Applying a 'presumably plausible' principle in a new one-time financial compensation system for occupational diseases in the Netherlands.

OBJECTIVES: In the Netherlands, a new regulation has been adopted for recognition and compensation of serious substance-related occupational diseases. A national advisory committee has a key task of providing advice on the protocols for operationalisation of individual causality assessment in this new context. METHODS: Protocol development involves gathering the best available population-level evidence on causality and using this evidence to determine individual causality. Here, the presumably plausible principle was adopted, which stipulates that uncertainties in individual causality should be weighed in favour of a fast and transparent one-time compensation for (ex-)workers. RESULTS: In monocausal diseases, a limited workplace exposure assessment is considered sufficient to determine whether individual causality is presumably plausible in the Dutch context. For multicausal occupational diseases, individual causality assessment is more complicated. Modelling of existing data on the exposure-response relation helps establish the probability of causation, that is, the risk of the disease attributable to a work-related exposure. This operationalisation, applied in some protocols, makes use of the probability of causation, while being prudent in establishing exposure limits. An example from asbestos and lung cancer is provided in this short report. CONCLUSIONS: We propose a pragmatic approach to individual causality assessment of substance-related occupational diseases, considering statistical and diagnostic uncertainties. This approach substantiates protocols towards a one-time financial compensation without long-winding recognition procedures.

Associations of occupational and leisure-time physical activity with all-cause mortality: an individual participant data meta-analysis.

OBJECTIVE: Health effects of different physical activity domains (ie, during leisure time, work and transport) are generally considered positive. Using Active Worker consortium data, we assessed independent associations of occupational and leisure-time physical activity (OPA and LTPA) with all-cause mortality. DESIGN: Two-stage individual participant data meta-analysis. DATA SOURCE: Published and unpublished cohort study data. ELIGIBILITY CRITERIA: Working participants aged 18-65 years. METHODS: After data harmonisation, we assessed associations of OPA and LTPA with all-cause mortality. In stage 1, we analysed data from each study separately using Cox survival regression, and in stage 2, we pooled individual study findings with random-effects modelling. RESULTS: In 22 studies with up to 590 497 participants from 11 countries, during a mean follow-up of 23.1 (SD: 6.8) years, 99 743 (16%) participants died. Adjusted for LTPA, body mass index, age, smoking and education level, summary (ie, stage 2) hazard ration (HRs) and 95% confidence interval (95% CI) for low, moderate and high OPA among men (n=2 96 134) were 1.01 (0.99 to 1.03), 1.05 (1.01 to 1.10) and 1.12 (1.03 to 1.23), respectively. For women (n=2 94 364), HRs (95% CI) were 0.98 (0.92 to 1.04), 0.96 (0.92 to 1.00) and 0.97 (0.86 to 1.10), respectively. In contrast, higher levels of LTPA were inversely associated with mortality for both genders. For example, for women HR for low, moderate and high compared with sedentary LTPA were 0.85 (0.81 to 0.89), 0.78 (0.74 to 0.81) and 0.75 (0.65 to 0.88), respectively. Effects were attenuated when adjusting for income (although data on income were available from only 9 and 6 studies, for men and women, respectively). CONCLUSION: Our findings indicate that OPA may not result in the same beneficial health effects as LTPA.

Should workers be physically active after work? Associations of leisure-time physical activity with cardiovascular and all-cause mortality across occupational physical activity levels-An individual participant data meta-analysis.

BACKGROUND: There is insufficient evidence to provide recommendations for leisure-time physical activity among workers across various occupational physical activity levels. This study aimed to assess the association of leisure-time physical activity with cardiovascular and all-cause mortality across occupational physical activity levels. METHODS: This study utilized individual participant data from 21 cohort studies, comprising both published and unpublished data. Eligibility criteria included individual-level data on leisure-time and occupational physical activity (categorized as sedentary, low, moderate, and high) along with data on all-cause and/or cardiovascular mortality. A 2-stage individual participant data meta-analysis was conducted, with separate analysis of each study using Cox proportional hazards models (Stage 1). These results were combined using random-effects models (Stage 2). RESULTS: Higher leisure-time physical activity levels were associated with lower all-cause and cardiovascular mortality risk across most occupational physical activity levels, for both males and females. Among males with sedentary work, high compared to sedentary leisure-time physical activity was associated with lower all-cause (hazard ratios (HR) = 0.77, 95% Confidence interval(95%CI): 0.70-0.85) and cardiovascular mortality (HR = 0.76, 95%CI: 0.66-0.87) risk. Among males with high levels of occupational physical activity, high compared to sedentary leisure-time physical activity was associated with lower all-cause (HR = 0.84, 95%CI: 0.74-0.97) and cardiovascular mortality (HR = 0.79, 95%CI: 0.60-1.04) risk, while HRs for low and moderate levels of leisure-time physical activity ranged between 0.87 and 0.97 and were not statistically significant. Among females, most effects were similar but more imprecise, especially in the higher occupational physical activity levels. CONCLUSION: Higher levels of leisure-time physical activity were generally associated with lower mortality risks. However, results for workers with moderate and high occupational physical activity levels, especially women, were more imprecise. Our findings suggests that workers may benefit from engaging in high levels of leisure-time physical activity, irrespective of their level of occupational physical activity.

The effects of working with a passive arm-support exoskeleton on objective and self-reported measures during field tasks - a randomised cross-over study.

Musculoskeletal disorders (MSDs) are prevalent under poor working situations. Where it is not possible to remove the root cause of MSDs, passive exoskeletons could be a solution. In this randomised cross-over field study we investigated the effect of a passive arm-support exoskeleton. Ten participants, recruited from a Dutch gas company, were measured with and without exoskeleton assessing muscle activity, heart rate (HR), arm elevation, and reported about their experiences. Participants spent more time in high arm elevation levels with the exoskeleton than without. Muscle activity was lower in the trapezius (Beta: -1.8 [-3.1; -0.4]) and deltoid (Beta: -1.4 [-2.3; -0.6]) muscles, but not the biceps muscle, during the measurements with exoskeleton than without, suggesting effectiveness of the exoskeleton. HR and discomfort did not statistically significantly differ between the two conditions. Participants would recommend an exoskeleton to their colleagues, but mainly for repetitive work. Their opinions about the usefulness during work varied.

This randomised cross-over field study examined the effect of a passive arm-supporting exoskeleton during field tasks by participants working at a Dutch gas company. It turned out that the exoskeleton had a positive effect on reducing muscle activity. Although most participants would recommend an exoskeleton to their colleagues, some participants reported discomfort while using the exoskeleton and less than half of the participants would use the exoskeleton more often themselves.

(Cost-)effectiveness of personalised multimodal physiotherapy compared to surgery in patients with cervical radiculopathy: A systematic review.

RATIONALE: Cervical radiculopathy is initially typically managed conservatively. Surgery is indicated when conservative management fails or with severe/progressive neurological signs. Personalised multimodal physiotherapy could be a promising conservative strategy. However, aggregated evidence on the (cost-)effectiveness of personalised multimodal physiotherapy compared to surgery with/without post-operative physiotherapy is lacking. AIM/OBJECTIVES: To systematically summarise the literature on the (cost-)effectiveness of personalised multimodal physiotherapy compared to surgery with or without post-operative physiotherapy in patients with cervical radiculopathy. METHODS: PubMed, Embase, CINAHL, PsycINFO and Web of Science were searched from inception to 1st of March 2023. Primary outcomes were effectiveness regarding costs, arm pain intensity and disability. Neck pain intensity, perceived recovery, quality of life, neurological symptoms, range-of-motion, return-to-work, medication use, (re)surgeries and adverse events were considered secondary outcomes. Randomised clinical trials comparing personalised multimodal physiotherapy versus surgical approaches with/without post-operative physiotherapy were included. Two independent reviewers performed study selection, data-extraction, and risk of bias assessment using the Cochrane RoB 2 and Consolidated Health Economic Evaluation Reporting Standards statement. Certainty of the evidence was determined using Grading of Recommendations, Assessment, Development and Evaluations. RESULTS: From 2109 records, eight papers from two original trials, with 117 participants in total were included. Low certainty evidence showed there were no significant differences on arm pain intensity and disability, except for the subscale 'heavy work' related disability (12 months) and disability at 5-8 years. Cost-effectiveness was not assessed. There was low certainty evidence that physiotherapy improved significantly less on neck pain intensity, sensory loss and perceived recovery compared to surgery with/without physiotherapy. Low certainty evidence showed there were no significant differences on numbness, range of motion, medication use, and quality of life. No adverse events were reported. CONCLUSION: Considering the clinical importance of accurate management recommendations and the current low level of certainty, high-quality cost-effectiveness studies are needed.

What have we learned about risk assessment and interventions to prevent work-related musculoskeletal disorders and support work participation?

OBJECTIVE: The Scandinavian Journal of Work, Environment & Health (SJWEH) was established half a century ago. This paper provides an overview of research on musculoskeletal disorders (MSD) published over these 50 years. Three themes are described: risk assessment, interventions to prevent work-related MSD, and interventions to support work participation. Finally, implications for future research are highlighted. METHODS: A systematic literature search was performed for all papers on MSD published in SJWEH. Each paper was coded on several criteria including research topic, type of MSD, risk factor(s), and number of citations. Findings were tabulated, and discussions within the author team defined the main results and future research directions. RESULTS: The search resulted in 1056 papers, of which 474 were included. The most reported-on MSD was low-back pain (LBP, 18%) and the most reported-on work-related risk factors were physically demanding work (14%) and psychosocial factors (12%). Research has contributed to improving case definitions, refining work-related exposure criteria, and recognizing the varying importance of physical and psychosocial factors across different MSD. Research on the association between work-related risk factors and LBP continues to emerge. Effective interventions for prevention of MSD are characterised by sufficient exposure reduction, while supporting work participation requires integrating health care, with multidisciplinary actions directed at factors involving the worker, employer, and workplace. CONCLUSION: Research has provided valuable insights into risk assessment, interventions for preventing work-related MSD, and supporting work participation. Intervention studies remain warranted and new areas include adopting whole-system approaches to prevent work-related MSD and promoting the concept of musculoskeletal health.

Critical assessment of variant prioritization methods for rare disease diagnosis within the rare genomes project.

BACKGROUND: A major obstacle faced by families with rare diseases is obtaining a genetic diagnosis. The average "diagnostic odyssey" lasts over five years and causal variants are identified in under 50%, even when capturing variants genome-wide. To aid in the interpretation and prioritization of the vast number of variants detected, computational methods are proliferating. Knowing which tools are most effective remains unclear. To evaluate the performance of computational methods, and to encourage innovation in method development, we designed a Critical Assessment of Genome Interpretation (CAGI) community challenge to place variant prioritization models head-to-head in a real-life clinical diagnostic setting. METHODS: We utilized genome sequencing (GS) data from families sequenced in the Rare Genomes Project (RGP), a direct-to-participant research study on the utility of GS for rare disease diagnosis and gene discovery. Challenge predictors were provided with a dataset of variant calls and phenotype terms from 175 RGP individuals (65 families), including 35 solved training set families with causal variants specified, and 30 unlabeled test set families (14 solved, 16 unsolved). We tasked teams to identify causal variants in as many families as possible. Predictors submitted variant predictions with estimated probability of causal relationship (EPCR) values. Model performance was determined by two metrics, a weighted score based on the rank position of causal variants, and the maximum F-measure, based on precision and recall of causal variants across all EPCR values. RESULTS: Sixteen teams submitted predictions from 52 models, some with manual review incorporated. Top performers recalled causal variants in up to 13 of 14 solved families within the top 5 ranked variants. Newly discovered diagnostic variants were returned to two previously unsolved families following confirmatory RNA sequencing, and two novel disease gene candidates were entered into Matchmaker Exchange. In one example, RNA sequencing demonstrated aberrant splicing due to a deep intronic indel in ASNS, identified in trans with a frameshift variant in an unsolved proband with phenotypes consistent with asparagine synthetase deficiency. CONCLUSIONS: Model methodology and performance was highly variable. Models weighing call quality, allele frequency, predicted deleteriousness, segregation, and phenotype were effective in identifying causal variants, and models open to phenotype expansion and non-coding variants were able to capture more difficult diagnoses and discover new diagnoses. Overall, computational models can significantly aid variant prioritization. For use in diagnostics, detailed review and conservative assessment of prioritized variants against established criteria is needed.

Training for Supervisors to Improve Sustainable Employment of Employees with a work Disability: A Longitudinal Effect and Process Evaluation from an Intervention Study with Matched Controls.

PURPOSE: Supervisors play a crucial role in sustainable employment of employees with a work disability. The 'Mentorwijs' (literal translation: Mentorwise) training was developed to train supervisors in knowledge, attitudes and skills needed to guide these employees. This study evaluated the effect of 'Mentorwijs' on employees' employment and supervisors' behavioral outcomes. METHODS: Register- and questionnaire data were obtained from 73 employees and 1,526 matched controls to measure employment (≥ 1/month, ≥ 12 h/week and ≥ 3 consecutive months (≥ 1 h/month)) during a 12-month follow-up period. Questionnaire data were obtained from 127 supervisors who followed the 'Mentorwijs' training, to assess their knowledge, self-efficacy, intention to adopt and applied behaviors. RESULTS: Employment for ≥ 1 h/month did not significantly improve after 3 (ß = 0.05; CI=-0.07-0.16), 6 (ß = 0.07; CI=-0.04-0.18), 9 (ß = 0.08; CI=-0.02-0.18) and 12 (ß = 0.01; CI=-0.08-0.10) months among employees whose supervisors followed 'Mentorwijs' compared to those who did not. Significant effects were found after 8 months (ß = 0.11; CI = 0.01-0.21). Comparable effects were found for employment ≥ 12 hour/week and ≥ 3 consecutive months (≥ 1 hour/month). Supervisors' knowledge and self-efficacy significantly improved as a result of 'Mentorwijs', but no effects were found for intention to adopt and applied behaviors. CONCLUSIONS: 'Mentorwijs' is a promising training to improve the guidance of employees with a work disability. Further research is needed to examine how long-term effects of 'Mentorwijs' on employment can be sustained.

'Wait , let me tell you, if I worked for a boss, I would be on sick leave': A Qualitative Study of Self-Employed Workers in Physically Demanding Jobs in the Netherlands.

PURPOSE: The purpose of this study was to explore the perspectives of self-employed workers with a physically demanding job on work participation. METHODS: We interviewed self-employed workers with a physically demanding job, using semi-structured interviews, which were audio recorded. The main topic addressed was the workers' health in relation with their work participation, work demands, and preventive measures. The interviews were transcribed verbatim and coded by three team members of the research team in several steps. We used the consolidated criteria for reporting qualitative research (COREQ) checklist to report our findings. RESULTS: We interviewed 18 self-employed workers: 83% male, 49 years (SD 7), self-employed for 18 years (SD 9) and the majority (n = 14) worked in the construction sector. Thematic analysis revealed facilitators and barriers for work participation across three main themes: personal factors, work factors, and healthcare. Personal factors compassed sub-themes such as health and financial consequences. Work factors included sub-themes related to work demands and adaptations and healthcare encompassed sub-themes associated with work-related care and medication. CONCLUSION: To our knowledge, this is the first qualitative study that investigated the perspectives of self-employed workers in physically demanding jobs regarding work participation. While most facilitators and barriers were consistent with those described in the literature for employees, certain factors, such as financial consequences of ceasing work, emerged important factors for work participation among self-employed workers.

Work-related experiences and unmet needs of patients with a malignant glioma and relevant professionals: the BrainWork study.

PURPOSE: Many patients with a malignant (i.e., grade II-IV) glioma are of working age, yet they are rarely included in "cancer and work" studies. Here, we explored (1) the work-related experiences and unmet needs of patients with a malignant glioma and (2) the experiences and needs of relevant healthcare and occupational (health) professionals ("professionals") in providing work-related support to this patient group. METHODS: Individual semi-structured interviews were held with patients with a malignant glioma who were of working age and had an employment contract at diagnosis, and relevant professionals. Interviews were transcribed verbatim and analysed thematically. RESULTS: Patients (n = 22) were on average 46 ± 13 years of age (64% male) and diagnosed with a grade II (n = 12), III (n = 4), or IV glioma (n = 6). Professionals (n = 16) had on average 15 ± 9 years of relevant work experience with the patient group. Four themes emerged from the data: (1) having a malignant glioma: experienced consequences on work ability, (2) communicating about the consequences of a malignant glioma at work, (3) distilling the right approach: generic or tailored work-related support, and (4) accessibility of work-related support. CONCLUSIONS: Glioma-specific consequences on patients' work ability necessitate better communication between, and tailored guidance for, patients, relevant professionals, and the workplace. Suggestions for improvement, e.g., the periodic use of comprehensive neuropsychological assessments, are provided in the article. IMPLICATIONS FOR CANCER SURVIVORS: Patients with a malignant glioma would benefit from tailored and proactive outreach about work-related issues bv relevant professionals.

Changes in Desk-Based Workers' Sitting, Standing, and Stepping Time: Short- and Longer-Term Effects on Musculoskeletal Pain.

PURPOSE: Sitting at work can be associated with musculoskeletal pain, but the effect of reductions in sitting is not well understood. We examined relationships with musculoskeletal pain of changes in sitting, standing, stepping, and short and long bouts of these behaviors. METHODS: Analyses pooled data from 224 desk workers (68.4% women; mean ± SD age = 45.5 ± 9.4 yr; body mass index = 28.1 ± 6.1 kg⋅m -2 ) in intervention trial. Device-assessed (activPAL3) sitting, standing, and stepping time and multisite musculoskeletal pain (Nordic Questionnaire; 12 body areas) were assessed at baseline, 3 months, and 12 months. Compositional data analyses in linear mixed-effects regressions examined relationships within 16 waking hours of the behaviors and their short and long bouts, with changes from baseline in acute and chronic multisite musculoskeletal pain at 3 and 12 months. Analyses were adjusted for initial group randomization and relevant covariates. RESULTS: At 3 months, increased standing relative to changes in other compositions was significantly associated with increased multisite musculoskeletal pain (acute: ß = 1.54, 95% confidence interval [CI] = 0.10 to 2.98; chronic: ß = 1.49, 95% CI = 0.12 to 2.83). By contrast, increased stepping relative to changes in other compositions was significantly associated with reduced multisite musculoskeletal pain (acute: ß = -1.49, 95% CI = -2.97 to -0.02; chronic: ß = -1.87, 95% CI = -3.75 to -0.01). Neither sitting reduction relative to changes in other compositions nor changes in short bouts relative to long bouts of the behaviors were significantly associated with multisite musculoskeletal pain changes. At 12 months, there were no significant associations for any of the compositional changes. CONCLUSIONS: In the short term, while increasing standing with reduced sitting time can be unfavorable, concurrently increasing stepping could potentially reduce musculoskeletal pain. In the longer term, musculoskeletal pain may not be increased by moderate reductions in sitting time through spending more time standing or stepping.

Adapting shift work schedules for sleep quality, sleep duration, and sleepiness in shift workers.

BACKGROUND: Shift work is associated with insufficient sleep, which can compromise worker alertness with ultimate effects on occupational health and safety. Adapting shift work schedules may reduce adverse occupational outcomes. OBJECTIVES: To assess the effects of shift schedule adaptation on sleep quality, sleep duration, and sleepiness among shift workers. SEARCH METHODS: We searched CENTRAL, PubMed, Embase, and eight other databases on 13 December 2020, and again on 20 April 2022, applying no language restrictions. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and non-RCTs, including controlled before-after (CBA) trials, interrupted time series, and cross-over trials. Eligible trials evaluated any of the following shift schedule components. • Permanency of shifts • Regularity of shift changes • Direction of shift rotation • Speed of rotation • Shift duration • Timing of start of shifts • Distribution of shift schedule • Time off between shifts • Split shifts • Protected sleep • Worker participation We included studies that assessed sleep quality off-shift, sleep duration off-shift, or sleepiness during shifts. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the titles and abstracts of the records recovered by the search, read through the full-text articles of potentially eligible studies, and extracted data. We assessed the risk of bias of included studies using the Cochrane risk of bias tool, with specific additional domains for non-randomised and cluster-randomised studies. For all stages, we resolved any disagreements by consulting a third review author. We presented the results by study design and combined clinically homogeneous studies in meta-analyses using random-effects models. We assessed the certainty of the evidence with GRADE. MAIN RESULTS: We included 11 studies with a total of 2125 participants. One study was conducted in a laboratory setting and was not considered for drawing conclusions on intervention effects. The included studies investigated different and often multiple changes to shift schedule, and were heterogeneous with respect to outcome measurement. Forward versus backward rotation Three CBA trials (561 participants) investigated the effects of forward rotation versus backward rotation. Only one CBA trial provided sufficient data for the quantitative analysis; it provided very low-certainty evidence that forward rotation compared with backward rotation did not affect sleep quality measured with the Basic Nordic Sleep Questionnaire (BNSQ; mean difference (MD) -0.20 points, 95% confidence interval (CI) -2.28 to 1.89; 62 participants) or sleep duration off-shift (MD -0.21 hours, 95% CI -3.29 to 2.88; 62 participants). However, there was also very low-certainty evidence that forward rotation reduced sleepiness during shifts measured with the BNSQ (MD -1.24 points, 95% CI -2.24 to -0.24; 62 participants). Faster versus slower rotation Two CBA trials and one non-randomised cross-over trial (341 participants) evaluated faster versus slower shift rotation. We were able to meta-analyse data from two studies. There was low-certainty evidence of no difference in sleep quality off-shift (standardised mean difference (SMD) -0.01, 95% CI -0.26 to 0.23) and very low-certainty evidence that faster shift rotation reduced sleep duration off-shift (SMD -0.26, 95% CI -0.51 to -0.01; 2 studies, 282 participants). The SMD for sleep duration translated to an MD of 0.38 hours' less sleep per day (95% CI -0.74 to -0.01). One study provided very low-certainty evidence that faster rotations decreased sleepiness during shifts measured with the BNSQ (MD -1.24 points, 95% CI -2.24 to -0.24; 62 participants). Limited shift duration (16 hours) versus unlimited shift duration Two RCTs (760 participants) evaluated 80-hour workweeks with maximum daily shift duration of 16 hours versus workweeks without any daily shift duration limits. There was low-certainty evidence that the 16-hour limit increased sleep duration off-shift (SMD 0.50, 95% CI 0.21 to 0.78; which translated to an MD of 0.73 hours' more sleep per day, 95% CI 0.30 to 1.13; 2 RCTs, 760 participants) and moderate-certainty evidence that the 16-hour limit reduced sleepiness during shifts, measured with the Karolinska Sleepiness Scale (SMD -0.29, 95% CI -0.44 to -0.14; which translated to an MD of 0.37 fewer points, 95% CI -0.55 to -0.17; 2 RCTs, 716 participants). Shorter versus longer shifts One RCT, one CBA trial, and one non-randomised cross-over trial (692 participants) evaluated shorter shift duration (eight to 10 hours) versus longer shift duration (two to three hours longer). There was very low-certainty evidence of no difference in sleep quality (SMD -0.23, 95% CI -0.61 to 0.15; which translated to an MD of 0.13 points lower on a scale of 1 to 5; 2 studies, 111 participants) or sleep duration off-shift (SMD 0.18, 95% CI -0.17 to 0.54; which translated to an MD of 0.26 hours' less sleep per day; 2 studies, 121 participants). The RCT and the non-randomised cross-over study found that shorter shifts reduced sleepiness during shifts, while the CBA study found no effect on sleepiness. More compressed versus more spread out shift schedules One RCT and one CBA trial (346 participants) evaluated more compressed versus more spread out shift schedules. The CBA trial provided very low-certainty evidence of no difference between the groups in sleep quality off-shift (MD 0.31 points, 95% CI -0.53 to 1.15) and sleep duration off-shift (MD 0.52 hours, 95% CI -0.52 to 1.56). AUTHORS' CONCLUSIONS: Forward and faster rotation may reduce sleepiness during shifts, and may make no difference to sleep quality, but the evidence is very uncertain. Very low-certainty evidence indicated that sleep duration off-shift decreases with faster rotation. Low-certainty evidence indicated that on-duty workweeks with shift duration limited to 16 hours increases sleep duration, with moderate-certainty evidence for minimal reductions in sleepiness. Changes in shift duration and compression of workweeks had no effect on sleep or sleepiness, but the evidence was of very low-certainty. No evidence is available for other shift schedule changes. There is a need for more high-quality studies (preferably RCTs) for all shift schedule interventions to draw conclusions on the effects of shift schedule adaptations on sleep and sleepiness in shift workers.

Within-individual changes in physical work demands associated with self-reported health and musculoskeletal symptoms: a cohort study among Dutch workers.

PURPOSE: This study aimed to investigate changes in physical work demands in association with self-rated health and musculoskeletal symptoms. METHODS: Data from five waves over the period 2019-2021 of the Netherlands Working Conditions Survey COVID-19 were available for 7191 participants aged 19-64 years who worked (partly) on-site during at least two consecutive waves. Logistic generalized estimated equations (GEE) were used to estimate the odds ratios (OR) with 95% confidence interval (CI) for changes (increase or decrease compared to no change) in physical work demands between two waves and poor self-rated health and musculoskeletal symptoms in the following wave, adjusted for the health outcome at the first wave, age, educational level, working hours and hours worked from home. RESULTS: In females, a statistically significant association was found between an increase in physical work demands compared to no change and musculoskeletal symptoms (OR 1.39, 95% CI 1.17-1.65). A decrease in physical work demands in females was not statistically significantly associated with musculoskeletal symptoms (OR 0.93, 95% CI 0.80-1.08). Similar trends were found for poor self-rated health, although non-statistically significant. For males, comparable but attenuated associations were found. CONCLUSION: While our study showed that increasing physical work demands are associated with adverse health (self-reported and musculoskeletal), it did not appear to benefit worker's health to reduce work demands. Future research with multiple measurements in a shorter period and additionally using devices to measure physical work demands will be needed to confirm our study results.

Critical assessment of variant prioritization methods for rare disease diagnosis within the Rare Genomes Project.

Background: A major obstacle faced by rare disease families is obtaining a genetic diagnosis. The average "diagnostic odyssey" lasts over five years, and causal variants are identified in under 50%. The Rare Genomes Project (RGP) is a direct-to-participant research study on the utility of genome sequencing (GS) for diagnosis and gene discovery. Families are consented for sharing of sequence and phenotype data with researchers, allowing development of a Critical Assessment of Genome Interpretation (CAGI) community challenge, placing variant prioritization models head-to-head in a real-life clinical diagnostic setting. Methods: Predictors were provided a dataset of phenotype terms and variant calls from GS of 175 RGP individuals (65 families), including 35 solved training set families, with causal variants specified, and 30 test set families (14 solved, 16 unsolved). The challenge tasked teams with identifying the causal variants in as many test set families as possible. Ranked variant predictions were submitted with estimated probability of causal relationship (EPCR) values. Model performance was determined by two metrics, a weighted score based on rank position of true positive causal variants and maximum F-measure, based on precision and recall of causal variants across EPCR thresholds. Results: Sixteen teams submitted predictions from 52 models, some with manual review incorporated. Top performing teams recalled the causal variants in up to 13 of 14 solved families by prioritizing high quality variant calls that were rare, predicted deleterious, segregating correctly, and consistent with reported phenotype. In unsolved families, newly discovered diagnostic variants were returned to two families following confirmatory RNA sequencing, and two prioritized novel disease gene candidates were entered into Matchmaker Exchange. In one example, RNA sequencing demonstrated aberrant splicing due to a deep intronic indel in ASNS, identified in trans with a frameshift variant, in an unsolved proband with phenotype overlap with asparagine synthetase deficiency. Conclusions: By objective assessment of variant predictions, we provide insights into current state-of-the-art algorithms and platforms for genome sequencing analysis for rare disease diagnosis and explore areas for future optimization. Identification of diagnostic variants in unsolved families promotes synergy between researchers with clinical and computational expertise as a means of advancing the field of clinical genome interpretation.

Prospective Association of Occupational and Leisure-Time Physical Activity With Cardiovascular Risk Factors in Early Adulthood: Findings From Pelotas (Brazil) 1982 Birth Cohort.

BACKGROUND: The benefits of physical activity in health outcomes are well established. However, recent evidence suggests that benefits may differ by domain and population. Thus, we aimed to investigate the prospective association of occupational (OPA) and leisure-time physical activity (LTPA) with cardiovascular risk factors. METHODS: In 1982, the maternity hospitals of Pelotas were visited daily; those live births whose families lived in urban areas were evaluated, and their mothers were later interviewed (n = 5914). In the 2004/5 follow-up (23 y old), both OPA and LTPA were measured in 4295 participants using their respective sections of the International Physical Activity Questionnaire. In the 2012 follow-up (30 y old), the following cardiovascular risk factors were collected: high-density lipoprotein (in milligrams per deciliter), low-density lipoprotein (in milligrams per deciliter), triglycerides (in milligrams per deciliter), glucose (in milligrams per deciliter), and blood pressure (in millimeters of mercury). Multivariable linear regressions were performed to evaluate associations between OPA and LTPA with these specific cardiovascular risk factors. RESULTS: In total, 3241 participants were analyzed. Our main findings suggest that there was no association between OPA and LTPA with high- and low-density lipoprotein. There were inverse associations between OPA and lower levels of triglycerides among males (ß = -0.002; 95% confidence interval, -0.003 to -0.000) and positive associations between LTPA and higher levels of diastolic blood pressure among females (ß = 0.111; 95% confidence interval, 0.005-0.216). CONCLUSION: In conclusion, our findings suggest that there was no association, or association with limited clinical relevance, of OPA and LTPA with cardiovascular risk factors in early adulthood.

Insomnia and workplace productivity loss among young working adults: a prospective observational study of clinical sleep disorders in a community cohort.

OBJECTIVE: To examine associations between three clinically significant sleep disorders (chronic insomnia, obstructive sleep apnoea, restless legs syndrome) and workplace productivity losses among young Australian adults. DESIGN, SETTING: Prospective, observational study; 22-year follow-up of participants in the longitudinal birth cohort Raine Study (Perth, Western Australia). PARTICIPANTS: Currently employed 22-year-old Raine Study participants who underwent in-laboratory sleep disorder screening for moderate to severe obstructive sleep apnoea (apnoea-hypopnea index of more than fifteen events/hour or obstructive sleep apnoea syndrome) and were assessed for insomnia and restless legs syndrome using validated measures. MAIN OUTCOME MEASURES: Total workplace productivity loss over twelve months, assessed with the World Health Organization Health and Work Performance Questionnaire. RESULTS: Of 1235 contactable 22-year-old Raine Study cohort members, 554 people (44.9%; 294 women [53%]) underwent overnight polysomnography, completed the baseline sleep questionnaire, and completed at least three quarterly workplace productivity assessments. One or more clinically significant sleep disorders were identified in 120 participants (21.7%); 90 participants had insomnia (17%), thirty clinically significant obstructive sleep apnoea (5.4%), and two restless legs syndrome (0.4%). Seventeen people (14% of those with sleep disorders) had previously been diagnosed with a sleep disturbance by a health professional, including fourteen with insomnia. Median total workplace productivity loss was greater for participants with sleep disorders (164 hours/year; interquartile range [IQR], 0-411 hours/year) than for those without sleep disorders (30 hours/year; IQR, 0-202 hours/year); total workplace productivity loss was 40% greater for participants with sleep disorders (adjusted incidence rate ratio, 1.40; bias-corrected and accelerated 95% confidence interval, 1.10-1.76). The estimated population total productivity loss (weighted for disorder prevalence) was 28 644 hours per 1000 young workers per year, primarily attributable to insomnia (28 730 hours/1000 workers/year). CONCLUSION: Insomnia is a risk factor for workplace productivity loss in young workers. Tailored interventions are needed to identify and manage sleep disorders, particularly as most of the sleep disorders detected in the Raine Study had not previously been diagnosed.