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.

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.

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.

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.

Cancer survivors and adverse work outcomes: associated factors and supportive interventions.

INTRODUCTION: The number of cancer survivors in a working age is rising. An awareness of factors associated with adverse work outcomes, and of supportive interventions, is needed. SOURCES OF DATA: A narrative review of research obtained via several databases, including Medline and PsycINFO, was conducted. AREAS OF AGREEMENT: A range of factors is associated with adverse work outcomes such as prolonged sick leave, delayed return to work, disability pension and unemployment in cancer survivors. They include the cancer type and treatment, fatigue, cognitive functioning, work factors and elements of health care systems. Effective supportive interventions encompass physical and multicomponent interventions. AREAS OF CONTROVERSY: The role of behaviour determinants and legislative and insurance systems is unclear. It is furthermore uncertain what the optimal timing of delivering supportive interventions is. GROWING POINTS: Further focus on vulnerable groups, including specific cancer types and those with lower income, lower educational level and in precarious employment, is needed. AREAS TIMELY FOR DEVELOPING RESEARCH: Recent developments are tailored and timely interventions.

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.

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.

(Cost-)effectiveness of a personalized multidisciplinary eHealth intervention for knee arthroplasty patients to enhance return to activities of daily life, work and sports - rationale and protocol of the multicentre ACTIVE randomized controlled trial.

BACKGROUND: With the worldwide rising obesity epidemic and the aging population, it is essential to deliver (cost-)effective care that results in enhanced societal participation among knee arthroplasty patients. The purpose of this study is to describe the development, content, and protocol of our (cost-)effectiveness study that assesses a perioperative integrated care program, including a personalized eHealth app, for knee arthroplasty patients aimed to enhance societal participation post-surgery compared to care as usual. METHODS: The intervention will be tested in a multicentre randomized controlled trial with eleven participating Dutch medical centers (i.e., hospitals and clinics). Working patients on the waiting-list for a total- or unicompartmental knee arthroplasty with the intention to return to work after surgery will be included. After pre-stratification on medical centre with or without eHealth as usual care, operation procedure (total- or unicompartmental knee arthroplasty) and recovery expectations regarding return to work, randomization will take place at the patient-level. A minimum of 138 patients will be included in both the intervention and control group, 276 in total. The control group will receive usual care. On top of care as usual, patients in the intervention group will receive an intervention consisting of three components: 1) a personalized eHealth intervention called ikHerstel ('I Recover') including an activity tracker, 2) goal setting using goal attainment scaling to improve rehabilitation and 3) a referral to a case-manager. Our main outcome is quality of life, based on patient-reported physical functioning (using PROMIS-PF). (Cost-)effectiveness will be assessed from a healthcare and societal perspective. Data collection has been started in 2020 and is expected to finish in 2024. DISCUSSION: Improving societal participation for knee arthroplasty is relevant for patients, health care providers, employers and society. This multicentre randomized controlled trial will evaluate the (cost-)effectiveness of a personalized integrated care program for knee arthroplasty patients, consisting of effective intervention components based on previous studies, compared to care as usual. TRIAL REGISTRATION: Trialsearch.who.int; reference no. NL8525, reference date version 1: 14-04-2020.

'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.

Lifetime high occupational physical activity and total and cause-specific mortality among 320 000 adults in the NIH-AARP study: a cohort study.

OBJECTIVES: We examined the associations of history and duration in high occupational physical activity (OPA) with long-term total and cause-specific mortality. METHODS: The sample included 322 126 participants (135 254 women) from the National Institutes of Health-AARP Diet and Health Study, established in 1995-1996. History and duration in high OPA were reported by participants. All-cause, cardiovascular, cancer and other cause mortality records available through 31 December 2011. RESULTS: The prevalence of high OPA was 52.1% in men and 16.1% in women. During 13.6 years (SD, 3.3) of follow-up, 73 563 participants (25 219 women) died. In age-adjusted models, the risk of death was higher among men (HR 1.14, 95% CI 1.12 to 1.16) and women (HR 1.22, 95% CI 1.18 to 1.26) with a history of high OPA. However, these associations were substantially attenuated in women (HR 1.04, 95% CI 1.00 to 1.07, an 81.8% attenuation) and eliminated in men (HR 1.02, 95% CI 0.99 to 1.04, 85.7% attenuation) after multivariable adjustments. Similar important attenuation results were found when examining duration in high OPA, as well as using cause-specific deaths as the outcomes. Educational attainment and smoking patterns were the main contributors in the excess mortality among people working in highly physically active jobs in both men and women. CONCLUSION: Participating in high OPA was not consistently associated with a higher mortality risk, after adjustments for education and smoking factors. Workers in high OPA should be aware that they might not be getting all well-known health benefits of being physically active if they are only very active at work.

Can the Borg CR-10 scale for neck and low back discomfort predict future neck and low back pain among high-risk office workers?

PURPOSE: Perceived discomfort could indicate an early sign of pain, for example, as a result of a biomechanical load on the musculoskeletal system. Assessing discomfort can, therefore, help to identify workers at increased risk of musculoskeletal disorders for targeted intervention development. We aimed: (1) to identify the optimal cut-off value of neck and low back discomfort among office workers and (2) to evaluate its predictive validity with future neck and low back pain, respectively. METHODS: At baseline healthy participants (n = 100) completed questionnaires, including the Borg CR-10 discomfort scale (on a 0-10 scale), and were followed for six months, during which musculoskeletal pain was assessed monthly. Logistic regression analyses were performed to assess the associations of baseline discomfort with the onset of future neck or low back pain. Sensitivity, specificity, and the area under the receiver operating characteristics curve were estimated to identify the optimal discomfort cut-off value predicting future pain. RESULTS: Borg CR-10 scores ≥ 3.5 for perceived neck and low back discomfort had acceptable sensitivity and specificity to predict future neck and low back pain, respectively. Perceived discomfort at baseline as a dichotomous measure (using the ≥ 3.5 cut-off) was a statistically significant predictor of future neck pain (OR = 10.33) and low back pain (OR = 11.81). CONCLUSION: We identified the optimal cut-off value of the Borg CR-10 discomfort scale to identify office workers at increased risk of developing neck and low back pain. These findings might benefit ergonomists, primary health care providers, and occupational health researchers in developing targeted interventions.

The economic burden of knee and hip osteoarthritis: absenteeism and costs in the Dutch workforce.

BACKGROUND: This study aimed to quantify the absenteeism costs of knee and hip osteoarthritis in the Netherlands for the Dutch workforce and specific groups of workers. METHODS: We used a longitudinal, dynamic database from a large occupational health service in which occupational physicians register information about personal information and sick leave of workers with the diagnosis of knee- and/or hip osteoarthritis. We included all employees aged 15 to 75 years performing paid work and diagnosed with knee and/or hip osteoarthritis. Costs were calculated annually and per episode for different subgroups from an employer's perspective using the Human Capital Approach. In the Netherlands, the employer has to pay 70% of the employee's wage out of pocket for the first two years of sick leave and also for the occupational health care. In this way, employers receive information about the costs of workers on sick leave due to knee or hip osteoarthritis. This might stimulate investments in targeted prevention and work-directed care. RESULTS: For the period 2015-2017, 1399 workers fulfilled the inclusion criteria. An average sick leave episode of knee osteoarthritis had a duration of 186 calendar days and was associated with €15,550 in costs. For hip osteoarthritis these data were 159 calendar days and €12,482 in costs. These costs are particularly high among male workers and workers with a higher number of weekly working hours. The average annual costs for the Dutch workforce due to sick leave for knee and hip osteoarthritis were €26.9 million and €13.8 million, respectively. Sick leave costs decreased for hip and not for knee osteoarthritis during 2015-2017. CONCLUSIONS: Annual sick leave costs due to knee and hip osteoarthritis are about €40 million for the Dutch workforce and approximately twice as high for knee compared to hip osteoarthritis. Average costs per sick leave episode are particularly high among male workers and workers with a higher number of weekly working hours.

Sick Leave Due to Stress, What are the Costs for Dutch Employers?

Purpose Stress-related illnesses are prevalent in Western society, causing sick leave and putting a heavy economic burden on employers and society. For Dutch employers it is particularly relevant to have insight into the costs of absenteeism due to stress-related illness, as they are legally obligated to continue payment of wages. Therefore, this study assessed the duration and costs of an episode of sick leave due to stress-related illness for Dutch employers. Methods Data on sick leave due to various stress-related illnesses were obtained from a nationwide occupational health service database. Stress-related illnesses included tension complaints, burn-out, overexertion, and other reactions to stress. The duration per sick leave episode was estimated in working days, after which the average cost per sick leave period was estimated using age- and gender-specific price weights. Results During the study period, 16,676 employees took 17,338 episodes of sick leave due to stress-related illness. On average, one episode of sick leave lasted 101 working days, for which the costs for the employer were on average €19,151 per worker. Women were responsible for most episodes of sick leave and were on average 37 days more absent per episode compared to men. Moreover, of all kinds of stress-related illnesses, burn-out had the longest duration of sick leave with 313 calendar days and 163 working days, resulting in an average cost of €30,770. Conclusions Sick leave due to stress-related illness places a heavy burden on employers and thus society. Further research should be conducted on how to reduce this burden.

Large variability in recommendations for return to daily life activities after knee arthroplasty among Dutch hospitals and clinics: a cross-sectional study.

BACKGROUND AND PURPOSE: Recommendations concerning the return to daily life activities, including work and sport, after knee arthroplasty (KA) are essential for setting realistic patient expectations. Fulfillment of these expectations contributes to more satisfaction and enhanced recovery after KA. However, scientific evidence for such recommendations is limited, and recommendations are often based only on healthcare professionals' expert opinions. We summarized the current recommendations regarding return to daily life activities provided by Dutch hospitals and clinics to KA patients. MATERIAL AND METHODS: Recommendations of 43 Dutch hospitals and clinics were identified, representing the advice provided to 70% of the total Dutch KA patients. Recommendations were retrieved from content from websites (n = 8), brochures (n = 40), and mobile phone applications (n = 9). RESULTS: Recommendations for 24 daily life activities were identified. Individual hospitals and clinics provided recommendations for, on average, 9 (0-15) of these activities. Recommendations varied greatly. For example, recommendations regarding when to resume cycling after KA were provided by 36 of the 43 hospitals and clinics and varied from 3 weeks to 3 months. INTERPRETATION: Recommendations for return to daily life activities are often missing and vary considerably between Dutch hospitals and clinics. These findings show the need for more uniformity across healthcare providers regarding recommendations for postoperative return to daily life activities.

Cancer survivors' experiences with conversations about work-related issues in the hospital setting.

OBJECTIVE: Early access to work-related psychosocial cancer care can contribute to return to work of cancer survivors. We aimed to explore: (a) the extent to which hospital healthcare professionals conduct conversations about work-related issues with cancer survivors, (b) whether cancer survivors experience these conversations as helpful, and (c) the possible financial implications for cancer survivors of (not) discussing their work early on. METHODS: The Dutch Federation of Cancer Patient Organizations developed and conducted a cross-sectional online survey, consisting of 27 items, among cancer survivors in the Netherlands. RESULTS: In total, 3500 survivors participated in this study (71% female; mean age (SD) 56 (11) years). Thirty-two percent reported to have had a conversation about work-related issues with a healthcare professional in the hospital. Fifty-four percent indicated that this conversation had been helpful to them. Conversations about work-related issues took place more frequently with male cancer survivors, those aged 55 years or below, those diagnosed with gynecological, prostate, breast, and hematological or lymphatic cancer, those diagnosed ≤2 years ago, or those who received their last treatment ≤2 years ago. There was no statistically significant association between the occurrence of conversations about work-related issues and experiencing the financial consequences of cancer and/or its treatment as burdensome. CONCLUSIONS: Although conversations about work-related issues are generally experienced as helpful by cancer survivors, early access to work-related psychosocial cancer care in the hospital setting is not yet systematically offered.

The effect of leisure time physical activity and sedentary behaviour on the health of workers with different occupational physical activity demands: a systematic review.

BACKGROUND: Although it is generally accepted that physical activity reduces the risk for chronic non-communicable disease and mortality, accumulating evidence suggests that occupational physical activity (OPA) may not confer the same health benefits as leisure time physical activity (LTPA). It is also unclear if workers in high OPA jobs benefit from LTPA the same way as those in sedentary jobs. Our objective was to determine whether LTPA and leisure time sedentary behaviour (LTSB) confer the same health effects across occupations with different levels of OPA. METHODS: Searches were run in Medline, Embase, PsycINFO, ProQuest Public Health and Scopus from inception to June 9, 2020. Prospective or experimental studies which examined the effects of LTPA or LTSB on all-cause and cardiovascular mortality and cardiovascular disease, musculoskeletal pain, diabetes, metabolic syndrome, arrhythmias and depression among adult workers grouped by OPA (low OPA/sitters, standers, moderate OPA/intermittent movers, high OPA/heavy labourers) were eligible. Results were synthesized using narrative syntheses and harvest plots, and certainty of evidence assessed with GRADE. RESULTS: The review includes 38 papers. Across all outcomes, except cardiovascular mortality, metabolic syndrome and atrial fibrillation, greater LTPA was consistently protective among low OPA, but conferred less protection among moderate and high OPA. For cardiovascular mortality and metabolic syndrome, higher levels of LTPA were generally associated with similar risk reductions among all OPA groups. Few studies examined effects in standers and none examined effects of LTSB across OPA groups. CONCLUSIONS: Evidence suggests that LTPA is beneficial for all workers, but with larger risk reductions among those with low compared to high OPA jobs. This suggests that, in our attempts to improve the health of workers through LTPA, tailored interventions for different occupational groups may be required. More high-quality studies are needed to establish recommended levels of LTPA/LTSB for different OPA groups. PROTOCOL REGISTRATION: PROSPERO # CRD42020191708 .

Supporting participation in paid work of cancer survivors and their partners in the Netherlands: protocol of the SusTained Employability in cancer Patients and their partnerS (STEPS) multi-centre randomized controlled trial and cohort study.

BACKGROUND: Many cancer survivors experience physical and/or psychosocial problems affecting return to work (RTW) and work retention. Current interventions on RTW lack evidence regarding effectiveness, while interventions for work retention are missing. Partners of cancer survivors may also experience work- and health-related outcomes; yet, these consequences are not well understood. Here, the protocol of the STEPS study is described. The study aims are to: 1) evaluate the (cost-)effectiveness of a rehabilitation program for RTW and work retention in cancer survivors, and 2) assess health- and work-related outcomes among cancer survivors' partners. METHODS: In a multicentre Randomized Controlled Trial (RCT), 236 working-age cancer survivors with an employment contract will be randomly allocated to a usual care group or an intervention group receiving a multidisciplinary rehabilitation program, combining occupational therapy facilitating work retention (e.g., energy management and self-efficacy training) and reintegration consultation addressing work-related issues (e.g., RTW planning and discussing workplace or task modifications with the supervisor). Alongside the RCT, a prospective cohort study will be conducted among cancer survivors' partners (n = 267). Participants in the RCT and cohort study will be asked to complete questionnaires at baseline, and after six and 12 months, assessing work- and health-related outcomes. Generalized estimating equations will be used to assess intervention's effectiveness, compared to usual care, regarding primary (i.e., working hours per week) and secondary outcomes. Also economic and process evaluations will be performed. For the cohort study, logistic or linear regression modelling will be applied assessing work- and health-related outcomes (primary outcome: working hours) of cancer survivors' partners, and what factors predict these outcomes. RESULTS: The study is planned to start in September 2021; results are expected in 2023. CONCLUSION: Compared to usual care, the STEPS intervention is hypothesized to be (cost-)effective and the intervention could be a valuable addition to standard care helping cancer survivors to sustain employment. Further, it is expected that living with a cancer survivor has a substantial impact on work and health of partners, while specific groups of partners that are at particular risk for this impact are likely to be identified. TRIAL REGISTRATION: Dutch Trial Register ( NTR;NL9094 ; 15-12-2020).

Cross-cultural translation and adaptation of the Readiness for Return To Work questionnaire for Dutch cancer survivors.

OBJECTIVE: Effective interventions supporting cancer survivors in work participation are lacking, possibly due to the poor fit between interventions and cancer survivors' needs. The 'Readiness for Return To Work' (RRTW) questionnaire could facilitate intervention development tailored to cancer survivors' needs. We performed a cross-cultural translation and adaptation of this questionnaire into Dutch and pre-tested its psychometric properties among cancer survivors. METHODS: Questionnaire translation and adaptation were conducted using a systematic approach of: forward translation, synthesis, backward translation, consolidation of translations with an expert committee, and pre-testing. Pre-testing consisted of interviewing 40 cancer survivors, who completed the questionnaire. RESULTS: The translated and adapted RRTW questionnaire showed reasonable psychometric properties, that is high item-to-stage correlations and internal consistency for all RRTW stages, except for the prepared for action - self-evaluative stage. CONCLUSIONS: The translated and adapted RRTW questionnaire may be useful for tailoring interventions to support cancer survivors in returning to and maintaining at work. However, some items showed poor psychometric properties and several factors, important for work participation, are not captured, for example personal, disease-, treatment- and/or work-related characteristics. We recommend to further test the RRTW questionnaire and to use it in combination with additional measurement instruments when developing tailored work participation interventions.