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Aims: We aimed to assess the cross-sectional association of heated tobacco product (HTP) use with prediabetes and diabetes. Methods: The present analysis included 8950 workers from 5 companies (Study I) and 31,341 workers from another large company (Study II), who participated in the Japan Epidemiology Collaboration on Occupational Health Study. The participants were divided into five groups: never smokers, past smokers, exclusive HTP users, dual users of cigarettes and HTPs, and exclusive cigarette smokers. Diabetes and prediabetes were defined according to the fasting blood glucose and HbA1c levels and self-reported diabetes treatment, using the American Diabetes Association criteria. We analyzed the data of Study I and II separately, and then pooled these estimates using the fixed-effect models, with adjustment for a wide range of covariates. Results: In this study that included 40,291 participants (mean age, 46.6 years; men, 84.3%), about half of the current tobacco-related product users reported using HTPs. Exclusive HTP users had higher odds of prediabetes (pooled odds ratio 1.36; 95% CI 1.25–1.47) and diabetes (1.68; 95% CI 1.45–1.94) than never smokers. Similarly, dual users also had increased odds of prediabetes (pooled odds ratio, 1.26; 95% CI 1.13–1.39) and diabetes (1.93; 95% CI 1.63–2.29). The strength of these associations was comparable to that of cigarette smokers. We observed significantly higher HbA1c and fasting blood glucose levels among both exclusive HTP users and dual users compared to never smokers. Conclusion: HTP use was associated with an increased likelihood of prediabetes and diabetes. Prospective studies are warranted to confirm the cross-sectional association. [ABSTRACT FROM AUTHOR]

Secreted protein acidic and rich in cysteine (SPARC), an exercise-induced myokine, has been suggested as a potential endogenous factor that suppresses colon tumorigenesis. However, the effects of different exercise protocols on circulating SPARC levels are unclear. The main purpose of this study was to examine the effects of both exercise intensity and duration on circulating SPARC levels. This study also examined the relationship between responsiveness of SPARC levels and physical characteristics, including body composition and skeletal muscle function. Nineteen healthy adult men participated in four experimental interventions: two 30-min exercises at workloads corresponding to 60% (W60) and 40% (W40) peak oxygen uptake (VO2peak), a 45-min session of W40, and a 30-min session of complete rest. Blood SPARC and lactate concentrations were measured before and after each session. Only W60 significantly increased serum SPARC levels (p < 0.05), and a significant correlation was found between changes in SPARC levels and lactate concentrations (r = 0.411, p < 0.05). The relative changes in SPARC levels during W60 demonstrated significant positive correlations with skeletal muscle mass and knee extensor muscle strength (both p < 0.05). The increase in serum SPARC levels might be mediated by lactate accumulation and might not, hence, be induced during exercise at the intensity of the first ventilatory threshold levels even though the duration is prolonged. Our results provide fundamental insight into exercise prescription of both exercise intensity and duration for SPARC response, leading to a better understanding of the preventive effects of exercise on colon cancer. This study found that the increase in serum secreted protein acidic and rich in cysteine (SPARC) levels might be mediated by lactate accumulation and might, hence, be influenced by exercise intensity rather than exercise duration. An association was found between SPARC response to exercise and skeletal muscle mass. Our results provide a better understanding of the preventive effects of exercise on colon cancer. [ABSTRACT FROM AUTHOR]

Purpose: Brain-derived neurotrophic factor (BDNF) is a known essential mediator responsible for the beneficial effects of physical activity on brain health. Exercise-induced lactate is a potential endogenous factor that may increase BDNF expression, and the selection of cadence in exercise prescription is thought to influence lactate concentrations. The aim of this study was to examine the effect of pedaling cadence on circulating BDNF levels through lactate production in healthy adult men. Methods: Seventeen healthy adult men participated in three experimental sessions: a 40-min session of cycle-ergometry exercise with a pedaling cadence of 60 rpm at a workload of 40% peak oxygen uptake (Ex.60), a 40-min cycling exercise with a pedaling cadence of 100 rpm at the same workload as the Ex.60 (Ex.100), and a session of complete rest for 40 min (CON). Serum BDNF levels were measured before and after each session, and heart rate (HR) and lactate concentrations were evaluated after each session. Results: Ex.100 significantly increased serum BDNF and lactate levels (p < 0.05, respectively), while CON and Ex.60 induced no significant increases in these variables (all p > 0.05). The relative change in BDNF levels had a significant strong correlation with relative change in lactate (p < 0.05) but not with change in HR (p > 0.05). Conclusion: High-cadence aerobic exercise can increase peripheral BDNF levels through an increase in lactate concentrations, whereas the workload is low to moderate. This study indicates that exercise regimen considering pedaling cadence may have the possibility of inducing better brain health. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: Brain-derived neurotrophic factor (BDNF) is well known for its potential to promote brain plasticity. It has been proposed that combining cognitive and physical exercise (CCPE) may have the potential to generate more synergistic benefits in cognitive function than either cognitive exercise (CE) or physical exercise (PE) alone. The purpose of this study was to examine acute responses of peripheral BDNF levels and cognitive performance to CE, PE, and CCPE. Methods: Thirteen healthy adult men participated in four experimental sessions; a 30-min CE, a 30-min cycling PE at an intensity of 60% peak oxygen uptake, a 30-min CCPE at the same intensity as PE, and a 30-min session of complete rest. Plasma BDNF levels and cognitive performance were measured before and after each session. Results: Both PE and CCPE significantly increased plasma BDNF levels (p < .05). CE led to no significant increase (p ≥ .05), and there was no significant difference in peripheral BDNF levels between PE and CCPE (p ≥ .05). No session induced a significant change in cognitive performance (p ≥ .05). Conclusions: Our study suggests that CE and PE have different responses of peripheral BDNF levels and that CCPE had no additional or synergistic effect on peripheral BDNF levels compared with PE alone. This study offers further insights into the potential mechanisms underlying the respective roles of CE, PE, and CCPE for peripheral BDNF levels and cognitive performance. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to examine the effect of prolonged neuromuscular electrical stimulation (NMES) on the metabolic profile and cognition-related blood parameters in patients with type 2 diabetes mellitus (T2DM).Methods: Fourteen patients with T2DM (63.2 ± 3.0 years, 76.1 ± 3.5 kg) participated in a randomized controlled cross-over study, in which 8-week-long NMES interventions were performed on both legs. The NMES training protocol consisted of 40-min sessions, 5 days per week, for 8 weeks. The relative changes in glucose and lipid profiles, and cognition-related blood parameters were evaluated.Results: NMES training induced significant changes in the fasting glucose concentration (p < 0.05) and percent body fat (p < 0.05), although there were no significant changes in HbA1c and blood lipid levels (p ≥ 0.05). The change in plasma brain-derived neurotrophic factor (BDNF) levels was significantly higher in the NMES period than in the control period (p < 0.05).Conclusions: This study showed that an 8-week NMES training program could induce greater changes in the blood glucose concentration, percent body fat, and plasma BDNF levels than the control intervention in patients with T2DM. NMES training might prove to be an alternative exercise method for patients who might have difficulties in performing adequate voluntary exercise. [ABSTRACT FROM AUTHOR]

The aim of this study is examining the effects of multiple sets of high-velocity resistance exercise (HVRE) on cardiovascular responses. Fifteen healthy adult men participated in two experimental sessions: one comprised three sets of resistance exercise performed against high-intensity resistance exercise (HIRE) at low velocity and the other three sets of HVRE performed against reduced load at high velocity. Blood pressure (BP), heart rate (HR), stroke volume (SV) and cardiac output (CO) during both sessions were evaluated using impedance electrocardiography. The increases in BP, HR and CO were significantly lowered during HVRE compared with HIRE (p< 0.05). In contrast, there was no significant difference in SV between sessions (p> 0.05). This study suggested that the increases in BP and CO during HVRE were lower than those during HIRE although HVRE required performing fast movement. HVRE might be applied to patients for whom HIRE is contraindicated because of cardiovascular diseases. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the effect of low-intensity exercise training using belt electrode skeletal muscle electrical stimulation on muscle strength and cardiorespiratory fitness in healthy subjects. Nineteen healthy subjects were allocated into control or intervention groups; in both groups the participants kept regular physical activity while the intervention group underwent 30 min B-SES training at 3–4 METs for four weeks. Knee extensor muscle strength and cardiorespiratory endurance during incremental exercise test were measured at baseline and after four weeks for all participants. The relative change of knee extensor muscle strength in the intervention group was significantly higher than control group (p < .05). Also, oxygen uptake at ventilator threshold and peak oxygen uptake during incremental exercise test significantly increased in the intervention group when compared with control group (p < .05). This study showed that prolonged low-intensity B-SES training resulted in significant increases in muscle strength and cardiorespiratory fitness in healthy subjects. Our present work suggested that B-SES training could assist patients who might have difficulty performing adequate voluntary exercise because of excessive obesity, orthopaedic problems and chronic diseases such as cardiovascular disease and type 2 diabetes. An intervention study conducted for such patients is strongly recommended. [ABSTRACT FROM PUBLISHER]

Objective: The aim of this study was to examine whether or not there is a gender difference in metabolic responses to surface electrical muscle stimulation (sEMS) in type 2 diabetes (T2DM). Methods: Ten men and eight women with T2DM participated in two sessions; in both sessions the subjects were investigated after a breakfast and that in one occasion they underwent 30-min sEMS while in the other they were followed while resting. Blood and gas exchange data were compared between genders as to the extent of blood glucose and non-esterified fatty acids responses to sEMS. Results: The time course change of blood glucose concentration after sEMS did not statistically differ between genders while sEMS could attenuate postprandial blood glucose level regardless of gender ( p < 0.05). Women had a lower respiratory quotient and lactate concentration during sEMS when compared with men ( p < 0.05). Conclusions: This study indicated that sEMS might have resulted in lower anaerobic glycolysis in women as compared to men with T2DM. sEMS is expected to be a new exercise method in T2DM. Determining the possible gender differences and precise mechanisms might further shed some light for the efficacy of sEMS use for clinical practice. [ABSTRACT FROM AUTHOR]

Abstract: Aim: The purpose of the present study is to investigate spatial surface electromyography (SEMG) potential distribution pattern in type 2 diabetes mellitus (T2DM) patients. Methods: Nine T2DM patients and nine age-matched healthy men (CON) performed a sustained isometric knee extension at 10% of maximal voluntary contraction for 120s. Multi-channel SEMG was recorded from the vastus lateralis muscle by means of 64 electrodes. To characterize spatial SEMG potential distribution pattern, modified entropy and correlation coefficients between same electrode locations were calculated at 15, 60 and 120s for the root mean square values. Results: At 60 and 120s, modified entropy in T2DM was significantly lower than those in CON (p <0.05). Correlation coefficients for T2DM were significantly higher than those for CON at 60 and 120s (p <0.05). Conclusion: From these results, we suggested that T2DM patients continue to recruit limited and same motor units during the sustained contraction at low force level. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

Abstract: Aims: The aim of this study was to examine whether percutaneous electrical muscle stimulation (EMS) attenuates postprandial hyperglycemia in type 2 diabetes. Methods: Eleven patients with type 2 diabetes participated in two experimental sessions; one was a 30-min EMS 30min after a breakfast (EMS trial) and the other was a complete rest after a breakfast (Control trial). In each trial, blood was sampled before and at 30, 60, 90, and 120min after the meal. Results: Postprandial glucose level was significantly attenuated in EMS trial at 60, 90, and 120min after a meal (p <0.05). The C-peptide concentration was also significantly lowered in EMS trial (p <0.01). On the other hand, there was no significant increase in creatine phosphokinase (CPK) concentration in each trial. Conclusions: The present results provide first evidence indicating that EMS is a new exercise method for treating postprandial hyperglycemia in individuals with type 2 diabetes, especially who cannot perform adequate voluntary exercise because of excessive obesity, orthopedic diseases, or severe diabetic complications. [Copyright &y& Elsevier]

Abstract: β2-glycoprotein I (β2GPI) is a five-domain protein associated with the antiphospholipid syndrome (APS), however, its normal biological function is yet to be defined. β2GPI is N-glycosylated at several asparagine residues and the glycan moiety conjugated to residue 143 has been proposed to interact with the Gly40–Arg43 motif of β2GPI. The Gly40–Arg43 motif has also been proposed to serve as the epitope for the anti-β2GPI autoantibody associated with APS. We hypothesized that the structure or composition of the glycan at Asn-143 might be associated with the APS symptom by shielding or exposing the Gly40–Arg43 motif towards the anti-β2GPI autoantibody. To test this hypothesis we used mass spectrometry (MS) for comparative glycopeptide profiling of human β2GPI obtained from blood serum from four healthy test subjects and six APS patients. It revealed significant differences in the extent of sialylation and branching of glycans at Asn-143. Biantennary glycans were more abundant than triantennary glycans at Asn-143 in both healthy subjects and patients. In APS patient samples we observed a decrease in sialylated triantennary glycans and an increase in sialylated biantennary glycan structures, as compared to controls. These data indicate that some APS patients have β2GPI molecules with a reduced number of negatively charged sialic acid units in the glycan structure at Asn-143. This alteration of the electrostatic properties of the glycan moiety may attenuate the intramolecular interactions with the positively charged Gly40–Arg43 motif of β2GPI and, in turn, leads to conformational instability and exposure of the disease-related linear epitope Gly40–Arg43 to the circulating autoantibody. Thus, our study suggests a link between site-specific glycan profiles of β2GPI and the pathology of antiphospholipid syndrome. [Copyright &y& Elsevier]

The authors undertook this study to determine changes in the daily concentration of cadmium, copper, and zinc in Japanese workers' urine over a 13-year period from 1985 to 1998. The workers were aged between 20 and 59 years. The authors studied 277 subjects in 1985, 320 in 1993, and 292 in 1998, for a total of 889 (464 men and 425 women). Although, in both men and women, urinary excretions of cadmium and copper were lower in 1993 and 1998 than in 1985, they were not substantially lower in 1998 than in 1993. The authors observed no marked changes between 1985, 1993, and 1998 regarding the excretion of zinc in any of the age groups in either men or women. Furthermore, the excretion of urinary cadmium in 1998 still exceeded the tolerable limit levels in the general population of the investigated region in Japan. This fact suggests the necessity of further nationwide investigation and comprehensive measures to reduce cadmium exposure in Japanese society. [ABSTRACT FROM AUTHOR]

Objective: To investigate the impact of dysphagia on long‐term survival and swallowing function outcomes in patients with idiopathic inflammatory myopathy other than inclusion body myositis. Methods: We retrospectively evaluated consecutive patients with idiopathic inflammatory myopathy other than inclusion body myositis to investigate the impact of dysphagia and its severity assessed using the Food Intake LEVEL Scale on survival and swallowing function outcomes. Time‐to‐event analyses were used, including Kaplan‐Meier curves with log‐rank (trend) test, cumulative incidence with Gray's test, and Cox proportional hazards models. Results: Of the 254 patients, 26 were dysphagic, including eight severe (Food Intake LEVEL Scale [FILS] score 2, 3) and six most severe (FILS score 1) cases; 210 were non‐dysphagic, and 18 were indeterminate cases. During the 5 years after myositis diagnosis, 15 (57.7%) dysphagic and 31 (14.8%) non‐dysphagic patients died, and dysphagic patients had significantly shorter survival. However, multivariate analysis showed that shorter survival was significantly associated with baseline age‐adjusted Charlson Comorbidity Index (hazard ratio [HR] 1.57, 95% confidence interval [CI] 1.36‐1.82]), but not with dysphagia (HR 1.46, 95% CI 0.69‐3.10). Dysphagia severity was significantly associated with delayed recovery of dysphagia. In 20 non‐severe or severe dysphagic cases, 19 restored swallowing function within 1 year. The most severe cases had a significantly higher cumulative probability of death before recovery from dysphagia than severe cases. Conclusion: The poor survival of dysphagic myositis patients was largely confounded by advanced age and comorbid malignancies. However, patients with the most severe dysphagia had a significantly worse swallowing function and survival prognosis than those with milder dysphagia. [ABSTRACT FROM AUTHOR]

Trimethoprim-sulfamethoxazole (TMP-SMX) is an effective treatment for Pneumocystis jirovecii pneumonia (PCP) in immunocompromised patients with and without HIV infection; however, a high incidence of adverse events has been observed. Low-dose TMP-SMX is a potentially effective treatment with fewer adverse events; however, evidence is limited. What is the efficacy and safety of low-dose TMP-SMX for non-HIV PCP compared with conventional-dose TMP-SMX after adjusting for patient background characteristics? In this multicenter retrospective cohort study, we included patients diagnosed with non-HIV PCP and treated with TMP-SMX between June 2006 and March 2021 at three institutions. The patients were classified into low-dose (TMP < 12.5 mg/kg/d) and conventional-dose (TMP 12.5-20 mg/kg/d) groups. The primary end point was 30-day mortality, and the secondary end points were 180-day mortality, adverse events grade 3 or higher per the Common Terminology Criteria for Adverse Events v5.0, and initial treatment completion rates. Background characteristics were adjusted using the overlap weighting method with propensity scores. Fifty-five patients in the low-dose group and 81 in the conventional-dose group were evaluated. In the overall cohort, the average age was 70.7 years, and the proportion of women was 55.1%. The average dose of TMP-SMX was 8.71 mg/kg/d in the low-dose group and 17.78 mg/kg/d in the conventional-dose group. There was no significant difference in 30-day mortality (6.7% vs 18.4%, respectively; P =.080) or 180-day mortality (14.6% vs 26.1%, respectively; P =.141) after adjusting for patient background characteristics. The incidence of adverse events, especially nausea and hyponatremia, was significantly lower in the low-dose group (29.8% vs 59.0%, respectively; P =.005). The initial treatment completion rates were 43.3% and 29.6% in the low-dose and conventional-dose groups (P =.158), respectively. Survival was similar between the low-dose and conventional-dose TMP-SMX groups, and low-dose TMP-SMX was associated with reduced adverse events in patients with non-HIV PCP. [Display omitted] [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: To evaluate patient–physician communication and patients' understanding of treatment goals in rheumatoid arthritis (RA). Methods: A cross-sectional online survey of patients with RA and physicians treating RA was conducted between 16 and 30 June 2021. Participants were asked to rate the importance of 17 goals on a 6-point Likert scale, and mean scores were compared between patients and physicians by the Wilcoxon rank sum test. Patients' satisfaction with physician communication and their understanding of treatment goals were also assessed. Results: The responses of 502 patients and 216 physicians were analyzed. The most common patient age group was 50–59 years (28.5%), and the mean disease duration was 10.3 years. Physicians had a mean of 19.2 years of treatment experience and were treating a mean of 44.3 patients. Among the 17 goals assessed, patients placed significantly more importance on drug tapering or discontinuation as short-term goals (3–6 months) and on performing basic activities of daily living, being able to engage in daily tasks, achieving and maintaining remission, maintaining better laboratory values, and drug tapering or discontinuation as long-term goals (5–10 years; all adjusted p < 0.05). Patient treatment satisfaction was significantly associated with disease activity, a feeling of treatment effectiveness, satisfaction with physician communication, and agreement with physician goals. Conclusion: Differences exist among patients with RA and physicians treating RA regarding the importance of short- and long-term treatment goals. Good patient–physician communication appears to be important for improving patient satisfaction. Trial registration: University Hospital Medical Information Network identifier: UMIN000044463. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

We aimed to assess the association between heated tobacco product (HTP) use and high-density lipoprotein cholesterol (HDL-C) concentration. Our study included 12,268 workers from five companies (Study I) and 36,503 workers from another large company (Study II). Participants were categorized into five groups: never smokers, past smokers, exclusive HTP users, dual users of cigarettes and HTPs, and exclusive cigarette smokers. We analyzed the data of Studies I and II separately and then pooled these estimates using a fixed-effect model. Of the 48,771 participants, 9.3% were exclusive HTP users, and 6.0% were dual users. Exclusive HTP users had modestly but significantly lower concentrations of HDL-C than never smokers, with the pooled mean difference being − 1.1 (95% CI − 1.5 to − 0.6) mg/dL. Dual users showed a further reduction (mean difference − 3.7 (− 4.2 to − 3.2) mg/dL), which was comparable to that of exclusive cigarette smokers versus never smokers (mean difference − 4.3 (− 4.7 to − 3.9) mg/dL). The pooled odds ratios (95% CIs) of having low HDL-C (< 40 mg/dL for men and 50 mg/dL for women) were 1, 0.99 (0.90–1.11), 1.25 (1.09–1.43), 2.02 (1.76–2.32), and 2.09 (1.88–2.32) for never smokers, past smokers, exclusive HTP users, dual users, and exclusive cigarette smokers, respectively. In conclusion, exclusive HTP users had lower HDL-C concentrations than never smokers, although higher than exclusive cigarette smokers. Moreover, dual users had HDL-C concentrations similar to those in exclusive cigarette smokers. [ABSTRACT FROM AUTHOR]

The coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 has led to rapid progress in vaccine development to prevent the spread of the disease. Although COVID-19 vaccines have excellent effectiveness in reducing morbidity and disease severity with minor adverse reactions, some patients develop late hypersensitivity events as autoimmune reactions such as rheumatoid arthritis, lupus nephritis, and vasculitis following COVID-19 vaccination. Herein, we describe a case of pneumonitis following COVID-19 mRNA vaccination in a patient with rheumatoid arthritis, which resolved spontaneously. [ABSTRACT FROM AUTHOR]

Aims: Data are limited regarding how shift work is linked to the development of type 2 diabetes, especially among workers at high risk of diabetes. We examined the risk of diabetes according to shift-work conditions over several years among Japanese adults. Methods: This prospective study enrolled 17,515 workers (age 40–78 years). Shift work was self-reported at annual health examinations over time from 2004 to 2017 and categorized as shift workers or non-shift workers. Diabetes was defined as fasting plasma glucose, random glucose, HbA1c, and self-reported use of antidiabetic medications. The association of shift work and diabetes was quantified using Cox regression. Results: During a follow-up of 8.1 years in median, 2071 incident cases of diabetes were documented. Compared with non-shift work, shift work showed a significantly elevated hazard ratios of developing diabetes. Shift work showed a 19% (95% confidence intervals: 3–37%) higher hazard ratios for diabetes, after adjustment for demographic-, cardiometabolic-, and work-related factors. Further adjustment for lifestyle factors and body mass index did not materially change this association (a 16% increase; 95% confidence intervals, 1–34%). This relationship was replicated among workers with prediabetes. Conclusions: Engaging in shift work may increase the risk of developing diabetes independently of lifestyle factors and body mass index, even among prediabetic workers. [ABSTRACT FROM AUTHOR]

Objective: Coatomer subunit alpha (COPA) syndrome, also known as autoinflammatory interstitial lung, joint, and kidney disease, is caused by heterozygous mutations in COPA. We identified a novel COPA variant in 4 patients in one family. We undertook this study to elucidate whether and how the variant causes manifestations of COPA syndrome by studying these 4 patients and by analyzing results from a gene‐targeted mouse model. Methods: We performed whole‐exome sequencing in 7 family members and measured the type I interferon (IFN) signature of the peripheral blood cells. We analyzed the effects of COPA variants in in vitro experiments and in Copa mutant mice that were generated. Results: We identified a heterozygous variant of COPA (c.725T>G, p.Val242Gly) in the 4 affected members of the family. The IFN score was high in the members carrying the variant. In vitro analysis revealed that COPA V242G, as well as the previously reported disease‐causing variants, augmented stimulator of interferon genes (STING)–induced type I IFN promoter activities. CopaV242G/+ mice manifested interstitial lung disease and STING‐dependent elevation of IFN‐stimulated gene expression. In CopaV242G/+ dendritic cells, the STING pathway was not constitutively activated but was hyperactivated upon stimulation, leading to increased type I IFN production. Conclusion: V242G, a novel COPA variant, was found in 4 patients from one family. In gene‐targeted mice with the V242G variant, interstitial lung disease was recapitulated and augmented responses of the STING pathway, leading to an increase in type I IFN production, were demonstrated. [ABSTRACT FROM AUTHOR]

Recently, treatment for rheumatoid arthritis has dramatically improved but increases the risk of bacterial and opportunistic infections. Herein, we report a fatal case of concurrent disseminated tuberculosis, pneumocystis pneumonia, and septic shock due to pyelonephritis caused by extended-spectrum β-lactamase-producing Escherichia coli in a patient with rheumatoid arthritis who received methotrexate, glucocorticoid, and tocilizumab. Despite undergoing intensive treatment, the patient developed respiratory failure and died after 7 days of admission. An autopsy indicated that pulmonary tuberculosis were the ultimate causes of death, while pyelonephritis was controlled. [ABSTRACT FROM AUTHOR]

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 (HbA1c) 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 HbA1c, 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 HbA1c-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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aims/Introduction: We examined a prospective association between serum creatinine levels and diabetes. Materials and Methods: The present study included 31,343 male workers without diabetes, and aged between 20 and 64 years at baseline. We calculated the cumulative average of their serum creatinine over the study period. We defined diabetes as either glycated hemoglobin levels ≥6.5%, random glucose levels ≥200 mg/dL, fasting glucose levels ≥126 mg/dL or receiving antidiabetic treatment. Cox proportional hazards regression analysis was carried out to estimate the hazard ratio (HR) and 95% confidence interval (CI). Results: With a median observation of 7.7 years, 2,509 participants developed diabetes. After adjusting for age, smoking, body mass index, hypertension and dyslipidemia, lower cumulative average serum creatinine levels were related to a greater diabetes risk: HRs were 1.56 (95% CI 1.35–1.82), 1.22 (1.09–1.35) and 1.06 (0.96–1.17) for the participants with serum creatinine <0.70, 0.70–0.79 and 0.80–0.89 mg/dL, respectively, compared with those with 0.90–1.20 mg/dL (P for trend <0.001). The serum creatinine‐diabetes association was more pronounced among older adults (serum creatinine <0.70 vs 0.90–1.20 mg/dL, HR 1.66, 95% CI 1.37–2.00) than younger adults (HR 1.32, 95% CI 1.02–1.71; P for interaction by age group = 0.001). Conclusions: Low serum creatinine is associated with an increased risk of diabetes. Screening serum creatinine levels can be used to identify those who are at high risk of diabetes. [ABSTRACT FROM AUTHOR]

In situ x-ray diffraction measurements were carried out for investigating the liquid structure in the ultrasonic fountain jet to consider the mechanism of the “ultrasonic ethanol separation” reported by Sato et al. [J. Chem. Phys. 114, 2382 (2001)]. For pure liquids (water and ethanol), it was found that the high frequency ultrasound does not affect the liquid structure microscopically. For the 20 mol % ethanol-water mixture, the estimated ethanol mole fraction in the ultrasonic fountain jet by using the position of the main maximum in the x-ray diffraction profile coincided with that in the reservoir. This result suggests that the ethanol separation is not caused by any distorted liquid structure under the ultrasound irradiation and occurs when or after the generation of the liquid droplet mist. [ABSTRACT FROM AUTHOR]

Abstract 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. [ABSTRACT FROM AUTHOR]

Abstract Background and aims We aimed to examine the risk of cardiovascular disease (CVD) with persistent prediabetes during the last four years prior to a CVD event in a large occupational cohort in Japan. Methods We performed a nested case-control study using data from the Japan Epidemiology Collaboration on Occupational Health Study. A total of 197 registered cases of CVD were identified and matched individually with 985 controls according to age, sex, and worksite. Prediabetes was defined as fasting plasma glucose 100-125 mg/dL and/or HbA1c 5.7–6.4%. Persistent prediabetes was defined as having prediabetes at years one and four prior to the onset/index date; persistent normoglycemia was similarly defined. Associations between prediabetes and CVD risk were assessed using conditional logistic regression models. Results Compared with people with persistent normoglycemia over the four years prior to the onset/index date, the unadjusted odds ratio (95% confidence interval) for CVD was 2.88 (1.56, 5.32) for people with persistent prediabetes. After adjusting for BMI, smoking, hypertension, and dyslipidemia assessed four years before the onset/index date, the association was slightly attenuated to an OR (95% confidence interval) of 2.62 (1.31, 5.25). Prediabetes assessed at single time points was also associated with an elevated risk of CVD, with multivariable-adjusted odds ratio (95% confidence interval) of 1.72 (1.12, 2.64) and 2.13 (1.32, 3.43) for prediabetes at one and four years prior to the onset/index date, respectively. Conclusions Prediabetes is associated with an increased risk of CVD. Identification and management of prediabetes are important for the prevention of CVD. Highlights • Prediabetes assessed at single time points was associated with an elevated risk of CVD. • Much higher risk of CVD was observed among people with persistent prediabetes compared with persistent normoglycemia. • Prediabetes is associated with a higher risk of CVD. [ABSTRACT FROM AUTHOR]

Abstract: 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. [ABSTRACT FROM AUTHOR]

We prospectively examined diabetes risk in association with a summary measure of degree and duration of weight change. The study participants were 51,777 employees from multiple companies in Japan, who were aged 30-59years, free of diabetes at baseline, and followed up for 7years (2008-2015). Exposure was cumulative body mass index (BMI)-years, which was defined as the area of BMI units above or below baseline BMI during follow-up, and was treated as a time-dependent variable in the Cox proportional hazards regression models. During the 263,539 person-years of follow-up, 3465 participants developed diabetes. The adjusted hazard ratio (HR) of diabetes for a 1-unit increase in cumulative BMI-years was 1.11 (95% confidence interval (CI): 1.09, 1.12). The association was more pronounced among overweight (HR=1.11; 95% CI: 1.08, 1.14) and obese (HR=1.12; 95% CI: 1.08, 1.15) adults compared with normal- and under-weight (HR=1.07; 95% CI: 1.03, 1.11) adults (P for interaction of cumulative BMI-years X baseline BMI-group=0.002). The association of higher cumulative BMI-years with incident diabetes did not substantially differ by metabolic phenotype. The present results emphasize the importance of avoiding additional weight gain over an extended period of time for the prevention of type 2 diabetes, especially among overweight and obese adults, irrespective of metabolic health status. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: Risk models and scores have been developed to predict incidence of type 2 diabetes in Western populations, but their performance may differ when applied to non-Western populations. We developed and validated a risk score for predicting 3-year incidence of type 2 diabetes in a Japanese population. Methods: Participants were 37,416 men and women, aged 30 or older, who received periodic health checkup in 2008–2009 in eight companies. Diabetes was defined as fasting plasma glucose (FPG) ≥126 mg/dl, random plasma glucose ≥200 mg/dl, glycated hemoglobin (HbA1c) ≥6.5%, or receiving medical treatment for diabetes. Risk scores on non-invasive and invasive models including FPG and HbA1c were developed using logistic regression in a derivation cohort and validated in the remaining cohort. Results: The area under the curve (AUC) for the non-invasive model including age, sex, body mass index, waist circumference, hypertension, and smoking status was 0.717 (95% CI, 0.703–0.731). In the invasive model in which both FPG and HbA1c were added to the non-invasive model, AUC was increased to 0.893 (95% CI, 0.883–0.902). When the risk scores were applied to the validation cohort, AUCs (95% CI) for the non-invasive and invasive model were 0.734 (0.715–0.753) and 0.882 (0.868–0.895), respectively. Participants with a non-invasive score of ≥15 and invasive score of ≥19 were projected to have >20% and >50% risk, respectively, of developing type 2 diabetes within 3 years. Conclusions: The simple risk score of the non-invasive model might be useful for predicting incident type 2 diabetes, and its predictive performance may be markedly improved by incorporating FPG and HbA1c. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aims: To examine the association of smoking status, smoking intensity, and smoking cessation with the risk of type 2 diabetes (T2D) using a large database. Methods: The present study included 53,930 Japanese employees, aged 15 to 83 years, who received health check-up and did not have diabetes at baseline. Diabetes was defined as fasting plasma glucose ≥126 mg/dl, random plasma glucose ≥200 mg/dl, HbA1c ≥6.5% (≥48 mmol/mol), or receiving medication for diabetes. Cox proportional-hazards regression models were used to investigate the association between smoking and the risk of diabetes. Results: During 3.9 years of median follow-up, 2,441 (4.5%) individuals developed T2D. The multivariable-adjusted hazard ratios (95% CI) for diabetes were 1 (reference), 1.16 (1.04 to 1.30) and 1.34 (1.22 to 1.48) for never smokers, former smokers, and current smokers, respectively. Diabetes risk increased with increasing numbers of cigarette consumption among current smokers (P for trend <0.001). Although the relative risk of diabetes was greater among subjects with lower BMIs (< 23 kg/m2), attributable risk was greater in subjects with higher BMIs (≥ 23 kg/m2). Compared with individuals who had never smoked, former smokers who quit less than 5 years, 5 to 9 years, and 10 years or more exhibited hazards ratios for diabetes of 1.36 (1.14 to 1.62), 1.23 (1.01 to 1.51), and 1.02 (0.85 to 1.23), respectively. Conclusions: Results suggest that cigarette smoking is associated with an increased risk of T2D, which may decrease to the level of a never smoker after 10 years of smoking cessation. [ABSTRACT FROM AUTHOR]

Long working hours have been associated with an increased risk of cardiovascular disease, but its relationship with hypertension remains unclear. The objective of this study is to examine the relationship between overtime and presence of hypertension using data from a large-scale multi-company study in Japan. Participants were 52 365 workers of four companies that provided both health-checkup data and self-reported data on overtime worked. Hypertension was defined as systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg, and/or the use of antihypertensive drug. Logistic regression analysis was performed to determine the odds ratio for hypertension for each category of overtime work (<45, 45-79, 80-99 or ≥100 h/month) with adjustments for age, sex, company, smoking status and body mass index. The prevalence of hypertension tended to decrease with increasing overtime work: 17.5, 12.0, 11.1 and 9.1% for the shortest (<45 h/month) through the longest overtime category (≥100 h/month). The age-, sex- and company-adjusted odds ratios (95% confidence interval) were 1.00 (reference), 0.81 (0.75-0.86), 0.73 (0.62-0.86), 0.58 (0.44-0.76), respectively ( p for linear trend <0.001). In a sub-cohort, the inverse association remained statistically significant after an additional adjustment for other potential confounders. Results of the present large-scale study among Japanese workers suggest an inverse association between overtime work and presence of hypertension. [ABSTRACT FROM AUTHOR]

Aims Few studies have examined the prevalence of diabetes using glycated hemoglobin (HbA1c), a newly recommended diagnostic test. We examined the prevalence of diabetes and pre-diabetes using both HbA1c and fasting plasma glucose (FPG) and their associations with risk factors for type 2 diabetes in a large-scale Japanese working population. Methods Participants were 47,172 men and 8280 women aged 20–69 years who received periodic health checkup in nine companies which participated in the Japan Epidemiology Collaboration on Occupational Health study. Participants were categorized into diabetes (HbA1c ≥6.5% (≥48 mmol/mol), FPG ≥126 mg/dl (≥7.0 mmol/L), or medication for diabetes), pre-diabetes (HbA1c 6.0–6.4% (42–46 mmol/mol) or FPG 110–125 mg/dl (6.1–6.9 mmol/L) among those without diabetes), and normal glucose regulation. Results The prevalence of diabetes was 8.0% and 3.3% in men and women, respectively. Of individuals with diabetes, approximately 80% were defined by HbA1c ≥6.5% (≥48 mmol/mol) criterion. The prevalence of pre-diabetes was 14.1% in men and 9.2% in women. Prevalence of these glucose abnormalities increased with advancing age, especially during mid-40s and 50s. Higher body mass index and waist circumference, hypertension, dyslipidemia, and current smoking were each associated with higher prevalence of diabetes in both men and women. Conclusions Using HbA1c and FPG criteria or current medication, one in 13 men and one in 30 women had diabetes in the present Japanese working population. Interventions targeted for those in an early stage of impaired glucose metabolism would be required to prevent diabetes. [ABSTRACT FROM AUTHOR]

Objective: Epidemiologic evidence on long working hour and diabetes has been conflicting. We examined the association between overtime work and prevalence of diabetes among Japanese workers. Methods: The subjects were 40,861 employees (35,170 men and 5,691 women), aged 16 to 83 years, of 4 companies in Japan. Hours of overtime were assessed using self-reported questionnaires. Diabetes was defined as a fasting plasma glucose ≥126 mg/dl (7.0 mmol/l), hemoglobin A1c ≥6.5% (48 mmol/mol), or current use of anti-diabetic drug. Multiple logistic regression analysis was used to calculate odds ratio of diabetes for each category of overtime. Results: After adjustment for age, sex, company, smoking, and BMI, there was a suggestion of U-shaped relationship between overtime work and prevalence of diabetes (P for quadratic trend = 0.07). Compared with those who worked <45 hours of overtime per month, the adjusted odds ratios (95% confidence interval) of diabetes were 0.86 (0.77–0.94), 0.69 (0.53–0.89), and 1.03 (0.72–1.46) for those who worked 45–79, 80–99, and ≥100 hours of overtime per month, respectively. In one company (n = 33,807), where other potential confounders including shift work, job position, type of department, alcohol consumption, sleep duration, leisure time physical activity, and family history of diabetes was additionally adjusted for, similar result was obtained (P for quadratic trend = 0.05). Conclusions: Long hours of overtime work may not be associated with increased prevalence of diabetes among Japanese workers. [ABSTRACT FROM AUTHOR]

ABSTRACT Introduction: We investigated the motor unit (MU) firing pattern in type 2 diabetes mellitus (T2DM) patients by means of multichannel surface electromyography (SEMG). Methods: Eight T2DM patients and 8 age-matched, healthy men performed a ramp-up contraction to 20% of maximal voluntary contraction (MVC). They also performed a sustained contraction at 10% of MVC during isometric knee extension. Multichannel SEMG signals recorded from the vastus lateralis muscle were decomposed with the convolution kernel compensation technique to extract individual MU firing patterns. Results: During the ramp contraction, the extent of MU firing modulation was significantly attenuated in T2DM. Variability of MU firing rate was significantly higher in T2DM at later periods during the sustained contraction. Conclusions: Our findings suggest that T2DM patients manifest characteristic MU activity patterns due possibly to some degree of neuromuscular impairment affecting the integrity of MU firing modulation. Muscle Nerve 48:806-813, 2013 [ABSTRACT FROM AUTHOR]

. Purpose: To identify symptoms potentially related to glaucomatous visual field abnormalities (VFAs) in a population-based setting, and to assess the applicability of using these symptoms to identify persons at risk of developing glaucoma. Methods: In this study, 10 214 Japanese male general workers (mean age, 45.3 ± 8.8 years) filled out a self-administered questionnaire and underwent frequency doubling technology (FDT) perimetry testing. The questionnaire inquired about whether the participant was suffering from any of nine symptoms, with scores for each response graded on a four-item Likert scale: 0 (none), 1 (rarely), 2 (sometimes), and 3 (always). Results from the questionnaire were compared among three groups: participants without any VFAs (9767), participants with VFAs as determined by the FDT test (FDT-VFA; 447), and 227 participants (of the 447 FDT-VFA participants) with glaucomatous VFAs who were newly diagnosed by ophthalmologic examinations. Results: The mean summed scores for the total items were significantly (p < 0.01) higher in FDT- and glaucomatous VFA groups than in normal subjects. In particular, responses citing the symptoms 'feeling of something in the front of the eye' and 'feeling of hardness to see in dark places' were significantly (p < 0.05) more frequent in subjects with FDT- and glaucomatous VFAs than among normal participants. However, the respective areas under the receiver operating characteristic curve of summed scores for the nine total items and for the two items which showed significant differences for the glaucoma groups were 0.57 (95% confidence interval = 0.53-0.60) and 0.58 (95% confidence interval = 0.54-0.61). Conclusion: Although the symptoms 'feeling of hardness to see in dark places' and 'feeling of something in the front of the eye' could be associated with glaucomatous VFA in a population-based setting, inquiring about symptoms is of little aid in identifying subjects with glaucomatous VFA as a strategy for public health. [ABSTRACT FROM AUTHOR]

Study objective: To study the association between computer use and visual field abnormalities (YFA) and to assess whether heavy computer users have an increased risk of glaucoma. Design: Cross sectional multicentre study. Subjects and observation procedures: A total of 10 202 randomly selected Japanese workers (mean (SD) age 43.2 (9.8) years) were screened for YFA using the frequency doubling technology perimetry (FDT- YFA), in addition to undergoing a general medical check up, and then ophthalmologically examined. Information about their computer use and refractive errors was obtained from a questionnaire and interview, respectively. Main results: As a result of FDT test, 522 and 8602 subjects were positive and negative for FDT-VFA, respectively. A significant (p =0.004) interaction was found between computer use and refractive errors regarding the risk of FDT-VFA. In stratified analysis, heavy computer users with refractive errors showed a significant positive association with FDT-VFA (odds ratio (OR) = 1.74, 95% confidence interval (CI) 1.28 to 2.37), while those without refractive errors did not. Comparison of 165 subjects with an ophthalmological diagnosis of glaucoma and 2918 controls showed that the OR for glaucoma of heavy computer users with refractive errors was 1.82 (95% Cl 1.06 to 3.12). Of 165 subjects with glaucoma, 141 had refractive errors, especially myopia (96.4%, 136 of 141). Conclusions: Although there are limitations to this study, such as its cross sectional design, heavy computer users with refractive errors seem to have an increased risk of FDT-YFA. Glaucoma might be involved in an underlying disease and myopia in a risk factor for FDT-VFA. [ABSTRACT FROM AUTHOR]

Purpose: To report the performance of glaucoma mass screening with only a visual field test utilizing frequency- doubling technology (FDT) perimetry in general populations.Design: Hospital and population-based cross-sectional study.Methods: This study took place in a multicenter setting. One hundred three consecutive glaucomatous patients and 14,814 persons were randomly selected. We had created a glaucoma screening protocol (GSP) using FDT perimetry (FDT-GSP). Frequency-doubling technology-glaucoma screening protocol was tested on consecutive glaucoma patients diagnosed with Humphrey visual field analyzer (30-2 SITA standard), and then FDT-GSP was applied to general populations. Frequency-doubling technology-glaucoma screening protocol positive subjects were ophthalmologically diagnosed. Detection ability of FDT-GSP was determined in consecutive patients, and the positive predictive value (PPV) of FDT-GSP to detect definitive glaucoma was estimated in general populations.Results: Frequency-doubling technique-glaucoma screening protocol detected 83.3% and 100% of definitive glaucoma patients with an early (mean deviation [MD] > -6 dB) and more advanced stage (MD < or = -6 dB), respectively. In the population-based screening, there were 660 (4.5%) subjects who had positive FDT-GSP, including 512 in whom no visual field abnormalities (VFA) had been pointed out previously. Of them, 370 subjects underwent ophthalmologic diagnosis. Then, 266 (71.9%, 266/370) subjects had a glaucomatous disk and 167 had definitive glaucomatous VFA. Fifty-five (14.9%) and 39 (10.5%) subjects were diagnosed as having other diseases and as normal, respectively. The PPV of FDT-GSP ranged from 32.6% (167/512)-45.1% (167/370).Conclusions: Frequency-doubling technology-based screening with only a visual field test showed reasonable performance on mass screening for detection of definitive glaucoma in this study population, considering the glaucoma prevalence. [ABSTRACT FROM AUTHOR]