Alain Chamoux

The long-term effects of occupational exposure to vinyl chloride monomer on microcirculation : a cross-sectional study 15 years after retirement

Objectives To assess residual long-term microcirculation abnormalities by capillaroscopy, 15 years after retiring from occupational exposure to vinyl chloride monomer (VCM). Design Cross-sectional study. Setting Allier, one of the major areas of polyvinyl chloride production in France. Participants We screened 761 (97% men) retired workers exposed to chemical toxics. Exposure to chemicals other than VCM excluded potential participants. Primary and secondary outcome measures These participants underwent a medical examination including a capillaroscopy, symptoms of Raynaud and comorbidities, as well as a survey to determine exposure time, direct or indirect contact, type of occupation, smoking status and time after exposure. A double blind analysis of capillaroscopic images was carried out. A control group was matched in age, sex, type of occupation. Results 179/761 retired workers were only exposed to VCM at their work, with 21 meeting the inclusion criteria and included. Exposure time was 29.8±1.9 years and time after exposure was 15.9±2.4 years. Retired workers previously exposed to VCM had significantly higher capillaroscopic modifications than the 35 controls: enlarged capillaries (19% vs 0%, p<0.001), dystrophy (28.6% vs 0%, p=0.0012) and augmented length (33% vs 0%, p<0.001). Time exposure was linked (p<0.001) with enlarged capillaries (R2=0.63), dystrophy (R2=0.51) and capillary length (R2=0.36). They also had higher symptoms of Raynaud (19% vs 0%, p=0.007) without correlation with capillaroscopic modifications. Conclusions Although VCM exposure was already known to affect microcirculation, our study demonstrates residual long-term abnormalities following an average of 15 years’ retirement, with a time-related exposure response. Symptoms of Raynaud, although statistically associated with exposure, were not related to capillaroscopic modifications; its origin remains to be determined.

Comparison of the ultra-low-dose Veo algorithm with the gold standard filtered back projection for detecting pulmonary asbestos-related conditions: a clinical observational study

Objectives Radiation delivered during CT is a major concern, especially for individuals undergoing repeated screening. We aimed to compare a new ultra-low-dose algorithm called Veo with the gold standard filtered back projection (FBP) for detecting pulmonary asbestos-related conditions. Setting University Hospital CHU G. Montpied, Clermont-Ferrand, France Participants Asbestos-exposed workers were recruited following referral to screening for asbestos-related conditions. Two acquisitions were performed on a 64-slice CT: the gold standard FBP followed by Veo reconstruction. Outcome measures Two radiologists independently assessed asbestos-related abnormalities, pulmonary nodules, radiation doses and image quality (noise). Results We included 27 asbestos-exposed workers (63.3±6.5 years with 11.9±9.7 years of asbestos exposure). We observed 297 pleural plaques in 20 participants (74%). All patients (100%) had pulmonary nodules, totalling 167 nodules. Detection rates did not differ for pleural plaques (Veo 87% vs FBP 97%, NS), pleural thickening (100% for both) and pulmonary nodules (80% for both). Interstitial abnormalities were depicted less frequently with Veo than FBP. False negative and false positive did not exceed 2.7%. Compared with FBP, Veo decreased the radiation dose up to 87% (Veo 0.23±0.07 vs FBP 1.83±0.88 mSv, p<0.001). The objective image noise also decreased with Veo as much as 23% and signal-to-noise ratio increased up to 33%. Conclusions A low-dose CT with Veo reconstruction substantially reduced radiation. Veo compared favourably with FBP in detecting pleural plaques, pleural thickening and pulmonary nodules. These results should be confirmed on a larger sample size before the use of Veo in clinical routine practice in asbestos-related conditions, especially regarding the low prevalence of interstitial abnormalities in this study. Trial registration number NCT01955018.

Urinary Interleukin-8 Is a Biomarker of Stress in Emergency Physicians, Especially with Advancing Age — The JOBSTRESS* Randomized Trial

Background Emergency physicians are exposed to greater stress during a 24-hour shift (24 hS) than a 14-hour night shift (14 hS), with an impact lasting several days. Interleukin-8 (IL-8) is postulated to be a chronic stress biomarker. However, no studies have tracked IL-8 over several shifts or used it for monitoring short-term residual stress. The IL-8 response to the shifts may also increase with age. Conveniently, IL-8 can be measured non-intrusively from urine. Methods We conducted a shifts-randomized trial comparing 17 emergency physicians’ urinary IL-8 levels during a 24 hS, a 14 hS, and a control day (clerical work on return from leave). Mean levels of IL-8 were compared using a Wilcoxon matched-pairs test. Independent associations of key factors including shifts, stress, and age with IL-8 levels were further assessed in a multivariable generalized estimating equations model. Results Mean urinary IL-8 levels almost doubled during and after a 24 hS compared with a 14 hS or a control day. Furthermore, IL-8 levels failed to return to control values at the end of the third day after the shift despite a rest day following the 24 hS. In the multivariable model, engaging in a 24 hS, self-reported stress, and age were independently associated with higher IL-8 levels. A 24 hS significantly increased IL-8 levels by 1.9 ng (p = .007). Similarly, for every unit increase in self-reported stress, there was a 0.11 ng increase in IL-8 levels (p = .003); and for every one year advance in age of physicians, IL-8 levels also increased by 0.11 ng (p = .018). Conclusion The 24 hS generated a prolonged response of the immune system. Urinary IL-8 was a strong biomarker of stress under intensive and prolonged demands, both acutely and over time. Because elevated IL-8 levels are associated with cardiovascular disease and negative psychological consequences, we suggest that emergency physicians limit their exposure to 24 hS, especially with advancing age.

Prevalence of dry eye disease in visual display terminal workers: a systematic review and meta-analysis

Objective To evaluate the prevalence and risk factors of dry eye disease (DED) in workers using visual display terminals (VDT). Design Systematic review and meta-analysis. Data sources We searched PubMed, Cochrane Library, Embase and Science Direct databases for studies reporting DED prevalence in VDT workers. Results 16 of the 9049 identified studies were included, with a total of 11 365 VDT workers. Despite a global DED prevalence of 49.5% (95% CI 47.5 to 50.6), ranging from 9.5% to 87.5%, important heterogeneity (I2=98.8%, p<0.0001) was observed. Variable diagnosis criteria used within studies were: questionnaires on symptoms, tear film anomalies and corneoconjunctival epithelial damage. Some studies combined criteria to define DED. Heterogeneous prevalence was associated with stratifications on symptoms (I2=98.7%, p<0.0001), tears (I2=98.5%, p<0.0001) and epithelial damage (I2=96.0%, p<0.0001). Stratification of studies with two criteria adjusted the prevalence to 54.0% (95% CI 52.1 to 55.9), whereas studies using three criteria resulted in a prevalence of 11.6% (95% CI 10.5 to 12.9). According to the literature, prevalence of DED was more frequent in females than in males and increased with age. Conclusions Owing to the disparity of the diagnosis criteria studied to define DED, the global prevalence of 49.5% lacked reliability because of the important heterogeneity. We highlight the necessity of implementing common DED diagnostic criteria to allow a more reliable estimation in order to develop the appropriate preventive occupational actions.

'Do Well B.': Design Of WELL Being monitoring systems. A study protocol for the application in autism.

Introduction Individuals with autism spectrum disorder (ASD) have difficulties in communication and social interaction resulting from atypical perceptual and cognitive information processing, leading to an accumulation of anxiety. Extreme overloading experienced internally may not be externally visible. Identifying stressful situations at an early stage may avoid socially problematic behaviour from occurring, such as self-injurious behaviour. Activation of the autonomous nervous system (ANS) is involved in the response to anxiety, which can be measured through heart rate variability and skin conductance with the use of portable devices, non-intrusively and pain-free. Thus, developing innovative analysis of signal perception and reaction is necessary, mainly for non-communicative individuals with autism. Methods and analysis The protocol will take place in real life (home and social environments). We aim to associate modifications of the ANS with external events that will be recorded in a synchronous manner through a specific design (spy glasses with video/audio recording). Four phases will be carried out on ASD participants and aged-matched controls: (1) 24-hour baseline pre-experiment (physical activity, sleep), (2) 2 h in a real life situation, (3) 30 min in a quiet environment, interrupted by a few seconds of stressful sound, (4) an interview to record feelings about events triggering anxiety. ASD and control participants will be together for phases 2 and 3, revealing different physiological responses to the same situations, and thus identifying potentially problematic events. The novelty will be to apply time-series analyses (which led to several Nobel Prizes in quantitative finance) on ANS series (heart rate, heart rate variability, skin conductance) and wrist motion. Ethics and dissemination Ethical approval has been obtained from Ethics Committee of Clermont-Ferrand (South-East I), France (2014-A00611–46). Trial findings will be disseminated via open-access peer-reviewed publications, conferences, clinical networks, public lectures and our websites. Trial registration number ClinicalTrials identifier NCT02275455.

Paradoxical dissociation between heart rate and heart rate variability following different modalities of exercise in individuals with metabolic syndrome: The RESOLVE study.

Aims To analyse the effects of different modalities of exercise training on heart rate variability (HRV) in individuals with metabolic syndrome (MetS). Methods and results Eighty MetS participants (aged 50–70 years) were housed and managed in an inpatient medical centre for 21 days, including weekends. Physical activity and food intake/diet were intensively monitored. Participants were randomly assigned into three training groups, differing only by intensity of exercise: moderate-endurance-moderate-resistance (re), high-resistance-moderate-endurance (Re), and moderate-resistance-high-endurance (rE). HRV was recorded before and after the intervention by 24-hour Holter electrocardiogram. Although mean 24-hour heart rate decreased more in Re than re (–11.6 ± 1.6 vs. –4.8 ± 2.1%; P = 0.010), low frequency/high frequency decreased more in re than Re (–20.4 ± 5.5% vs. + 20.4 ± 9.1%; P = 0.002) and rE (–20.4 ± 5.5% vs. –0.3 ± 11.1%; P = 0.003). Very low frequency increased more in Re than re (+121.2 ± 35.7 vs. 42.9 ± 11.3%; P = 0.004). For all HRV parameters, rE ranged between re and Re values. Low frequency/high frequency changes were linked with visceral fat loss only in re (coefficient 5.9, 95% CI 1.9–10.0; P = 0.004). By day 21, HRV parameters of MetS groups (heart rate –8.6 ± 1.0%, standard deviation of R-R intervals + 34.0 ± 6.6%, total power + 63.3 ± 11.1%; P < 0.001) became closer to values of 50 aged-matched healthy controls. Conclusions A 3-week residential programme with intensive volumes of physical activity (15–20 hours per week) enhanced HRV in individuals with MetS. Participants with moderate intensity of training had greater improvements in sympathovagal balance, whereas those with high intensity in resistance training had greater decreases in heart rate and greater increases in very low frequency. Modality-specific relationships were observed between enhanced HRV and visceral fat loss. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00917917.

A Dimensionally Reduced Clustering Methodology for Heterogeneous Occupational Medicine Data Mining

Clustering is a set of techniques of the statistical learning aimed at finding structures of heterogeneous partitions grouping homogenous data called clusters. There are several fields in which clustering was successfully applied, such as medicine, biology, finance, economics, etc. In this paper, we introduce the notion of clustering in multifactorial data analysis problems. A case study is conducted for an occupational medicine problem with the purpose of analyzing patterns in a population of 813 individuals. To reduce the data set dimensionality, we base our approach on the Principal Component Analysis (PCA), which is the statistical tool most commonly used in factorial analysis. However, the problems in nature, especially in medicine, are often based on heterogeneous-type qualitative-quantitative measurements, whereas PCA only processes quantitative ones. Besides, qualitative data are originally unobservable quantitative responses that are usually binary-coded. Hence, we propose a new set of strategies allowing to simultaneously handle quantitative and qualitative data. The principle of this approach is to perform a projection of the qualitative variables on the subspaces spanned by quantitative ones. Subsequently, an optimal model is allocated to the resulting PCA-regressed subspaces.

Occupational exposure factors for mental and behavioral disorders at work: The FOREC thesaurus

Background Mental disorders in the workplace are a major public health problem. Knowledge of the impact of the psychosocial work environment on mental and behavioral disorders can assist occupational physicians in the identification and description of occupational risk situations, and help to define priority actions. However, no classification for occupational exposure factors is currently available. We aimed to build a thesaurus of “Organizational, Relational, Ethical and other Contributing Factors” (FOREC) linked with the onset of mental and behavioral disorders. Methods The French Agency for Food, Environmental and Occupational Health and Safety (ANSES) initiated and supervised a multidisciplinary working group consisting of the representatives of the main French occupational and public health actors. All decisions were accepted on a consensus basis. This collaborative work led to the classification of occupational exposure factors for mental and behavioral disorders in the workplace. To test this thesaurus in clinical practice, a French multicenter study was implemented. Patients were workers referred to the Occupational Disease Centers for mental health issues at work. Factors contributing to mental and behavioral disorders among workers were identified and coded retrospectively from the worker’s point of view using the FOREC thesaurus. Results We recruited 323 workers, aged 44.9±9.2 years, of which 31.3% were men. The most commonly encountered disorders were generalized anxiety disorders (106 workers, 32.8%) and moderate depressive episodes (86 workers, 26.7%). We identified 1357 factors, i.e. an average of 4.2 factors per worker. Among them, 575 (42.4%) were relational and 515 (37.9%) were organizational. All factors identified during consultations were described in the thesaurus. Conclusions We built the first thesaurus of “Organizational, Relational, Ethical and other Contributing Factors” (FOREC) that may help to generate profiles of mental and behavioral disorders at work. Encoding and describing these exposure factors, as well as using a worldwide standardized and shared terminology, will help to identify specific workplace prevention programs.

Urine cytology screening of French workers exposed to occupational urinary tract carcinogens: a prospective cohort study over a 20-year period

Objectives To demonstrate that urine cytology screening can provide relevant epidemiological data for earlier detection of urothelial cancer caused by occupational exposure. Design Prospective cohort study. Setting Industries using urothelial carcinogens in France. Urine samples were collected on site, after a work week and were analysed at the University Hospital of Clermont-Ferrand, France. Participants Participants were workers exposed to urothelial carcinogens. Women and current smokers at time of study recruitment were exclusion criteria. Outcomes Urine cells atypia were ranged into three classes: negative/normal, atypical/suspicious/dysplasia or positive/malignant. Results We included 2020 workers over a period of 20 years from 1993 to 2013: 606 worked in rubber manufacturing, 692 from metal processing, 245 in chemical industry and 477 in roadwork and building industry. Workers had a mean exposure of 15.2±10.4 years before their first urine cytology screening. There was a mean of 3.4±4.3 urine cytology screenings per worker between 1993 and 2013. 6478 cytology were normal, 462 suspicious and 13 malignant. Suspicious and malignant cytology occurred in 4.8% of workers exposed for 1–10 years, 6.2% for 11–20 years of exposure, 7.6% for 21–30 years and 8.6% for >30 years (p<0.001). Using exposure for 1–10 years as reference, the adjusted OR of receiving a suspicious or malignant diagnosis increased with duration of exposure: OR=1.50 (95% CI 1.10 to 2.05, p=0.01) for 21–30 years and OR=1.78 (95% CI 1.23 to 2.56, p=0.002) for >30 years of exposure. Using metal processing as reference, the risk of pathological urine cytology results increased for rubber manufacturing (OR=1.32, 95% CI 1.05 to 1.65, p=0.02), with a trend for roadwork and building industry (OR=1.39, 95% CI 0.98 to 1.97, p=0.07) and for chemical industry (OR=1.34, 95% CI 0.94 to 1.93, p=0.11). Conclusions Urine cytology is a useful tool in occupational medicine. We promote new guidelines with an early screening of urothelial cancer by cytology, starting with beginning of exposure.

Report of three cases of renal oncocytoma in the same French chemical industrial factory.

To the Editor: Renal oncocytoma is a rare benign tumor, accounting for 3% to 7% of primary renal tumors. There are no clearly established etiological factors. Three cases of renal oncocytoma detected between 2000 and 2008 in employees or subcontractors working for the same factory “F” in central France during a systematic screening campaign by ultrasonography are reported. The company specializes in vitamin and amino acid synthesis, in particular, vitamin A, vitamin E, and methionine. The factory is currently undergoing epidemiological investigations by the National Health and Work Department of the National Health Watch Institute (InVS) following nine cases of renal cell carcinoma (RCC) detected in workers between 1994 and 2002, at first by chance and later by systematic ultrasonography. The company began systematic screening for hepatic angiosarcoma in 1986 by yearly abdominal ultrasonography of employees exposed to monomer vinyl chloride (MVC). In 1992, the screening program was extended to workers exposed to chloracetal C5. This molecule is an intermediate chemical produced in the course of a new process for vitamin A synthesis called NAVAS (new vitamin A synthesis) first implemented in the factory in 1982. At that time, the molecule was known to be mutagenic in vitro. Since 2002, all company employees undergo ultrasound screening on a voluntary basis. To date, 28 cases of RCC have been detected in this company; most were clear-cell and papillary RCC, but there were also three cases of oncocytoma and one angiomyolipoma. We describe the cases of oncocytoma with particular focus on the possible relation to occupational exposure.