kidney transplant (58%, 11/19). These results suggested the relationship of chronic renal failure and the incidence of allergic reactions in patients undergoing therapeutic plasma exchange using fresh frozen plasma., (© 2019 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)

Venous thromboembolism (VTE) is a multifactorial disease. Cancer and older age are risk factors for both recurrent VTE and bleeding under anticoagulant therapy. Oral direct factor Xa inhibitors (Xa inhibitors) have been widely used to treat VTE. However, their effectiveness and safety in cancer and elderly patients have not been fully elucidated. A total of 187 consecutive patients who started Xa inhibitors for VTE therapy between September 2014 and September 2016 were recruited. Patients' demographics, changes in VTE amount, VTE recurrence, clinically relevant bleeding, and death until February 2017 were compared between 92 cancer and 95 non-cancer patients, and 57 elderly (≥ 75 years) and 130 non-elderly patients. Compared with non-cancer patients, cancer patients had a significantly higher incidence of deep vein thrombosis (DVT) in the proximal legs, superior vena cava, and upper extremities (p = 0.034), although the patients' demographics and incidence of pulmonary thromboembolism (PE) were similar between the two groups. There were no significant differences in VTE recurrence (p = 0.328) and clinically relevant bleeding (p = 0.078) between the two groups. Death occurred in 29 cancer patients, 23 of whom died of cancer, while there were no deaths among the non-cancer patients. Elderly patients had a lower body weight and creatinine clearance than non-elderly patients. No significant differences between the two groups were found in relation to PE (p = 0.544), DVT site (p = 0.054), recurrent VTE (p = 0.194), clinically relevant bleeding (p = 0.130) and death (p = 0.241). In comparisons among the four groups (elderly and non-elderly patients with and without cancer), recurrent VTE and clinically relevant bleeding were comparable (p = 0.493 and 0.227, respectively), while death was more frequent in cancer patients regardless of age (p < 0.001). The efficacy and safety of Xa inhibitors as VTE treatment were comparable between cancer and non-cancer patients, and in elderly and non-elderly patients. This suggests that Xa inhibitors may be promising drugs for VTE treatment, irrespective of age and comorbid cancer.

Background: Lupus nephritis (LN) is a major risk factor for overall morbidity and mortality in systemic lupus erythematosus (SLE)., Methods: We retrospectively analyzed cases of proliferative and membranous LN patients who underwent a renal biopsy at our hospital in 1993-2016. We analyzed the association between complete renal response (CR) rates at 12 months after induction therapy and predictive factors for CR and their association with renal flares., Results: Of the 95 cases analyzed, we were able to track the therapeutic responses of 81 patients at 12 months after their induction therapy. The median follow-up duration after renal biopsy was 51 months (interquartile range: 16.5-154.5 months). The Cox proportional hazards model showed that, compared to not attaining CR at 12 months, the attainment of CR at 12 months was correlated with being free from renal flares. The multivariate logistic analysis revealed that the predictive factors for CR at 12 months were the anti-La/SSB antibodies (U/ml) (odds ratio (OR) 1.22, 95% confidence interval (CI) 1.01-1.63, p = 0.0220), blood urea nitrogen (BUN) (OR 0.68, 95% CI 0.44-0.90, p = 0.00048) and serum β2 microglobulin (MG) (OR 0.26, 95% CI 0.06-0.74, p = 0.00098) levels., Conclusions: Among LN patients, being free from renal flares was associated with attaining CR at 12 months after induction therapy. Anti-La/SSB antibodies were a positive predictive factor, and BUN and serum β2MG levels were negative predictive factors of CR at 12 months.

Introduction: We aimed to determine the prospective association of smoking status, smoking intensity, and smoking cessation with the risk of hearing loss in a large Japanese cohort., Methods: The cohort study included 50195 employees, who were aged 20-64 years and free of hearing loss at baseline. Participants were followed up for a maximum of 8 years. Pure-tone audiometric testing was performed annually to identify hearing loss at 1 and 4 kHz. Cox proportional hazards regression models were used to investigate the association between smoking and hearing loss., Results: During follow-up, 3532 individuals developed high-frequency hearing loss, and 1575 developed low-frequency hearing loss. The hazard ratio (HR) associated with current smokers was 1.6 (95% confidence interval [CI] = 1.5 to 1.7) and 1.2 (95% CI = 1.1 to 1.4) for high- and low-frequency hearing loss, respectively, as compared with never smokers. The risk of high- and low-frequency hearing loss increased with the number of cigarettes smoked per day (both p for trend <.001). The HR associated with former smokers was 1.2 (95% CI = 1.1 to 1.3) and 0.9 (95% CI = 0.8 to 1.1) for high- and low-frequency hearing loss, respectively. The analysis by quitting years showed a decline in risk of hearing loss after quitting smoking, even among those who quitted less than 5 years before baseline., Conclusions: Smoking is associated with increased risk of hearing loss, especially at the high frequency, in a dose-response manner. The excess risk of hearing loss associated with smoking disappears in a relatively short period after quitting., Implications: The prospective association between smoking and hearing loss has not been well studied. To the best of our knowledge, our study is the largest to date investigating the association between smoking and incident hearing loss. Our results indicate that smoking is associated with increased risk of hearing loss in a dose-response manner. Quitting smoking virtually eliminates the excess risk of hearing loss, even among quitters with short duration of cessation. These results suggest that smoking may be a causal factor for hearing loss, although further research would be required to confirm this. If so, this would emphasize the need for tobacco control to prevent or delay the development of hearing loss., (© The Author(s) 2018. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Breakfast consumption has been suggested to influence mood, but prospective evidence on this issue is limited. We prospectively investigated the association between the frequency of breakfast consumption and the risk of depressive symptoms in Japanese employees. Participants were 716 employees aged 19-68 years who were free from depressive symptoms and mental disorders at baseline and who attended the 3-year follow-up survey. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale. The frequency of breakfast consumption was categorized into "daily", "5-6 times/week", "3-4 times/week", "1-2 times/week", or "≤1 times/week". Logistic regression was used to estimate odds ratios of depressive symptoms according to breakfast consumption adjusted for dietary and lifestyle factors. Participants who consumed breakfast ≤1 times/week had an increased risk of depressive symptoms compared to those who ate breakfast every day, even after adjusting for other dietary factors (multivariable-adjusted odds ratio 2.92; 95% confidence interval, 1.37-6.22) The risk of depressive symptoms tended to increase with decreasing frequency of breakfast consumption (P for trend = 0.02). The omission of breakfast is related to increased risk of depressive symptoms among Japanese employees, independently of other dietary and non-dietary factors., (Copyright © 2019. Published by Elsevier B.V.)

This study aimed to examine the cross-sectional association of demographic and lifestyle factors with serum brain-derived neurotrophic factor (BDNF) concentrations in a Japanese working population. Participants were 1678 men and 172 women aged 19-69 years who received health check-ups and participated in a nutrition and health survey. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) scale. Dietary intake was assessed using a validated self-administered diet history questionnaire. Serum BDNF concentrations were measured using a solid phase sandwich enzyme-linked immunosorbent assay. Multiple linear regression analysis was used to estimate the mean and 95% confidence interval of serum BDNF concentrations according to demographic and lifestyle factors. Higher body mass index (BMI) was significantly associated with higher circulating BDNF concentrations. Current smokers had significantly higher mean BDNF concentrations than never-smokers. BDNF concentrations were not associated with folate and 25-hydroxyvitamin D concentrations in serum, or dietary eicosapentaenoic acid and docosahexaenoic acid intake. Serum BDNF concentrations were not associated with depressive symptoms or CES-D score per se. In this study, higher BMI and smoking were associated with higher concentrations of serum BDNF, while nutrients that have been linked to depression were not associated with BDNF concentrations among Japanese workers., (Copyright © 2018. Published by Elsevier B.V.)

Objective: To investigate associations of work-related stressors and their changes over time with the risk of developing metabolic syndrome (MetS) among Japanese manufacturing workers., Methods: Participants were 1,040 employees aged 19 to 68 years who were free from MetS at baseline and completed the three year-interval follow-up survey. MetS was defined according to the Joint Interim Statement. Work-related stressors (job strain, job demands, job control, and worksite social support) were assessed based on the Job Content Questionnaire and were split into two categories (low and high) by the median value at each survey. Multivariable logistic regression was performed to investigate the associations of baseline work-related stressors and their changes over time with the incidence of MetS., Results: Three years later, 61 workers developed MetS. Higher job demands at baseline were significantly associated with a lower risk of MetS (adjusted odds ratio 0.46, 95% confidential interval: 0.24, 0.89). In the analyses of the changes in stressors over time, those whose job demands changed from low to high showed significantly higher risk of MetS (adjusted odds ratio 3.27, 95% confidential interval: 1.46, 7.34), compared with those who reported low job demands in both surveys., Conclusions: Results suggest that an increase in job demands over time, but not higher job demands at baseline, is associated with increased risk of MetS.

Background: The effect of smoking on mortality in working-age adults remains unclear. Accordingly, we compared the effects of cigarette smoking and smoking cessation on total and cause-specific mortality in a Japanese working population., Methods and results: This study included 79,114 Japanese workers aged 20-85 years who participated in the Japan Epidemiology Collaboration on Occupational Health Study. Deaths and causes of death were identified from death certificates, sick leave documents, family confirmation, and other sources. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated via Cox proportional hazards regression. During a maximum 6-year follow-up, there were 252 deaths in total. Multivariable-adjusted HRs (95% CIs) for total mortality, cardiovascular disease (CVD) mortality, and tobacco-related cancer mortality were 1.49 (1.10-2.01), 1.79 (0.99-3.24), and 1.80 (1.02-3.19), respectively, in current vs. never smokers. Among current smokers, the risks of total, tobacco-related cancer, and CVD mortality increased with increasing cigarette consumption (P trend <0.05 for all). Compared with never smokers, former smokers who quit <5 and ≥5 years before baseline had HRs (95% CIs) for total mortality of 1.80 (1.00-3.25) and 1.02 (0.57-1.82), respectively., Conclusions: In this cohort of workers, cigarette smoking was associated with increased risk of death from all and specific causes (including CVD and tobacco-related cancer), although these risks diminished 5 years after smoking cessation.

Background: We estimated the cumulative risk of type 2 diabetes from age 30 to 65 years in a large working population in Japan., Methods: We used data from the Japan Epidemiology Collaboration on Occupational Health Study. Participants (46,065 men and 7,763 women) were aged 30-59 years, free of diabetes at baseline, and followed up for a maximum of 7 years. Incident type 2 diabetes was defined based on fasting and casual glucose, glycated hemoglobin, and current medical treatment for type 2 diabetes. We calculated the sex-specific cumulative risk of type 2 diabetes using the Practical Incidence Estimator macro, which was created to produce several estimates of disease incidence for prospective cohort studies based on a modified Kaplan-Meier method., Results: During 274,349 person-years of follow-up, 3,587 individuals (3,339 men and 248 women) developed type 2 diabetes. The cumulative risk was 34.7% (95% confidence interval, 33.1-36.3%) for men and 18.6% (95% confidence interval, 15.5-21.7%) for women. In BMI-stratified analysis, obese (BMI ≥30 kg/m 2 ) and overweight (BMI 25-29.9 kg/m 2 ) men and women had a much higher cumulative risk of type 2 diabetes (obese: 77.3% for men and 64.8% for women; overweight: 49.1% and 35.7%, respectively) than those with BMI <25 kg/m 2 (26.2% and 13.4% for men and women, respectively)., Conclusions: The present data highlight the public health burden of type 2 diabetes in the working population. There is a need for effective programs for weight management and type 2 diabetes screening, especially for young obese employees, to prevent or delay the development of type 2 diabetes.