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Although vitamin D insufficiency has been correlated with an increased risk of cardiovascular disease (CVD), there are few data on the association between 25-hydroxyvitamin D (25(OH)D) and atherogenic indices predictive of CVD. This study investigated the relationship of vitamin D status with lipid profile and atherogenic indices in adult women in Morocco. Three hundred women aged 18 to 50 years from Meknes were included. Fasting 25(OH)D and lipid concentrations were assayed by a one-step electrochemiluminescence-based immunoassay and an enzymatic method, respectively. Atherogenic indices (atherogenic index of plasma (AIP), atherogenic coefficient (AC), non-HDL cholesterol (non-HDL-C), Castelli risk indices I and II (CRI-I and II), and CHOLIndex (CI)) were calculated using conventional lipid parameters. Logistic regression models and operating characteristic curve (ROC) analysis were used to assess the relationship of the variables and estimate the threshold of 25(OH)D levels associated with high atherogenic indices. 25(OH) D below 20 ng/mL was significantly associated with an enhanced risk of hypertriglyceridemia and elevated values of AIP, AC, non-HDL-C, and CRI-I with an OR (95% CI) of 4.904 (1.856–12.959), 3.637 (2.149–6.158), 3.589 (1.673–7.700), 2.074 (1.215–3.540), and 2.481 (1.481–4.123), respectively. According to the ROC analysis, the likelihood of hypertriglyceridemia and high values of AIP, AC, non-HDL-C, and CRI-I were associated with 25(OH)D thresholds ≤15.15 ng/mL, ≤17.5 ng/mL, ≤19.8 ng/mL, ≤20.1 ng/mL, and ≤19.5 ng/mL, respectively, all p < 0.01. Based on the atherogenic indices, this study indicates that vitamin D below 20 ng/mL may increase the risk of cardiovascular disease in adult women. Additional health measures are essential to raise awareness among women and health professionals of preventing and controlling cardiovascular risk factors, particularly among young individuals.

Abstract Prenatal exposure to toxins can adversely affect long-term health outcomes of the offspring. Though chemotherapeutics are now standard of care for treating cancer patients during pregnancy, certain compounds are known to cross the placenta and harm placental tissue. The consequences for the fetus are largely unexplored. Here we examined the responses of newborn cord blood mononuclear cells in tissue culture to two chemotherapeutic drugs, cyclophosphamide and epirubicin, when either directly exposed to these drugs, or indirectly after crossing a placenta trophoblast bilayer barrier. Cord blood mononuclear cells exposed to the conditioned media obtained from cyclophosphamide-exposed trophoblast barriers showed a significant 2.4-fold increase of nuclear ROS levels compared to direct exposure to cyclophosphamide. Indirect exposure to epirubicine-exposed trophoblast barriers not only enhanced nuclear ROS levels but also significantly increased the fraction of cord blood cells with double strand breaks, relative to directly exposed cells. Neither apoptosis nor proliferation markers were affected in cord mononuclear blood cells upon direct or indirect exposure to cyclophosphamide or epirubicin. Our data suggests that trophoblast cells exposed to cyclophosphamide or epirubicine may induce an indirect ‘bystander’ effect and can aggravate genotoxicity in the fetal compartment.

Abstract Background Occupational medicine (OM) faces considerable challenges today, one of them related to the university training of future physicians considered suboptimal at a global level as it has been pointed out in many studies. The aim of this study is to update the state of OM medical education in European universities. Methods Between March and August 2022, an e-mail survey regarding OM training to undergraduate medical students was conducted among OM professors at European universities in 28 countries (n = 347). Results Of the 347 universities, 53 medical schools from 19 countries responded (response rate = 15.3%). In 89% of cases, OM was taught. The average number of hours per academic year was 24.3, with significant variation within the same country. Lectures were the most popular teaching technique (98%), with a considerable use of modern approaches such as problem-based learning (61%), and e-learning (57%). While occupational diseases and principles of prevention were covered, other subjects such as the environmental impact or collaboration with an OM physician were poorly represented in the educational program. Conclusion According to data, several European medical schools may provide insufficient OM education and training to their students. The education of undergraduate occupational medicine students in European medical schools should be designed to equip them with the knowledge and skills required to meet today’s challenges. It is critical that undergraduate OM education in European medical schools be enhanced, harmonized, and standardized.

Abstract Background Burnout is a growing problem in medical education, and is usually characterised by three dimensions: emotional exhaustion, cynicism, and reduced professional efficacy. Currently, the majority of burnout studies have been conducted in western high-income countries, overshadowing findings from low- and middle-income countries. Our objective is to investigate burnout and its associated predictive factors in Morocco, aiming to guide intervention strategies, while also assessing differences between the preclinical and clinical years. Methods A cross-sectional, self-administered online survey assessing burnout dimensions and its main determinants was distributed among medical students at Université Mohammed VI des Sciences et de la Santé (UM6SS, Casablanca, Morocco). Descriptive analyses involved computing mean scores, standard deviations and Pearson correlations. Further, t-tests were performed to check for significant differences in burnout dimensions across the preclinical and clinical learning phase, and stepwise linear regression analyses were conducted using a backward elimination method to estimate the effects of the selected variables on the three burnout dimensions. Results A t-test assessing the difference in cynicism found a significant difference between students at the preclinical phase and the clinical phase, t(90) = -2.5, p = 0.01. For emotional exhaustion and reduced professional efficacy no significant difference was observed. A linear regression analysis showed that emotional exhaustion was significantly predicted by workload, work-home conflict, social support from peers and neuroticism. Cynicism was predicted by the learning phase, workload, meaningfulness and neuroticism; and reduced professional efficacy by neuroticism only. Conclusions Our findings suggest a potential gradual increase in cynicism during medical education in Morocco. Conducting this study in a low- and middle income country has enhanced the scientific understanding of burnout in these regions. Given the identified predictive factors for burnout, such as workload, work-home conflict, support from peers, neuroticism, and meaningfulness, it is necessary to focus on these elements when developing burnout interventions.

Background: Multiple factors can fuel nurses’ intention to leave their employing hospital or their profession. Job dissatisfaction and burnout are contributors to this decision. Sociodemographic and work context factors can also play a role in explaining nurses’ intention to leave. Objective: To investigate the role of sociodemographic and work context factors, including job resources, job demands, job dissatisfaction, depersonalization, and emotional exhaustion, on nurses’ intention to leave their hospital or their profession. Design: Multicentre cross-sectional study. Setting(s): Eight European hospitals, two per each country, including Belgium, the Netherlands, Italy, and Poland. Participants: From May 16 to September 30, 2022, we collected 1,350 complete responses from nurses working at the selected hospitals (13 % response rate). Methods: The intention to leave was assessed through two 5-Likert scale outcomes, agreeing with the intention to leave the profession and the intention to leave the hospital. Logistic regression models were used for statistical analysis. Results: At the multivariable analysis, a higher intention to leave the hospital was observed for: younger age, having served on the frontline against COVID-19, lack of quipment, living in the Netherlands, emotional exhaustion, dissatisfaction with work prospects, and dissatisfaction with the use of professional abilities. There was a higher intention to leave the profession for: younger age, living in the Netherlands, having work-related health problems, depersonalization, emotional exhaustion, low possibilities of professional development, dissatisfaction with work prospects, lack of use of professional abilities, overall ob issatisfaction, and dissatisfaction with salary. Nurses living in Italy expressed the lowest intention to leave. Conclusion: While confirming the role of job dissatisfaction and burnout, we found higher intention to leave for young nurses, nurses with work-related health problems, and caregivers during the COVID-19 pandemic. Dissatisfaction with work prospects, professional development, and salary also increased the intention to leave. We call for educators, managers, and policymakers to address these factors to retain at-risk nursing categories, implementing strategies to mitigate intentions to leave.

Objectives Studies usually investigate a limited number or a predefined combinations of risk factors for sickness absence in employees with pain. We examined frequently occurring combinations across a wide range of work-related factors and pain perceptions.Design Cross-sectional study.Setting Belgian companies that are under supervision of IDEWE, an external service for prevention and protection at work.Participants In total, 249 employees experiencing pain for at least 6 weeks were included and filled out an online survey.Outcomes Latent profile analysis was used to differentiate profiles of work-related factors (physical demands, workload, social support and autonomy) and pain perceptions (catastrophising, fear-avoidance beliefs and pain acceptance). Subsequently, profiles were compared on sociodemographics (age, gender, level of education, work arrangement, duration of complaints, multisite pain and sickness absence in the previous year) and predictors of sickness absence (behavioural intention and perceived behavioural control).Results Four profiles were identified. Profile 1 (38.2%) had favourable scores and profile 4 (14.9%) unfavourable scores across all indicators. Profile 2 (33.3%) had relatively high physical demands, moderate autonomy levels and favourable scores on the other indicators. Profile 3 (13.7%) showed relatively low physical demands, moderate autonomy levels, but unfavourable scores on the other indicators. Predictors of profiles were age (OR 0.93 and 95% CI (0.89 to 0.98)), level of education (OR 0.28 and 95% CI (0.1 to 0.79)) and duration of sickness absence in the previous year (OR 2.29 and 95% CI (0.89 to 5.88)). Significant differences were observed in behavioural intention (χ2=8.92, p=0.030) and perceived behavioural control (χ2=12.37, p=0.006) across the four profiles.Conclusion This study highlights the significance of considering the interplay between work-related factors and pain perceptions in employees. Unfavourable scores on a single work factor might not translate into maladaptive pain perceptions or subsequent sickness absence, if mitigating factors are in place. Special attention must be devoted to employees dealing with unfavourable working conditions along with maladaptive pain perceptions. In this context, social support emerges as an important factor influencing sickness absence.

Background: GPs are particularly vulnerable to job burnout. Tailored prevention and intervention strategies are needed. Aim: To investigate organisational, interpersonal, and individual factors contributing to exhaustion and disengagement at work among GPs. Design & setting: We conducted a cross-sectional study in a sample of Belgian GPs. Method: A total of 358 doctors (73% females, 301 with complete data) completed an online anonymous questionnaire assessing job burnout, psychosocial characteristics of the work environment, perceived social support in the private domain, emotional competence, and self-compassion. Results: GPs reported moderate levels of exhaustion and disengagement. Regression models showed that included factors jointly explained 69% of the variance in exhaustion and 63% in disengagement. Exhaustion was significantly predicted by female sex (β effect size = −0.1), high perceived emotional demands (β = 0.19), as well as low self-compassion (β = −0.14) and low emotional competence (β = 0.09). Disengagement was significantly predicted by low seniority (β = −0.12) and limited opportunities for development (β = −0.16). Both exhaustion and disengagement were predicted by low perceived quality of work (β = −0.19 and −0.14, respectively), meaning of work (β = −0.17 and −0.31, respectively), and role clarity (β = 0.09 and 0.12, respectively), as well as high perceived work–life conflict (β = 0.46 and 0.21, respectively). Moreover, GPs working in a multidisciplinary group reported lower levels of exhaustion and disengagement than those working in a monodisciplinary group or a solo practice, and this difference was associated with factors such as work–life conflict. Conclusion: Organisational, interpersonal, and intrapersonal factors interact to predict a substantial part of burnout in general practice. The most significant risk factors were perceived work–life conflict and poor meaning of work. Policymakers should work to support more sustainable practices based on the specific needs and constraints reported by GPs.

Introduction Lymphoedema is a chronic condition caused by lymphatic insufficiency. It leads to swelling of the limb/midline region and an increased risk of infection. Lymphoedema is often associated with mental and physical problems limiting quality of life. The first choice of treatment is a conservative treatment, consisting of exercises, skin care, lymph drainage and compression. Reconstructive lymphatic surgery is also often performed, that is, lymphovenous anastomoses, lymph node transfer or a combination. However, robust evidence on the effectiveness of reconstructive lymphatic surgery is missing. Therefore, the objective of this trial is to investigate the added value of reconstructive lymphatic surgery to the conservative treatment in patients with lymphoedema.Methods and analysis A multicentre randomised controlled and pragmatic trial was started in March 2022 in three Belgian university hospitals. 90 patients with arm lymphoedema and 90 patients with leg lymphoedema will be included. All patients are randomised between conservative treatment alone (control group) or conservative treatment with reconstructive lymphatic surgery (intervention group). Assessments are performed at baseline and at 1, 3, 6, 12, 18, 24 and 36 months. The primary outcome is lymphoedema-specific quality of life at 18 months. Key secondary outcomes are limb volume and duration of wearing the compression garment at 18 months. The approach of reconstructive lymphatic surgery is based on presurgical investigations including clinical examination, lymphofluoroscopy, lymphoscintigraphy, lymph MRI or CT angiography (if needed). All patients receive conservative treatment during 36 months, which is applied by the patient’s own physical therapist and by the patient self. From months 7 to 12, the hours a day of wearing the compression garment are gradually decreased.Ethics and dissemination The study has been approved by the ethical committees of University Hospitals Leuven, Ghent University Hospital and CHU UCL Namur. Results will be disseminated via peer-reviewed journals and presentations.Trial registration number NCT05064176

ObjectivesWork-related stress is highly prevalent. Recent systematic reviews concluded on a significant association between common work-related stress measures and depression. Our scoping review aims to explore whether work-related psychosocial stress is generally associated with depression or depressiveness, the extent and methodology of the primary research undertaken on this topic and to elucidate inconsistencies or gaps in knowledge.MethodsWe searched for literature in Pubmed, PsycInfo and Web of Science including full reports in seven languages published between 1999 and 2022 and applied the PRISMA statement for scoping reviews criteria.ResultsOf 463 primarily identified articles, 125 were retained after abstract and full-text screening. The majority report significant associations between work-related stress and depression. Cross-sectional studies are most prevalent. Sufficient evidence exists only for job strain and effort-reward imbalance. Most studies are from Asia, North America and Europe. The health sector is the most studied. Several research gaps such as the lack of interventional studies were identified.ConclusionThe consistency of most studies on the significant association between work-related stress and depression is remarkable. More studies are needed to improve evidence and to close research gaps.

Introduction Around 1 in 1000–2000 pregnancies are affected by a cancer diagnosis. Previous studies have shown that chemotherapy during pregnancy has reassuring cognitive and cardiac neonatal outcomes, and hence has been proposed as standard of care. However, although these children perform within normal ranges for their age, subtle differences have been identified. Given that chemotherapeutic compounds can cross the placenta, the possibility that prenatal chemotherapy exposure mutates the offspring’s genome and/or epigenome, with potential deleterious effects later in life, urges to be investigated.Methods and analyses This multicentric observational study aims to collect cord blood, meconium and neonatal buccal cells at birth, as well as peripheral blood, buccal cells and urine from infants when 6, 18 and/or 36 months of age. Using bulk and single-cell approaches, we will compare samples from chemotherapy-treated pregnant patients with cancer, pregnant patients with cancer not treated with chemotherapy and healthy pregnant women. Potential chemotherapy-related newborn genomic and/or epigenomic alterations, such as single nucleotide variants, copy number variants and DNA-methylation alterations, will be identified in mononuclear and epithelial cells, isolated from blood, buccal swabs and urine. DNA from maternal peripheral blood and paternal buccal cells will be used to determine de novo somatic mutations in the neonatal blood and epithelial cells. Additionally, the accumulated exposure of the fetus, and biological effective dose of alkylating agents, will be assessed in meconium and cord blood via mass spectrometry approaches.Ethics and dissemination The Ethics Committee Research of UZ/KU Leuven (EC Research) and the Medical Ethical Review Committee of University Medical Center Amsterdam have approved the study. Results of this study will be disseminated via presentations at (inter)national conferences, through peer-reviewed, open-access publications, via social media platforms aimed to inform patients and healthcare workers, and through the website of the International Network on Cancer, Infertility and Pregnancy (www.cancerinpregnancy.org).

Chronic pain is a prevalent condition with a multifaceted pathogenesis, where epigenetic modifications, particularly DNA methylation, might play an important role. This review delves into the intricate mechanisms by which DNA methylation and demethylation regulate genes associated with nociception and pain perception in nociceptive pathways. We explore the dynamic nature of these epigenetic processes, mediated by DNA methyltransferases (DNMTs) and ten-eleven translocation (TET) enzymes, which modulate the expression of pro- and anti-nociceptive genes. Aberrant DNA methylation profiles have been observed in patients with various chronic pain syndromes, correlating with hypersensitivity to painful stimuli, neuronal hyperexcitability, and inflammatory responses. Genome-wide analyses shed light on differentially methylated regions and genes that could serve as potential biomarkers for chronic pain in the epigenetic landscape. The transition from acute to chronic pain is marked by rapid DNA methylation reprogramming, suggesting its potential role in pain chronicity. This review highlights the importance of understanding the temporal dynamics of DNA methylation during this transition to develop targeted therapeutic interventions. Reversing pathological DNA methylation patterns through epigenetic therapies emerges as a promising strategy for pain management.

Objectives Healthcare systems in European countries, including METEOR partner countries, are faced with the aging population, an increase in costs for innovative technologies and medication, a shortage of health professionals, and inequality in access to healthcare. Presented paper aimed to recognize and compare the functioning of healthcare systems between METEOR partner countries and simultaneously check if the current epidemiological situation of COVID-19 has some relationship with the number of medical staff, yearly gross domestic product, or documented percentage of fully vaccinated people. Material and Methods In the model of descriptive epidemiological study, available demographic, socioeconomic, and healthcare organizational data in the Netherlands, Belgium, Italy, and Poland were compared to the epidemiological situation of the COVID-19 pandemic (percentage of fully vaccinated people, incidence, and mortality) in all mentioned countries. Results Obtained data confirmed that the lowest number of physicians, as well as the life expectancy and gross domestic product per capita, is in Poland. Simultaneously, the lower number of medical staff and lower gross domestic product (GDP) correspond to higher mortality due to COVID-19. The percentage of fully vaccinated with the last dose of the primary series was also the lowest in Poland. Conclusions Obtained results confirmed that higher mortality due to COVID-19 in METEOR participants’ countries is related to a lower number of medical staff and weaker GDP. The worse situation was noted in Poland, a country with problems in the functioning healthcare system, including hospital care and a serious shortage of practicing medical staff. Int J Occup Med Environ Health. 2023;36(3):417–27

Abstract Background Insights around second victims (SV) and patient safety has been growing over time. An overview of the available evidence is lacking. This review aims to describe (i) the impact a patient safety incident can have and (ii) how healthcare professionals can be supported in the aftermath of a patient safety incident. Methods A literature search in Medline, EMBASE and CINAHL was performed between 1 and 2010 and 26 November 2020 with studies on SV as inclusion criteria. To be included in this review the studies must include healthcare professionals involved in the aftermath of a patient safety incident. Results In total 104 studies were included. SVs can suffer from both psychosocial (negative and positive), professional and physical reactions. Support can be provided at five levels. The first level is prevention (on individual and organizational level) referring to measures taken before a patient safety incident happens. The other four levels focus on providing support in the aftermath of a patient safety incident, such as self-care of individuals and/or team, support by peers and triage, structured support by an expert in the field (professional support) and structured clinical support. Conclusion The impact of a patient safety incident on healthcare professionals is broad and diverse. Support programs should be organized at five levels, starting with preventive actions followed by self-care, support by peers, structured professional support and clinical support. This multilevel approach can now be translated in different countries, networks and organizations based on their own culture, support history, structure and legal context. Next to this, they should also include the stage of recovery in which the healthcare professional is located in.

Persistent pollutants, namely brominated flame retardants (BFRs) and heavy metals, are compounds that are added to a wide range of products and materials for preventing ignition, increasing the functionality of materials or improving their performance, e.g. electric conductivity. The exposure of children might consequently be inferred, through indoor dust and hand-to-mouth or toy-chewing behaviors. The current study is aimed at assessing the exposure of Moroccan children to BFRs and heavy metal elements, and evaluating their associations with global DNA methylation. First, parents responded to a questionnaire pertaining to children’s lifestyle, then blood and urine samples were collected from (n = 93) children aged between 5 and 11 years for biomonitoring and DNA methylation analysis. BFRs were detected in 54.84% of samples with a median concentration of 0.01 nmol/mL (range: 0.004–0.051 nmol/mL) while metal elements were detected in more than 90% of samples. BFRs showed no variations with global DNA methylation, unlike metal elements, which revealed significant associations with global DNA methylation markers, namely 5-mC, 5-hmC and N⁶-mA levels. Moroccan children may be exposed to flame retardants and heavy metals through several routes. Further research is required to assess the exposure and the health impacts of environmental pollutants and ultimately protect the Moroccan population by the prevention of adverse health effects.

Objective: To identify the essential attributes of biopsychosocial rehabilitation for chronic low back pain in the working population. Design: A concept analysis was conducted according to the 8-step method of Walker and Avant. This framework provides a clear concept and theoretical and operational definitions. Methods: Five databases were searched, followed by a systematic screening. Subsequently, attributes, illustrative cases, antecedents, consequences and empirical referents were formulated. Results: Of the 3793 studies identified, 42 unique references were included. Eleven attributes were identified: therapeutic exercise, psychological support, education, personalization, self-management, participation, follow-up, practice standard, goal-setting, social support, and dietary advice. Subsequently, illustrative cases were described. Antecedents, such as motivation, preparedness and a multidisciplinary team, were found, together with consequences such as decreased pain, less sick-leave and increased function and work status. Finally, examples of empirical referents were given. Conclusion: This study identified the attributes that are necessary to develop biopsychosocial rehabilitation intervention programmes for chronic low back pain. The defined concept of biopsychosocial rehabilitation for chronic low back pain may serve as a solid base to further develop and apply interventions. Future research should focus on the objectification of biopsychosocial rehabilitation and conceptualization regarding how personalization is done.

Abstract Background For patients with therapy-refractory persistent spinal pain syndrome type II (PSPS-T2), spinal cord stimulation (SCS) may serve as an effective minimally invasive treatment. Despite the evidence that SCS can improve return to work (RTW), only 9.5 to 14% of patients implanted with SCS are effectively capable of returning to work. Thus, it seems that current post-operative interventions are not effective for achieving RTW after SCS implantation in clinical practice. The current objective is to examine whether a personalised biopsychosocial rehabilitation programme specifically targeting RTW alters the work ability in PSPS-T2 patients after SCS implantation compared to usual care. Methods A two-arm, parallel-group multicentre randomised controlled trial will be conducted including 112 patients who will be randomised (1:1) to either (a) a personalised biopsychosocial RTW rehabilitation programme of 14 weeks or (b) a usual care arm, both with a follow-up period until 12 months after the intervention. The primary outcome is work ability. The secondary outcomes are work status and participation, pain intensity, health-related quality of life, physical activity and functional disability, functional capacities, sleep quality, kinesiophobia, self-management, anxiety, depression and healthcare expenditure. Discussion Within the OPERA project, we propose a multidisciplinary personalised biopsychosocial rehabilitation programme specifically targeting RTW for patients implanted with SCS, to tackle the high socio-economic burden of patients that are not re-entering the labour market. The awareness is growing that the burden of PSPS-T2 on our society is expected to increase over time due to the annual increase of spinal surgeries. However, innovative and methodologically rigorous trials exploring the potential to decrease the socio-economic burden when patients initiate a trajectory with SCS are essentially lacking. Trial registration ClinicalTrials.gov NCT05269212. Registered on 7 March 2022.

Abstract Background Catechol-O-methyltransferase (COMT) has been shown to influence clinical pain, descending modulation, and exercise-induced symptom worsening. COMT regulates nociceptive processing and inflammation, key pathophysiological features of Chronic Fatigue Syndrome and Fibromyalgia (CFS/FM). We aimed to determine the interactions between genetic and epigenetic mechanisms regulating COMT and its influence on inflammatory markers and symptoms in patients with CFS/FM. Methods. A case-control study with repeated-measures design was used to reduce the chance of false positive and increase the power of our findings. Fifty-four participants (28 patients with CFS/FM and 26 controls) were assessed twice within 4 days. The assessment included clinical questionnaires, neurophysiological assessment (pain thresholds, temporal summation, and conditioned pain modulation), and blood withdrawal in order to assess rs4818, rs4633, and rs4680 COMT polymorphisms and perform haplotype estimation, DNA methylation in the COMT gene (both MB-COMT and S-COMT promoters), and cytokine expression (TNF-α, IFN-γ, IL-6, and TGF-β). Results. COMT haplotypes were associated with DNA methylation in the S-COMT promoter, TGF-β expression, and symptoms. However, this was not specific for one condition. Significant between-group differences were found for increased DNA methylation in the MB-COMT promoter and decreased IFN-γ expression in patients. Discussion Our results are consistent with basic and clinical research, providing interesting insights into genetic-epigenetic regulatory mechanisms. MB-COMT DNA methylation might be an independent factor contributing to the pathophysiology of CFS/FM. Further research on DNA methylation in complex conditions such as CFS/FM is warranted. We recommend future research to employ a repeated-measure design to control for biomarkers variability and within-subject changes.

There is a growing evidence that methylation at the N6 position of adenine (6-mA), whose modulation occurs primarily during development, would be a reliable epigenetic marker in eukaryotic organisms. The present study raises the question as to whether early-life exposure to α-hexabromocyclododecane (α-HBCDD), a brominated flame retardant, may trigger modifications in 6-mA epigenetic hallmarks in the brain during the development which, in turn could affect the offspring behaviour in adulthood. Pregnant Wistar rats were split into two groups: control and α-HBCDD (66 ng/kg/per os, G0-PND14). At PND1, α-HBCDD levels were assessed in brain and liver by LC-MS/MS. At PND14, DNA was isolated from the offspring’s cerebellum. DNA methylation was measured by 6-mA-specific immunoprecipitation and Illumina® sequencing (MEDIP-Seq). Locomotor activity was finally evaluated at PND120. In our early-life exposure model, we confirmed that α-HBCDD can cross the placental barrier and be detected in pups at birth. An obvious post-exposure phenotype with locomotor deficits was observed when the rats reached adulthood. This was accompanied by sex-specific over-methylation of genes involved in the insulin signaling pathway, MAPK signaling pathway as well as serotonergic and GABAergic synapses, potentially altering the normal process of neurodevelopment with consequent motor impairments crystalized at adulthood.

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 number of individual experts. Evidence from human, animal and mechanistic data suggests that occupational exposure to dusts and/or fibres (silica, asbestos and coal dust) causes pneumoconiosis. In this paper, we present a systematic review and meta-analysis of the prevalences and levels of occupational exposure to silica, asbestos and coal dust. These estimates of prevalences and levels will serve as input data for estimating (if feasible) the number of deaths and disability-adjusted life years that are attributable to occupational exposure to silica, asbestos and coal dust, for the development of the WHO/ILO Joint Estimates. Objectives: We aimed to systematically review and meta-analyse estimates of the prevalences and levels of occupational exposure to silica, asbestos and coal dust among working-age (≥ 15 years) workers. Data sources: We searched electronic academic databases for potentially relevant records from published and unpublished studies, including Ovid Medline, PubMed, EMBASE, and CISDOC. We also searched electronic grey literature databases, Internet search engines and organizational websites; hand-searched reference lists of previous systematic reviews and included study records; 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 (< 15 years) and unpaid domestic workers. We included all study types with objective dust or fibre measurements, published between 1960 and 2018, that directly or indirectly reported an estimate of the prevalence and/or level of occupational exposure to silica, asbestos and/or coal dust. 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, then data were extracted from qualifying studies. We combined prevalence estimates by industrial sector (ISIC-4 2-digit level with additional merging within Mining, Manufacturing and Construction) using random-effects meta-analysis. Two or more review authors assessed the risk of bias and all available authors assessed the quality of evidence, using the ROB-SPEO tool and QoE-SPEO approach developed specifically for the WHO/ILO Joint Estimates. Results: Eighty-eight studies (82 cross-sectional studies and 6 longitudinal studies) met the inclusion criteria, comprising > 2.4 million measurements covering 23 countries from all WHO regions (Africa, Americas, Eastern Mediterranean, South-East Asia, Europe, and Western Pacific). The target population in all 88 included studies was from major ISCO groups 3 (Technicians and Associate Professionals), 6 (Skilled Agricultural, Forestry and Fishery Workers), 7 (Craft and Related Trades Workers), 8 (Plant and Machine Operators and Assemblers), and 9 (Elementary Occupations), hereafter called manual workers. Most studies were performed in Construction, Manufacturing and Mining. For occupational exposure to silica, 65 studies (61 cross-sectional studies and 4 longitudinal studies) were included with > 2.3 million measurements collected in 22 countries in all six WHO regions. For occupational exposure to asbestos, 18 studies (17 cross-sectional studies and 1 longitudinal) were included with > 20,000 measurements collected in eight countries in five WHO regions (no data for Africa). For occupational exposure to coal dust, eight studies (all cross-sectional) were included comprising > 100,000 samples in six countries in five WHO regions (no data for Eastern Mediterranean). Occupational exposure to silica, asbestos and coal dust was assessed with personal or stationary active filter sampling; for silica and asbestos, gravimetric assessment was followed by technical analysis.Risk of bias profiles varied between the bodies of evidence looking at asbestos, silica and coal dust, as well as between industrial sectors. However, risk of bias was generally highest for the domain of selection of participants into the studies.The largest bodies of evidence for silica related to the industrial sectors of Construction (ISIC 41–43), Manufacturing (ISIC 20, 23–25, 27, 31–32) and Mining (ISIC 05, 07, 08). For Construction, the pooled prevalence estimate was 0.89 (95% CI 0.84 to 0.93, 17 studies, I2 91%, moderate quality of evidence) and the level estimate was rated as of very low quality of evidence. For Manufacturing, the pooled prevalence estimate was 0.85 (95% CI 0.78 to 0.91, 24 studies, I2 100%, moderate quality of evidence) and the pooled level estimate was rated as of very low quality of evidence. The pooled prevalence estimate for Mining was 0.75 (95% CI 0.68 to 0.82, 20 studies, I2 100%, moderate quality of evidence) and the pooled level estimate was 0.04 mg/m3 (95% CI 0.03 to 0.05, 17 studies, I2 100%, low quality of evidence). Smaller bodies of evidence were identified for Crop and animal production (ISIC 01; very low quality of evidence for both prevalence and level); Professional, scientific and technical activities (ISIC 71, 74; very low quality of evidence for both prevalence and level); and Electricity, gas, steam and air conditioning supply (ISIC 35; very low quality of evidence for both prevalence and level).For asbestos, the pooled prevalence estimate for Construction (ISIC 41, 43, 45,) was 0.77 (95% CI 0.65 to 0.87, six studies, I2 99%, low quality of evidence) and the level estimate was rated as of very low quality of evidence. For Manufacturing (ISIC 13, 23–24, 29–30), the pooled prevalence and level estimates were rated as being of very low quality of evidence. Smaller bodies of evidence were identified for Other mining and quarrying (ISIC 08; very low quality of evidence for both prevalence and level); Electricity, gas, steam and air conditioning supply (ISIC 35; very low quality of evidence for both prevalence and level); and Water supply, sewerage, waste management and remediation (ISIC 37; very low quality of evidence for levels).For coal dust, the pooled prevalence estimate for Mining of coal and lignite (ISIC 05), was 1.00 (95% CI 1.00 to 1.00, six studies, I2 16%, moderate quality of evidence) and the pooled level estimate was 0.77 mg/m3 (95% CI 0.68 to 0.86, three studies, I2 100%, low quality of evidence). A small body of evidence was identified for Electricity, gas, steam and air conditioning supply (ISIC 35); with very low quality of evidence for prevalence, and the pooled level estimate being 0.60 mg/m3 (95% CI −6.95 to 8.14, one study, low quality of evidence). Conclusions: Overall, we judged the bodies of evidence for occupational exposure to silica to vary by industrial sector between very low and moderate quality of evidence for prevalence, and very low and low for level. For occupational exposure to asbestos, the bodies of evidence varied by industrial sector between very low and low quality of evidence for prevalence and were of very low quality of evidence for level. For occupational exposure to coal dust, the bodies of evidence were of very low or moderate quality of evidence for prevalence, and low for level. None of the included studies were population-based studies (i.e., covered the entire workers’ population in the industrial sector), which we judged to present serious concern for indirectness, except for occupational exposure to coal dust within the industrial sector of mining of coal and lignite. Selected estimates of the prevalences and levels of occupational exposure to silica by industrial sector are considered suitable as input data for the WHO/ILO Joint Estimates, and selected estimates of the prevalences and levels of occupational exposure to asbestos and coal dust may perhaps also be suitable for estimation purposes.Protocol identifier:https://doi.org/10.1016/j.envint.2018.06.005.PROSPERO registration number:CRD42018084131.

Pesticides, a major group of biocides, are designed to control harmful and/or unwanted organisms [...]

Abstract Objectives The main purpose of this longitudinal study was to elucidate the impact of external job mobility, due to a change of employer, on mental health. Methods A cohort of Belgian employees from the IDEWE occupational medicine registry was followed-up for twenty-seven years, from 1993 to 2019. The use of drugs for neuropsychological diseases was considered as an objective indicator of mental health. The covariates were related to demographic, physical, behavioural characteristics, occupational and work-related risks. Propensity scores were calculated with a Cox regression model with time-varying covariates. The PS matching was used to eliminate the systematic differences in subjects’ characteristics and to balance the covariates’ distribution at every time point. Results The unmatched sample included 11,246 subjects, with 368 (3.3%) that changed their job during the baseline year and 922 (8.2%) workers that left their employer during the follow-up. More than half of the matched sample were males, were aged less than 38 years old, did not smoke, were physically active, and normal weighted, were not exposed to shift-work, noise, job strain or physical load. A strong association between job mobility and neuropsychological treatment was found in the matched analysis (HR = 2.065, 95%CI = 1.397–3.052, P-value

Introduction: Co-creation is becoming increasingly popular to develop interventions that can achieve results beyond scientific findings. Workshops are one of the main ways to collect data and generate ideas in co-creation, which traditionally have been conducted at a fixed, physical location. However, organising face-to-face workshops is considered challenging, due to the transportation time, low flexibility and high costs. This study aims to investigate the online format of co-creation workshops and to discuss methodological considerations. Methods: Co-creation workshops were organised with 78 medical students, general practitioner (GP) trainees and specialist trainees from five Belgian universities. The study included four different cohorts, namely first-year bachelors ( n = 12), first-year masters ( n = 13), first-year GP trainees ( n = 14) and first-year specialist trainees ( n = 39). Three consequential online workshops were organised for each cohort, resulting in 12 workshops in total. The collected data included qualitative data (video-and audio recordings, notes from interdisciplinary team discussions, Miro boards) and quantitative data (registrations and actual attendance rates). All workshops were transcribed verbatim and thematically analysed using NVivo. Results: The participants reported increased flexibility and reduced costs as main benefits of the online format. In addition, the online platforms Miro and Microsoft Teams were considered dynamic and inspiring, facilitating high levels of engagement and interactivity. However, the online format also showed some challenges, such as the need for a digitally educated population and a stable internet connection. Conclusion: This study has shown that online workshops, also in the highly interactive method of co-creation, provide a viable alternative to collect data and generate ideas. This is particularly the case, when the target population is geographically dispersed, has a high workload and is digitally educated. Online workshops, however, also face limitations and challenges that need to be considered when choosing this format.

The shortage of healthcare workers is a growing problem across the globe. Nurses and physicians, in particular, are vulnerable as a result of the COVID-19 pandemic. Understanding why they might leave is imperative for improving retention. This systematic review explores both the prevalence of nurses and physicians who are intent on leaving their position at hospitals in European countries and the main determinants influencing job retention among nurses and physicians of their respective position in a hospital setting in both European and non-European countries. A comprehensive search was fulfilled within 3 electronic databases on June 3rd 2021. In total 345 articles met the inclusion criteria. The determinants were categorized into 6 themes: personal characteristics, job demands, employment services, working conditions, work relationships, and organizational culture. The main determinants for job retention were job satisfaction, career development and work-life balance. European and non-European countries showed similarities and differences in determinants influencing retention. Identifying these factors supports the development of multifactorial interventions, which can aid the formulation of medical strategies and help to maximize retention.

OBJECTIVES: In many countries, organisations are legally obliged to have occupational physicians screen employees regularly. However, this system is time-intensive, and there may be more cost-effective alternatives. Our objective is to compare the short-term effectiveness of periodic occupational health screening of hospital employees by an occupational physician with a system of electronic screening with targeted follow-up. METHODS: A randomized controlled trial was set up among personnel of four Belgian hospitals, with three measurement moments between June 2019 and December 2020, to compare differences in self-assessed health, healthcare use, productivity and intermediate outcomes over 19 months. Mixed effects models were used to assess differences in effectiveness. Superiority and non-inferiority post-hoc tests were used as a robustness check. The experiment coincided with the first two COVID-19 waves during which hospital employees were exposed to an exceptional period of occupational stress. RESULTS: In total, 1077 employees (34% of the target population) participated. Although we observed some immediate effects of the intervention (less trust in the physician, absenteeism, and healthcare use), all these effects disappeared over time. After 19 months, including two waves of COVID-19 hospitalizations, no significant differences were observed between employees screened through face-to-face contact and those screened electronically. CONCLUSIONS: Our study finds no indication that, in the short-term, substituting physician screening of the workforce with a quicker survey-based screening with targeted follow-up has different effects on the studied endpoints. However, as health and disease are often the result of a long-term process, more evidence is needed to determine long-term effects.

Highlights • Team worker is the most frequently preferred team role among medical students, regardless of gender or specialty. • Female students scored higher on the Team Worker role compared to male students. • Team Workers were more present in future general practitioners and lower in technique-oriented specialties, with students who chose a person-centered specialty in the middle. • Medical education should stimulate teamwork skills throughout the entire educational career, from the admission process to curricula to residency .

IntroductionEpigenetic marks have been proposed as early changes, at the subcellular level, in disease development. To find more specific biomarkers of effect in occupational exposures to toxicants, DNA methylation studies in peripheral blood cells have been performed. The goal of this review is to summarize and contrast findings about DNA methylation in blood cells from workers exposed to toxicants.MethodsA literature search was performed using PubMed and Web of Science. After first screening, we discarded all studies performed in vitro and in experimental animals, as well as those performed in other cell types other than peripheral blood cells. Results: 116 original research papers met the established criteria, published from 2007 to 2022. The most frequent investigated exposures/labor group were for benzene (18.9%) polycyclic aromatic hydrocarbons (15.5%), particulate matter (10.3%), lead (8.6%), pesticides (7.7%), radiation (4.3%), volatile organic compound mixtures (4.3%), welding fumes (3.4%) chromium (2.5%), toluene (2.5%), firefighters (2.5%), coal (1.7%), hairdressers (1.7%), nanoparticles (1.7%), vinyl chloride (1.7%), and others. Few longitudinal studies have been performed, as well as few of them have explored mitochondrial DNA methylation. Methylation platforms have evolved from analysis in repetitive elements (global methylation), gene-specific promoter methylation, to epigenome-wide studies. The most reported observations were global hypomethylation as well as promoter hypermethylation in exposed groups compared to controls, while methylation at DNA repair/oncogenes genes were the most studied; studies from genome-wide studies detect differentially methylated regions, which could be either hypo or hypermethylated.DiscussionSome evidence from longitudinal studies suggest that modifications observed in cross-sectional designs may be transitory; then, we cannot say that DNA methylation changes are predictive of disease development due to those exposures.ConclusionDue to the heterogeneity in the genes studied, and scarcity of longitudinal studies, we are far away from considering DNA methylation changes as biomarkers of effect in occupational exposures, and nor can we establish a clear functional or pathological correlate for those epigenetic modifications associated with the studied exposures.

Objective Synthesising evidence of the effects of interventions to improve work participation among people with health problems is currently difficult due to heterogeneity in outcome measurements. A core outcome set for work participation is needed.Study design and setting Following the Core Outcome Measures in Effectiveness Trials methodology, we used a five-step approach to reach international multistakeholder consensus on a core outcome set for work participation. Five subgroups of stakeholders took part in two rounds of discussions and completed two Delphi voting rounds on 26 outcomes. A consensus of ≥80% determined core outcomes and 50%–80% consensus was required for candidate outcomes.Results Fifty-eight stakeholders took part in the Delphi rounds. Core outcomes were: ‘any type of employment including self-employment’, ‘proportion of workers that return to work after being absent because of illness’ and ‘time to return to work’. Ten candidate outcomes were proposed, among others: ‘sustainable employment’, ‘work productivity’ and ‘workers’ perception of return to work’.Conclusion As a minimum, all studies evaluating the impact of interventions on work participation should include one employment outcome and two return to work outcomes if workers are on sick leave prior to the intervention.

Abstract The Covid-19 pandemic is primarily viewed as a threat to physical health, and therefore, biomedical sciences have become an integral part of the public discourse guiding policy decisions. Nonetheless, the pandemic and the measures implemented have an impact on the population’s psychosocial health. The impact of Covid-19 on the psychosocial care system should be thoroughly investigated to mitigate this effect. In this context, the present study was conducted to establish a consensus about the impact of Covid-19 on psychosocial health and the care system in Belgium. Using the Belgian Superior Health Council’s expert database, a three-round Delphi consensus development process was organized with psychosocial experts (i.e., professionals, patients, and informal caregiver representatives). Overall, 113 of the 148 experts who participated in round 1 fully completed round 2 (76% response rate). Consensus (defined as >70% agreement and an interquartile interval (IQR) of no more than 2) was reached in round 2 for all but three statements. Fifty experts responded to round 3 by providing some final nuances, but none of them reaffirmed their positions or added new points to the discussion (44.25% response rate). The most robust agreement (>80%) was found for three statements: the pandemic has increased social inequalities in society, which increase the risk of long-term psychosocial problems; the fear of contamination creates a constant mental strain on the population, wearing people out; and there is a lack of strategic vision about psychosocial care and an underestimation of the importance of psychosocial health in society. Our findings show that experts believe the psychosocial impact of Covid-19 is underappreciated, which has a negative impact on psychosocial care in Belgium. Several unmet needs were identified, but so were helpful resources and barriers. The Delphi study’s overarching conclusion is that the pandemic does not affect society as a whole in the same way or with the same intensity. The experts, thereby, warn that the psychosocial inequalities in society are on the rise.

The shortage of healthcare workers is a growing concern. The COVID-19 pandemic and retirement wave have accelerated turnover rates. This systematic review aimed to identify and analyse the existing interventions for job retention of healthcare workers, in terms of nurses and physicians, in a hospital setting. A comprehensive search was conducted within three electronic databases, guided by the preferred reporting items for systematic review and meta-analyses (PRISMA) and synthesis without meta-analysis (SWiM) guidelines, this resulted in 55 records that met the inclusion criteria. The intervention outcomes are categorized into substantial themes: onboarding, transition program to a different unit, stress coping, social support, extra staffing, coping with the demands of patient care, work relationships, development opportunities and department resources, job environment, work organization, recruitment approach, and technological innovations. Considering the literature, onboarding programs and mentoring for nurses and physicians are recommended. Additionally, other interventions described in this review could positively affect the retention of nurses and physicians. When selecting an intervention for implementation, managers and human resources should consider the intervention that matches the determinant of intention to leave of their healthcare workers and the hospital’s mission, vision, and values. Sharing the success stories of implemented interventions may benefit healthcare organizations.

Firefighters are exposed via multi-route exposure to a multitude of chemicals (PAHs, VOCs, flame retardants, dioxins, etc.) that may cause acute and long-term health effects. The dermal absorption of contaminants is a major contributor to the overall exposure and can be reduced by wearing appropriate personal protective equipment. As leather firefighters’ gloves cannot be decontaminated regularly by wet cleaning, many Belgian firefighters wear supplementary undergloves made of nitrile butadiene rubber (NBR) to protect against the accumulation of toxicants. However, the safety of this practice has been questioned. In this commentary, the current practice and risks are outlined for the first time, assessed by an interdisciplinary working group of the Belgian Superior Health Council. As NBR sticks to the skin more at high temperatures, the contact time on removal will be prolonged, posing an additional risk for deeper burns. However, based on the physicochemical properties of NBR and the existing experience of firefighters and burn centers, it is estimated that such incidents occur relatively rarely in practice. On the other hand, the risk of repeated exposure to contaminated gloves if no undergloves are worn is unacceptable. Despite the slightly increased risk for deeper burns, it is concluded that wearing disposable NBR gloves under regular firefighters’ gloves is an appropriate and effective preventive measure against toxic contamination. The nitrile butadiene rubber must always be fully covered to avoid any contact with the heat.

BackgroundInternational research emphasizes the importance of providing early, hospital-based support in return to work (RTW) for cancer patients. Even though oncology health professionals are aware of the scientific evidence, it remains unclear whether they implement this knowledge in current practice. This paper presents the knowledge and viewpoints of health care professionals (HCPs) on their potential role in their patients' RTW process.MethodsSemi-structured interviews with oncology HCPs were used to describe current practice. Results of these interviews served as input for focus group discussions with managers in oncology hospitals, which led to an agreement on of best practice.ResultsThis research had the participation of 75% of Belgian institutions involved in oncology health care services. Five themes were identified that influence care providers and staff to implement scientific evidence on RTW in cancer patients: (1) Opinions on the role that care institutions can take in RTW support; (2) Current content of RTW support during oncology care; (3) Scientific bases; (4) Barriers and success factors; and (5) Legislation and regulations. The key elements of the best practice included a generic approach adapted to the needs of the cancer patient supported by a RTW coordinator.ConclusionsHealth care providers include RTW support in their current care, but in very varied ways. They follow a process that starts with setting the indication (meaning the identification of patients for whom the provision of work-related care would be useful) and ends with a clear objective agreed upon by HCPs and the patient. We recommend that specific points of interest be included in regulation at both the patient and hospital levels.

BackgroundIgG anti-spike (S) antibodies arise after SARS-CoV-2 infection as well as vaccination. Levels of IgG anti-S are linked to neutralizing antibody titers and protection against (re)infection.MethodsWe measured IgG anti-S and surrogate neutralizing antibody kinetics against Wild Type (WT) and 4 Variants of Concern (VOC) in health care workers (HCW) 3 and 10 months after natural infection (“infection”, n=83) or vaccination (2 doses of BNT162b2) with (“hybrid immunity”, n=17) or without prior SARS-CoV-2 infection (“vaccination”, n=97).ResultsThe humoral immune response in the “vaccination” cohort was higher at 3 months, but lower at 10 months, compared to the “infection” cohort due to a faster decline. The “hybrid immunity” cohort had the highest antibody levels at 3 and 10 months with a slower decline compared to the “vaccination” cohort. Surrogate neutralizing antibody levels (expressed as %inhibition of ACE-2 binding) showed a linear relation with log10 of IgG anti-S against WT and four VOC. IgG anti-S corresponding to 90% inhibition ranged from 489 BAU/mL for WT to 1756 BAU/mL for Beta variant. Broad pseudoneutralization predicted live virus neutralization of Omicron BA.1 in 20 randomly selected high titer samples.ConclusionsHybrid immunity resulted in the strongest humoral immune response. Antibodies induced by natural infection decreased more slowly than after vaccination, resulting in higher antibody levels at 10 months compared to vaccinated HCW without prior infection. There was a linear relationship between surrogate neutralizing activity and log10 IgG anti-S for WT and 4 VOC, although some VOC showed reduced sensitivity to pseudoneutralization.

OBJECTIVE: A consensual definition of occupational burnout is currently lacking. We aimed to harmonize the definition of occupational burnout as a health outcome in medical research and reach a consensus on this definition within the Network on the Coordination and Harmonisation of European Occupational Cohorts (OMEGA-NET). METHODS: First, we performed a systematic review in MEDLINE, PsycINFO and Embase (January 1990 to August 2018) and a semantic analysis of the available definitions. We used the definitions of burnout and burnout-related concepts from the Systematized Nomenclature of Medicine Clinical Terms (SNOMED-CT) to formulate a consistent harmonized definition of the concept. Second, we sought to obtain the Delphi consensus on the proposed definition. RESULTS: We identified 88 unique definitions of burnout and assigned each of them to 1 of the 11 original definitions. The semantic analysis yielded a first proposal, further reformulated according to SNOMED-CT and the panelists` comments as follows: "In a worker, occupational burnout or occupational physical AND emotional exhaustion state is an exhaustion due to prolonged exposure to work-related problems”. A panel of 50 experts (researchers and healthcare professionals with an interest for occupational burnout) reached consensus on this proposal at the second round of the Delphi, with 82% of experts agreeing on it. CONCLUSION: This study resulted in a harmonized definition of occupational burnout approved by experts from 29 countries within OMEGA-NET. Future research should address the reproducibility of the Delphi consensus in a larger panel of experts, representing more countries, and examine the practicability of the definition.

IntroductionBurnout is a growing problem among young researchers, affecting individuals, organizations and society. Our study aims to identify burnout profiles and highlight the corresponding job demands and resources, resulting in recommendations to reduce burnout risk in the academic context.MethodsThis cross-sectional study collected data from young researchers (n = 1,123) at five Flemish universities through an online survey measuring burnout risk, work engagement, sleeping behavior, and the most prominent job demands (e.g., publication pressure) and resources (e.g., social support). We conducted Latent Profile Analysis (LPA) to identify burnout profiles in young researchers and subsequently compared these groups on job demands and resources patterns.ResultsFive burnout profiles were identified: (1) High Burnout Risk (9.3%), (2) Cynical (30.1%), (3) Overextended (2.3%), (4) Low Burnout Risk (34.8%), and (5) No Burnout Risk (23.6%). Each burnout profile was associated with a different pattern of job demands and resources. For instance, high levels of meaningfulness (OR = −1.96) decreased the odds to being classified in the Cynical profile.ConclusionOur findings show that the Cynical profile corresponds to a relatively high number of young researchers, which may imply that they are particularly vulnerable to the cynicism dimension of burnout. Additionally, work-life interference and perceived publication pressure seemed the most significant predictors of burnout risk, while meaningfulness, social support from supervisor and learning opportunities played an important protective role.

Background: The World Health Organization (WHO) and the International Labour Organization (ILO) have produced the WHO/ILO Joint Estimates of the Work-related Burden of Disease and Injury (WHO/ILO Joint Estimates). For these, systematic reviews of studies estimating the prevalence of exposure to selected occupational risk factors have been conducted to provide input data for estimations of the number of exposed workers. A critical part of systematic review methodology is to assess the quality of evidence across studies. In this article, we present the approach applied in these WHO/ILO systematic reviews for performing such assessments on studies of prevalence of exposure. It is called the Quality of Evidence in Studies estimating Prevalence of Exposure to Occupational risk factors (QoE-SPEO) approach. We describe QoE-SPEO’s development to date, demonstrate its feasibility reporting results from pilot testing and case studies, note its strengths and limitations, and suggest how QoE-SPEO should be tested and developed further. Methods: Following a comprehensive literature review, and using expert opinion, selected existing quality of evidence assessment approaches used in environmental and occupational health were reviewed and analysed for their relevance to prevalence studies. Relevant steps and components from the existing approaches were adopted or adapted for QoE-SPEO. New steps and components were developed. We elicited feedback from other systematic review methodologists and exposure scientists and reached consensus on the QoE-SPEO approach. Ten individual experts pilot-tested QoE-SPEO. To assess inter-rater agreement, we counted ratings of expected (actual and non-spurious) heterogeneity and quality of evidence and calculated a raw measure of agreement (Pi) between individual raters and rater teams for the downgrade domains. Pi ranged between 0.00 (no two pilot testers selected the same rating) and 1.00 (all pilot testers selected the same rating). Case studies were conducted of experiences of QoE-SPEO’s use in two WHO/ILO systematic reviews. Results: We found no existing quality of evidence assessment approach for occupational exposure prevalence studies. We identified three relevant, existing approaches for environmental and occupational health studies of the effect of exposures. Assessments using QoE-SPEO comprise three steps: (1) judge the level of expected heterogeneity (defined as non-spurious variability that can be expected in exposure prevalence, within or between individual persons, because exposure may change over space and/or time), (2) assess downgrade domains, and (3) reach a final rating on the quality of evidence. Assessments are conducted using the same five downgrade domains as the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach: (a) risk of bias, (b) indirectness, (c) inconsistency, (d) imprecision, and (e) publication bias. For downgrade domains (c) and (d), the assessment varies depending on the level of expected heterogeneity. There are no upgrade domains. The QoE-SPEO’s ratings are “very low”, “low”, “moderate”, and “high”. To arrive at a final decision on the overall quality of evidence, the assessor starts at “high” quality of evidence and for each domain downgrades by one or two levels for serious concerns or very serious concerns, respectively. In pilot tests, there was reasonable agreement in ratings for expected heterogeneity; 70% of raters selected the same rating. Inter-rater agreement ranged considerably between downgrade domains, both for individual rater pairs (range Pi: 0.36–1.00) and rater teams (0.20–1.00). Sparse data prevented rigorous assessment of inter-rater agreement in quality of evidence ratings. Conclusions: We present QoE-SPEO as an approach for assessing quality of evidence in prevalence studies of exposure to occupational risk factors. It has been developed to its current version (as presented here), has undergone pilot testing, and was applied in the systematic reviews for the WHO/ILO Joint Estimates. While the approach requires further testing and development, it makes steps towards filling an identified gap, and progress made so far can be used to inform future work in this area.

Abstract Background The terms agglomerates and aggregates are frequently used in the regulatory definition(s) of nanomaterials (NMs) and hence attract attention in view of their potential influence on health effects. However, the influence of nanoparticle (NP) agglomeration and aggregation on toxicity is poorly understood although it is strongly believed that smaller the size of the NPs greater the toxicity. A toxicologically relevant definition of NMs is therefore not yet available, which affects not only the risk assessment process but also hinders the regulation of nano-products. In this study, we assessed the influence of NP agglomeration on their toxicity/biological responses in vitro and in vivo. Results We tested two TiO2 NPs with different primary sizes (17 and 117 nm) and prepared ad-hoc suspensions composed of small or large agglomerates with similar dispersion medium composition. For in vitro testing, human bronchial epithelial (HBE), colon epithelial (Caco2) and monocytic (THP-1) cell lines were exposed to these suspensions for 24 h and endpoints such as cytotoxicity, total glutathione, epithelial barrier integrity, inflammatory mediators and DNA damage were measured. Large agglomerates of 17 nm TiO2 induced stronger responses than small agglomerates for glutathione depletion, IL-8 and IL-1β increase, and DNA damage in THP-1, while no effect of agglomeration was observed with 117 nm TiO2. In vivo, C57BL/6JRj mice were exposed via oropharyngeal aspiration or oral gavage to TiO2 suspensions and, after 3 days, biological parameters including cytotoxicity, inflammatory cell recruitment, DNA damage and biopersistence were measured. Mainly, we observed that large agglomerates of 117 nm TiO2 induced higher pulmonary responses in aspirated mice and blood DNA damage in gavaged mice compared to small agglomerates. Conclusion Agglomeration of TiO2 NPs influences their toxicity/biological responses and, large agglomerates do not appear less active than small agglomerates. This study provides a deeper insight on the toxicological relevance of NP agglomerates and contributes to the establishment of a toxicologically relevant definition for NMs.

Abstract Background The regulatory definition(s) of nanomaterials (NMs) frequently uses the term ‘agglomerates and aggregates’ (AA) despite the paucity of evidence that AA are significantly relevant from a nanotoxicological perspective. This knowledge gap greatly affects the safety assessment and regulation of NMs, such as synthetic amorphous silica (SAS). SAS is used in a large panel of industrial applications. They are primarily produced as nano-sized particles (1–100 nm in diameter) and considered safe as they form large aggregates (> 100 nm) during the production process. So far, it is indeed believed that large aggregates represent a weaker hazard compared to their nano counterpart. Thus, we assessed the impact of SAS aggregation on in vitro cytotoxicity/biological activity to address the toxicological relevance of aggregates of different sizes. Results We used a precipitated SAS dispersed by different methods, generating 4 ad-hoc suspensions with different aggregate size distributions. Their effect on cell metabolic activity, cell viability, epithelial barrier integrity, total glutathione content and, IL-8 and IL-6 secretion were investigated after 24 h exposure in human bronchial epithelial (HBE), colon epithelial (Caco2) and monocytic cells (THP-1). We observed that the de-aggregated suspension (DE-AGGR), predominantly composed of nano-sized aggregates, induced stronger effects in all the cell lines than the aggregated suspension (AGGR). We then compared DE-AGGR with 2 suspensions fractionated from AGGR: the precipitated fraction (PREC) and the supernatant fraction (SuperN). Very large aggregates in PREC were found to be the least cytotoxic/biologically active compared to other suspensions. SuperN, which contains aggregates larger in size (> 100 nm) than in DE-AGGR but smaller than PREC, exhibited similar activity as DE-AGGR. Conclusion Overall, aggregation resulted in reduced toxicological activity of SAS. However, when comparing aggregates of different sizes, it appeared that aggregates > 100 nm were not necessarily less cytotoxic than their nano-sized counterparts. This study suggests that aggregates of SAS are toxicologically relevant for the definition of NMs.

Background: As part of the development of the World Health Organization (WHO)/International Labour Organization (ILO) Joint Estimates of the Work-related Burden of Disease and Injury, WHO and ILO carried out several systematic reviews to determine the prevalence of exposure to selected occupational risk factors. Risk of bias assessment for individual studies is a critical step of a systematic review. No tool existed for assessing the risk of bias in prevalence studies of exposure to occupational risk factors, so WHO and ILO developed and pilot tested the RoB-SPEO tool for this purpose. Here, we investigate the assessor burden, inter-rater agreement, and user experience of this new instrument, based on the abovementioned WHO/ILO systematic reviews. Methods: Twenty-seven individual experts applied RoB-SPEO to assess risk of bias. Four systematic reviews provided a total of 283 individual assessments, carried out for 137 studies. For each study, two or more assessors independently assessed risk of bias across the eight RoB-SPEO domains selecting one of RoB-SPEO’s six ratings (i.e., “low”, “probably low”, “probably high”, “high”, “unclear” or “cannot be determined”). Assessors were asked to report time taken (i.e. indicator of assessor burden) to complete each assessment and describe their user experience. To gauge assessor burden, we calculated the median and inter-quartile range of times taken per individual risk of bias assessment. To assess inter-rater reliability, we calculated a raw measure of inter-rater agreement (Pi) for each RoB-SPEO domain, between Pi = 0.00, indicating no agreement and Pi = 1.00, indicating perfect agreement. As subgroup analyses, Pi was also disaggregated by systematic review, assessor experience with RoB-SPEO (≤10 assessments versus > 10 assessments), and assessment time (tertiles: ≤25 min versus 26–66 min versus ≥ 67 min). To describe user experience, we synthesised the assessors’ comments and recommendations. Results: Assessors reported a median of 40 min to complete one assessment (interquartile range 21–120 min). For all domains, raw inter-rater agreement ranged from 0.54 to 0.82. Agreement varied by systematic review and assessor experience with RoB-SPEO between domains, and increased with increasing assessment time. A small number of users recommended further development of instructions for selected RoB-SPEO domains, especially bias in selection of participants into the study (domain 1) and bias due to differences in numerator and denominator (domain 7). Discussion: Overall, our results indicated good agreement across the eight domains of the RoB-SPEO tool. The median assessment time was comparable to that of other risk of bias tools, indicating comparable assessor burden. However, there was considerable variation in time taken to complete assessments. Additional time spent on assessments may improve inter-rater agreement. Further development of the RoB-SPEO tool could focus on refining instructions for selected RoB-SPEO domains and additional testing to assess agreement for different topic areas and with a wider range of assessors from different research backgrounds.