Diagnosis-specific Cumulative Incidence of Return-to-work, Resignation, and Death Among Long-term Sick-listed Employees: Findings From the Japan Epidemiology Collaboration on Occupational Health Study.

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.

Smoking and Long-Term Sick Leave in a Japanese Working Population: Findings of the Japan Epidemiology Collaboration on Occupational Health Study.

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.

Cross-Sectional Study on the Association between Dietary Non-Enzymatic Antioxidant Capacity and Serum Liver Enzymes: The Furukawa Nutrition and Health Study.

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.

Prospective study on the association between dietary non-enzymatic antioxidant capacity and depressive symptoms.

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.

Association between anthropometric indices of obesity and risk of cardiovascular disease in Japanese men.

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.

Meat subtypes and colorectal cancer risk: A pooled analysis of 6 cohort studies in Japan.

Red meat and processed meat have been suggested to increase risk of colorectal cancer (CRC), especially colon cancer. However, it remains unclear whether these associations differ according to meat subtypes or colon subsites. The present study addressed this issue by undertaking a pooled analysis of large population-based cohort studies in Japan: 5 studies comprising 232 403 participants (5694 CRC cases) for analysis based on frequency of meat intake, and 2 studies comprising 123 635 participants (3550 CRC cases) for analysis based on intake quantity. Study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using the Cox proportional hazards model and then pooled using the random effect model. Comparing the highest vs lowest quartile, beef intake was associated with an increased risk of colon cancer in women (pooled HR 1.20; 95% CI, 1.01-1.44) and distal colon cancer (DCC) risk in men (pooled HR 1.30; 95% CI, 1.05-1.61). Frequent intake of pork was associated with an increased risk of distal colon cancer in women (pooled HR 1.44; 95% CI, 1.10-1.87) for "3 times/wk or more" vs "less than 1 time/wk". Frequent intake of processed red meat was associated with an increased risk of colon cancer in women (pooled HR 1.39; 95% CI, 0.97-2.00; P trend = .04) for "almost every day" vs "less than 1 time/wk". No association was observed for chicken consumption. The present findings support that intake of beef, pork (women only), and processed red meat (women only) might be associated with a higher risk of colon (distal colon) cancer in Japanese.

Higher Dietary Non-enzymatic Antioxidant Capacity Is Associated with Decreased Risk of All-Cause and Cardiovascular Disease Mortality in Japanese Adults.

BACKGROUND: Few studies have assessed associations of non-enzymatic antioxidant capacity (NEAC) in the overall diet with all-cause or specific mortality, and their results have been inconsistent. OBJECTIVES: The present study investigated the association between dietary NEAC and all-cause or cause-specific mortality. METHODS: The study was a large-scale population-based prospective cohort study in Japan consisting of 42,520 men and 50,207 women aged 44-76 y, who had no history of cancer, stroke, ischemic heart disease, or chronic liver disease. We evaluated FFQ-based dietary NEAC with use of published databases in which the NEACs of individual foods were analyzed by ferric reducing antioxidant power (FRAP) and oxygen radical absorbance capacity (ORAC) assays. Dietary NEAC was calculated by multiplying the estimated NEAC with the consumed amount and summing up those values for all foods, and was categorized in quartiles. We identified death and cause of death with use of residential registry and death certificates. HRs and 95% Cls for death from the second survey, which was conducted from April 1995 to December 2014 were estimated with Cox proportional hazards regression analysis. RESULTS: After 1,498,308 person-years of follow-up, 12,978 total deaths occurred. The multivariable-adjusted HRs (95% Cls) for all-cause mortality for the highest compared with the lowest quartile of FRAP and ORAC were 0.85 (0.80, 0.89) and 0.84 (0.79, 0.89), respectively. Dietary NEACs were inversely associated with mortality from cardiovascular disease (CVD), but not from cancer. The multivariable-adjusted HRs (95% Cls) for CVD for the highest compared with the lowest quartile of FRAP and ORAC were 0.83 (0.75, 0.92) and 0.79 (0.70, 0.89), respectively. CONCLUSIONS: Higher dietary NEACs from FRAP and ORAC were associated with lower risk of all-cause mortality and mortality from CVD in Japanese adults.

Relationship between dietary non-enzymatic antioxidant capacity and type 2 diabetes risk in the Japan Public Health Center-based Prospective Study.

OBJECTIVE: Intake of antioxidants may reduce the risk for type 2 diabetes (T2D) by reducing oxidative stress. However, it is unclear whether dietary non-enzymatic antioxidant capacity (NEAC), which represents the cumulative action of dietary antioxidants and their synergistic effects in foods, is associated with decreased T2D risk. The aim of this study was to investigate the associations between dietary NEAC and T2D. METHODS: The study included 64 660 adults (27 809 men and 36 851 women), 44 to 76 y of age without history of T2D in the Japan Public Health Center-based Prospective Study. Dietary NEAC was estimated using databases of NEAC measurements compiled from results for three different assays: ferric reducing-antioxidant power (FRAP), oxygen radical absorbance capacity (ORAC), and total radical-trapping antioxidant parameter (TRAP). A multiple logistic regression model was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of self-reported physician-diagnosed T2D over 5 y with adjustment for potential confounders. RESULTS: In all, 1191 cases of newly diagnosed T2D were reported. Dietary NEACs were not significantly associated with T2D. The multivariate-adjusted ORs were 1.04 (95% CI, 0.88-1.23; Ptrend = 0.56) for FRAP, 1.11 (95% CI, 0.93-1.32; Ptrend = 0.26) for ORAC, and 0.99 (95% CI, 0.84-1.18; Ptrend = 0.84) for TRAP. Similar associations were observed in men and women (Pinteraction = 0.46 for FRAP, 0.35 for ORAC, and 0.63 for TRAP). In stratified analyses of major prooxidant factors, no notable associations with smoking and obesity status were observed. CONCLUSIONS: This finding suggests that dietary NEAC may not be appreciably associated with T2D in Japanese adults.

Smoking, Smoking Cessation, and the Risk of Hearing Loss: Japan Epidemiology Collaboration on Occupational Health Study.

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.

Smoking, Smoking Cessation, and Risk of Mortality in a Japanese Working Population　- Japan Epidemiology Collaboration on Occupational Health Study.

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 (Ptrend<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.

Haemoglobin A1c and hearing impairment: longitudinal analysis using a large occupational health check-up data of Japan.

OBJECTIVES: The aim of this study was to determine whether haemoglobin A1c (HbA1c) level is associated with the incidence of hearing impairment accounting for smoking status and diabetic condition at baseline. METHODS: Participants were 131 689 men and 71 286 women aged 30-65 years and free of hearing impairment at baseline (2008) who attended Japanese occupational annual health check-ups from 2008 to 2015. We defined low-frequency hearing impairment at a hearing threshold >30 dB at 1 kHz and high frequency at >40 dB at 4 kHz in the better ear in pure-tone audiometric tests. HbA1c was categorised into seven categories. The association between HbA1c and hearing impairment was assessed using the Cox proportional hazards model. RESULTS: On 5 years mean follow-up, high HbA1c was associated with high-frequency hearing impairment. In non-smokers, HbA1c≥8.0% was associated with high-frequency hearing impairment, with a multivariable HR (95% CI) compared with HbA1c 5.0%-5.4% of 1.46 (1.10 to 1.94) in men and 2.15 (1.13 to 4.10) in women. There was no significant association between HbA1c and hearing impairment in smokers. A J-shaped association between HbA1c and high-frequency hearing impairment was observed for participants with diabetes at baseline. HbA1c was not associated with low-frequency hearing impairment among any participants. CONCLUSIONS: HbA1c ≥8.0% of non-smokers and ≥7.3% of participants with diabetes was associated with high-frequency hearing impairment. These findings indicate that appropriate glycaemic control may prevent diabetic-related hearing impairment.

The Validity and Reproducibility of Dietary Non-enzymatic Antioxidant Capacity Estimated by Self-administered Food Frequency Questionnaires.

BACKGROUND: High dietary non-enzymatic antioxidant capacity (NEAC) has been inversely related to the incidence of degenerative diseases. However, few studies have investigated the validity and reproducibility of dietary NEAC estimated from a food frequency questionnaire (FFQ). We assessed the validity and reproducibility of FFQ-based dietary NEAC against a dietary record (DR). METHODS: Participants were 244 men and 253 women who completed a 28-day DR and FFQs. NEAC for each food item was estimated according to available databases of antioxidant capacity, as measured by ferric reducing-antioxidant power (FRAP), oxygen radical absorbance capacity (ORAC), and total radical-trapping antioxidant parameter (TRAP). Using Spearman's rank correlation coefficients (CCs), we assessed the validity for dietary NEACs from a 28-day DR and a FFQ, and the reproducibility for them from two FFQs administered at a 1-year interval. Additionally, joint classification and the Bland-Altman method were applied to assess agreement between the two methods. RESULTS: Regarding validation, deattenuated CCs for the energy-adjusted overall dietary NEACs between FFQ and DR for FRAP, ORAC, and TRAP were 0.52, 0.54, and 0.52, respectively, for all subjects. Extreme miscategorization rates by joint classification analysis were 2% for FRAP and ORAC and 1% for TRAP. Regarding reproducibility, CCs between the energy-adjusted dietary NEACs from two FFQs were 0.64 for FRAP and 0.65 for ORAC and TRAP. CONCLUSION: The validity and reproducibility of dietary NEAC of total food from the FFQ were moderate. Estimations of dietary NEAC using FFQ would be useful in studying disease relationships by categorizing habitual dietary NEAC.

Determinants and Temporal Trends of Perfluoroalkyl Substances in Pregnant Women: The Hokkaido Study on Environment and Children's Health.

Perfluoroalkyl substances (PFAS) are persistent bio-accumulative chemicals that impact the health of pregnant women and their children. PFAS derive from environmental and consumer products, which depend on human lifestyle, socioeconomic characteristics, and time variation. Here, we aimed to explore the temporal trends of PFAS in pregnant women and the characteristics related to maternal PFAS concentration. Our study is part of the Hokkaido Study on Environment and Children's Health, the Hokkaido large-scale cohort that recruited pregnant women between 2003 and 2011. Blood samples were acquired from pregnant women during the third trimester to measure PFAS and cotinine concentrations. Maternal basic information was collected with a baseline structured questionnaire. Eleven PFAS were measured from 2123 samples with ultra-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry. Eight PFAS were above 80% detection rate and were included in the final analysis. We used multivariable linear regression to analyze the association of pregnant women characteristics with the levels of eight PFAS. The temporal trend of PFAS was observed in two periods (August 2003 to January 2006 and February 2006 to July 2012). The concentration of perfluorooctane sulfonate (PFOS) significantly decreased from August 2003 to January 2006 and from February 2006 to July 2012. The concentrations of perfluorododecanoic acid (PFDoDA), perfluoroundecanoic acid (PFUnDA), and perfluorotridecanoic acid (PFTrDA) increased significantly between August 2003 and January 2006, whereas they decreased significantly between February 2006 and July 2012. Women with pre-pregnancy body mass index (BMI) >25 kg/m² had lower PFUnDA, PFDoDA, and PFTrDA levels than did those with normal BMI (18.5⁻24.9 kg/m²). Pregnant women, who were active smokers (cotinine > 11.49 ng/mL), had higher PFOS than the non-smokers (cotinine < 0.22 ng/mL). Lower levels of PFHxS, PFOS, PFOA, PFNA, and PFDA were observed in women, who had given birth to more than one child. There were also significant positive associations between PFAS levels and annual income or maternal education. PFAS levels varied in women with higher pre-pregnancy BMI, active smoking status, higher education level and annual income. The causes of the individual PFAS differences should be explored in an independent study.

Dietary non-enzymatic antioxidant capacity and DNA damage in a working population.

OBJECTIVE: The aim of this study was to investigate the potential links between dietary non-enzymatic antioxidant capacity (NEAC) in overall diet and separately from foods and beverages and markers of DNA damage. METHODS: The participants were 513 employees, 20 to 65 y of age. Urinary levels of 8-hydroxydeoxyguanosine (8-OHdG) and 7-methylguanine (m7 Gua) were measured using column-switching high-performance liquid chromatography. Dietary NEAC was determined from databases of NEAC measurements obtained by different assays: ferric reducing-antioxidant power (FRAP), oxygen radical absorbance capacity (ORAC), and total radical-trapping antioxidant parameter (TRAP). Dietary NEAC for each participant was calculated by multiplying the estimated NEAC values with the consumed amount and summing up those values, which was ascertained by a validated brief self-administered diet history questionnaire. Multiple-regression analyses were performed to assess the associations between dietary NEAC and 8-OHdG and m7 Gua, with adjustment for potential confounders. RESULTS: No statistically significant associations were found between overall dietary NEAC or NEAC from either foods or beverages and urinary 8-OHdG levels, after adjustment for potential confounders (overall: FRAP, Ptrend = 0.40; ORAC, P = 0.27; TRAP, P = 0.45). Likewise, no association was found between overall dietary NEAC and m7 Gua levels (FRAP, Ptrend = 0.30; ORAC, P = 0.65; TRAP, P = 0.41). However, we did identify significant inverse association between NEAC from foods, as estimated by TRAP, and m7 Gua levels (Ptrend = 0.049). CONCLUSION: Overall, dietary NEAC was not associated with 8-OHdG or m7 Gua levels. In contrast, dietary NEAC from foods but not beverages may be inversely associated with DNA damage caused by methylation.

Coffee drinking and colorectal cancer and its subsites: A pooled analysis of 8 cohort studies in Japan.

Coffee is a rich source of bioactive compounds that have potential anticarcinogenic effects. However, it remains unclear whether coffee drinking is associated with colorectal cancer. Also, despite different etiological factors involved in gut physiology, few studies have investigated this association by anatomical site of the lesion. To address these issues, this study examined the association between coffee drinking and colorectal cancer in a pooled analysis from 8 cohort studies conducted in Japan. Among 320,322 participants followed up for 4,503,274 person-years, 6,711 incident colorectal cancer cases were identified. Study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models and then pooled using the random effects model. Coffee drinking was not materially associated with colorectal cancer risk in men or women (pooled HR 0.92, 95% CI 0.82-1.03 in men and pooled HR 0.90, 95% CI 0.76-1.07 in women). Analysis by subsite showed a lower risk of colon cancer among female drinkers of ≥3 cups coffee/day (pooled HR 0.80, 95% CI 0.64-0.99). There was no such association in men. Coffee drinking was not associated with risk of rectal cancer in men or women. Results were virtually the same among never smokers except for an increased risk of rectal cancer associated with frequent coffee consumption. Coffee drinking may be associated with lower risk of colon cancer in Japanese women.

Development and validation of risk models to predict the 7-year risk of type 2 diabetes: The Japan Epidemiology Collaboration on Occupational Health Study.

AIMS/INTRODUCTION: We previously developed a 3-year diabetes risk score in the working population. The objective of the present study was to develop and validate flexible risk models that can predict the risk of diabetes for any arbitrary time-point during 7 years. MATERIALS AND METHODS: The participants were 46,198 Japanese employees aged 30-59 years, without diabetes at baseline and with a maximum follow-up period of 8 years. Incident diabetes was defined according to the American Diabetes Association criteria. With routine health checkup data (age, sex, abdominal obesity, body mass index, smoking status, hypertension status, dyslipidemia, glycated hemoglobin and fasting plasma glucose), we developed non-invasive and invasive risk models based on the Cox proportional hazards regression model among a random two-thirds of the participants, and used another one-third for validation. RESULTS: The range of the area under the receiver operating characteristic curve increased from 0.73 (95% confidence interval 0.72-0.74) for the non-invasive prediction model to 0.89 (95% confidence interval 0.89-0.90) for the invasive prediction model containing dyslipidemia, glycated hemoglobin and fasting plasma glucose. The invasive models showed improved integrated discrimination and reclassification performance, as compared with the non-invasive model. Calibration appeared good between the predicted and observed risks. These models performed well in the validation cohort. CONCLUSIONS: The present non-invasive and invasive models for the prediction of diabetes risk up to 7 years showed fair and excellent performance, respectively. The invasive models can be used to identify high-risk individuals, who would benefit greatly from lifestyle modification for the prevention or delay of diabetes.

Age-, sex-, and diagnosis-specific incidence rate of medically certified long-term sick leave among private sector employees: The Japan Epidemiology Collaboration on Occupational Health (J-ECOH) study.

BACKGROUND: Long-term sick-leave is a major public health problem, but data on its incidence in Japan are scarce. We aimed to present reference data for long-term sick-leave among private sector employees in Japan. METHODS: The study population comprised employees of 12 companies that participated in the Japan Epidemiology Collaboration on Occupational Health Study. Details on medically certified sick-leave lasting ≥30 days were collected from each company. Age- and sex-specific incidence rate of sick-leave was calculated for the period of April 2012 to March 2014. RESULTS: A total of 1422 spells in men and 289 in women occurred during 162,989 and 30,645 person-years of observation, respectively. The three leading causes of sick-leave (percentage of total spells) were mental disorders (52%), neoplasms (12%), and injury (8%) for men; and mental disorders (35%), neoplasms (20%), and pregnancy-related disease (14%) for women. Incidence rate of sick-leave due to mental disorders was relatively high among men in their 20s-40s but tended to decrease with age among women. Incidence rate of sick-leave due to neoplasms started to increase after age 50 in men and after age 40 in women, making neoplasms the leading cause of sick-leave after age 50 for women and after age 60 for men and the second leading cause after age 40 for women and after age 50 for men. Pregnancy-related disease was the second leading cause of sick-leave among women aged 20-39 years. CONCLUSIONS: These results suggest that mental disorder, neoplasms, and pregnancy-related disease are the major causes of long-term sick-leave among private sector employees in Japan.

Circulating ferritin concentrations are differentially associated with serum adipokine concentrations in Japanese men and premenopausal women.

PURPOSE: Increased iron storage, as measured by circulating ferritin, has been linked to an increased risk of various diseases including diabetes. We examined the association of circulating ferritin with serum adiponectin, leptin, resistin, plasminogen activator inhibitor-1 (PAI-1), and visfatin levels. METHODS: We conducted a cross-sectional study among 429 Japanese employees (284 men and 145 premenopausal women, mean age: 42.5 ± 10.5 years). Serum adipokines were measured using Luminex suspension bead-based multiplexed array, and serum ferritin was determined using a chemiluminescence immunoassay. Multivariable regression analysis was performed to calculate mean concentrations of adipokine according to the tertile of ferritin concentrations with adjustment for potential confounders. RESULTS: Leptin and visfatin concentrations increased with increasing ferritin concentrations in men after multivariable adjustment of physical activity, smoking, alcohol use, and body mass index (P for trend = 0.02 and 0.01 for leptin and visfatin, respectively). Serum ferritin concentrations were inversely and significantly associated with adiponectin in women (P for trend = 0.01). Resistin and PAI-1 were not appreciably associated with ferritin concentration. CONCLUSIONS: Increased iron storage may be associated with higher circulating concentrations of leptin and visfatin in men and with lower concentrations of adiponectin in women.

Hba1c, Blood Pressure, and Lipid Control in People with Diabetes: Japan Epidemiology Collaboration on Occupational Health Study.

AIMS: The control of blood glucose levels, blood pressure (BP), and low-density lipoprotein cholesterol (LDL-C) levels reduces the risk of diabetes complications; however, data are scarce on control status of these factors among workers with diabetes. The present study aimed to estimate the prevalence of participants with diabetes who meet glycated hemoglobin (HbA1c), BP, and LDL-C recommendations, and to investigate correlates of poor glycemic control in a large working population in Japan. METHODS: The Japan Epidemiology Collaboration on Occupational Health (J-ECOH) Study is an ongoing cohort investigation, consisting mainly of employees in large manufacturing companies. We conducted a cross-sectional analysis of 3,070 employees with diabetes (2,854 men and 216 women) aged 20-69 years who attended periodic health examinations. BP was measured and recorded using different company protocols. Risk factor targets were defined using both American Diabetes Association (ADA) guidelines (HbA1c < 7.0%, BP < 140/90 mmHg, and LDL-C < 100 mg/dL) and Japan Diabetes Society (JDS) guidelines (HbA1c < 7.0%, BP < 130/80 mmHg, and LDL-C < 120 mg/dL). Logistic regression models were used to explore correlates of poor glycemic control (defined as HbA1c ≥ 8.0%). RESULTS: The percentages of participants who met ADA (and JDS) targets were 44.9% (44.9%) for HbA1c, 76.6% (36.3%) for BP, 27.1% (56.2%) for LDL-C, and 11.2% (10.8%) for simultaneous control of all three risk factors. Younger age, obesity, smoking, and uncontrolled dyslipidemia were associated with poor glycemic control. The adjusted odds ratio of poor glycemic control was 0.58 (95% confidence interval, 0.46-0.73) for participants with treated but uncontrolled hypertension, and 0.47 (0.33-0.66) for participants with treated and controlled hypertension, as compared with participants without hypertension. There was no significant difference in HbA1c levels between participants with treated but uncontrolled hypertension and those with treated and controlled hypertension. CONCLUSION: Data from a large working population, predominantly composed of men, suggest that achievement of HbA1c, BP, and LDL-C targets was less than optimal, especially in younger participants. Uncontrolled dyslipidemia was associated with poor glycemic control. Participants not receiving antihypertensive treatment had higher HbA1c levels.

Coffee drinking and colorectal cancer risk: an evaluation based on a systematic review and meta-analysis among the Japanese population.

OBJECTIVE: It remains unclear whether coffee drinking is associated with colorectal cancer risk. We performed a systematic review and meta-analysis of epidemiologic studies on this issue among the Japanese population. METHODS: Original data were obtained from MEDLINE searches using PubMed or from searches of the 'Ichushi' database, complemented with manual searches. Meta-analysis was performed by using the random effects model to estimate the summary relative risk with 95% confidence interval according to the study design. The final judgment was made based on a consensus of the research group members with consideration for both epidemiological evidence and biological plausibility. RESULTS: We identified five cohort studies and nine case-control studies. Of these, one cohort study reported a strong inverse association (in women only), whereas three case-control studies reported a strong inverse association with colon or rectal cancer. In meta-analysis, high consumption of coffee was not appreciably associated with colorectal cancer risk among cohort studies, whereas it was associated with significantly lower risk of colorectal or colon cancer among case-control studies. The summary relative risk/odds ratio (95% confidence interval) for the highest versus lowest categories of coffee consumption was 0.95 (0.77-1.17) and 0.78 (0.65-0.95) for cohort and case-control studies, respectively. CONCLUSIONS: The evidence is insufficient to support that coffee drinking increases or decreases the risk of colorectal cancer among the Japanese population.