ECETOC TRAv3: An In-depth Comparison of Publicly Available Measurement Data Sets With Modelled Estimates of Occupational Inhalation Exposure to Chemicals.

In this study, 129 exposure situations (ESs) with six or more measured inhalation exposures to dust from solids or vapour from liquids in occupational settings were compared with modelled European Centre of Ecotoxicology and Toxicology of Chemicals (ECETOC) targeted risk assessment tool, version 3 (TRAv3) estimates. The measurement data were extracted from previously published studies examining TRAv3 performance and pooled into a curated database. The comparison exercise focussed on the vapour exposure scenarios, as there were too few dust scenarios for a meaningful analysis of any required model corrections. A group of experts in the exposure modelling field retrieved and reviewed the input parameters used in these ESs. Where considered appropriate, modifications were applied to better match the input parameter definitions and the scope of applicability of the TRAv3. Differences and mean absolute error (MAE) were calculated between the log-transformed modelled exposure value and the 75th percentile of each measured data set and regression analysis was performed. The results indicated that the TRAv3 overestimated 80% of the measured data sets. Both over- and underestimations were mostly by factors 1-5. The calculated MAE for liquids was 0.7, indicating that on average the difference between the 75th percentile and the TRAv3 estimate was less than one order of magnitude. A multiple linear regression showed that some input parameters such as medium volatility, certain process categories (PROC), industrial setting, and the presence of local exhaust ventilation are associated with underestimations. The results of the regression analysis can be used by TRAv3 users to review the degree of over- or underestimation in their current exposure assessments, compared to the curated database. Although multiple linear regression is an appropriate methodology to characterize the TRAv3's performance, more data sets are still needed in view of some remaining data gaps. Nevertheless, the results of the current analysis are being used by ECETOC to further develop the tool as a suitably conservative screening tool for use in REACH chemical safety assessment of occupational exposure to chemicals.

Exposure modelling in Europe: how to pave the road for the future as part of the European Exposure Science Strategy 2020-2030.

Exposure models are essential in almost all relevant contexts for exposure science. To address the numerous challenges and gaps that exist, exposure modelling is one of the priority areas of the European Exposure Science Strategy developed by the European Chapter of the International Society of Exposure Science (ISES Europe). A strategy was developed for the priority area of exposure modelling in Europe with four strategic objectives. These objectives are (1) improvement of models and tools, (2) development of new methodologies and support for understudied fields, (3) improvement of model use and (4) regulatory needs for modelling. In a bottom-up approach, exposure modellers from different European countries and institutions who are active in the fields of occupational, population and environmental exposure science pooled their expertise under the umbrella of the ISES Europe Working Group on exposure models. This working group assessed the state-of-the-art of exposure modelling in Europe by developing an inventory of exposure models used in Europe and reviewing the existing literature on pitfalls for exposure modelling, in order to identify crucial modelling-related strategy elements. Decisive actions were defined for ISES Europe stakeholders, including collecting available models and accompanying information in a living document curated and published by ISES Europe, as well as a long-term goal of developing a best-practices handbook. Alongside these actions, recommendations were developed and addressed to stakeholders outside of ISES Europe. Four strategic objectives were identified with an associated action plan and roadmap for the implementation of the European Exposure Science Strategy for exposure modelling. This strategic plan will foster a common understanding of modelling-related methodology, terminology and future research in Europe, and have a broader impact on strategic considerations globally.

Procode: A Machine-Learning Tool to Support (Re-)coding of Free-Texts of Occupations and Industries.

Procode is a free of charge web-tool that allows automatic coding of occupational data (free-texts) by implementing Complement Naïve Bayes (CNB) as a machine-learning technique. The paper describes the algorithm, performance evaluation, and future goals regarding the tool's development. Almost 30 000 free-texts with manually assigned classification codes of French classification of occupations (PCS) and French classification of activities (NAF) were used to train CNB. A 5-fold cross-validation found that Procode predicts correct classification codes in 57-81 and 63-83% cases for PCS and NAF, respectively. Procode also integrates recoding between two classifications. In the first version of Procode, this operation, however, is only a simple search function of recoding links in existing crosswalks. Future focus of the project will be collection of the data to support automatic coding to other classification and to establish a more advanced method for recoding.

Skimmed Milk Applied as a Phytopharmaceutical Product: A Risk for Allergic Populations?

Milk allergy is among the most common food-related allergies. Milk-based products are recognized as plant protection products (PPPs) in several countries as alternatives to synthetic pesticides. The potential health risk for allergic workers, as well as the general population, is yet to be assessed. An investigation was conducted in the Vaud Canton of Switzerland, where milk-based products are sprayed by helicopter over vineyards. Air lactose concentration was measured at 14 locations via 25 mm IOM Multidust samplers. Residual lactose concentration was measured on the surface of leaves over 7 days following spraying. Surface contamination downwind from the treated area was estimated through computer-based modeling using AgDRIFT® software. The average milk protein concentration inside and outside the vineyard was 0.47 and 0.16 µg/m3, respectively. Milk residues persisted on the leaf surface for an average of three days. Modelling results revealed an estimated order of magnitude of 0.1-0.5 µg/m3 in milk proteins within one hour after the treatment in the close vicinity of the treated area. Our results reveal that the potential exposure to milk proteins in and around helicopter-treated vineyards is not negligible and that prevention messages targeted to individuals with severe allergies should be considered.

TREXMO plus: an advanced self-learning model for occupational exposure assessment.

In Europe, several occupational exposure models have been developed and are recommended for regulatory exposure assessment. Only some information on the substance of interest (e.g., vapor pressure) and the workplace conditions (e.g., ventilation rate) is required in these models to predict an exposure value that will be later used to characterize the risk. However, it has been shown that models may differ in their predictions and that usually, one of the models best fits a given set of exposure conditions. Unfortunately, there are no clear rules on how to select the best model. In this study, we developed a new modeling approach that together uses the three most popular models, Advanced REACH Tool, Stoffenmanger, and ECETOC TRAv3, to obtain a unique exposure prediction. This approach is an extension of the TREXMO tool, and is called TREXMO+. TREXMO+ applies a machine-learning technique on a set of exposure data with the measured values to split them into smaller subsets, corresponding to exposure conditions sharing similar characteristics. For each subset, TREXMO+ then establishes a regression model with the three REACH tools used as the exposure predictors. The performance of the new model was tested and a comparison was made between the results obtained by TREXMO+ and those obtained by conventional tools. TREXMO+ model was found to be less biased and more accurate than the REACH models. Its prediction differs generally from measurements by a factor of 2-3 from measurements, whereas conventional models were found to differ by a factor 2-14. However, as the available test dataset is limited, its results will need to be confirmed by larger-scale tests.

Inter-assessor Agreement for TREXMO and Its Models Outside the Translation Framework.

Within the framework of Registration, Evaluation, Authorization, and restriction of CHemicals (REACH), occupational exposure models are often used to predict the levels of exposure at a workplace. Poor inter-assessor agreement with their use poses a concern that may lead to different and dangerous risk conclusions. TREXMO (v1, 2016), a web tool providing parameter translations between six exposure models under REACH, is expected to improve the inter-assessor agreement. In this study, 18 assessors performed exposure assessment for six exposure situations within and outside the framework of this translation tool. In more than half of the evaluated cases, the results showed better agreement between assessors selecting the exposure parameters within the framework of TREXMO than when manually coding. The most affected were the parameters related to activity (such as "handling types" of Stoffenmanager) and exposure control (such as local controls). Furthermore, the agreement between the estimates calculated by different assessors was also improved when performing the translations between the models. For Stoffenmanager, for example, the relative standard deviation of 70-121%, obtained for vapors without applying the translation system, was 29-94% with the translations from ART. These findings showed a potential of TREXMO to impact the inter-assessor agreement. Because the study was limited to 18 assessors and only six exposure situations were assessed, further investigations are suggested.

Evaluation of Exposure Assessment Tools under REACH: Part I-Tier 1 Tools.

Tier 1 occupational exposure assessment tools recommended for use under the Registration, Evaluation, Authorization, and restriction of CHemicals (REACH) were evaluated using newly collected measurement data. Evaluated tools included the ECETOC TRAv2 and TRAv3, MEASEv1.02.01, and EMKG-EXPO-TOOL. Fifty-three exposure situations (ESs) based on tasks/chemicals were developed from National Institute for Occupational Safety and Health field surveys. During the field surveys, high quality contextual information required for evaluating the tools was also collected. For each ES, applicable tools were then used to generate exposure estimates using a consensus approach. Among 53 ESs, only those related to an exposure category of liquids with vapor pressure (VP) > 10 Pa had sufficient numbers of exposure measurements (42 ESs with n = 251 for TRAv2 and TRAv3 and 40 ESs with n = 243 for EMKG-EXPO-TOOL) to be considered in detail. The results for other exposure categories (aqueous solutions, liquids with VP ≤ 10 Pa, metal processing, powders, and solid objects) had insufficient measurement to allow detailed analyses (results listed in the Supplementary File). Overall, EMKG-EXPO-TOOL generated more conservative results than TRAv2 and TRAv3 for liquids with high VP. This finding is at least partly due to the fact that the EMKG-EXPO-TOOL only considers pure substances and not mixtures of chemical agents. For 34 out of 40 ESs available for chemicals with VP > 10 Pa, the liquid was a mixture rather than a pure substance. TRAv3 was less conservative than TRAv2, probably due to additional refinement of some input parameters. The percentages of exposure measurement results exceeding the corresponding tool estimates for liquids with VP > 10 Pa by process category and by input parameters were always higher for TRAv3 compared to those for TRAv2. Although the conclusions of this study are limited to liquids with VP > 10 Pa and few process categories, this study utilized the most transparent contextual information compared to previous studies, reducing uncertainty from assumptions for unknown input parameters. A further validation is recommended by collecting sufficient exposure data covering other exposure categories and all process categories under REACH.

Evaluation of Exposure Assessment Tools under REACH: Part II-Higher Tier Tools.

Stoffenmanager®v4.5 and Advanced REACH Tool (ART) v1.5, two higher tier exposure assessment tools for use under REACH, were evaluated by determining accuracy and robustness. A total of 282 exposure measurements from 51 exposure situations (ESs) were collected and categorized by exposure category. In this study, only the results of liquids with vapor pressure (VP) > 10 Pa category having a sufficient number of exposure measurements (n = 251 with 42 ESs) were utilized. In addition, the results were presented by handling/activity description and input parameters for the same exposure category. It should be noted that the performance results of Stoffenmanager and ART in this study cannot be directly compared for some ESs because ART allows a combination of up to four subtasks (and nonexposed periods) to be included, whereas the database for Stoffenmanager, separately developed under the permission of the legal owner of Stoffenmanager, permits the use of only one task to predict exposure estimates. Thus, it would be most appropriate to compare full-shift measurements against ART predictions (full shift including nonexposed periods) and task-based measurements against task-based Stoffenmanager predictions. For liquids with VP > 10 Pa category, Stoffenmanager®v4.5 appeared to be reasonably accurate and robust when predicting exposures [percentage of measurements exceeding the tool's 90th percentile estimate (%M > T) was 15%]. Areas that could potentially be improved include ESs involving the task of handling of liquids on large surfaces or large work pieces, allocation of high and medium VP inputs, and absence of local exhaust ventilation input. Although the ART's median predictions appeared to be reasonably accurate for liquids with VP > 10 Pa, the %M > T for the 90th percentile estimates was 41%, indicating that variance in exposure levels is underestimated by ART. The %M > T using the estimates of the upper value of 90% confidence interval (CI) of the 90th percentile estimate (UCI90) was considerably reduced to 18% for liquids with VP > 10 Pa. On the basis of this observation, users might be to consider using the upper limit value of 90% CI of the 90th percentile estimate for predicting reasonable worst case situations. Nevertheless, for some activities and input parameters, ART still shows areas to be improved. Hence, it is suggested that ART developers review the assumptions in relation to exposure variability within the tool, toward improving the tool performance in estimating percentile exposure levels. In addition, for both tools, only some handling/activity descriptions and input parameters were considered. Thus, further validation studies are still necessary.

ART, Stoffenmanager, and TRA: A Systematic Comparison of Exposure Estimates Using the TREXMO Translation System.

Several occupational exposure models are recommended under the EU's REACH legislation. Due to limited availability of high-quality exposure data, their validation is an ongoing process. It was shown, however, that different models may calculate significantly different estimates and thus lead to potentially dangerous conclusions about chemical risk. In this paper, the between-model translation rules defined in TREXMO were used to generate 319000 different in silico exposure situations in ART, Stoffenmanager, and ECETOC TRA v3. The three models' estimates were computed and the correlation and consistency between them were investigated. The best correlated pair was Stoffenmanager-ART (R, 0.52-0.90), whereas the ART-TRA and Stoffenmanager-TRA correlations were either lower (R, 0.36-0.69) or no correlation was found. Consistency varied significantly according to different exposure types (e.g. vapour versus dust) or settings (near-field versus far-field and indoors versus outdoors). The percentages of generated situations for which estimates differed by more than a factor of 100 ranged from 14 to 97%, 37 to 99%, and 1 to 68% for Stoffenmanager-ART, TRA-ART, and TRA-Stoffenmanager, respectively. Overall, the models were more consistent for vapours than for dusts and solids, near-fields than for far-fields, and indoor than for outdoor exposure. Multiple linear regression analyses evidenced the relationship between the models' parameters and the relative differences between the models' predictions. The relative difference can be used to estimate the consistency between the models. Furthermore, the study showed that the tiered approach is not generally applicable to all exposure situations. These findings emphasize the need for a multiple-model approach to assessing critical exposure scenarios under REACH. Moreover, in combination with occupational exposure measurements, they might also be used for future studies to improve prediction accuracy.

Comparing the Advanced REACH Tool's (ART) Estimates With Switzerland's Occupational Exposure Data.

The Advanced REACH Tool (ART) is the most sophisticated tool used for evaluating exposure levels under the European Union's Registration, Evaluation, Authorisation and restriction of CHemicals (REACH) regulations. ART provides estimates at different percentiles of exposure and within different confidence intervals (CIs). However, its performance has only been tested on a limited number of exposure data. The present study compares ART's estimates with exposure measurements collected over many years in Switzerland. Measurements from 584 cases of exposure to vapours, mists, powders, and abrasive dusts (wood/stone and metal) were extracted from a Swiss database. The corresponding exposures at the 50th and 90th percentiles were calculated in ART. To characterize the model's performance, the 90% CI of the estimates was considered. ART's performance at the 50th percentile was only found to be insufficiently conservative with regard to exposure to wood/stone dusts, whereas the 90th percentile showed sufficient conservatism for all the types of exposure processed. However, a trend was observed with the residuals, where ART overestimated lower exposures and underestimated higher ones. The median was more precise, however, and the majority (≥60%) of real-world measurements were within a factor of 10 from ART's estimates. We provide recommendations based on the results and suggest further, more comprehensive, investigations.

Basic Features and Clinical Applicability of 'Preliminary Universal Surgical Invasiveness Score' (pUSIS): A Multi-Centre Pilot Study.

OBJECTIVE: There is still a lack of a universally applicable and comprehensive scoring system for documenting the invasiveness of surgical procedures. The proposed preliminary 'Universal Surgical Invasiveness Score' (pUSIS) is intended to fill this gap. METHODS: We used the recently developed pUSIS to obtain values from 8 types of surgery and 80 individual interventions. The results were analysed using descriptive statistical methods. The degree of difficulty on a scale from 0 (very easy) to 10 (extremely difficult) and time expenditures for assessing pUSIS were documented. RESULTS: Individual pUSIS values ranged from 8 in a laparoscopic cholecystectomy case to 36 in a total hip replacement case. The lowest median pUSIS value of 11.5 was found for laparoscopic cholecystectomy and the highest value of 24.5 was found for open thoracic surgery. The correlation between pUSIS values and the duration of surgery resulted in a tight linear regression (R2=0.6419). The lowest mean (±SD) difficulty level to obtain pUSIS values was 1.6±0.6 for sleeve gastrectomy and the highest one was 2.9±0.6 for knee replacement. The duration to finalise the calculations was 4.1±1.1 min for video-assisted thoracoscopy (VATS) and 9.4±1.3 min for sleeve gastrectomy. CONCLUSION: We concluded that pUSIS has the potential to be a useful, simply obtainable and universal assessment tool for quantification of the magnitude and invasiveness of individual surgical operations and can serve as a means to quantify surgical interventions for outcome research and evaluate surgical performance.

TREXMO: A Translation Tool to Support the Use of Regulatory Occupational Exposure Models.

Occupational exposure models vary significantly in their complexity, purpose, and the level of expertise required from the user. Different parameters in the same model may lead to different exposure estimates for the same exposure situation. This paper presents a tool developed to deal with this concern-TREXMO or TRanslation of EXposure MOdels. TREXMO integrates six commonly used occupational exposure models, namely, ART v.1.5, STOFFENMANAGER(®) v.5.1, ECETOC TRA v.3, MEASE v.1.02.01, EMKG-EXPO-TOOL, and EASE v.2.0. By enabling a semi-automatic translation between the parameters of these six models, TREXMO facilitates their simultaneous use. For a given exposure situation, defined by a set of parameters in one of the models, TREXMO provides the user with the most appropriate parameters to use in the other exposure models. Results showed that, once an exposure situation and parameters were set in ART, TREXMO reduced the number of possible outcomes in the other models by 1-4 orders of magnitude. The tool should manage to reduce the uncertain entry or selection of parameters in the six models, improve between-user reliability, and reduce the time required for running several models for a given exposure situation. In addition to these advantages, registrants of chemicals and authorities should benefit from more reliable exposure estimates for the risk characterization of dangerous chemicals under Regulation, Evaluation, Authorisation and restriction of CHemicals (REACH).

Peripartum Cardiomyopathy in Intensive Care Unit: An Update.

Peripartum cardiomyopathy (PPCM) is a systolic heart failure that occurs during the last month of pregnancy or within 5 months after delivery. It is an uncommon disease of unknown etiopathogenesis and has a very high rate of maternal mortality. Because of similarity between symptoms of PPCM and physiological discomforts during pregnancy, the early diagnosis of PPCM presents a major challenge. Since hemodynamic changes during PPCM can vitally jeopardize the mother and the fetus, patients with severe forms of PPCM require a multidisciplinary approach in intensive care units. This review summarizes the current state of knowledge about the diagnosis, monitoring, and the treatment of PPCM. Having reviewed the recent researches, it gives insight into the new treatment strategies of this rare disease.

Beyond the Limits: Clinical Utility of Novel Cardiac Biomarkers.

Preoperative assessment of cardiovascular risk is essential when it comes to extensive noncardiac surgery procedures. Therefore, accurate and timely diagnosis of myocyte damage is vital. In modern medical practice it is believed that the so-called "multimarker" approach is the most appropriate and most accurate, but new research points out that there are novel biomarkers which could be used independently. Studies that evaluate miRNA, H-FABP, and MR-PAMP give encouraging results. When it comes to miRNA clinical studies show high statistical significance, especially in the case of acute myocardial infarction (P = 0.001). Statistical significance of P = 0.007 was found in acute coronary syndrome, when H-FABP was measured. Biochemical marker MR-PAMP showed statistical significance of P < 0.0001 in most clinical studies.

Late complication of a renal calculus: fistulisation to the psoas muscle, skin and bronchi.

Kidney disease presenting with cutaneous fistula is a rare condition. We present a case of a 90-year-old woman with dementia who had no prior urological problems and had a cutaneous fistula in the left lumbar region. A fistulogram and computer tomography examination revealed a large staghorn calculus with signs of xanthogranulomatous pyelonephritis in the left kidney and renal fistulisation to the psoas muscle, skin and bronchi. To our knowledge this is the first report in the literature of coexisting renal fistulisation to the psoas major muscle, skin and bronchi. This report illustrates how computed tomography in combination with fistulography can resolve the diagnostic dilemma that pertains to the complex spread of the disease in cases involving nephrocutaneous fistula. Furthermore, the report shows how a renal calculus, even asymptomatic, can cause a serious medical condition, and highlights the importance of early medical intervention.

Late complication of a renal calculus: fistulisation to the psoas muscle, skin and bronchi

ABSTRACTKidney disease presenting with cutaneous fistula is a rare condition. We present a case of a 90-year-old woman with dementia who had no prior urological problems and had a cutaneous fistula in the left lumbar region. A fistulogram and computer tomography examination revealed a large staghorn calculus with signs of xanthogranulomatous pyelonephritis in the left kidney and renal fistulisation to the psoas muscle, skin and bronchi. To our knowledge this is the first report in the literature of coexisting renal fistulisation to the psoas major muscle, skin and bronchi. This report illustrates how computed tomography in combination with fistulography can resolve the diagnostic dilemma that pertains to the complex spread of the disease in cases involving nephrocutaneous fistula. Furthermore, the report shows how a renal calculus, even asymptomatic, can cause a serious medical condition, and highlights the importance of early medical intervention.

Risk factors associated with carotid artery puncture following landmark-guided internal jugular vein cannulation attempts.

OBJECTIVE: The relationship between certain risk factors and carotid artery puncture (CAP) as an early mechanical complication following internal jugular vein cannulation attempts (IJVCAs) was evaluated. METHODS: In a retrospective 1-year observational single-center study, 86 IJVCAs conducted in the operating room by 4 competent anesthesiologists were evaluated. Age, gender, puncture side, number of cannulation attempts, circumstances of the procedure and incidence of CAP were obtained from medical records. RESULTS: Of the 86 IJVCAs performed in patients aged 18-75 years, CAP occurred in 8 (9.3%): 5 (5.8%) in patients >65 years and 3 (3.5%) in patients <65 years of age. CAP was not associated with patient's age (p = 0.11) and gender (p = 0.76). Multiple cannulation attempts (OR = 26.25; 95% CI = 4.52-152.51; p < 0.001) and placement of CVC under emergency conditions (OR = 14.84; 95% CI = 1.73-127.22; p = 0.014) increased the risk for CAP significantly. Also, the risk for CAP was higher when IJVCAs were performed before induction of general anesthesia (OR = 15.75; 95% CI = 1.83-135.1; p = 0.019). CAP was more likely to happen during left-sided than right-sided IJVCA (OR = 5.98; 95% CI = 1.29-27.59; p = 0.022). In addition, left-sided attempts considerably increased the risk for multiple cannulation attempts (OR = 2.782; 95% CI = 1.342-3.965; p < 0.01). Also, manifold cannulation attempts were more frequent if the IJVCA was performed before induction of anesthesia (OR = 4.219; CI = 1.579-11.271; p = 0.004). CONCLUSIONS: Our results strongly suggest that left-sided, multiple IJVCAs, performed under emergency conditions in conscious patients in the operating room, represent considerable risks for possible CAP.