Diabetes, Prediabetes, and the Risk of a Composite Outcome of Long-term Sickness Absence and Pre-retirement Death Due to Physical Disorders.

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.

Metabolic syndrome and the risk of severe cancer events: a longitudinal study in Japanese workers.

BACKGROUND: Metabolic syndrome (MetS) is associated with cancer risk; however, little is known regarding its relationship with the risk of cancer-related premature death and long-term sick leave (LTSL), which can lead to a substantial loss in working years. The present study aimed to quantify the all-site and site-specific associations between MetS and the risk of severe cancer events (a composite outcome of LTSL and mortality due to cancer) in a large working population in Japan. METHODS: We recruited 70,875 workers (59,950 men and 10,925 women), aged 20-59 years, who attended health check-ups in 2011 (10 companies) and 2014 (2 companies). All workers underwent follow up for severe cancer events until March 31, 2020. MetS was defined in accordance with the Joint Interim Statement. Cox regression models were used to quantify the association between baseline MetS and severe cancer events. RESULTS: During 427,379 person-years of follow-up, 523 participants experienced the outcome consisting of 493 LTSLs of which 124 eventually resulted in death, and 30 deaths without taking LTSL. The adjusted hazard ratios (HR) (95% confidence intervals [CI]) for composite severe events due to all-site, obesity-related, and non-obesity-related cancer among those with vs. without MetS were 1.26 (1.03, 1.55), 1.37 (1.04, 1.82), and 1.15 (0.84, 1.56), respectively. In cancer site-specific analyses, MetS was associated with an increased risk of severe events due to pancreatic cancer (HR, 2.06; 95% CI, 0.99-4.26). When mortality was treated solely as the endpoint, the association was significant for all-site (HR, 1.58; 95% CI, 1.10-2.26), and obesity-related (HR, 1.59; 95% CI, 1.00-2.54) cancer. Additionally, a greater number of MetS components was associated with a greater risk of both severe cancer events and cancer-related mortality (P trend < 0.05). CONCLUSION: Among Japanese workers, MetS was associated with an increased risk of severe cancer events, especially those due to obesity-linked cancer.

Metabolic Syndrome and the Increased Risk of Medically Certified Long-term Sickness Absence: A Prospective Analysis 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.

The association between living alone and depressive symptoms and the role of pet ownership among Japanese workers.

BACKGROUND: Living alone has been positively associated with the prevalence of depressive symptoms. We examined how a combination of living alone and pet ownership relates to depressive symptoms. METHODS: As part of the Japan Epidemiology Collaboration on Occupational Health Study, we conducted a survey on health-related lifestyles, including living arrangements and pet ownership, among 12,763 employees of five companies in 2018-2021. Depressive symptoms were assessed using the 11-item Center for Epidemiological Studies-Depression Scale (cutoff score ≥ 9). A Poisson regression model with a robust variance estimator was used to calculate prevalence ratio and 95% confidence interval (CI) while adjusting for covariates. RESULTS: Among the participants, 30.9% were depressed, 17.7% had pets, and 29.1% lived alone. Compared to individuals living with others but not with a pet, those living alone and not with a pet had a 1.17 times higher prevalence ratio of depressive symptoms (95% CI: 1.08-1.26). The corresponding figures were 1.03 (95% CI: 0.95-1.11) for those living with others and pet(s) and 1.42 (95% CI: 1.18-1.69) for those living alone but with pet(s). CONCLUSION: Living alone was significantly associated with a higher prevalence of depressive symptoms. The association was rather stronger among individuals with vs. without pets. Pet ownership may not be associated with decreased depressive symptoms.

Relationship Between Physical Activity and Estimated Glomerular Filtration Rate in Renal Transplant Recipients: A Cross-sectional Study Analyzing Isotemporal Substitution Model.

OBJECTIVES: Successful renal transplantation reduces mortality rates. However, the decline in the estimated glomerular filtration rate (eGFR) after transplantation is strongly associated with premature mortality in renal transplant recipients (RTRs). Physical activity (PA) is a modifiable lifestyle factor with the potential to maintain or improve eGFR. However, the effects of the type or intensity of PA and sedentary behavior (SB) on eGFR in RTRs remain unclear. The purpose of this study was to clarify the association between accelerometry-measured PA and SB and eGFR in RTRs using isotemporal substitution (IS) analysis. METHODS: A total of 82 renal transplant outpatients participated in this cross-sectional study, of which 65 (average age, 56.9 years; average time post-transplant, 83.0 months) were finally analyzed. All RTRs wore a triaxial accelerometer to measure PA for 7 consecutive days. The measured PA was classified based on intensity into light PA, moderate-to-vigorous PA (MVPA), and SB. The association of each type of PA with eGFR was examined using multi-regression analyses of single-factor, partition, and IS models. The IS model was applied to examine the estimated effects of substituting 30 minutes of SB with an equal amount of time of light PA or MVPA on eGFR. RESULTS: The partition model showed that MVPA was an independent explanatory variable for eGFR (ß = 5.503; P < .05), and the IS model identified that the substitution of time spent in SB with MVPA led to improvements in eGFR (ß = 5.902; P < .05). CONCLUSIONS: The present study suggests that MVPA has an independent and positive association with eGFR, and replacing 30 minutes of SB with MVPA after renal transplantation might lead to the maintenance or improvement of eGFR in RTRs.

Selection of treatment regimens based on shared decision-making in patients with rheumatoid arthritis on remission in the FREE-J study.

OBJECTIVE: To compare the outcome of various treatment de-escalation regimens in patients with RA who achieved sustained remission. METHODS: At period 1, 436 RA patients who were treated with MTX and bDMARDs and had maintained DAS28(ESR) at <2.6 were divided into five groups based on shared patient/physician decision-making; continuation, dose reduction and discontinuation of MTX or bDMARDs. At end of year 1, patients who achieved DAS28(ESR) <3.2 were allowed to enrol in period 2 for treatment using the de-escalation regimens for another year. The primary and secondary endpoints were the proportion of patients with DAS28(ESR) <2.6 at year 1 and 2, respectively. RESULTS: Based on shared decision-making, 81.4% elected de-escalation of treatment and 48.4% selected de-escalation of MTX. At end of period 1, similar proportions of patients maintained DAS28(ESR) <2.6 (continuation, 85.2%; MTX dose reduction, 79.0%; MTX-discontinuation, 80.0%; bDMARD dose reduction, 73.9%), although the rate was significantly different between the continuation and bDMARD-discontinuation. At end of period 2, similar proportions of patients of the MTX groups maintained DAS28(ESR) <2.6 (continuation or de-escalation), but the rates were significantly lower in the bDMARD-discontinuation group. However, half of the latter group satisfactorily discontinued bDMARDs. Adverse events were numerically lower in MTX and bDMARD-de-escalation groups during period 1 and 2, compared with the continuation group. CONCLUSIONS: After achieving sustained remission by combination treatment of MTX/bDMARDs, disease control was achieved comparably by continuation, dose reduction or discontinuation of MTX and dose reduction of bDMARDs at end of year 1. Subsequent de-escalation of MTX had no impacts on disease control but decreased adverse events in year 2.

Effect of Post-diagnosis Physical Activity on Breast Cancer Recurrence: a Systematic Review and Meta-analysis.

PURPOSE OF REVIEW: Breast cancer (BC) recurrence dramatically decreases 5-year survival, which causes a fear of BC recurrence among a majority of BC survivors. Evidence is currently inconsistent on whether post-diagnosis recreational physical activity (rPA) can prevent BC recurrence due to the small number of included studies, as well as methodological heterogeneity among the studies. This systematic review aimed to clarify the association between post-diagnosis rPA and the risk of BC recurrence, by conducting a meta-analysis while controlling for the categories of rPA across the existing studies. RECENT FINDINGS: Prospective cohort studies were searched, and five studies were eligible for the meta-analysis. Of 10,094 patients with BC, 1561 had recurrence during the follow-up period ranging from 12 to 156 months. The meta-analysis revealed that patients whose post-diagnosis rPA was ≥ 7.5 metabolic equivalents (MET-h/week) had a lower BC risk than patients whose rPA was 0-3 MET-h/week (hazard ratio [HR], 0.65; 95% CI, 0.58-0.73, p < 0.00001, I2 = 0%). The review indicated that a post-diagnosis rPA of ≥ 7.5 MET-h/week could reduce the risk of BC recurrence by 35%. Although it is necessary to investigate randomized controlled studies in the future, this result will strengthen strategies for the care and/or treatment of patients after BC and can motivate BC survivors to participate in rPA programs after BC diagnosis.

Overtime Work and the Incidence of Long-term Sickness Absence Due to Mental Disorders: A Prospective Cohort Study.

BACKGROUND: Although previous research has focused on the association between long working hours and several mental health outcomes, little is known about the association in relation to mental health-related sickness absence, which is a measure of productive loss. We aimed to investigate the association between overtime work and the incidence of long-term sickness absence (LTSA) due to mental disorders. METHODS: Data came from the Japan Epidemiology Collaboration on Occupational Health Study (J-ECOH). A total of 47,422 subjects were followed-up in the period between April 2012 and March 2017. Information on LTSA was obtained via a study-specific registry. Baseline information was obtained at an annual health checkup in 2011; overtime working hours were categorized into <45; 45-79; 80-99; and ≥100 hours/month. RESULTS: During a total follow-up period of 211,443 person-years, 536 people took LTSA due to mental disorders. A Cox proportional hazards model showed that compared to those with less than 45 hours/month of overtime work, those with 45-79 hours/month were at a lower risk of LTSA due to mental health problems (hazard ratio [HR] 0.63; 95% confidence interval [CI], 0.56-0.71) while those with overtime work of ≥100 hours/month had a 2.11 (95% CI, 1.12-3.98) times higher risk of LTSA due to mental health problems. CONCLUSION: Engaging in excessive overtime work was linked with a higher risk of LTSA due to mental health problems while the lower risk observed among individuals working 45-79 hours/month of overtime work might have been due to a healthy worker effect.

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 Cessation, Weight Gain, and the Trajectory of Estimated Risk of Coronary Heart Disease: 8-Year Follow-up From a Prospective Cohort Study.

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.

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.

Loss of Working Life Years Due to Mortality, Sickness Absence, or Ill-health Retirement: A Comprehensive Approach to Estimating Disease Burden in the Workplace.

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.

Patterns of changes in overtime working hours over 3 years and the risk for progression to type 2 diabetes in adults with pre-diabetes.

No information exists regarding the effects of working hours on glucose metabolism in adults with pre-diabetes, a high-risk group for developing diabetes. Further, longitudinal patterns in working hours and their effects on glucose metabolism have not been described previously. We investigated the association between changes in overtime working hours over 3 years and the risk for progression to type 2 diabetes among adults with pre-diabetes. We analyzed patterns of overtime working hours from 2008 to 2011 among 18,172 workers in Japan (16,474 men, aged 30 to 64 years) with pre-diabetes in 2011 (baseline) using the sub-cohort data from the Japan Epidemiology Collaboration on Occupational Health Study. Participants were followed up to March 2016. Overtime working hours per month were self-reported annually in 2008-2011 and trajectory patterns were identified using group-based trajectory modeling. Type 2 diabetes was diagnosed by fasting or random plasma glucose test, hemoglobin A1c, and history of diabetes. Multivariable-adjusted hazard ratios of incident diabetes were calculated using Cox regression. We identified 3 distinct trajectories of overtime work: persistently short, long-to-short, and persistently long. During a mean follow-up of 3.5 years, 1613 participants (8.9%) developed diabetes. Compared with persistently short overtime working hours, no material increase in diabetes risk was observed for either long-to-short working hours or persistently long working hours. After adjustment for potential confounders, this association was materially unchanged. The results suggest that among individuals with pre-diabetes, persistently long working hours over 3 years were not associated with an increased risk of developing type 2 diabetes.

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.

Effectiveness and safety of lower dose sulfamethoxazole/trimethoprim therapy for Pneumocystis jirovecii pneumonia in patients with systemic rheumatic diseases: A retrospective multicenter study.

OBJECTIVES: To evaluate the effectiveness and safety of lower-dose sulfamethoxazole/trimethoprim therapy (SMX/TMP) for Pneumocystis jirovecii pneumonia (PCP) in patients with systemic rheumatic diseases. METHODS: In this multicenter retrospective study, we compared effectiveness and safety of SMX/TMP for the treatment of PCP among patients divided into three groups according to the initial dosage of SMX/TMP: the low, ≤10 mg/kg/day; the intermediate, 10-15 mg/kg/day; and the high and conventional, 15-20 mg/kg/day for TMP dose. RESULTS: Eighty-one patients, including 22, 30, and 29 patients in the low-, the intermediate- and the high-dose group could be analyzed and the 30-day survival rate were 100%, 93.3%, and 96.7%, respectively (P = 0.28). There were significant dose-dependent increasing trends of severe adverse drug reactions (ADRs) for SMX/TMP that were graded as ≥3 according to the Common Terminology Criteria for Adverse Events. When stratified by presence of severe hypoxemia defined by alveolar-arterial O2 gradient ≥45 mmHg, the 30-day survival and treatment modification rate were similar among the three groups, but frequency of severe ADRs were significantly decreased in the low-dose group. The low-dose group was independently and negatively associated with treatment modification within 14 days and severe ADRs. CONCLUSIONS: Lower dose SMX/TMP therapy with ≤10 mg/kg/day for TMP was as effective as higher dose therapy for the treatment of PCP and associated with lower rates of treatment modification and severe ADRs in patients with systemic rheumatic diseases.

Serum cholesterol levels preceding to suicide death in Japanese workers: a nested case-control study.

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.

Osteoporosis complication is a risk factor for frailty in females with type 2 diabetes mellitus.

[Purpose] This study aimed to examine the effect of osteoporosis complications on the physical function, frailty in patients with type 2 diabetes mellitus. [Participants and Methods] The participants were 27 female type 2 diabetes mellitus patients aged ≥65 years. Of these, 14 patients had osteoporosis. In order to evaluate the physical function, we measured the lower limb muscle strength, handgrip, gait speed, etc. We performed statistical comparison of both the groups and examined the applicable number of items on the Linda Fried Frailty scale and the correlation by evaluating the physical function. [Results] The lower limb muscle strength of patients with osteoporosis and type 2 diabetes mellitus was significantly lower than that of type 2 diabetes mellitus patients without osteoporosis. Factors of the osteoporosis group that inversely correlated to the Linda Fried Frailty scale included lower limb muscle strength, handgrip, and gait speed. [Conclusion] We found that osteoporosis reduced lower limb muscle strength in type 2 diabetes mellitus patients and was correlated with frailty.

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.

Metabolic Syndrome Over 4 Years Before the Onset of Cardiovascular Disease　- Nested Case-Control Study.

BACKGROUND: We investigated the risk of cardiovascular disease (CVD) with duration of metabolic syndrome (MetS) for the past 4 years before the CVD event.Methods and Results:We performed a nested case-control study within the Japan Epidemiology Collaboration on Occupational Health Study. A total of 139 registered cases of CVD and 561 self-reported cases of CVD were identified and matched individually on age, sex, and worksite with 695 and 2,803 controls, respectively. MetS was defined by the Joint Interim Statement definition. The odds ratio (95% confidence interval) for registered CVD was 4.7 (2.9, 7.5) for people with persistent MetS (positive for MetS for ≥3 assessments) and 1.9 (1.1, 3.3) for those with intermittent MetS (positive for MetS for 1-2 assessments), compared with people without MetS during the past 4 years before the event/index date (P for trend <0.001). The corresponding odds ratio for self-reported CVD was 2.7 (2.2, 3.5) and 1.8 (1.4, 2.3) (P for trend <0.001). The association with MetS duration was stronger for myocardial infarction than for other CVD subtypes. Similar results were obtained when using the Japanese MetS criteria. CONCLUSIONS: The risk of CVD increases with increasing MetS duration. These findings contribute to risk stratification and encourage lifestyle modification for people with MetS to minimize their health risk.

Sleep Duration Modifies the Association of Overtime Work With Risk of Developing Type 2 Diabetes: Japan Epidemiology Collaboration on Occupational Health Study.

BACKGROUND: Evidence linking working hours and the risk of type 2 diabetes mellitus (T2DM) is limited and inconsistent in Asian populations. No study has addressed the combined association of long working hours and sleep deprivation on T2DM risk. We investigated the association of baseline overtime work with T2DM risk and assessed whether sleep duration modified the effect among Japanese. METHODS: Participants were Japanese employees (28,489 men and 4,561 women) aged 30-64 years who reported overtime hours and had no history of diabetes at baseline (mostly in 2008). They were followed up until March 2014. New-onset T2DM was identified using subsequent checkup data, including measurement of fasting/random plasma glucose, glycated hemoglobin, and self-report of medical treatment. Hazard ratios (HRs) of T2DM were estimated using Cox regression analysis. The combined association of sleep duration and working hours was examined in a subgroup of workers (n = 27,590). RESULTS: During a mean follow-up period of 4.5 years, 1,975 adults developed T2DM. Overtime work was not materially associated with T2DM risk. In subgroup analysis, however, long working hours combined with insufficient sleep were associated with a significantly higher risk of T2DM (HR 1.42; 95% CI, 1.11-1.83), whereas long working hours with sufficient sleep were not (HR 0.99; 95% CI, 0.88-1.11) compared with the reference (<45 hours of overtime with sufficient sleep). CONCLUSIONS: Sleep duration modified the association of overtime work with the risk of developing T2DM. Further investigations to elucidate the long-term effect of long working hours on glucose metabolism are warranted.