Treatment preferences among Japanese patients and physicians for epidermal growth factor receptor-mutant non-small cell lung cancer.

INTRODUCTION: Evidence is limited on preferences of Japanese patients and physicians in treatment for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). Several oral or intravenous novel agents for EGFR exon 20 insertions are under development. The aim of our study was to investigate which attributes of novel treatments influenced selection of oral or intravenous agents among treated patients and treating physicians in Japan. METHODS: The study was designed by board-certified oncologists, patient representatives, and analytics specialists. Eligible participants completed an online survey with a discrete choice experiment presenting two treatment profiles described by attributes: mode of administration (oral or intravenous); frequency of administration; overall response rate (ORR); average progression-free survival (PFS); chance of experiencing severe side effects (SEs); mild-moderate gastrointestinal SEs; mild-moderate skin-related SEs; and patient out-of-pocket costs. RESULTS: Fifty-four patients (all self-reported EGFR-mutant) and 74 physicians participated from December 2021 to August 2022. All attributes being equal, there was greater preference for oral administration. However, there was greater preference for intravenous over oral, when ORR and PFS improved by 10% and 1 month, and severe SEs reduced by 10%. Physicians exhibited greater preference for PFS compared to patients (p < 0.01). Ranked order of attribute importance was as follows: (1) PFS; (2) ORR; (3) severe SEs, expressed by patients and physicians alike. CONCLUSIONS: Our study revealed Japanese physician and patient preferences in treatment options for EGFR-mutant NSCLC. Compared to the strong preference for a more efficacious drug, the preference of oral versus intravenous revealed a smaller impact.

Corrigendum: What kind of intervention is effective for improving subjective well-being among workers? A systematic review and meta-analysis of randomized controlled trials.

[This corrects the article DOI: 10.3389/fpsyg.2020.528656.].

Work-related psychosocial factors and inflammatory markers: A systematic review and meta-analysis.

OBJECTIVE: We conducted a systematic review and meta-analysis to evaluate the prospective effect of adverse work-related psychosocial factors on increases in inflammatory markers. METHODS: A systematic literature search was conducted in PubMed, Embase, PsycINFO, PsycARTICLES, and the Japan Medical Abstracts Society database. Studies were eligible for inclusion if they examined associations between work-related psychosocial factors and inflammatory markers (interleukin-6, tumor necrosis factor-alpha, and C-reactive protein), used longitudinal or prospective cohort designs, were conducted among workers, were original articles written in English or Japanese, and were published up to 2017 for the first search, October 2020 for the second, and November 2022 for the third. A meta-analysis was conducted using a random-effects model to assess the pooled effect size for the associations. A meta-regression analysis was used to estimate the association between length of follow-up and effect size. The ROBINS-I tool was used to assess risk of bias. RESULTS: Of the 11,121 studies identified in the first search, 29,135 studies from the second, and 9448 studies from the third, eleven were eligible for this review and meta-analysis. The pooled coefficient between adverse work-related psychosocial factors and inflammatory markers was significant and positive (ß = 0.014, 95% confidence interval: 0.005-0.023). However, a clear association was only observed for interleukin-6, and all the studies included had serious risks of bias. Meta-regression showed the effect size decreased depending on the follow-up period. CONCLUSION: This study revealed a weak positive association between adverse work-related psychosocial factors and increases in inflammatory markers. TRIAL REGISTRATION: PROSPERO CRD42018081553 (https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=81553).

Celastrol suppresses humoral immune responses and autoimmunity by targeting the COMMD3/8 complex.

Celastrol, a bioactive molecule extracted from the Tripterygium wilfordii plant, has been shown to exhibit anti-inflammatory properties. However, its mechanism of action has not been fully elucidated. Here, we show that celastrol suppresses humoral immune responses and autoimmunity by disabling a protein complex consisting of copper metabolism MURR1 domain-containing (COMMD) 3 and COMMD8 (COMMD3/8 complex), a signaling adaptor for chemoattractant receptors. Having demonstrated the involvement of the COMMD3/8 complex in a mouse model of rheumatoid arthritis, we identified celastrol as a compound that covalently bound to and dissociated the COMMD3/8 complex. Celastrol inhibited B cell migration, reduced antibody responses, and blocked arthritis progression, recapitulating deficiency of the COMMD3/8 complex. These effects of celastrol were abolished in mice expressing a celastrol-resistant mutant of the COMMD3/8 complex. These findings establish that celastrol exerts immunosuppressive activity by targeting the COMMD3/8 complex. Our study suggests that the COMMD3/8 complex is a potentially druggable target in autoimmune diseases and points to celastrol as a lead pharmacologic candidate in this capacity.

A proposed definition of participatory organizational interventions.

Participatory organizational interventions offer an effective way to promote occupational safety and health. Despite an increasing number of studies, a common definition of participatory organizational interventions has yet to be established. Therefore, we aimed to form a definition using the following process. First, we developed a tentative draft definition of organizational interventions and participatory elements, based on the relevant literature. The tentative definition was revised in several rounds of an extensive discussion by the authors. This resulted in the draft definition. We asked 15 selected international experts in occupational safety and health to review and comment on the draft definition. We carefully reviewed their comments, and formulated our final proposed definition. To summarize the key points of the final version of the definition, organizational interventions are planned actions that primarily directly target working conditions with the aim of promoting and maintaining of the highest degree of physical, mental, and social well-being of workers in all occupations. In addition, as participatory elements of organizational interventions in the final definition, ideally, all workers participate in every step of the intervention, while participating in part of the steps of the intervention in some cases. Furthermore, in principle, all workers participate in each step of intervention, while it is also acceptable that only elected representatives among workers participate in the intervention.

Usage of the Brief Job Stress Questionnaire: A Systematic Review of a Comprehensive Job Stress Questionnaire in Japan from 2003 to 2021.

The Brief Job Stress Questionnaire (BJSQ) is used widely in occupational health studies and practice. Summarizing scientific production based on measurement is crucial. This study aimed to systematically review observational studies that used the BJSQ and the New BJSQ to show their usability. A systematic search was conducted for studies investigating relationships between the BJSQ or the New BJSQ subscales and other validated measurements on 13 September 2021, in various literature databases. The BJSQ subscales, scoring methods, and other validated measurements in the studies were qualitatively summarized. In total, 145 published reports between 2003 and 2021 were included. Among the BJSQ subscales, job stressors (n = 95) such as quantitative job overload (n = 65) and job control (n = 64) were most often used. The subscales were utilized to investigate the relationships with several other measurements. Five reports used subscales from the New BJSQ. In the last two decades, the BJSQ and the New BJSQ help measure psychosocial factors (PF) at work and contribute to the publication of scientific papers in the occupational health field. This study would encourage the utilization of the questionnaires for future research and practice.

The impact of workplace psychosocial factors on menstrual disorders and infertility: a protocol for a systematic review and meta-analysis.

INTRODUCTION: Workplace environment, especially psychosocial factors at work such as job strain, workplace social support, and shift work, may affect the menstrual abnormalities and fertility of female workers. However, the association between psychosocial factors at work and menstrual abnormalities or fertility is not well understood. To address this relationship, we will conduct a systematic review and a meta-analysis of the literature that has utilized a longitudinal or prospective cohort design. METHODS AND ANALYSIS: The inclusion criteria for this systematic review and meta-analysis are defined as follows: (P) adult female workers (over 18 years old), (E) the presence of adverse psychosocial factors at work, (C) the absence of adverse psychosocial factors at work, and (O) any menstrual cycle disorders, menstrual-related symptoms, or fertility. The MEDLINE, Embase, PsycINFO, PsycArticles, and Japan Medical Abstracts Society electronic databases will be used to search for published studies. The statistical synthesis of the studies included in the meta-analysis will be conducted to estimate pooled coefficients and 95% CIs. For the main analysis, we will synthesize measures of association between psychosocial factors at work and menstrual-related disorders/symptoms. At least three eligible studies will have to be gathered to conduct a meta-analysis; otherwise (i.e., if only one or two studies will be eligible and included), the results will be presented in a narrative table. We will use the Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) to determine the quality of selected studies. To assess meta-bias, Egger's test, along with a funnel plot, will be used to check for publication bias. Lastly, we will examine heterogeneity using the χ2 test with Cochran's Q statistic and I2. ETHICS AND DISSEMINATION: The results and findings will be submitted and published in a scientific peer-reviewed journal and will be disseminated broadly to researchers and policymakers interested in the translatability of scientific evidence into good practices. SYSTEMATIC REVIEW REGISTRATION: The study protocol was registered at the UMIN registry (registration number: UMIN000039488). The registration date is on 14 Feb 2020. URL: https://upload.umin.ac.jp/cgi-bin/ctr/ctr_view_reg.cgi?recptno=R000044704.

STRENGTH AND LIMITATIONS OF THIS STUDY: • This systematic review and a meta-analysis will investigate the associations between psychosocial factors at work and menstrual abnormalities or fertility. • This review will include only the literature that has utilized a longitudinal design. • Various outcomes related to reproductive health in female workers will be examined (e.g., fertility, premenstrual symptoms, cycle disorders, menopausal symptoms).

Assessing workplace civility: Validity and 1-year test-retest reliability of a Japanese version of the CREW Civility Scale.

OBJECTIVES: This study aimed to examine the reliability and validity of the Japanese version of the eight-item CREW Civility Scale which measures workplace civility norms and compare the civility scores among various occupations. METHODS: A longitudinal study included all employees in a social care organization (N = 658) and a cross-sectional study included all civil servants in one city (N = 3242) in Japan. Structural validity was tested through confirmatory factor analyses (CFA). Construct validity was assessed through Pearson's correlations of civility with other variables. Internal consistency was assessed by Cronbach's alpha and 1-year test-retest reliability was assessed by the Intraclass Correlation Coefficient (ICC). RESULTS: The results of CFA showed an acceptable level of model fit (TLI =0.929; CFI =0.949; and SRMR =0.034). CREW Civility Scale scores were significantly positively correlated with supervisor support, co-worker support, and work engagement, while significantly negatively correlated with incivility, workplace bullying, intention to leave, and psychological distress, which were consistent with our hypotheses. Cronbach's alpha coefficient was 0.93 and ICC was 0.52. Younger, high-educated, and managerial employees and, childminder/nursery staff reported higher civility. High school graduates and respondents who did not graduate from high school, part-time employees, nurses, paramedical staff, and care workers reported lower civility. CONCLUSIONS: The Japanese version of the CREW Civility scale is a reliable, valid measure of civility, appropriate for Japanese workplaces as well as for use in multi-national studies alongside other existing versions of this scale in English, Portuguese and Farsi.

[Current status and intention to change indoor smoking rules by enforcing smoke-free legislation in Japan].

Objective　In Japan, the revised Health Promotion Act and the Tokyo Metropolitan Ordinance to Prevent Exposure to Second-hand Smoke have been in place since April 1, 2020. However, regional differences in the prohibition of smoking in restaurants have raised concerns that some restaurants are not regulated by the smoke-free legislation. In addition, outdoor smoking rules have been in place in municipalities prior to the smoke-free legislation, so smoking outside restaurants may occur, and this may obstruct progress in the prohibition of smoking. In this study, we examined the indoor smoking rules before and after the enforcement of the smoke-free legislation, as well as what influenced the changes in these rules.Methods　We conducted a self-administered questionnaire survey in 6,000 restaurants in Tokyo, Osaka, and Aomori prefectures from February to March 2020. We examined the indoor smoking rules before and after the enforcement of the smoke-free legislation and calculated the proportion of change by categorizing the indoor smoking rules into "smoking prohibited," "smoking permitted in separate area," and "smoking permitted."Results　Of the 879 restaurants that responded, 603 indicated that they were not regulated by the smoke-free legislations. The percentage of restaurants that switched from "smoking permitted in separate area" and "smoking permitted" to "smoking prohibited" was 5.2% (3/58) in Tokyo, 23.1% (31/134) in Osaka, and 17.2% (57/326) in Aomori. In addition, when we included restaurants that were already "smoking prohibited" before the enforcement and did not plan to change the rules after the enforcement, the percentage was 46.6% (55/118) in Tokyo, 49.6% (113/228) in Osaka, and 48.6% (125/257) in Aomori.Conclusion　In total, 17.6% (91/518) of the restaurants that were not regulated by the smoke-free legislations would plan to change their indoor smoking rules from "smoking permitted in separate area" and "smoking permitted" to "smoking prohibited." There is a concern regarding the reduction in customers and sales due to the prohibition of smoking, and the existence of outdoor smoking rules prior to the smoke-free legislation may obstruct progress in the prohibition of smoking. It will be important to examine changes in the number of customers and sales resulting from changes to the indoor smoking rules to deal with smokers when smoking is prohibited, and to improve environments set as public smoking spaces in Japan.

The effect of exposure to long working hours on depression: A systematic review and meta-analysis from the WHO/ILO Joint Estimates of the Work-related Burden of Disease and Injury.

BACKGROUND: The World Health Organization (WHO) and the International Labour Organization (ILO) are developing the WHO/ILO Joint Estimates of the Work-related Burden of Disease and Injury (WHO/ILO Joint Estimates), supported by a large number of individual experts. Evidence from previous reviews suggests that exposure to long working hours may cause depression. In this article, we present a systematic review and meta-analysis of parameters for estimating (if feasible) the number of deaths and disability-adjusted life years from depression that are attributable to exposure to long working hours, for the development of the WHO/ILO Joint Estimates. OBJECTIVES: We aimed to systematically review and meta-analyse estimates of the effect of exposure to long working hours (three categories: 41-48, 49-54 and ≥55 h/week), compared with exposure to standard working hours (35-40 h/week), on depression (three outcomes: prevalence, incidence and mortality). DATA SOURCES: We developed and published a protocol, applying the Navigation Guide as an organizing systematic review framework where feasible. We searched electronic academic databases for potentially relevant records from published and unpublished studies, including the WHO International Clinical Trial Registers Platform, Medline, PubMed, EMBASE, Web of Science, CISDOC and PsycInfo. We also searched grey literature databases, Internet search engines and organizational websites; hand-searched reference lists of previous systematic reviews; and consulted additional experts. STUDY ELIGIBILITY AND CRITERIA: We included working-age (≥15 years) workers in the formal and informal economy in any WHO and/or ILO Member State but excluded children (aged <15 years) and unpaid domestic workers. We included randomized controlled trials, cohort studies, case-control studies and other non-randomized intervention studies with an estimate of the effect of exposure to long working hours (41-48, 49-54 and ≥55 h/week), compared with exposure to standard working hours (35-40 h/week), on depression (prevalence, incidence and/or mortality). STUDY APPRAISAL AND SYNTHESIS METHODS: At least two review authors independently screened titles and abstracts against the eligibility criteria at a first stage and full texts of potentially eligible records at a second stage, followed by extraction of data from qualifying studies. Missing data were requested from principal study authors. We combined odds ratios using random-effects meta-analysis. Two or more review authors assessed the risk of bias, quality of evidence and strength of evidence, using Navigation Guide and GRADE tools and approaches adapted to this project. RESULTS: Twenty-two studies (all cohort studies) met the inclusion criteria, comprising a total of 109,906 participants (51,324 females) in 32 countries (as one study included multiple countries) in three WHO regions (Americas, Europe and Western Pacific). The exposure was measured using self-reports in all studies, and the outcome was assessed with a clinical diagnostic interview (four studies), interview questions about diagnosis and treatment of depression (three studies) or a validated self-administered rating scale (15 studies). The outcome was defined as incident depression in all 22 studies, with first time incident depression in 21 studies and recurrence of depression in one study. We did not identify any study on prevalence of depression or on mortality from depression. For the body of evidence for the outcome incident depression, we had serious concerns for risk of bias due to selection because of incomplete outcome data (most studies assessed depression only twice, at baseline and at a later follow-up measurement, and likely have missed cases of depression that occurred after baseline but were in remission at the time of the follow-up measurement) and due to missing information on life-time prevalence of depression before baseline measurement. Compared with working 35-40 h/week, we are uncertain about the effect on acquiring (or incidence of) depression of working 41-48 h/week (pooled odds ratio (OR) 1.05, 95% confidence interval (CI) 0.86 to 1.29, 8 studies, 49,392 participants, I2 46%, low quality of evidence); 49-54 h/week (OR 1.06, 95% CI 0.93 to 1.21, 8 studies, 49,392 participants, I2 40%, low quality of evidence); and ≥ 55 h/week (OR 1.08, 95% CI 0.94 to 1.24, 17 studies, 91,142 participants, I2 46%, low quality of evidence). Subgroup analyses found no evidence for statistically significant (P < 0.05) differences by WHO region, sex, age group and socioeconomic status. Sensitivity analyses found no statistically significant differences by outcome measurement (clinical diagnostic interview [gold standard] versus other measures) and risk of bias ("high"/"probably high" ratings in any domain versus "low"/"probably low" in all domains). CONCLUSIONS: We judged the existing bodies of evidence from human data as "inadequate evidence for harmfulness" for all three exposure categories, 41-48, 48-54 and ≥55 h/week, for depression prevalence, incidence and mortality; the available evidence is insufficient to assess effects of the exposure. Producing estimates of the burden of depression attributable to exposure to long working appears not evidence-based at this point. Instead, studies examining the association between long working hours and risk of depression are needed that address the limitations of the current evidence.

[Expected research in the workplace among Japanese female workers: A cross-sectional online survey based on the framework of patient and public involvement].

OBJECTIVES: This study aimed to investigate the work-related health and social problems among Japanese female workers and the expected research in the workplace. METHOD: A cross-sectional study using an Internet survey was conducted on female workers in Japan. Using an original questionnaire, we obtained data on "a system that can be used by female workers," "female workers' problems (physical symptoms, mental symptoms, menstrual problems, pregnancy/childbirth problems, work-life balance, etc.)," and "expected research in the workplace." The last two were compared using the chi-square test and considering demographic characteristics (age, marital status, having children, having preschool children, employment status, occupation). We conducted the chi-square test to examine the relationship between the presence of symptoms and four expected studies. The survey was carried out in July 2019 by using a patient and public involvement (PPI) framework in medical research. RESULTS: We obtained 416 responses that highlighted that those who have work-related problems also have physical symptoms (89%), menstrual problems (65%), psychiatric symptoms (49%), and work-life balance problems (39%), followed by career as well as pregnancy and childbirth concerns (38%). Regarding the system, the respondents' usage rate was an infertility treatment communication card (0%), flextime and telework (1 to 3%), menstrual leave (4%), and short-time work system (8%). Expected workplace studies included "Research to ease stiff shoulders and back pain" (45%), "Research to improve women's mental health" (41%), "Research on menstruation and work performance" (35%), and "Research to improve work-life balance" (34%). Expectations for research on "mental health" and "menstruation" were high among subjects in their 20s and 30s, with no spouse or children, and working full-time. Among those who lived with preschoolers, expectations for research on "mental support after childbirth," "physical support after childbirth," and "prevention of postpartum depression" were significantly higher, but research related to work-life balance was not remarkably different. There was a significant association between having menstrual problems, work-life balance challenges, and study expectations. However, the percentage of those experiencing certain symptoms who expected workplace studies was about 48%. CONCLUSIONS: Menstruation-related symptoms are frequently observed to make work difficult and it is expected that health issues, such as mental and physical conditions related to gynecology, will be the subject of future research regarding female workers. However, discrepancies between having difficulties and whether or not they wish to accept research in the workplace should be carefully considered in each context.

What Kind of Intervention Is Effective for Improving Subjective Well-Being Among Workers? A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Objectives: This study aimed to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) to improve subjective well-being (SWB), including evaluative, hedonic, and eudemonic well-being, and the mental component of quality of life (QOL) of working population. Methods: A literature search was conducted, using PubMed, Embase, PsycINFO, and PsycARTICLES. Eligible studies included those that were RCTs of any intervention, conducted among healthy workers, measured SWB as a primary outcome, and original articles in English. Study characteristics, intervention, outcomes, and results on SWB outcomes were extracted by the investigators independently. After a brief narrative summarizing and classifying the contents of the interventions, the included outcomes were categorized into each aspect of SWB (evaluative, hedonic, and eudemonic well-being, and the mental component of QOL). Finally, the characteristics of the effective interventions for increasing each aspect were summarized, and the pooled effect of interventions on SWB was investigated by a meta-analysis. Publication bias was investigated by drawing a funnel plot and conducting Egger's test. Results: From the 5,450 articles found, 39 met the inclusion criteria for the systematic review. The interventions included in this review were classified into six categories (physical activity, ergonomics, psychological, environmental, multicomponent intervention, and others). The meta-analysis from 31 studies showed that the pooled effect of included interventions on SWB was significantly positive (standardized mean difference (SMD) = 0.51; standard error (SE) = 0.10). A funnel plot showed there were extremely large or small SMDs, and Egger's test was significant. Thus, we conducted sensitivity analysis, excluding these extreme SMDs, and confirmed that the estimated pooled effect was also significantly positive. Subgroup analyses for separate types of interventions showed the effects of psychological interventions (e.g., mindfulness, cognitive behavioral based approach, and other psychological interventions) were also significantly positive. Conclusion: The current study revealed the effectiveness of interventions for increasing SWB. Specifically, psychological interventions (e.g., mindfulness, cognitive behavioral based approach, and other psychological interventions) may be useful for improving SWB.

Association between dietary intake and serum biomarkers of long-chain PUFA in Japanese preschool children.

OBJECTIVE: Recent research supports the importance of PUFA intake in children, particularly of EPA and DHA; however, few verified methods to assess whether PUFA intake is adequate are available. DESIGN: We assessed the correlation between serum PUFA and lipid concentrations with seafood and PUFA intake measured using a brief-type self-administered diet history questionnaire for Japanese preschool children (BDHQ3y). SETTING: Single centre birth cohort in Japan. PARTICIPANTS: A total of 152 36-month-old Japanese children. RESULTS: Average dietary intake of daily seafood, EPA and DHA was 13·83 (sd 10·36) g, 49·4 (sd 43·5) mg and 98·3 (sd 64·6) mg, respectively. Significant weak-to-moderate correlations were observed between dietary intake and serum EPA (Spearman rho = 0·41, P < 0·001; Pearson r = 0·44, P < 0·001); DHA (Spearman rho = 0·40, P < 0·001; Pearson r = 0·42, P < 0·001) and AA (arachidonic acid) (Spearman rho = 0·33, P < 0·001; Pearson r = 0·32, P < 0·001), whereas no significant correlation was observed for dihomo-γ-linolenic acid (DGLA) (Spearman rho = 0·06, P = 0·484; Pearson r = 0·07, P = 0·387). Correlations between seafood intake and serum EPA and DHA were also moderate (0·39-0·43). A negative correlation between serum TAGs and serum EPA, as well as positive correlations between serum cholesterol (total cholesterol, LDL and HDL) with serum EPA and DHA were observed, whereas no significant correlations between seafood intake and serum lipid profiles. Based on this model, we estimated 61-98 g/week of seafood intake is required to meet current EPA/DHA intake recommendations by the WHO (100-150 mg/d). CONCLUSIONS: For children of 2-4 years of age, weekly intake of 61-98 g of seafood is required to meet WHO recommendations of EPA/DHA intake.

The Association Between Unit-Level Workplace Social Capital and Intention to Leave Among Employees in Health Care Settings: A Cross-Sectional Multilevel Study.

OBJECTIVE: The aim of this study was to investigate the multilevel association between workplace social capital and intention to leave among employees in health care settings in Japan. METHODS: This study was a secondary data analysis of the cross-sectional data. A sample of 658 Japanese employees in health care settings with 17 facilities were recruited using a self-administered questionnaire. Multilevel linear regression analysis of intention to leave on unit-level workplace social capital (average score for each unit) was conducted. RESULTS: Among 317 respondents from 49 units, after adjusting for demographic and work-related variables, both unit-level and individual-level workplace social capital were significantly negatively associated with intention to leave (P < 0.001). CONCLUSIONS: The current study found that there was a significant negative association between unit-level workplace social capital and intention to leave in the health care field.

Association between psychosocial factors at work and health outcomes after retirement: a protocol for a systematic review and meta-analysis.

INTRODUCTION: The world's population is rapidly ageing, and health among older people is thus an important issue. Several previous studies have reported an association between adverse psychosocial factors at work before retirement and postretirement health. The objective of this systematic review and meta-analysis is to examine the association between psychosocial factors at work and health outcomes after retirement, based on a synthesis of well-designed prospective studies. METHODS AND ANALYSIS: The participants, exposures, comparisons and outcomes of the studies in this systematic review and meta-analysis are defined as follows: (P) people who have retired from their job, (E) presence of adverse psychosocial factors at work before retirement, (C) absence of adverse psychosocial factors at work before retirement and (O) any physical and mental health outcomes after retirement. Published studies were searched using the following electronic databases: MEDLINE, EMBASE, PsycINFO, PsycARTICLES and Japan Medical Abstracts Society. The included studies will be statistically synthesised in a meta-analysis to estimate pooled coefficients and 95% CIs. The quality of each included study will be assessed using the Risk Of Bias In Non-randomised Studies-of Interventions. For the assessment of meta-bias, publication bias will be assessed by using Egger's test, as well as visually on a funnel plot. Heterogeneity will be assessed using the χ² test with Cochran's Q statistic and I2. ETHICS AND DISSEMINATION: Results and findings will be submitted and published in a scientific peer-reviewed journal and will be disseminated broadly to researchers and policy-makers interested in the translatability of scientific evidence into good practices. PROSPERO REGISTRATION NUMBER: CRD42018099043.

Coffee Consumption and All-Cause and Cardiovascular Mortality　- Three-Prefecture Cohort in Japan.

BACKGROUND: Coffee, which contains various bioactive compounds, is one of the most popular beverages. Further accumulation of evidence is needed, however, to confirm whether coffee consumption would be effective in preventing cardiovascular disease in the general Japanese population. Methods and Results: We evaluated the association between coffee consumption frequency (never, sometimes, 1-2 cups/day, 3-4 cups/day and ≥5 cups/day) and mortality from all causes, heart disease, and cerebrovascular disease, in 39,685 men and 43,124 women aged 40-79 years at baseline, in a 3-prefecture cohort study. The coffee consumption frequency was assessed on questionnaire. Cox proportional hazards regression modeling was used to assess the association between coffee consumption frequency and all-cause and cardiovascular disease mortality with adjustment for potential confounders. During 411,341 and 472,433 person-years in men and women, respectively, a total of 7,955 men and 5,725 women died. Coffee consumption frequency was inversely associated with all-cause mortality in both genders (P for trend<0.001). In addition, the risks of mortality from cerebrovascular disease in men (P for trend<0.001), and heart disease in women (P for trend=0.031) were inversely associated with coffee consumption. CONCLUSIONS: In this Japanese population, coffee drinking has a preventive effect on all-cause and on cardiovascular mortality in men and/or women.

WHO/ILO work-related burden of disease and injury: Protocol for systematic reviews of exposure to long working hours and of the effect of exposure to long working hours on depression.

BACKGROUND: The World Health Organization (WHO) and the International Labour Organization (ILO) are developing a joint methodology for estimating the national and global work-related burden of disease and injury (WHO/ILO joint methodology), with contributions from a large network of experts. In this paper, we present the protocol for two systematic reviews of parameters for estimating the number of deaths and disability-adjusted life years from depression attributable to exposure to long working hours, to inform the development of the WHO/ILO joint methodology. OBJECTIVES: We aim to systematically review studies on occupational exposure to long working hours (Systematic Review 1) and systematically review and meta-analyse estimates of the effect of long working hours on depression (Systematic Review 2), applying the Navigation Guide systematic review methodology as an organizing framework, conducting both systematic reviews in tandem and in a harmonized way. DATA SOURCES: Separately for Systematic Reviews 1 and 2, we will search electronic academic databases for potentially relevant records from published and unpublished studies, including Medline, EMBASE, Web of Science, CISDOC and PsycINFO. We will also search electronic grey literature databases, Internet search engines and organizational websites; hand search reference list of previous systematic reviews and included study records; and consult additional experts. STUDY ELIGIBILITY AND CRITERIA: We will include working-age (≥15 years) participants in the formal and informal economy in any WHO and/or ILO Member State, but exclude child workers (<15 years) and unpaid domestic workers. For Systematic Review 1, we will include quantitative prevalence studies of relevant levels of occupational exposure to long working hours (i.e. 35-40, 41-48, 49-54 and ≥55 h/week) stratified by country, sex, age and industrial sector or occupation, in the years 2005-2018. For Systematic Review 2, we will include randomized controlled trials, cohort studies, case-control studies and other non-randomized intervention studies with an estimate of the relative effect of relevant level(s) of long working hours on the incidence of or mortality due to depression, compared with the theoretical minimum risk exposure level (i.e. 35-40 h/week). STUDY APPRAISAL AND SYNTHESIS METHODS: At least two review authors will independently screen titles and abstracts against the eligibility criteria at a first stage and full texts of potentially eligible records at a second stage, followed by extraction of data from qualifying studies. At least two review authors will assess risk of bias and the quality of evidence, using the most suited tools currently available. For Systematic Review 2, if feasible, we will combine relative risks using meta-analysis. We will report results using the guidelines for accurate and transparent health estimates reporting (GATHER) for Systematic Review 1 and the preferred reporting items for systematic reviews and meta-analyses guidelines (PRISMA) for Systematic Review 2. PROSPERO REGISTRATION NUMBER: CRD42018085729.

Serum 25-hydroxyvitamin D levels showed strong seasonality but lacked association with vitamin D intake in 3-year-old Japanese children.

Current guidelines provide a universal recommendation on vitamin D intake to prevent insufficiency. However, the relative influence of food, UVB and other factors on serum 25-hydroxyvitamin D (25(OH)D) insufficiency has been poorly investigated in preschool children. We assessed serum 25(OH)D quantities and their association with vitamin D intake using a brief-type self-administered diet history questionnaire for children aged 3-6 years (BDHQ3y), outdoor playing time and background UVB radiation level among 574 36-month-old Japanese children living at latitude 35°N. The average serum 25(OH)D concentration was 23·5 (sd 6·1) ng/ml, and 170 (29·6 %) children had vitamin D insufficiency (<20 ng/ml) despite high consumption of fish. Multiple logistic regression adjusting for social factors showed that when background UVB radiation level was <15 kJ/m2 (monthly average), there was a 1·89 (95 % CI 1·31, 2·74) times higher risk of vitamin D insufficiency, to which vitamin D intake nor time spent outdoors were significantly associated. ANOVA showed that the contribution of the variability in vitamin D intake on the variability of serum 25(OH)D level was 1·8 % of that of UVB exposure. The correlation between vitamin D intake and serum 25(OH)D level was not stronger when limited to measurements in winter. We found that nearly 30 % of 3-year-old Japanese children had vitamin D insufficiency despite high consumption of fish and living at relatively low latitude. We failed to observe an association between vitamin D intake and the risk of vitamin D insufficiency. This may be due to the extremely limited access to vitamin D-fortified food and supplements for children in Japan.

Psychosocial factors at work and inflammatory markers: protocol for a systematic review and meta-analysis.

INTRODUCTION: Chronic inflammation may be a mediator for the development of cardiovascular disease (CVD), metabolic diseases and psychotic and neurodegenerative disorders. Meta-analytic associations between work-related psychosocial factors and inflammatory markers have shown that work-related psychosocial factors could affect the flexibility and balance of the immune system. However, few systematic reviews or meta-analyses have investigated the association between work-related psychosocial factors and inflammatory markers. Based on prospective studies, the present investigation will conduct a comprehensive systematic review and meta-analysis of the association between work-related psychosocial factors and inflammatory markers. METHODS AND ANALYSIS: The systematic review and meta-analysis will include published studies identified from electronic databases (PubMed, EMBASE, PsycINFO, PsycARTICLES, Web of Science and Japan Medical Abstracts Society) according to recommendations of the Meta-analysis of Observational Studies in Epidemiology guideline. Inclusion criteria are studies that: examined associations between work-related psychosocial factors and increased inflammatory markers; used longitudinal or prospective cohort designs; were conducted among workers; provided sufficient data for calculating ORs or relative risk with 95% CIs; were published as original articles in English or Japanese; and were published up to the end of 2017. Study selection, data extraction, quality assessment and statistical syntheses will be conducted by 14 investigators. Any inconsistencies or disagreements will be resolved through discussion. The quality of studies will be evaluated using the Risk of Bias Assessment Tool for Non-randomized Studies. ETHICS AND DISSEMINATION: The investigation study will be based on published studies, so ethics approval is not required. The results of this study will be submitted for publication in a scientific peer-reviewed journal. The findings may be useful for assessing risk factors for increased inflammatory markers in the workplace and determining future approaches for preventing CVD, metabolic diseases and psychotic and neurodegenerative disorders. PROSPERO REGISTRATION NUMBER: CRD42018081553.

Associations of non-standard employment with cardiovascular risk factors: findings from nationwide cross-sectional studies in Japan.

This study aimed to examine the cross-sectional association of non-standard employment with cardiovascular disease risk factors. Five yr of data from the Comprehensive Survey of Living Conditions and National Health and Nutritional Survey were combined. We used logistic regression to examine the association of employment contract (non-standard [part-time, dispatched, or contract] vs. standard [full-time and permanent]) with eight cardiovascular disease risk factors among 1,636 men and 2,067 women aged 40-60 yr. There were significant associations between non-standard employment and cardiovascular disease risk factors such as current smoking among men (odds ratio [OR] 1.39; 95% confidential interval [CI], 1.13-1.86) and diabetes among women (OR 1.83; 95% CI, 1.10-3.09). Non-standard employment was associated with a few cardiovascular disease risk factors in this middle-aged cohort in Japan.