Validation of a full-shift benzene exposure empirical model developed for work on offshore petroleum installations on the Norwegian continental shelf

Workers on offshore petroleum installations might be exposed to benzene, a carcinogenic agent. Recently, a full-shift benzene exposure model was developed based on personal measurements. This study aimed to validate this exposure model by using datasets not included in the model. The exposure model was validated against an internal dataset of measurements from offshore installations owned by the same company that provided data for the model, and an external dataset from installations owned by another company. We used Tobit regression to estimate GM (geometric mean) benzene exposure overall and for individual job groups. Bias, relative bias, precision, and correlation were estimated to evaluate the agreement between measured exposures and the levels predicted by the model. Overall, the model overestimated exposure when compared to the predicted exposure level to the internal dataset with a factor of 1.7, a relative bias of 73%, a precision of 0.6, a correlation coefficient of 0.72 (p = 0.019), while the Lin’s Concordance Correlation Coefficient (CCC) was 0.53. The model underestimated exposure when compared to the external dataset with a factor of about 2, with a relative bias of −45%, a precision of 1.2, a correlation coefficient of 0.31 (p = 0.544), and a Lin’s CCC of 0.25. The exposure model overestimated benzene exposure in the internal validation dataset, while the precision and the correlation between the measured and predicted exposure levels were high. Differences in measurement strategies could be one of the reasons for the discrepancy. The exposure model agreed less with the external dataset.publishedVersio

Benzene Exposure From Selected Work Tasks on Offshore Petroleum Installations on the Norwegian Continental Shelf, 2002-2018

OBJECTIVES: Work on offshore petroleum installations may cause exposure to benzene. Benzene is a carcinogenic agent, and exposure among workers should be as low as reasonably practicable. We aimed to assess short-term (less than 60 min) benzene exposure from the most frequent work tasks on offshore installations on the Norwegian continental shelf and identify determinants of exposure. In addition, we aimed to assess the time trend in task-based benzene measurements from 2002 to 2018. METHODS: The study included 763 task-based measurements with a sampling duration of less than 60 min, collected on 28 offshore installations from 2002 to 2018. The measurements were categorized into 10 different tasks. Multilevel mixed-effect Tobit regression models were developed for two tasks: sampling and disassembling/assembling equipment. Benzene source, season, indoors or outdoors, design of process area, year of production start, sampling method, and work operation were considered as potential determinants for benzene exposure in the models. RESULTS: The overall geometric mean (GM) benzene exposure was 0.02 ppm (95% confidence intervals 95%(CI: 0.01-0.04). The pipeline inspection gauge (PIG) operation task was associated with the highest exposure, with a GM of 0.33 ppm, followed by work on flotation cells, disassembling/assembling, and sampling, with GMs of 0.16, 0.04, and 0.01 ppm, respectively. Significant determinants for the disassembling/assembling task were work operation (changing or recertifying valves, changing or cleaning filters, and breaking pipes) and benzene source. For sampling, the benzene source was a significant determinant. Overall, the task-based benzene exposure declined annually by 10.2% (CI 95%: -17.4 to -2.4%) from 2002 to 2018. CONCLUSIONS: The PIG operation task was associated with the highest exposure out of the ten tasks, followed by work on flotation cells and when performing disassembling/assembling of equipment. The exposure was associated with the type of benzene source that was worked on. Despite the decline in task-based exposure in 2002-2018, technical measures should still be considered in order to reduce the exposure

Validation of a full-shift benzene exposure empirical model developed for work on offshore petroleum installations on the Norwegian continental shelf

Workers on offshore petroleum installations might be exposed to benzene, a carcinogenic agent. Recently, a full-shift benzene exposure model was developed based on personal measurements. This study aimed to validate this exposure model by using datasets not included in the model. The exposure model was validated against an internal dataset of measurements from offshore installations owned by the same company that provided data for the model, and an external dataset from installations owned by another company. We used Tobit regression to estimate GM (geometric mean) benzene exposure overall and for individual job groups. Bias, relative bias, precision, and correlation were estimated to evaluate the agreement between measured exposures and the levels predicted by the model. Overall, the model overestimated exposure when compared to the predicted exposure level to the internal dataset with a factor of 1.7, a relative bias of 73%, a precision of 0.6, a correlation coefficient of 0.72 (p = 0.019), while the Lin’s Concordance Correlation Coefficient (CCC) was 0.53. The model underestimated exposure when compared to the external dataset with a factor of about 2, with a relative bias of −45%, a precision of 1.2, a correlation coefficient of 0.31 (p = 0.544), and a Lin’s CCC of 0.25. The exposure model overestimated benzene exposure in the internal validation dataset, while the precision and the correlation between the measured and predicted exposure levels were high. Differences in measurement strategies could be one of the reasons for the discrepancy. The exposure model agreed less with the external dataset

Occupational Benzene Exposure in the Norwegian Offshore Petroleum Industry, 2002-2018

Purpose Workers on offshore petroleum installations are at risk of being exposed to benzene which is carcinogenic to humans. The present study aimed to assess the time trend of full-shift benzene exposure from 2002 to 2018 in order to characterize benzene exposure among laboratory technicians, mechanics, process operators, and industrial cleaners, and to examine the possible determinants of benzene exposure. Methods A total of 924 measurements of benzene exposure from the Norwegian petroleum offshore industry were included. The median sampling duration was 680 min, ranging from 60 to 940 min. The overall geometric mean (GM) and 95% confidence interval, time trends, and determinants of exposure were estimated using multilevel mixed-effects tobit regression analyses. Time trends were estimated for sampling duration below and above 8 h, both overall and for job groups. The variability of exposure between installation and workers was investigated in a subset of data containing worker identification. Results The overall GM of benzene exposure was 0.004 ppm. When adjusting for job group, design of process area, season, wind speed, and sampling duration, industrial cleaners had the highest exposure (GM = 0.012). Laboratory technicians, mechanics, and process operators had a GM exposure of 0.004, 0.003, and 0.004 ppm, respectively. Overall, the measured benzene exposure increased by 7.6% per year from 2002 to 2018. Mechanics had an annual increase of 8.6% and laboratory technicians had an annual decrease of 12.6% when including all measurements. When including only measurements above 8 h, mechanics had an increase of 16.8%. No statistically significant time trend was found for process operators. Open process area, high wind speed, and wintertime were associated with reduced exposure level. Conclusions An overall increase in measured exposure was observed from 2002 to 2018. The increase may reflect changes in measurement strategy from mainly measuring on random days to days with expected exposure. However, the time trend varied between job groups and was different for sampling duration above or below 8 h. Industrial cleaners had the highest exposure of the four job groups while no differences in exposure were observed between laboratory technicians, mechanics, and process operators. The design of the process area, job group, wind speed, and season were all significant determinants of benzene exposure.publishedVersio

Sex differences in childhood cancer risk among children with major birth defects: a Nordic population-based nested case-control study

Background Childhood cancer is more common among children with birth defects, suggesting a common aetiology. Whether this association differs by sex is unclear. Methods We performed a population-based nested case-control study using nationwide health registries in four Nordic countries. We included 21 898 cancer cases (0–19 years) and 218 980 matched population controls, born 1967–2014. Associations between childhood cancer and major birth defects were calculated as odds ratios (ORs) with 95% confidence intervals (CIs) using logistic regression models. Effect modification was evaluated using a counterfactual framework to estimate confidence intervals and P-values for the natural indirect effects. Results Birth defects were present for 5.1% (1117/21 898) of childhood cancer cases and 2.2% (4873/218 980) of controls; OR of cancer was higher for chromosomal (OR = 10, 95% CI = 8.6–12) than for non-chromosomal defects (OR = 1.9, 95% CI = 1.8–2.1), strongest between genetic syndromes/microdeletion and renal tumours, Down syndrome and leukaemia, and nervous system defects and central nervous system tumours. The association between birth defects and cancer was stronger among females (OR = 2.8, 95% CI = 2.6–3.1) than males (OR = 2.1, 95% CI = 1.9–2.2, Pinteraction <0.001). Male sex was an independent risk factor for childhood cancer, but very little of the overall association between sex and childhood cancer was mediated through birth defects (4.8%, PNIE <0.001), although more at younger ages (10% below years and 28% below 1 year). Conclusions The birth defect–cancer associations were generally stronger among females than males. Birth defects did not act as a strong mediator for the modest differences in childhood cancer risk by sex, suggesting that other biological pathways are involved.publishedVersio

Efficacy and Safety of Analgesic Treatment for Depression in People with Advanced Dementia: Randomised, Multicentre, Double-Blind, Placebo-Controlled Trial (DEP.PAIN.DEM)

Background Chronic pain and depression often co-occur, and pain may exacerbate depression in people with dementia. Objective The objective of this study was to assess the efficacy and safety of analgesic treatment for depression in nursing home patients with advanced dementia and clinically significant depressive symptoms. Methods We conducted a multicentre, parallel-group, double-blind, placebo-controlled trial in 47 nursing homes, including 162 nursing home patients aged ≥ 60 years with dementia (Mini-Mental State Examination ≤ 20) and depression (Cornell Scale for Depression in Dementia ≥ 8). Patients were randomised to receive active analgesic treatment (paracetamol or buprenorphine transdermal system) or identical placebo for 13 weeks. The main outcome measure was the change in depression (Cornell Scale for Depression in Dementia) from baseline to 13 weeks, assessed using linear mixed models with fixed effects for time, intervention and their interaction in the models. Secondary outcomes were to assess whether any change in depression was secondary to change in pain (Mobilisation-Observation-Behaviour-Intensity-Dementia-2 Pain Scale) and adverse events. Results The mean depression change was − 0.66 (95% confidence interval − 2.27 to 0.94) in the active group (n = 80) and − 3.30 (− 4.68 to −1.92) in the placebo group (n = 82). The estimated treatment effect was 2.64 (0.55–4.72, p = 0.013), indicating that analgesic treatment had no effect on depressive symptoms from baseline to 13 weeks while placebo appeared to ameliorate depressive symptoms. There was no significant reduction in pain in the active treatment group (paracetamol and buprenorphine combined) vs. placebo; however, a subgroup analysis demonstrated a significant reduction in pain for paracetamol vs. placebo [by − 1.11 (− 2.16 to − 0.06, p = 0.037)] from week 6 to 13 without a change in depression. Buprenorphine did not have significant effects on depression [3.04 (− 0.11 to 6.19), p = 0.059] or pain [0.47 (− 0.77 to 1.71), p = 0.456] from 0 to 13 weeks. Thirty-five patients were withdrawn from the study because of adverse reactions, deterioration or death: 25 (31.3%) during active treatment [23 (52.3%) who received buprenorphine], and ten (12.2%) in the placebo group. The most frequently occurring adverse events were psychiatric (17 adverse reactions) and neurological (14 adverse reactions). Conclusion Analgesic treatment did not reduce depression while placebo appeared to improve depressive symptoms significantly by comparison, possibly owing to the adverse effects of active buprenorphine. The risk of adverse events warrants caution when prescribing buprenorphine for people with advanced dementia

Tolerability of buprenorphine transdermal system in nursing home patients with advanced dementia: a randomized, placebo-controlled trial (DEP.PAIN.DEM)

Purpose: Buprenorphine transdermal system is increasingly prescribed in people with advanced dementia, but no clinical trial has investigated the safety and factors associated with discontinuation due to adverse events in this population. Patients and methods: One hundred sixty-two people with advanced dementia and significant depression from 47 nursing homes were included and randomized to active analgesic treatment (acetaminophen/buprenorphine) or identical placebo for 13 weeks. In this secondary analysis, the main outcomes were time to and reasons for discontinuation of buprenorphine due to adverse events. Change in daytime activity as measured by actigraphy was a secondary outcome. Results: Of the 44 patients who received active buprenorphine 5 μg/hour, 52.3% (n=23) discontinued treatment due to adverse events compared to 13.3% (6 of 45) in the placebo group (p<0.001). Psychiatric and neurological adverse events were the most frequently reported causes of discontinuation (69.6%, n=16). Concomitant use of antidepressants significantly increased the risk of discontinuation (HR 23.2, 95% CI: 2.95–182, p=0.003). Adjusted for age, sex, cognitive function, pain and depression at baseline, active buprenorphine was associated with 24.0 times increased risk of discontinuation (Cox model, 95% CI: 2.45–235, p=0.006). Daytime activity dropped significantly during the second day of active treatment (-21.4%, p=0.005) and decreased by 12.9% during the first week (p=0.053). Conclusion: Active buprenorphine had significantly higher risk of discontinuation compared with placebo in people with advanced dementia and depression, mainly due to psychiatric and neurological adverse events. Daytime activity dropped significantly during the first week of treatment. Concomitant use of antidepressants further reduced the tolerability of buprenorphine

Tolerability of buprenorphine transdermal system in nursing home patients with advanced dementia: a randomized, placebo-controlled trial (DEP.PAIN.DEM)

Purpose: Buprenorphine transdermal system is increasingly prescribed in people with advanced dementia, but no clinical trial has investigated the safety and factors associated with discontinuation due to adverse events in this population. Patients and methods: One hundred sixty-two people with advanced dementia and significant depression from 47 nursing homes were included and randomized to active analgesic treatment (acetaminophen/buprenorphine) or identical placebo for 13 weeks. In this secondary analysis, the main outcomes were time to and reasons for discontinuation of buprenorphine due to adverse events. Change in daytime activity as measured by actigraphy was a secondary outcome. Results: Of the 44 patients who received active buprenorphine 5 μg/hour, 52.3% (n=23) discontinued treatment due to adverse events compared to 13.3% (6 of 45) in the placebo group (p<0.001). Psychiatric and neurological adverse events were the most frequently reported causes of discontinuation (69.6%, n=16). Concomitant use of antidepressants significantly increased the risk of discontinuation (HR 23.2, 95% CI: 2.95–182, p=0.003). Adjusted for age, sex, cognitive function, pain and depression at baseline, active buprenorphine was associated with 24.0 times increased risk of discontinuation (Cox model, 95% CI: 2.45–235, p=0.006). Daytime activity dropped significantly during the second day of active treatment (-21.4%, p=0.005) and decreased by 12.9% during the first week (p=0.053). Conclusion: Active buprenorphine had significantly higher risk of discontinuation compared with placebo in people with advanced dementia and depression, mainly due to psychiatric and neurological adverse events. Daytime activity dropped significantly during the first week of treatment. Concomitant use of antidepressants further reduced the tolerability of buprenorphine

Occupational Benzene Exposure in the Norwegian Offshore Petroleum Industry, 2002-2018

Purpose Workers on offshore petroleum installations are at risk of being exposed to benzene which is carcinogenic to humans. The present study aimed to assess the time trend of full-shift benzene exposure from 2002 to 2018 in order to characterize benzene exposure among laboratory technicians, mechanics, process operators, and industrial cleaners, and to examine the possible determinants of benzene exposure. Methods A total of 924 measurements of benzene exposure from the Norwegian petroleum offshore industry were included. The median sampling duration was 680 min, ranging from 60 to 940 min. The overall geometric mean (GM) and 95% confidence interval, time trends, and determinants of exposure were estimated using multilevel mixed-effects tobit regression analyses. Time trends were estimated for sampling duration below and above 8 h, both overall and for job groups. The variability of exposure between installation and workers was investigated in a subset of data containing worker identification. Results The overall GM of benzene exposure was 0.004 ppm. When adjusting for job group, design of process area, season, wind speed, and sampling duration, industrial cleaners had the highest exposure (GM = 0.012). Laboratory technicians, mechanics, and process operators had a GM exposure of 0.004, 0.003, and 0.004 ppm, respectively. Overall, the measured benzene exposure increased by 7.6% per year from 2002 to 2018. Mechanics had an annual increase of 8.6% and laboratory technicians had an annual decrease of 12.6% when including all measurements. When including only measurements above 8 h, mechanics had an increase of 16.8%. No statistically significant time trend was found for process operators. Open process area, high wind speed, and wintertime were associated with reduced exposure level. Conclusions An overall increase in measured exposure was observed from 2002 to 2018. The increase may reflect changes in measurement strategy from mainly measuring on random days to days with expected exposure. However, the time trend varied between job groups and was different for sampling duration above or below 8 h. Industrial cleaners had the highest exposure of the four job groups while no differences in exposure were observed between laboratory technicians, mechanics, and process operators. The design of the process area, job group, wind speed, and season were all significant determinants of benzene exposure