1666a Overview on sentinel and alert systems in occupational medicine

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The effect of exposure to long working hours on alcohol consumption, risky drinking and alcohol use disorder: 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 Joint Estimates of the work-related burden of disease and injury (WHO/ILO Joint Estimates), with contributions from a large network of experts. Evidence from mechanistic data suggests that exposure to long working hours may increase alcohol consumption and cause alcohol use disorder. In this paper, we present a systematic review and meta-analysis of parameters for estimating the number of deaths and disability-adjusted life years from alcohol consumption and alcohol use disorder 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 alcohol consumption, risky drinking (three outcomes: prevalence, incidence and mortality) and alcohol use disorder (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 We searched electronic bibliographic databases for potentially relevant records from published and unpublished studies, including the WHO International Clinical Trials Register, Ovid MEDLINE, PubMed, Embase, and CISDOC on 30 June 2018. Searches on PubMed were updated on 18 April 2020. We also searched electronic grey literature databases, Internet search engines and organizational websites; hand searched reference list of previous systematic reviews and included study records; and consulted additional experts.Study eligibility and criteria: We included working-age (15 years) and unpaid domestic workers. We considered for inclusion randomized controlled trials, cohort studies, case-control studies and other nonrandomized 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 alcohol consumption (in g/week), risky drinking, and alcohol use disorder (prevalence, incidence 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 publications related to qualifying studies. 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: Fourteen cohort studies met the inclusion criteria, comprising a total of 104,599 participants (52,107 females) in six countries of three WHO regions (Americas, South-East Asia, and Europe). The exposure and outcome were assessed with self-reported measures in most studies. Across included studies, risk of bias was generally probably high, with risk judged high or probably high for detection bias and missing data for alcohol consumption and risky drinking. Compared to working 35-40 h/week, exposure to working 41-48 h/week increased alcohol consumption by 10.4 g/week (95% confidence interval (CI) 5.59-15.20; seven studies; 25,904 participants, I2 71%, low quality evidence). Exposure to working 49-54 h/week increased alcohol consumption by 17.69 g/week (95% confidence interval (CI) 9.16-26.22; seven studies, 19,158 participants, I2 82%, low quality evidence). Exposure to working >55 h/week increased alcohol consumption by 16.29 g/week (95% confidence interval (CI) 7.93-24.65; seven studies; 19,692 participants; I2 82%, low quality evidence). We are uncertain about the effect of exposure to working 41-48 h/week, compared with working 35-40 h/week on developing risky drinking (relative risk 1.08; 95% CI 0.86-1.36; 12 studies; I2 52%, low certainty evidence). Working 49-54 h/week did not increase the risk of developing risky drinking (relative risk 1.12; 95% CI 0.90-1.39; 12 studies; 3832 participants; I2 24%, moderate certainty evidence), nor working >55 h/week (relative risk 1.11; 95% CI 0.95-1.30; 12 studies; 4525 participants; I2 0%, moderate certainty evidence). Subgroup analyses indicated that age may influence the association between long working hours and both alcohol consumption and risky drinking. We did not identify studies for which we had access to results on alcohol use disorder.Conclusions: Overall, for alcohol consumption in g/week and for risky drinking, we judged this body of evidence to be of low certainty. Exposure to long working hours may have increased alcohol consumption, but we are uncertain about the effect on risky drinking. We found no eligible studies on the effect on alcohol use disorder. Producing estimates for the burden of alcohol use disorder attributable to exposure to long working hours appears to not be evidence-based at this time. Protocol identifier: https://doi.org/10.1016/j.envint.2018.07.025. PROSPERO registration number: CRD42018084077</p

COVID-19: a new work-related disease threatening healthcare workers.

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Stress, burnout and depression : A systematic review on DNA methylation mechanisms

Despite that burnout presents a serious burden for modern society, there are no diagnostic criteria. Additional difficulty is the differential diagnosis with depression. Consequently, there is a need to dispose of a burnout biomarker. Epigenetic studies suggest that DNA methylation is a possible mediator linking individual response to stress and psychopathology and could be considered as a potential biomarker of stress-related mental disorders. Thus, the aim of this review is to provide an overview of DNA methylation mechanisms in stress, burnout and depression. In addition to state-of-the-art overview, the goal of this review is to provide a scientific base for burnout biomarker research. We performed a systematic literature search and identified 25 pertinent articles. Among these, 15 focused on depression, 7 on chronic stress and only 3 on work stress/burnout. Three epigenome-wide studies were identified and the majority of studies used the candidate-gene approach, assessing 12 different genes. The glucocorticoid receptor gene (NR3C1) displayed different methylation patterns in chronic stress and depression. The serotonin transporter gene (SLC6A4) methylation was similarly affected in stress, depression and burnout. Work-related stress and depressive symptoms were associated with different methylation patterns of the brain derived neurotrophic factor gene (BDNF) in the same human sample. The tyrosine hydroxylase (TH) methylation was correlated with work stress in a single study. Additional, thoroughly designed longitudinal studies are necessary for revealing the cause-effect relationship of work stress, epigenetics and burnout, including its overlap with depression

Stress, burnout and depression : A systematic review on DNA methylation mechanisms

Despite that burnout presents a serious burden for modern society, there are no diagnostic criteria. Additional difficulty is the differential diagnosis with depression. Consequently, there is a need to dispose of a burnout biomarker. Epigenetic studies suggest that DNA methylation is a possible mediator linking individual response to stress and psychopathology and could be considered as a potential biomarker of stress-related mental disorders. Thus, the aim of this review is to provide an overview of DNA methylation mechanisms in stress, burnout and depression. In addition to state-of-the-art overview, the goal of this review is to provide a scientific base for burnout biomarker research. We performed a systematic literature search and identified 25 pertinent articles. Among these, 15 focused on depression, 7 on chronic stress and only 3 on work stress/burnout. Three epigenome-wide studies were identified and the majority of studies used the candidate-gene approach, assessing 12 different genes. The glucocorticoid receptor gene (NR3C1) displayed different methylation patterns in chronic stress and depression. The serotonin transporter gene (SLC6A4) methylation was similarly affected in stress, depression and burnout. Work-related stress and depressive symptoms were associated with different methylation patterns of the brain derived neurotrophic factor gene (BDNF) in the same human sample. The tyrosine hydroxylase (TH) methylation was correlated with work stress in a single study. Additional, thoroughly designed longitudinal studies are necessary for revealing the cause-effect relationship of work stress, epigenetics and burnout, including its overlap with depression

Salivary cortisol and cortisone: UPLC-MS/MS method validation and temporal variability over one week

Aims: The present study aims to provide a comprehensive analytical and biological validation of an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for analysis of salivary cortisol and its inactive metabolite cortisone. Variation in cortisol awakening response (CAR) over one week were investigated. Methods: Saliva samples were collected from 19 healthy volunteers. To determine CAR, participants collected saliva samples at three time points: immediately after awakening, 15 and 30 minutes thereafter. The same procedure was repeated each morning over one week period. In addition, all participants filled in diaries containing information about duration of sleep, time of awakening, smoking, and coffee and alcohol intake. Upon collection, the saliva samples were stored at -20°C until analysis. Prior to analysis, the saliva samples were thawed and spiked with internal standard and extracted using solid phase extraction columns (Oasis Prime-HLB). The identification and quantification of cortisol and cortisone were performed using the developed UPLC-MS/MS method, on a Waters Aquity TQ-XS system. Results: The obtained limits of quantification (LoQ) were 1ng/ml for cortisol and 500pg/ml for cortisone. Intra-assay accuracy values of calibration points were between 83-111%. The mean levels of cortisol and cortisone in the total sample were 3.55 ± 1.99 ng/ml and 10.51 ± 3.46 ng/ml, respectively. In the first 30 minutes after awakening, there was a 70% increase in the average cortisol levels (CAR) and a 49% increase in the levels of cortisone. A high intra-individual variability of CAR was observed over the week (CV ranged between 17.9-68.9%), whereas the inter-individual variability of the average CAR equaled 28.2%. Furthermore, the changes in CAR were related to variables from participants’ diaries. Conclusion: The UPLC-MS/MS method has shown to be a sensitive and specific technique for determination of salivary cortisol and cortisone. However, in the clinical context, CAR data should be interpreted with precaution due to high inter- and intra-individual variability

Role of NR3C1 and SLC6A4 methylation in the HPA axis regulation in burnout

Background: Work-related stress and burnout have become major occupational health concerns. Dysregulation of HPA axis is considered one of the central mechanisms and is potentially moderated through epigenetics. In the present study, we aim to investigate epigenetic regulation of the HPA axis in burnout, by focusing on salivary cortisol and cortisone and DNA methylation of the glucocorticoid receptor gene (NR3C1) and the serotonin transporter gene (SLC6A4). Methods: We conducted a cross-sectional study with 59 subjects with burnout and 70 healthy controls recruited from the general population. All participants underwent a clinical interview and psychological assessment. Saliva samples were collected at 0, 30 and 60 min after awakening and were used to quantify cortisol and cortisone. Pyrosequencing was performed on whole blood-derived DNA to assess DNA methylation. Results: There were no between-group differences in cortisol levels, whereas burnout participants had higher levels of cortisone. Job stress was associated with increased cortisol and cortisone. We observed both increased and decreased NR3C1 and SLC6A4 methylation in the burnout group compared to the control group. Some of these methylation changes correlated with burnout symptoms dimensionally. Increased methylation in a specific CpG in the SLC6A4 promoter region moderated the association between job stress and burnout. DNA methylation in this CpG was also associated with increased cortisol. In addition, average methylation of NR3C1 was negatively associated with cortisone levels. Limitations: This is a cross-sectional study and therefore no conclusions on causality could be made. Conclusions: We provide first evidence of changes in DNA methylation of NR3C1 and SLC6A4 in burnout, which were further associated with cortisol and cortisone. Further, increased cortisol and cortisone seemed to reflect job stress rather than burnout itself

Epigenetic perspective on the role of brain-derived neurotrophic factor in burnout

Brain-derived neurotrophic factor (BDNF) plays a potential role in the neurobiology of burnout, but there are no studies investigating the underlying genetic and epigenetic mechanisms. Our aim is to further explore the role of BDNF in burnout, by focusing on the Val66Met polymorphism and methylation patterns of the BDNF gene and serum BDNF (sBDNF) protein expression. We conducted a cross-sectional study by recruiting 129 individuals (59 with burnout and 70 healthy controls). Participants underwent a clinical interview, psychological assessment and blood sample collection. Polymorphism and DNA methylation were measured on DNA from whole blood, using pyrosequencing and sBDNF levels were measured using ELISA. We found significantly increased methylation of promoter I and IV in the burnout group, which also correlated with burnout symptoms. In addition, DNA methylation of promoter I had a significant negative effect on sBDNF. For DNA methylation of exon IX, we did not find a significant difference between the groups, nor associations with sBDNF. The Val66Met polymorphism neither differed between groups, nor was it associated with sBDNF levels. Finally, we did not observe differences in sBDNF level between the groups. Interestingly, we observed a significant negative association between depressive symptoms and sBDNF levels. The current study is the first to show that BDNF DNA methylation changes might play an important role in downregulation of the BDNF protein levels in burnout. The presence of depressive symptoms might have an additional impact on these changes